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Neurodevelopment and the effects of a neurobehavioral intervention in verypreterm-born children

van Hus, J.W.P.

Publication date2014Document VersionFinal published version

Link to publication

Citation for published version (APA):van Hus, J. W. P. (2014). Neurodevelopment and the effects of a neurobehavioralintervention in very preterm-born children.

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VERDEDIGING

Hierbij bent u uitgenodigd voor de openbare verdediging

van het proefschrift van Janeline W. P. Van Hus

Neurodevelopment and the effects of a

neurobehavioral intervention in very

preterm-born children

Op vrijdag 5 december 2014om 10.00 uur

in de Agnietenkapel van de Universiteit van AmsterdamOudezijds Voorburgwal 231

1012 EZ Amsterdam

Janeline Van HusVrolikstraat 337C

1092 TA [email protected]

06 20 34 42 22

PARANIMFENIngrid Hofsteede

[email protected] 15 61 84 37

Jacqueline [email protected]

06 40 14 08 47

RECEPTIETer plaatse na afloop van de verdediging

Neurodevelopment and the effects of a neurobehavioral intervention in very preterm-born children

Janeline W.P. van Hus

Janeline van Hus werd geboren op 23 januari 1963 te Amsterdam. Na het behalen van haar HAVOdiploma aan de Chr. Scholengemeenschap “Buitenveldert” te Amsterdam in 1981, volgde zij de opleiding Fysiotherapie bij Stichting Academie voor Paramedische Beroepen ‘Leffelaar’, waar zij in 1985 met lof afstudeerde. Janeline’s eerste publicatie ‘De tiende hersenzenuw en de emotie van allergisch astmatici’ vloeide voort uit haar eindexamen scriptie en grote interesse in de ontwikkeling van kinderen. Janeline startte haar loopbaan in het Pediatric Rehabilitation Hospital and Center for severely handicapped children ‘Alyn’ te Jeruzalem (Israël) en het Universitätsspital “Inselspital” te Bern (Zwitserland), waar zij haar eerste ervaringen als kinderfysiotherapeut opdeed. In 1989 trad Janeline in dienst bij het Revalidatiecentrum ‘Rijndam-Adriaanstichting’ te R’dam, waar zij zich met veel plezier 12 jaar lang alle ins en out van de kinder-revalidatie eigen maakte, vele opleidingen en cursussen volgden en in 1997 haar registratie kinderfysiotherapie behaalde. Naast haar werk zette zij zich in voor korte ontwikkelingsprojecten in Thailand en Mozambique op het gebied van onderwijs en kinderrevalidatie. In 2000 maakte Janeline de overstap naar de afdeling Revalidatie van het Academisch Medisch Centrum te A’dam waar zij zich bezig houdt met de klinische kinder-fysiotherapeutische zorg. Geïnspireerd door het neurologisch gedragsonderzoek bij het prematuur geboren kind, volgde Janeline in 2002-2003 de IBAIP opleiding en participeerde in een effect onderzoek. Dit resulteerde in 2009 tot het opzetten van een vervolgonderzoek, beschreven in dit proefschrift. Tijdens het onderzoekstraject schoolde Janeline zich in epidemiologie, statistiek en klinisch data management aan de AMC Graduate School forMedical Science. Janeline is getrouwd met haar grote liefde Meijer die ze tijdens het uitvoeren van haar 3 passies; reizen, bergwandelen en fotografie, in 2006 in Patagonië ontmoette.



Academisch proefschriftUniversiteit van Amsterdam

Cover statue Tom Otterness ‘Sprookjesbeelden aan Zee’ Scheveningen 2012Cover design Annoek Louwers Janeline van HusPhotography Janeline van HusLay out & print Gildeprint, Enschede

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neurobehavioral intervention

in very preterm-born children


The studies presented in this thesis were carried out under the auspices of:

The department of Rehabilitation, Academic Medical Center, Amsterdam

The department of Neonatology, Academic Medical Center, Amsterdam

The studies were financially supported by:

Innovatie fonds Zorgverzekeraars (project 576)

Zorg Onderzoek Nederland (ZonMwproject 62200032)



Publication of this thesis was financially supported by:



De Nederlands Vereniging voor Fysiotherapie in de Kinder- en Jeugdgezondheidszorg

(NVFK)

Het Stimuleringsfonds van het Wetenschappelijk College Fysiotherapie van het Koninklijk

Nederlands Genootschap voor Fysiotherapie (KNGF).

Nutricia Nederland B.V.

ISBN 978-94-6108-807-9

Copyright© 2014 Janeline W.P. van Hus, Amsterdam, the Netherlands

All rights reserved. No part of this thesis may be reproduced, stored or transmitted in any

form or by any means, without prior permission of the author, or, when applicable, of

the publishers of the scientific papers.


neurobehavioral intervention

in very preterm-born children

ACADEMISCH PROEFSCHRIFT

ter verkrijging van de graad van doctor

aan de Universiteit van Amsterdam

op gezag van de Rector Magnificus

prof. dr. D.C. van den Boom

ten overstaan van een door het college voor promoties

ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel

op vrijdag 5 december 2014 te 10.00 uur

door

Jacqueline Wilhelmine Petronella van Hus

geboren te Amsterdam

PROMOTIECOMMISSIE

Promotoren: Prof. dr. J.H. Kok

Prof. dr. F. Nollet

Co-promotoren: Dr. M. Jeukens-Visser

Dr. A.G. van Wassenaer-Leemhuis

Overige leden: Prof. dr. J.G. Becher

Prof. dr. M.A. Grootenhuis

Prof. dr. M.J. Jongmans

Prof. dr. A.H.L.C. van Kaam

Prof. dr. M.W.G. Nijhuis-van der Sanden

Prof. dr. J. Oosterlaan

Faculteit der Geneeskunde

CONTENTS

Chapter 1 General introduction 7

Chapter 2 Reliability, sensitivity and responsiveness of the Infant 27

Behavioral Assessment in very preterm infants

Acta Paediatrica 2012;10:258-263

Chapter 3 Comparing two motor assessment tools to evaluate 41

neurobehavioral intervention effects in very low birth weight

infants at 1 year

Physical Therapy 2013;93:1475-1483

Chapter 4 Motor impairment in very preterm-born children: Links with 57

other developmental deficits at 5 years of age

Developmental Medicine & Child Neurology 2014;56;587-594

Chapter 5 Sustained developmental effects of the Infant Behavioral 75

Assessment and Intervention Program in very low birth

weight infants at 5.5 years

Journal of Pediatrics 2013; 163:1112-1119

Chapter 6 Longitudinal developmental effects of the Infant Behavioral 91

Assessment and Intervention Program in very low birth

weight infants

Submitted

Chapter 7 General discussion 107

Summary / Samenvatting 123

List of contributing authors 137

Dankwoord 141

Appendix 147

List of Abbreviations 151

Portfolio / Publications 155

Chapter 1

General introduction

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8 | Chapter 1

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General introduction | 9

1Introduction

The general aim of this thesis is to expand the knowledge on long-term effects of

an early intervention program for very preterm-born children, to provide optimal

neurodevelopmental care and support for these vulnerable children and their parents.

Very preterm or very low birth weight infants

Preterm birth is defined by the World Health Organization as infants born before 37

weeks of gestation as measured from the last day of the last menstrual period.1 Infants

less than 32 weeks’ gestation are classified as very preterm, and less than 28 weeks’

gestation as extremely preterm infants. Birth weight is also often used as an indicator

for a neonate’s maturity, because not always gestational age is exactly known. Low birth

weight infants are defined as infants with a birth weight less than 2500 grams, very low

birth weight as less than 1500 gram, and extremely low birth weight infants as less than

1000 gram. In this thesis we focus on infants with a gestational age less than 32 weeks

and/or a birth weight less than 1500 gram and we use the denomination “very low birth

weight” (VLBW). Improved and technologically more advanced care in the neonatal

intensive care unit (NICU) increased the survival rate of VLBW infants about 30% in the

late nineties.2 In the Netherlands, 1.5% (n=2633) of all infants, born alive in 2012, were

VLBW infants.3

Factors that influence neurodevelopment in VLBW infants

During the last trimester of pregnancy the organization and myelination of the central

nerve system (CNS) take place.4 The synaptogenesis of neuronal circuits is regulated by

endogenous factors on the one side and sensory input and experience on the other side.5

Scientific research has proven that these early experiences during sensitive period of

development plays an exceptionally important role in shaping the capacities of the brain

and future functioning of the infant.6

At 3 years of age, the child has about twice as many synapses as an adult. Those

synapses that have been reinforced by virtue of repeated activation give rise to chemical

changes that stabilize the synapses; the synapses that are not often used in early years,

appear to be eliminated.7 A major ingredient in this process is the “serve and return”

relationship between infants and their parents.8 Young infants naturally reach out for

interaction through facial expressions, babbling and gestures and adults respond at

them. These reciprocal and dynamic interactions of parental sensitive-responsiveness

and child participation are essential for neurodevelopmental progression and literally

shape the architecture of the developing brain.6,9

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10 | Chapter 1

There are factors, especially in VLBW infants, that have an adverse effect on brain-

and neurodevelopment, so-called biological and environmental risk factors. Biology

is a proxy for factors that determine the biologic make-up of the infant at birth and

environment is a proxy for social and postnatal factors.10

Biological risk factors

At the very important period of multiple brain developmental, the normal process of

brain maturation is confronted with preterm birth and the untimely change from intra-

uterine to extra-uterine environment. The immaturity of many organs and the combined

effects of circulatory, respiratory, immunogenic and metabolic derangements play a role

in the causation of brain injuries in VLBW infants. Cerebral complications with a high

incidence are intraventricular hemorrhages (IVH) and periventricular leucomalacie (PVL).

IVH occur in about 20% of the VLBW infants, taken high and low severity presentation

together, and varying degrees of cerebral white matter, PVL, even in 50%.11 IVH and

PVL occur isolated or in combination, and may both be accompanied by hydrocephalus.

The brain injuries are affecting volume, integrity, and connectivity of the cerebral white

matter, cortical grey matter, thalamus, basal ganglia, cerebral cortex, corpus callosum

and cerebellum.12-14 These brain alternations, for their part, have negative influences

on autonomic stability, state organization and motor maturation, and have profound

implications for cognitive, motor, and behavioral functioning.14-17

Several other biological risk factors play a role in the origin of altered brain

maturation and brain injuries and, subsequent neurodevelopmental deficits, most

importantly chronic lung diseases and infections. Bronchopulmonary dysplasia (BPD) has

emerged in the past decade as the leading cause of chronic lung disease in infancy and

develops in preterm neonates treated with oxygen and positive pressure ventilation.18

The pathogenesis is complex and results from injures in the small airways that interfere

with alveolarization and developing pulmonary vasculature. BPD affects at least one-

quarter of infants born with birth weights <1500 gram, when defined as an oxygen need

>28 days.19 The incidence of BPD, defined as an oxygen need at 36 weeks post menstrual

age, is about 35% for infants with birth weights <1500 gram.20,21 BPD is associated with

damage of white matter and striato-thalamic structures, because of periods of hypoxia

and hypercarbia, and a strong predictor of several long-term adverse health outcomes

and cognitive and academic achievement.18,22-24

Neonatal infections are also associated with poor neurodevelopmental and growth

outcome in early childhood.25-27 About 24% of the infants develop at least one episode

of sepsis beyond day 3 of life and 50% is treated for clinical or proven sepsis at least

once during hospital stay.28,29 A small number of infants develop necrotizing enterocolitis

(10%) and meningitis (5%).25,30 Sepsis is associated with the presence of pro-inflammatory



1cytokines in the central nerve system, which has been shown to inhibit proliferation

of neuronal precursor cells, activate astrogliosis, and stimulate oligodendrocyte cell

death, all of which increase the risk of white matter damage. Also hypo-perfusion

which often occurs during sepsis may play a role in the association between sepsis and

neurodevelopmental sequelae.31

Environmental risk factors

Biological factors account for only a portion of the variance associated with VLBW

infant’s long-term outcomes.32 There are several environmental factors to be taken into

account. Pain and stress during the NICU-period of the infant, in addition difficulties

to read behavioral signs of the infant, and parent-child interaction problems lasting

into school age, lower social-economic class, and post-traumatic stress, depression and

anxiety of the parents.

The influence of the environment of the VLBW infant, the parent-infant relationship

and the impact of preterm birth on parents are considered as potential environmental risk

factors.33,34 Social-economic status and educational level of the parents may have great

influence on gravidity, and motor and cognitive development in VLBW infants.35,36 The

environment of the NICU (including exposure to prolonged periods of light, unnatural

noise, repeated disturbances and discomfort and pain from caretaking procedures,

such as ventilation and punctures) causing frequently and persisting stress, can have a

negative influence on the immature brain of VLBW infants.32,37

The parent-infant relationship with the important ingredients of parental

sensitive-responsiveness and child participation, is at risk after very preterm birth.

Due to neurological immaturity and problems in self-regulation, VLBW infants are

showing behavioral signals which are difficult to read for parents, such as less actively

interactions, less eye contact, more gaze aversion, less positive facial expressions and

less vocalization.38-40 Parents of VLBW infants have to put more effort to initiate and

maintain interactions and they also receive fewer positive responds from their infants

than parents of term-born infants.41

For parents, preterm birth can be a difficult and distressing experience.42 Parents with

VLBW infants reported more financial, social and family stress than parents of healthy

term-born children.33,43,44 Between 26% to 41% of the mothers of VLBW infants reported

post-traumatic stress symptoms.45 In addition, parenting a VLBW infant can be more

demanding because of feeding problems, excessive crying and/or sleeping problems.46

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12 | Chapter 1

Consequences of preterm birth on neurodevelopment

VLBW infants are at great risk of major and minor disabilities. Although the incidence of

severe handicaps, like cerebral palsy, deafness, blindness and severe mental retardation

is decreasing slowly, VLBW infants still remain at great risk for a broad range of mild,

often co-occurring, neurodevelopmental deficits.47-50 Long-term follow-up to school age

revealed an even higher frequency of neurodevelopmental problems than in the first

two years. Some deficits, such as problems with attention and hyperactivity and minor

motor impairments, classified as developmental coordination disorder, are complex and

may be subtle, but often tend to become more obvious at later ages.51-53

Combinations of mild cognitive, motor and behavioral problems, with prevalence’s

of up to 50 to 75%, are the dominant developmental deficits reported in VLBW

infants.54-58 At 5 years of age, 45% of the children have mild neurological problems

(minor neurological dysfunction), 39% have cognitive deficits, 30% have motor deficits

and 27% have behavioral problems.59 These deficits often persists throughout childhood

and have a negative influence into adulthood because they crucially affect the child’s

exploration of the world and involvement in academic and social activities. VLBW adults

are three times more at risk for unemployment,60 are less active during leisure time,61 and

have more psychiatric disorders.62

Self-regulation

Self-regulation is the infants competence to organize the behavior in order to gain control

over his own body and the world around him.63 Selfreglatory efforts are modulatory

mechanism used by the infant to approach information and respond in an adaptive

way, to cope with sensory input, or to protect himself from too much stimulation.64

The altered connectivity in early brain development in VLBW infants, can disrupt the

emergence of self-regulation, resulting in less opportunities to self-regulate and to react

effectively on stimuli of the environment.65,66 Low self-regulation in VLBW infants lead

to higher prevalence of difficulties in sustained attention, emotional regulations with

both externalizing and internalizing behavioural problems, symptoms of impulsivity,

inattention and executive dysfunctions, throughout childhood.67-69

Measurement of neurodevelopmental outcomes

To measure neurodevelopmental outcomes of VLBW infants, a heterogeneous group

of neurodevelopmental assessments instruments are available. A systematic review of

neuromotor assessments for preterm-born infants recommended the use of more than

one assessment tool, in order to evaluate the efficacy of intervention programs in the first



1year of life.70 Because children grow and develop over time, measuring developmental

outcomes of children poses many challenges to choose the most appropriate measurement

instrument.71

Kirshner and Guyatt72,73 presented a methodological framework for assessing health

indices, based on the need to distinguish between health states measurements instruments

according to their purpose. They classified three categories. First, “discrimination”:

referring to instruments that are designed to measure cross-sectional differences

and required to be both reproducible and valid. Second, “prediction”: referring to

instruments that are used as a diagnostic tool to predict developmental outcome and,

third, “evaluation”: instruments that are designed to measure longitudinal differences

within children over time, requiring an additional property namely responsiveness (or

sensitivity to change).

Next to the goals and clinimetric properties of the instruments more practical issues,

such as the time needed to administer the test and the age of preterm-born children

play an important role in choosing the right instrument.71,74 Unfortunately, there are no

single measurement instruments for cognitive or motor developmental outcome that

cover all ages.

Assessment of cognitive and motor developmental outcomes

Intelligence is not one skill but a composite of multiple cognitive processes, including

visual and auditory memory, abstract reasoning, complex language processing,

understanding of syntax, visual perception, visual motor integration, visual spatial

processing and speed processing. Cognitive assessments of very young infants are limited

in their predictive ability to because of their reliance on assessments of visual motor and

perceptual abilities. As children mature, more verbal and abstract cognitive abilities can

be evaluated and scores more accurately reflect their specific abilities.75

During the major part of the previous century, motor development was basically

regarded as a neuromaturational process, but it became increasingly clear that motor

development is largely effected by experiences.76 The neuromaturational theory proposes

that changes in gross motor skills during infancy result only from the neurological

maturation of the CNS. The dynamic motor theory considers the CNS as one of many

subsystem that dynamically interacts to develop movements. Other elements that

explain movement changes are the infant’s biomechanical and psychological factors, and

the nature of the task or environment.76,77 The theoretical approaches of infant motor

development formed the basis of various, currently applied instruments, evaluating the

infants’ neuromotor development.

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14 | Chapter 1

Early intervention programs

Early intervention refers to prevention-focussed programs occurring soon after birth.

The distinctive feature of early intervention is that it starts when the plasticity of the

brain is maximum instead of addressing problems at a later time and thus interventions

are more likely to have maximal impact.78,79 Further advantages of early intervention

programs are the influence of genetics, environment and experiences during sensitive

periods of brain development which play an exceptional important role in shaping the

capacities of the brain, like ´wiring´ the highly integrated sets of neural circuits.80

In response to the high rate of neurodevelopmental deficits in VLBW infants, which

persist throughout childhood, a variety of early intervention programs for preterm-

born infants have been developed. The complex biological, medical, and environmental

elements that contribute to early development have led to programs that encompass

many different components, with services provided by a variety of disciplines.81 Early

intervention programs differ in type of intervention (medical, neurobehavioral,

paramedical, strength or weakness-bases), the focus of intervention (cognitive, motor, and/

or behavioral development of the child, mother–infant interaction, parental psychosocial

support, parent education), kind of interventionist (pediatrician/neonatologist, nurse,

psychologist, pediatric physical therapist), location (hospital or home-based), and the

timing, intensity and duration of program involvement.

In 2012, a Cochrane meta-analysis on the effect of post discharge early intervention

programs for preterm-born infants concluded that interventions that focus on both

the parent-infant relationship and on infant development have the greatest effect

on cognitive development and a small effect on motor development at infant and

pre-school age.82 Also other studies stated that positive outcomes are associated with

parental sensitive-responsiveness, child participation, and infant’s competence to self-

regulate.83-87 A systematic review suggest that home visiting for preterm-born infant

promotes improved mother-infant interaction.88 However, there is a paucity of long term

outcomes of randomized controlled trials involving multidimensional early interventions.

The Newborn Individualized Care and Assessment Program (NIDCAP) introduced by Als

et al89 in the mid-1980s is unique in its use of a combination of strategies in an attempt to

address the different early developmental issues in the NICU.90,91 The underlying concept

is designated the “synactive theory” to emphasize the simultaneous maturation and

mutual interplay of the different subsystem of behavior throughout development.38

Three RCTs,92-94 2 systematic reviews,95,96 and a Cochrane Review97 have reported positive

short-term effects on medical outcome (duration on ventilation, supplemental oxygen

supply, reduced incidence of IVH, BPD and reduced hospital stay), neurodevelopmental



1outcome (improved self-regulation, motor, cognitive, behavioral development), less

parenting stress and positive caregiving up to 12 months. A study with quantitative

3D-MRI techniques demonstrated beneficial structural changes in term NIDCAP infants

in tissue distributions as well as development of white matter.98 But the sample size

of all studies were small, shortcomings in design and methods were discussed and no

evidence was found that the NIDCAP improves long–term neurodevelopment. Except for

low risk preterm-born infants at 8 years where improved neuropsychological and neuro-

electrophysiological function and brain structure was found.96,97,99,100

IBAIP

The Infant Behavioral Assessment and Intervention Program© (IBAIP)101 is a post-discharge,

preventive neurobehavioral intervention program which addresses both the infant and

the parent at home. It is also based on the synactive theory of behavioral developmental

organization.38 The program aims to support the infants’ self-regulatory competence

and multiple developmental functions via responsive parent-infant interactions, focusing

on environmental, behavioral, and early developmental factors. The IBAIP-trained

interventionist evaluates the infant’s neurobehavioral organization and self-regulatory

competence, within the context of the environment, and positively guides and supports

the parents to sensitively and responsively interact with their infant. Facilitation strategies

may be offered to best support the infant’s neurodevelopmental progression and self-

regulation. The facilitation strategies address environmental facilitation (e.g. visual and

auditory input), handling and positioning (e.g. the infant’s position in supine or prone),

and cue-matched facilitation (e.g. hand to mouth, foot bracing, or hands to midline). The

IBAIP aims to provide ample opportunities for the infant to actively process and explore

information, while at the same time maintaining stable physiological and behavioral

functioning. Thus the program supports the infant’s growth, the infant’s motivation to

explore, and the possibility to learn from information.102 A detailed written report with

individual recommendations is provided to the parents after every session.

The intervention is guided by the Infant Behavioral Assessment© (IBA).103 The IBA is

an observational tool that systematically observes and interprets the developing infants’

neurobehavioral organization during interactions. Hundred and thirteen communicative

behaviors are categorized according to four subsystems: the autonomic system, the

motor system, the state system, and the attention/interaction system. Within each of the

four subsystems, the behaviors are interpreted as approach (stable/engagement), self-

regulatory, or stress (unstable/disengagement) behaviors.

The IBA is primarily intended to guide intervention strategies in infants from term

to 8 months CA. The IBA does not have normative data but provides information on the

quality and amount of information or support, appropriate for that particular infant at

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16 | Chapter 1

that particular time. Reliability scoring of more than 85% is required during training.

However, information on the clinimetric properties of the IBA was scarce.

The original RCT on the effects of the IBAIP

Between 2004 and 2007, a multicenter RCT was conducted in 7 hospitals in Amsterdam

to compare the effects of the IBAIP to standard follow-up care, with respect to cognitive

and motor development, infants’ behavioral regulation, the well-being of the parents,

and parent-infant interaction.104 In this RCT, infants of gestational age (GA) <32 weeks

and/or birth weight <1500 grams were included. Exclusion criteria were severe congenital

abnormalities of the infant, severe physical or mental illness/problems of the mother,

non-Dutch-speaking families for whom an interpreter could not be arranged, and

participating in other trials on post discharge management. After computer-generated

randomization, stratified for GA (< and ≥30 weeks) and recruitment site, with multiplets

assigned to the same group, 176 VLBW infants were assigned to an intervention (90)

or control group (86). The infants and the parents in the intervention group received

1 intervention session shortly before discharge and 6 to 8 sessions at home from an

IBAIP-trained pediatric physical therapist up to 6 months CA. The control group received

standard care.

Results of this study included improved cognitive, motor, behavioral development

and mother-infant interaction at 6 months CA 104,105 and improved motor development at

24 months CA,106 in favor of the parents and infants who received the IBAIP intervention.

Moreover, at 24 months CA, also improved cognitive development was found in high risk

subgroups who received the IBAIP. A follow-up study at the preschool age of 44 months

found improved independency in mobility in daily activities.107

Follow-up study at 5.5 years

In a second follow-up study the effects of the IBAIP at school age were evaluated.

Between 2009 and 2011, the parents of all children participating in the original RCT, were

invited to the participate in the follow-up study at the age of 5.5 years CA. The pediatric

and developmental assessments were performed at the follow-up clinic of the Academic

Medical Center in Amsterdam. Cognitive abilities were assessed by a psychologist, motor

development, visual-motor integration and, neurologic functions were assessed by a

pediatric physical therapist (JvH). The investigators were blinded for group assignment.

While their child was fulfilling the developmental assessments, the parents were asked

to fill out a questionnaire regarding the behavior of their child. Sociodemographic data,

school performances and the need for mental or paramedical support at 5.5 years CA

were obtained by parental interview.



1Assessment of cognitive development

At 6, 12, and 24 months CA, cognitive development was assessed with the mental scale of

second Dutch edition of Bayley Scales of Infant Development (BSID-II-NL).108 At 5.5 years

CA, the third Dutch edition of the Wechsler Preschool and Primary Scale of Intelligence

(WPPSI-III-NL) was used.109 The BSID-II-NL age range is from 1 to 42 months and it can be

used for discrimination and evaluation purposes. The WPPSI-III-NL, age range from 2.6

to 8 years, has the same purposes.110 In addition, components of intelligence, namely

visual motor integration and coordination and processing speed were assessed with the

Developmental Test of Visual Motor Integration (VMI)111 and tasks of the Amsterdam

Neuropsychological Tasks (ANT).112

Assessment of motor development

At 6, 12, and 24 months CA, motor development was assessed with the psychomotor

scale of the BSID-II-NL. At 5.5 years CA, the second edition of the Movement Assessment

Battery for Children (MABC-2) was used.113 The test construction of the BSID-II-NL is

based on general maturational principles.110 The MABC-2 age range is from 3 to 16 years,

its purpose can be discrimination or evaluation and its construct is based on the dynamic

theory.110 In addition, the Alberta Infant Motor Scale (AIMS)77 was used at 12 months CA

(in a subset of participating children), and the neurological examination according to

Touwen114 at 5.5 years CA. The age range of the AIMS is from term age to 18 months,

its purpose is discrimination and its construct is based on the dynamic theory.110 The age

range of Touwen is from 4 to 18 years, its purpose is discrimination and it is based on the

traditional neuropediatric neuromaturation concept.110

Assessment of behavior

The Strength and Difficulty Questionnaire (SDQ),115 a parental behavioral screening

questionnaire consisting of items hyperactivity/inattention, conduct problems, peer

problems, emotional symptoms and prosocial behavior was used to evaluate the impact

of behavior on motor development and on early intervention.

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18 | Chapter 1

Aim and outline of the thesis

The general aim of this thesis was to expand the knowledge on long-term effects of

an early intervention program for very preterm-born children, to provide optimal


The main objective of this thesis was to evaluate the effect of the Infant Behavioral

Assessment and Intervention Program (IBAIP) on cognitive, motor, and behavioral

development in VLBW infants at 5.5 years CA and longitudinally from 6 months up to

and including 5.5 years CA.

Additional objective was to elucidate the relation between motor impairment and

other developmental deficits in very preterm-born and term-born children at 5 years CA.

As the outcome of research depends on the quality of the assessment instruments

used in a study, other objectives were to investigate the clinimetric properties of the

Infant Behavior Assessment (IBA) in order to evaluate neurobehavioral organization

from term to 6 months, and to compare the Alberta Infant Motor Scale (AIMS) and the

Dutch second version of the Bayley Scale of Infant Development (BSID-II-NL) in their

ability to detect intervention effects at 12 months CA.

Outline

Chapter 1 presents a general introduction on VLBW infants and early intervention, and

objectives and outline of the thesis.

Chapter 2 and 3 focus on the developmental assessment instruments used in VLBW

infants.

Chapter 2 describes the reliability, sensitivity and responsiveness of the IBA.

Videotaped assessments of 176 VLBW infants participating in a RCT on the effect of the

IBAIP (86 infants received the IBAIP, 90 infants received standard care), served to evaluate

the standardized IBA observation.

Chapter 3 compares two motor developmental measurement instruments, the

AIMS and the psychomotor scale of the BSID-II-NL, in their ability to evaluate effects of

intervention in VLBW infants. At 12 months CA, 116 of the 176 VLBW infants participating

in the RCT on the effect of the IBAIP, were assessed both with the AIMS and the BSID-

II-NL. Intervention effects of the IBAIP on the AIMS and the psychomotor scale of the

BSID-II-NL were compared.

Chapter 4 concerns motor impairments and associated developmental deficits in very

preterm-born infants in comparison with term-born infants.



1In Chapter 4 the relation between motor impairments and other developmental

deficits was studied in a cohort of 81 children, born <30 weeks’ gestation and/or birth

weights <1000 gram, and 84 term-born children at 5 years CA. Motor impairments,

assessed with the MABC-2, was compared between the groups and the relation between

motor impairments and other developmental deficits, assessed with the neurologic

examination of Touwen, WPPSI-III-NL, processing speed and visuomotor coordination

tasks of the ANT and the SDQ, between the groups. Subsequently a mediation model

was tested to analyze the extent to which these deficits mediate the association between

preterm birth and motor impairments.

The last part of the thesis, chapter 5 and 6, concerns the Intervention effects of the IBAIP

at 5.5 years and over time.

Chapter 5 presents the results of the IBAIP on cognitive, neuromotor and behavioral

development in VLBW infants at 5.5 years CA. In the RCT, 86 VLBW infants received IBAIP

intervention until 6 months CA and 90 VLBW infants received standard care. At 5.5 years

CA, 69 IBAIP children and 67 control children were assessed with the WPPSI-III-NL, the

MABC-2, the VMI, the neurologic examination of Touwen and the SDQ.

Chapter 6 investigates the longitudinal effects of the IBAIP in VLBW infants on

cognitive and motor development from 6 months up to and including 5.5 years CA.

At 6, 12, and 24 months CA, cognitive and motor development were assessed with the

BSID-II-NL. At 5.5 years CA the WPPSI-III-NL and the MABC-2 were used. Longitudinal

data were analyzed with linear mixed models in the total group of 176 VLBW infants

and in three subgroups with biological or environmental or a combination of biological-

environmental risk factors.

Chapter 7 presents the general discussion, in which the findings and limitations of this

thesis are further emphasized and implications for clinical practice and recommendations

for future research are given. Finally, the results of the studies presented in this thesis are

summarized.

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20 | Chapter 1

References

1. World Health organization, International classification of diseases and related health problems. Version 2010, 10th revision, Geneva.

2. Stoelhorst GMSJ, Rijken M, Martens SE et al. Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age <32 weeks): the project on preterm and small for gestational age infants 1983 and the Leiden follow-up project on prematurity 1996-1997. Pediatrics 2005;115:396-405.

3. Stichting Perinatale Registratie Nederland. Perinatal care in the Netherlands 2012. Available at http://www.perinatreg.nl. Accessed February 2014.

4. Ment LR, Hirte D, Huppi PS. Imaging biomarkers of outcome in the developing preterm brain. Lancet Neurol 2009;11:1042-1055.

5. Penn AA, Shatz CJ. Brain waves and brain winning, the role of endogenous and sensory driven neural activity in development. Pediatr Res 1999;45:447-458.

6. National Scientific Council on the Developing Child at Harvard University (2007).The timing and quality of early experiences combine in shape brain architecture. Working paper #5. Retrieved April 2014, from http://www.developingchild.net.

7. Shonkoff JP, Philips D. From neurons to neighbourhoods. The science of early childhood development. Washington DC: National Academy Press, 2000.

8. National Scientific Council on the Developing Child at Harvard University (2007). The science of neglect: the persistent absence of responsive care disrupts the developing brain. Working paper# 12. Retrieved April 2014, from http://www.developingchild.net.

9. National Scientific Council on the Developing Child at Harvard University (2007). Young children develop in an environment of relationships. Working paper# 1. Retrieved April 2014, from http://www.developingchild.net.

10. Lester BM, Miller-Loncar CL. Biology versus environment in the extremely low–birth weight infant. Clin Perinatol 2000;27:461-481.

11. Volpe JJ. Cerebellum of the premature infant: rapidly developing, vulnerable, clinically important. J Child Neurol 2009;24:1085-1104.

12. De Kieviet JF, Zoetebier L, Van Elburg RM, Vermeulen RJ, Oosterlaan J. Brain development of very preterm and very low birth weight children in childhood and adolescence: a meta-analysis. Dev Med Child Neurol 2010;54:313-323.

13. Chau V, Synnes A, Grybau RE, Pokitt Kj, Brant R, Miller SP. Abnormal brain maturation in preterm neonates associated with adverse developmental outcomes. Neurology 2013;81:2082-2089.

14. Inder TE, Huppi PS, Warfiels S, et al. Periventricular white matter injury in the premature infant is followed by reduced cerebral grey matter volume at term. Ann Neurol 1999;5:755-760.

15. Spittle AJ, Cheong J, Doyle LW, Roberts G, Lee KJ, Lim J, et al. Neonatal white matter abnormality predicts childhood motor impairment in very preterm children. Dev Med Child Neurol 2011;53:1000-1006.

16. Bora S, Pritchard V, Chen Z, Inder TE, Woodward LJ. Neonatal cerebral morphometry and later risk of persistent inattention/hyperactivity in children born very premature. J Child Psychol Psychiatry 2014;55:828-835.

17. Bolisetty S, Dhawan A, Abdel-Latif M et al. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 2014;133;55-65.

18. National Heart, Lung and Blood institute, Division of Lung Diseases and Offices of Prevention, Education and Control. Bronchopulmonary Dysplasia. Washington, DC. National Institutes of health;1998. Publ. No 98-4081.



119. Short EJ, Klein NK, Lewis BA, et al. Cognitive and academic consequences of

Bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. Pediatrics 2003:112:359-366.

20. Smith VC, Zumanick JAF, Cormick MC, Croen LA,Greene J, Escobar GJ et al. Trend in severe bronchopulmonary dysplasia rates between 1994 and 2000. J Pediatr 2005;146:469- 473.

21. Jobe AH. What is BPD in 2012 and what will BPD become? Early Hum Dev 2012;88:27-28.

22. Subramian S, El-Mhandes A, Dhanireddy R, Koch MA. Association of bronchopulmonary dysplasia and hypercarbia in ventilated infants with birth weights of 500-1499 gram. Matern Child Health J 2011;1:17-26.

23. Gagliardi L, Bellu R, Zanini R, et al. Bronchopulmonary dysplasia and white matter damage in the preterm infant; a complex relationship. Peadiatr Perinat Epidemiol 2009;23:582-590.

24. Jensen EA, Schmitt B. Epidemiology of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol 2014;100:145-157.

25. Doctor BA, Newman N, Minich NM, Taylor HG, Fanaroff AA, Hack M. Clinical outcomes of neonatal meningitis in very low birth-weight infants. Clin Pediatr 2001;40:473-480.

26. Stoll BL, Hansen NI, Adams-Chapman I et al. Neurodevelopmental and growth impairment among extremely low birth weight infants with neonatal infection. JAMA 2004;292:2357-2365.

27. Spittle AJ, Orton J, Doyle LW, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev 2012;CD005495.

28. Boghosian NS, Page GP, Bell EF et al. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr 2013;162:1120-1124.

29. Stoll BJ, Hansen NI, Nelli I et al. Very low birth-weight preterm infants with early onset neonatal sepsis, the predominance of gram negative infections continues in the National Institute of Child Health and Human Developmental Research Network, 2002-2003. J Pediatr Infect Dis 2005;24:635-639.

30. Hintz SR, Kendrick DE, Stoll Bj et al. Neurodevelopmental and growth outcomes in extremely very low birth weight infants after neocrotizing entrocolitis. Pediatrics 2005;115:696-703.

31. Adams-Chapman I. Long-term impact of infection on the preterm neonate. Semin Perinatol 2012;36:462-470.

32. National Scientific Council on the Developing Child at Harvard University (2007). Excessive stress disrupts the architecture of the developing brain. Working paper #3. Retrieved April 2014, from http://www.developingchild.net.

33. Singer LT, Salvator A, Guo S, Collin M, Lilien L, Baley J. Maternal psychological distress and parenting stress after the birth of a very low birth weight infant. JAMA 1999;281:799-805.

34. Forcada-Cuex M, Borhini A, Pierrehumbert B, Ansermet F, Muller-Nix C. Prematurity, maternal posttraumatic stress and consequences on the mother-infant relationship. Early Hum Dev 2011;87:21-26.

35. Potijk MR, Kerstjens J, Bos AF, Reijneveld SA, De Winter AF. Developmental delay in moderately preterm-born children with low socioeconomic status; risks multiply. J Pediatr 2013;163:1289-1295.

36. Rodrigues MC, Mello RR, Silva KS, Carvalho ML. Risk factors for cognitive impairment in school-age children born preterm, application of a hierarchical model. Arq Neuropsquiatr 2010;70:583-589.

37. Smith GC, Gutovich J, Smyser C et al. Neonatal intensive care unit stress is associated with brain development in preterm infants. Ann Neurol 2011;70:541-549.

R1R2R3R4R5R6R7R8R9


22 | Chapter 1

38. Als H. Part 1: Theoretical Framework. A synactive model of neonatal behavioral organization: Framework for the assessment of neurobehavioral development in the premature infant and for support of infants and parents in the neonatal intensive care environment. Phys Occup Ther Ped 1986;6:3-53.

39. Eckerman CO, Hsu HC, Molitor A, Leung EH, Goldstein RF. Infant arousal in an enface exchange with a new partner: effects of prematurity and perinatal biological risks. Dev Psychology 1999;35:282-293.

40. Goldberg S, DiVitto B. Parenting children born preterm. In: Barenstein MH, Handbook of parenting Vol I: Children and parenting. Hillsdale; Lawrence Erlbaum Associates 1995. pp.209-231.

41. Singer LT, Fulton S, Davillier M, Koshy D, Salvator A, Baley J. Effects of infant risk status and maternal psychological distress on maternal-infant interactions during the first year of life. J Dev Behav Pediatr 2003;24:233-241.

42. O’Brien M, Heron Asay J, McCluskey-Fawcett K. Family functioning and maternal depression following premature birth. J Reprod and Inf Psych 1999;17:175-188.

43. Jaekel J, Wolke D, Chernova J. Mother and child behavior in very preterm and term dyads at 6 and 8 years. Dev Med Child Neurol 2010;54:716-723.

44. Taylor HG, Klein N, Minich NM, Hack M. Long-term family outcomes for children with very low birth weights. Arch Pediatr Adoles Med 2001;155:155-161.

45. Kersting A, Dorsch M, Wesselmann U et al. Maternal posttraumatic stress response after the birth of an very low birth weight infant. J Psychosom Research 2004;57:473-476.

46. Smid G, Schreier A, Meyer R, Wolke D. Predictors of crying, feeding and sleeping problems: a prospective study. Child Care Health Dev 2011;37:493-502.

47. Richardson DK, Gray JE, Gortmaker SL, Goldmann DA, Pursley DM, McCormick MK. Declining severity adjusted mortality: evidence of improving neonatal intensive care. Pediatrics 1998;102:893-899.

48. De Kleine MJ, Den Ouden AL, Kollee LA et al. Low mortality but higher neonatal morbidity of a decade in very preterm infants. Paediatr Perinat Epidemiol 2007;21:15-25.

49. Taylor HG, Klein N, Minich NM, Hack M. Long-term family outcomes for children with very low birth weights. Arch Pediatr Adoles Med 2001;155:155-161.

50. Hall A, McLeod A, Counsell C, Thompson I, Mutch L. School attainment, cognitive ability and motor function in a total Scottish very-low birthweight population at eight years: a controlled study. Dev Med Child Neurol 1995;37:1037-1050.

51. Botting N, Powls A, Cooke RWI, Marlow N. Cognitive and educational outcome of very-low birthweight children in early adolescence. Dev med Child Neurol 1998;40:652-660.

52. Hoy EA, Sykes DH, Bill JM, Haliday HL, McClure BG, Reid MM. The social competence of very-low birthweight children: teacher, peer and self-perceptions. J Abnorm Child Psychol 1992;20:123-150.

53. Edwards J, Berube M, Erlandson K et al. Developmental Coordination Disorder in school-aged children born very preterm and /or at very low birth weight; a systematic review. J Dev Behav Pediatr 2011;32:678-687.

54. Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002;288:728-737.

55. De Kieviet JF, Piek JP, Aarnoudse-Moens CS, Oosterlaan J. Motor development in preterm and very low birth weight children from birth to adolescence. JAMA 2009;302:2235-2242.

56. Anderson PJ. Neuropsychological outcomes of children born very preterm. Semin Fetal Neonatal Med 2014;19:90-96.



157. Healy E, Reichenberg A, Woo Nam K et al. Preterm birth and adolescent social

functioning-alterations in emotion-processing brain areas. J Pediatr 2013;163:1596-1604.

58. Hille ET, Weisglas-Kuperus N, Van Goudoever JB et al. Functional outcomes and participation of young adulthood for very preterm and very low birth weight infants: the Dutch project on preterm and small for gestational age infants at 19 years of age. Pediatrics 2007;120:587-595.

59. Potharst ES, Van Wassenaer AG, Houtzager BA, Van Hus JWP, Last BF, Kok JH. High incidence of multi-domain disabilities in very preterm children at five years of age. J Pediatr 2011;159:79-85.

60. Baumgardt M, Bucher HU, Mieth RA, Fauchere JC. Health-related quality of life of former very preterm infants in adulthood. Acta Peadiatr 2012;101:59-63.

61. Dahan-liel N, Mazer B, Majnemer A. Preterm birth and leisure participation. Dev Disabil 2012;33:1211-1220.

62. Moster D, Lie RT, Markestand T. Long-term medical and social consequences of preterm birth. N Engl J Med 2008;359:262-273.

63. Shonkoff JP, Phillips DA. Acquiring self-regulation. In Shonkoff JP, Philips DA, editors. From neurons to neighborhoods. The science of early childhood development. Washington D.C.: National Academy Press;2001; pp.93-123.

64. Arnand KJ, Scalzo FM. Can adverse neonatal experience alter brain development and subsequent behavior? Biol Neonate 2000;77:68-82.

65. Grunau RE. Neonatal pain, parenting stress and interaction in relation to cognitive and motor development at 8 and 18 months in preterm infants. Pain 2009;14:138-146.

66. Aarnoudse-Moens CSH, Weisglas-Kuperus N, Van Goudoever JB, Oosterlaan J. Meta-analysis of neurobehavioral outcomes in very preterm and or very low birth weight children. Pediatrics 2009:124:717-728.

67. Mulder H, Pitchford NJ, Hagger MS, Marlow N. Development of executive function and attention in preterm children: a systematic review. Dev Neuropsych 2009;34:393-421.

68. Pizzo R, Urban S, Van Der linden M et al. Attentional networks efficiency in preterm children. J Int Neuropsych Soc 2010;16:130-137.

69. Voight B, Pietz J, Pauen S, Kliegel M, Reuner G. Cognitive development in very vs moderate to late preterm and full-term children: can effortful control account for group differences in toddlerhood? Early Hum Dev 2012;88:307-312.

70. Spittle AJ, Doyle WL, Boyd RN. A systematic review of the clinimetric properties of neuromotor assessments for preterm infants during the first year of life. Dev Med Child Neurol 2008;50:254-266.

71. Schie Van PEM. Measuring motor outcome in childhood prognosis and evaluation. Thesis: VU University of Amsterdam 2008.

72. Kirshner B, Guyatt D. A methodological framework for assessing health indices. J Chronic Dis 1985;38:27-36.

73. Kirshner B, Guyatt D, Jeaschke R. Measuring health status: what are the necessary measurement properties? J Clin Epidemiol 1992;34:1341-1345.

74. Behrman RE. Neurodevelopmental, health, and family outcome for infants born preterm. In: Preterm birth: causes, consequences, and prevention. Behrman RE, Butler As, editors. Washington DC: National Academies Press (US); 2007.

75. Gesell A, Amantruda CS. Developmental Diagnosis: Normal and Abnormal Child Development. 2nd ed. New York (NY): Harper and Row;1947.

76. Hadders-Algra M. Variation and variability: key words in human motor development. Phys ther 2010;90:1823-1837.

R1R2R3R4R5R6R7R8R9


24 | Chapter 1

77. Piper MC, Darrah J. Motor Assessment of the Developing Infant. U.S.A. Philadelphia: W.B. Saunders Company;1994.

78. Nelson CA. The neurobiological base for early intervention. In: Shonkhoff JP, Meissels SI, editors. Handbook of early childhood intervention. Cambridge, Cambridge university Press, 2000.

79. Blackman JA. Early intervention: a global perspective. Infant and Young Children 2002;1511-1519.

80. Scientific Council on the Developing Child at Harvard University (2007). Early experiences can alter gene expression and affect long-term development. Working paper #10. Retrieved April 2014, from http://www.developingchild.net.

81. Berger SE, Holt-Turner I, Cupoli JM, Mass M, Hageman JR. Caring for the graduate from the neonatal intensive care unit: at home, in the office and in the community. Pediatr Clin Morth Am 1998;45:701-712.

82. Spittle AJ, Orton J, Doyle LW, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev 2012;CD005495.

83. Orton J, Spittle A, Doyle L, Anderson P, Boyd R. Do early intervention programs improve cognitive and motor outcomes for preterm infants after discharge? A systematic review. Dev Med Child Neurol 2009;851-859.

84. Guralnick MJ. Preventive Interventions for Preterm Children: Effectiveness and Developmental Mechanisms. J Dev Behav Pediatr 2012;33:1-13.

85. Treyvaus K, Anderson VA, Howard K et al. Parenting behavior is associated with the early neurobehavioral development of very preterm children. Pediatrics 2009;123:555-561.

86. Forcada-Guex M, Pierrehumbert B, Borghini A, Moessinger A, Muller-Nix C. Early dyadic patterns of mother-infant interactions and outcomes of prematurity at 18 months. Pediatrics 2006;118:107-114.

87. Van Der Veen JA, Massler D, Robertson CM, Kirpalani H. Early interventions involving parents to improve neurodevelopmental outcomes of premature infants: a meta-analysis. J Perinatol 2009;29:343-351.

88. Goyal NK, Teeters A, Ammerman T. Home visiting and outcome of preterm infants: a systematic review. Pediatrics 2013;132:502-516.

89. Als H, Gilkerson L. The role of relationship-based developmentally supportive newborn intensive care in strengthening outcome of preterm infants. Semin Perinatol 1997;21:178-189.

90. Hack M. Care of preterm infants in the neonatal intensive care unit. Pediatrics 2009;123:1246-1247.

91. Westrup B. Newborn Individualized Developmental Care and Assessment Program (NIDCAP)-family-centered developmentally supportive care. Early Hum Dev 2007;83:443-449.

92. Als H, Lawhon G, Duffy FH, McAnulty GB, Gibes-Grossman R, Blickman JG. Individualized developmental care for the very low birthweight preterm infant. Medical and neurofunctional effects. JAMA 1994;272:853-858.

93. Fleisher BE Vandenberg K, Constantinou j et al. Individualized developmental care for very low birthweight premature infants improves medical and neurodevelopmental outcome in neonatal intensive care unit. Clin Pediar 1995;34:523-529.

94. Als H, Gilkerson L, Duffy FH et al. A three-center, randomized controlled trial of individualized developmental supportive care for very low birthweight preterm infants: medical, neurodevelopmental, parenting and caregiving effects. J Dev Behav Pediatr 3002;24:399-408.



195. Legendre V, Burnter Pa, Martinez KL, Crowe TK. The evolving practice of developmental

care in the neonatal unit: a systematic review. Phys Occup Ther Ped 2011;31:315-338.

96. Wallin L, Eriksson M. Newborn Individual Developmental Care and Assessment Program (NIDCAP): a systematic review of the literature. Worldview Evid Based Nurs 2009;6:54-69.

97. Symington A, Pinelli J. Developmental care for promoting development and preventing morbidity in preterm infants. Cochrane Database Syst Rev 2006;CD001814.

98. Als H, Duffy FH, McAnulty G et al. Early experience alters brain function and structure. Pediatrics 2012;113:846-857.

99. Westrup B, Bohm B, Langercrantz H, Stjernqvist K. Preschool outcome in children born very prematurely and cared for according to the Newborn Individual Developmental Care and Assessment Program (NIDCAP). Acta Paediatr 2004;93:1-10.

100. McAnulty G, Duffy FH, Kosta S et al. School age effects of the Newborn Individual Developmental Care and Assessment Program for medically low-risk preterm infants: preliminary findings. J Clin Neonatol 2012;1:184-194.

101. Hedlund R. (1998). The Infant Behavioral Assessment and Intervention Program.© Available from: http://www.ibaip.org. Accessed Jan 12, 2012.

102. Koldewijn K. Supporting resilience in very preterm infants; The effect of the Infant Behavioral Assessment and intervention Program in very preterm infants and their parents. Thesis: University of Amsterdam 2009.

103. Hedlund R, Tatarka M. (1986,1988). The Infant Behavioral Assessment.© Available from: http://www.ibaip.org. Accessed Jan 12, 2012.

104. Koldewijn K, Wolf MJ, van Wassenaer A et al. The Infant Behavioral Assessment and Intervention Program for very low birth weight infants at 6 months corrected age. J Pediatr 2009;154:33-38.

105. Meijssen D, Wolf MJ, Koldewijn K et al. The effect of the Infant Behavioral Assessment and Intervention Program on mother-infant interaction after very preterm birth. J Child Psychol Psych 2010;51:1287-1295.

106. Koldewijn K, van Wassenaer A, Wolf MJ et al. A neurobehavioral intervention and assessment program in very low birth weight infants: outcome at 24 months. J Pediatr 2010;156:359-365.

107. Verkerk G, Jeukens-Visser M, Koldewijn K et al. The infant behavioral assessment and intervention program in very low birth weight infants improves independency in mobility in daily activities at preschool age. J Pediatr 2011;159:933-938.

108. Van der Meulen BF, Ruiter SAJ, Lutje Spelberg HC et al. The Bayley Scales of Infant Development – Second edition, Dutch Manual (BSID-II- NL). Lisse: Swets Test Publisher; 2002.

109. Hendrikson J, Hurks P. WPPSI-III-NL. Wechsler preschool and primary scale of intelligences. 3rd edition, Dutch version. Amsterdam: Pearson Assessment and Information BV; 2009.

110. Heineman KR, Hadders-Algra M. Evaluation of neuromotor function in infancy - A systematic review of available methods. J Dev Behav Pediatr 2008;29:315-323.

111. Beery KE, Beery NA. The Beery-Buktenica developmental Test of Visual-Motor Integration, Beery VMI. Administration, Scoring, and Teaching Manual, 5th edition. Minneapolis: NCS Pearson Inc.; 2010.

112. De Sonneville. Computer based Amsterdam Neuropsychological Test battery (ANT). 1999.

113. Henderson SE, Sugden DA, Barnett AL. Movement Assessment Battery for Children - 2nd edition (Movement ABC-2); Examiner’s manual. London: Harcourt Assessment; 2007.

R1R2R3R4R5R6R7R8R9


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114. Touwen BCL. Examination of the child with minor neurological dysfunction, second edition. Philadelphia: Lippencott; 1979.

115. Goodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psych 1997;38:581-586.

Chapter 2

Reliability, sensitivity and responsiveness

of the Infant Behavioral Assessment in very

preterm infants

Karen Koldewijn, Janeline W.P. Van Hus, Aleid G. Van Wassenaer-Leemhuis,

Martine Jeukens-Visser, Joke H. Kok, Frans Nollet, Marie-Jeanne Wolf

Acta Paediatrica 2012;10:258-263

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28 | Chapter 2

Abstract

Aim. The aim of this study is to investigate the reliability, sensitivity and responsiveness

of the Infant Behavioral Assessment (IBA) to evaluate neurobehavioral organization in

very preterm-born infants.

Methods. Videotaped assessments of very preterm-born infants participating in a recent

trial, served to evaluate a standardized IBA observation. Inter-rater reliability was based

on 40 videos scored by two independent observers, using percentage agreement and

weighted Kappa’s. Sensitivity was evaluated by comparing the IBA results of 169 infants

at 35-38 weeks postmenstrual age, dichotomized according to two developmental risk

factors. For responsiveness, the effect size (ES) was calculated between 0 and 6 months

corrected age in all intervention and control infants and in subgroups of high-risk

intervention and control infants with oxygen-dependency ≥28 days.

Results. Inter-rater agreement was 93% in the total assessment; Kappa agreement was

moderate to good in the behavioral categories. Significant differences were found

between groups with or without risk factors. Larger differences between ESs in the

randomized groups with oxygen-dependency ≥28 days than in the total randomized

groups reflect the responsiveness of the IBA.

Conclusion. In this study, we found satisfactory to good clinimetric characteristics of the

IBA in very preterm-born infants.


Clinimetric properties of the IBA | 29

2

Introduction

The Infant Behavioral Assessment© (IBA)1 is an assessment designed to evaluate the

infant’s neurobehavioral organization to support positive interactions of the infant

with the environment. The IBA was derived from the NIDCAP_ Observation Sheet2, the

‘Naturalistic Observation of Newborn Behavior’ by Als3, but intended for infants from 0–8

months of corrected age (CA). Hedlund and Tatarka further articulated Als’s4 theoretical

construct of the ‘Synactive Model of Newborn Behavioral Organization and Development’

for older infants at developmental risk, as well as infants who are typically developing.

The IBA is primarily intended to be used in a qualitative manner, in conjunction with the

corresponding intervention program: the Infant Behavioral Assessment and Intervention

Program© (IBAIP).5,6 The interventionist continuously observes and interprets the infant’s

behavior and the setting during the interaction with the IBA. This behavioral analysis

results in strengths-based recommendations to support the infant’s sensory approach of

information and neurobehavioral competence, and/or in environmental adaptations to

diminish the infant’s stress or discomfort.

The effectiveness of the IBAIP was evaluated in a randomized controlled trial (RCT),

enrolling infants born <32 weeks gestation and/or 1500 g. We already published that

IBA-guided interventions in this RCT lead to more positive and sensitive mother–

infant interactions at 6 months,7 more improvement of self-regulatory competence

and improved mental, motor and behavioral development in the infants at 6 months,8

improved motor outcome at 24 months,9 and to more independency of the infants at

preschool age.10

For an accurate role in early intervention, the clinimetric characteristics of the IBA

need to be explored. In two pilot studies,11,12 we described the theoretical background,

scoring and interpretation of the IBA. These studies showed that short quantified IBA

observations were able to detect considerable differences between low-risk preterm

and term infants,11 and between infants that received intervention and control infants

at term, 3 and 6 months CA.12 In addition, the IBA showed differences between term,

preterm and preterm intervention infants’ neurobehavioral development over time.11,12

The purpose of this study is to further investigate the clinimetric characteristics of the IBA,

by determining its reliability, sensitivity and responsiveness to evaluate neurobehavioral

organization in very preterm-born infants.

Patients and Methods

Data of a recent multicenter RCT, which evaluated the effect of the IBAIP in very preterm

infants after discharge from hospital, were used.8 Primary outcomes were the Bayley

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30 | Chapter 2

Scales of Infant Development-II (BSID-II)13 at 6 and 24 months CA.8,9 The trial included

176 infants of <32 weeks gestational age (GA) and/or <1500 g, born in one of the seven

Amsterdam hospitals, and with parents living in Amsterdam. GA was determined by

maternal history and ultrasound examination in early pregnancy, or postnatal with the

Dubowitz-score14 if ante-partum information was inconclusive. The infants’ mean (SD)

GA was 29.6 (2.2) weeks in the intervention group and 30 (2.2) weeks in the control

group; the mean (SD) birth weight was 1242 (332) g in the intervention group and 1306

(318) g in the control group.

The interventions consisted of one session shortly before discharge from hospital and

six to eight sessions at home, until 6 months CA. The interventionists used continuous

naturalistic IBA observations to systematically analyse the child’s behavior during

interactions, resulting in immediate strengths based recommendations to support the

infant and the parent. In addition, shortly before discharge, at 3 and 6 months CA,

standardized IBA observations were registered to evaluate the infants’ neurobehavioral

performance for research purposes.8 In this study, these observations are used to

determine the reliability and validity of the IBA. IBA observations of 169 infants were

available at baseline (35–38 weeks postmenstrual age, PMA), and 162 infants at 6 months

CA; data of 157 infants were available at both baseline and 6 months CA. Data loss was

because of technical problems with the video administration or a nonoptimal state of

the infant. A detailed description of perinatal and socio-demographic characteristics and

infant outcomes can be found in Koldewijn et al.8

The Infant Behavioral Assessment

The IBA is based on naturalistic observations, discriminating 113 behaviors in four

systems: 26 items in the autonomic system, 44 items in the motor system, 9 items in

the state system and 34 items in the attention ⁄ interaction system (Appendix 1). The

infant’s behaviors are scored as present (=1) if they are observed at least once during the

observational interval, or as absent (=0). Within each of the four systems, the behaviors

are interpreted as approach (stable / engagement), self-regulatory (utilized by the

infant to concentrate, cope and/or console himself), or stress (unstable ⁄ disengagement)

behaviors. For example, on the IBA score sheet (Appendix 1), the items in the motor

system, subsystem hands, are interpreted as follows: grasp and resting are considered to

communicate approach ⁄ stabile behavior; holding on, hand to midline, hand to mouth,

groping, hand on stomach, self-clasp and hand on head are considered self-regulatory

behavior; finger extension, finger splay and fisting are considered to express stress.1 The

categories approach and self-regulation demonstrate the infant’s unique behavioral

strengths to interact; stress behaviors show the infants’ vulnerabilities and needs.



2

The IBA is intended for use by health professionals who have experience with young

infants. Formal training and certification in the IBA is required; an inter-rater agreement

of at least 85% must be established.1 The IBA does not have normative data for either

term or preterm infants, as the test aims to assess the individual infant’s behavioral

strengths and needs in response to sensory information, to provide the quality and

amount of information or support that is appropriate for that particular infant, at that

particular time.

Data collection

Research use of the IBA requires careful standardization and grading of the challenge

for each specific infant group and/or age. The infant needs to be able to join in an age

appropriate interaction but should also be challenged enough to use self-regulatory

behaviors or show short moments of stress.

At baseline (35–38 PMA), the infant was recorded on video in hospital, during the

changing of a diaper by the mother. The infant was in supine in the bed, and a 2-minute

‘observation window’ was used to score the IBA, starting when the diaper was opened.

At 3 months CA, the infant was recorded at home. The infant was in an unsupported

supine position. A 2-minute ‘observation window’ was used to score the IBA, starting at

the moment the mother presented a bell and rattle as used in the BSID-II. At 6 months

CA, the BSID-II assessment at the follow-up clinic was recorded on video; a 2-minute

‘observation window’ during the ‘exploration of the bell’ was used to score the IBA,

again with the infant in an unsupported supine position. An awake state of the infant

was required;1 a full description of the standardizations is available by the author of this

paper.

All IBA fragments were scored from video by an IBAIP certified observer (JvH), who

was blinded for group assignment. The IBA was quantified by counting the occurrence

of ‘approach’ and ‘stress’ behaviors in the autonomic, motor, state and attention

⁄ interaction system, and for the IBA total scores of approach and stress; means were

calculated for each of the four systems and the IBA total score. Self-regulation is not

used as an outcome measure for the infant’s neurobehavioral organization, as self-

regulation has a mediating function that results either in the enhancement of approach

(by concentration) or the prevention⁄reduction of stress (by coping or consoling).

To evaluate the inter-observer reliability of the IBA, video fragments of 40 infants were

scored at the CA of 3 months by two independent certified and experienced observers

(KK and JvH). The age of 3 months was chosen as the IBA incorporates items for the age

of 0–8 months. Three-month old infants are expected to express behaviors throughout

the four systems. At term age, infants may express only few approach behaviors in the

attention ⁄ interaction system and at 6 months only few stress behaviors in the autonomic

system.

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32 | Chapter 2

To investigate the sensitivity of the IBA, we evaluated its ability to discriminate

between neurobehavioral outcomes of subgroups of infants with or without the

perinatal risk factors of GA ≤28 weeks and oxygen dependency >28 days at the age

of 35–38 weeks PMA. The IBA responsiveness to change was investigated over the

period from 0 to 6 months. As young infants are expected to make more adaptations

and changes in this period than at any time later in life, we expected large changes.

We therefore focused primarily on the responsiveness of the IBA to show differences in

change after intervention, in the total intervention and control group, and a subgroup

of intervention and control infants with oxygen dependency >28 days. This high-risk

group was chosen because oxygen dependency was found to be significantly associated

with the primary outcomes at 6 months in our RCT. Moreover, at 24 and 44 months, it

became clear that the intervention (IBAIP) benefited the development of infants with

long-term oxygen dependency most.9,10

Statistical analysis

Data were analyzed using the SPSS 15.0 program (SPSS, Chicago, IL, USA).

Percentage agreement for each item was calculated. Item-by-item percentage

agreement was calculated for the total and the three categories of approach, self-

regulation and stress. In addition, agreement between observers was calculated using

weighted Kappa statistics with quadratic weights for these three categories. According

to Landis and Koch,15 a Kappa of >0.80 is very good, 0.61–0.80 good, 0.40– 0.60 moderate

and <0.40 is poor. According to the instructions in the IBA Training Manual,1 the five

items for skin colour were removed, because colour cannot be scored from video.

The sensitivity of the IBA to discriminate between infants dichotomized according to

two developmental risk factors was analyzed with t-tests. An alpha level of 0.05 was

considered significant. For the responsiveness of the IBA, Cohen’s16 effect size (ES) was

used as a measure of change. ES was obtained by dividing the absolute change between

the outcomes at baseline and the outcomes at 6 months by the standard deviation of the

baseline measurement. An ES of ≥0.80 is considered large, an ES of 0.50 is medium and

an ES of 0.20 is considered small.

Results

Inter-observer reliability

Table 1 summarizes the inter-observer agreement on the IBA categories of approach,

self-regulation and stress, and the total item-by-item percentage agreement of the IBA

in 40 infants. Inter-observer agreement was moderate in the category of approach (Kw

= 0.58) and good in the categories self-regulation (Kw = 0.72) and stress (Kw = 0.75).



2

Observers achieved an average of 93% (range 85–97%) item-by-item agreement for the

total assessment. Of a total of 108 items, 97 had good to excellent agreement (>80%)

and 11 had moderate agreement (60–80%). Of the 11 items with moderate agreement,

seven were in the motor system, three in the attention ⁄ interaction system and one was

in the state system.

Table 1. Infant Behavioral Assessment. Inter-observer agreement (n = 40)Categories No of items Weighted Kappa Percentage agreementApproach 22 0.581 92Regulation 42 0.722 90Stress 44 0.754 95Total IBA 108 n.a. 93

n.a.: not applicable

Sensitivity of the IBA at term age

The differences on the IBA subsystem scores and total scores in the two high–risk groups

are shown in Table 2. All outcomes pointed in the expected direction, indicating less

approach and/or more stress in infants at biological risk. Significantly less autonomic

approach, more autonomic stress and less total approach were found in infants with a

GA ≤28 weeks. Infants with oxygen dependency >28 days showed less autonomic and

motor approach, more autonomic and state stress, less total approach and more total

stress.

Responsiveness of the IBA to change over time

Table 3 shows the responsiveness of the IBA subscores and total scores between 35–38

weeks PMA and 6 months CA. Approach in the state system could not be calculated

because of the preterm infants’ limited use of approach behaviors in the state system at

35–38 weeks PMA. As expected, the ESs were large, both in the randomized total groups

and in the oxygen-dependent high-risk groups, except for stress in the state system in the

randomized total groups. Again all outcomes pointed in the expected direction: ESs for

approach showed positive values (more approach over time) and ESs for stress showed

negative values (less stress over time). The ESs in the total intervention group were larger

for approach and stress than in the total control group. Largest changes were found in

intervention infants with oxygen dependency >28 days. In the control infants of this

high-risk subgroup, approach behavior increased to a higher extent (+5.72) than in the

total control group, but to a lesser extent than in the total intervention group. In this

high-risk control group, stress behavior, however, decreased to a lesser extent (-2.73)

than in all other groups.

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34 | Chapter 2

Table 2. Infant Behavioral Assessment (IBA). Differences between infant groups with or

without high-risk at 35-38 weeks postmenstrual age

Gestational age < 28 weeks Oxygen ≥ 28 days

IBA subscoresYes (n=30)Mean (SD)

No (n=139) Mean (SD)

Yes (n=50)Mean (SD)

No (n=119) Mean (SD)

Autonomic approach 0.56 (0.76) 1.02 (0.77)** 0.56 (0.76) 1.02 (0.77)** stress 2.73 (0.74) 2.33 (0.94)** 2.72 (0.88) 2.27 (0.89)**Motor approach 1.93 (1.29) 2.40 (1.29) 2.00 (1.25) 2.45 (1.30)* stress 6.43 (1.55) 6.38 (1.62) 6.58 (1.66) 6.31 (1.58)State approach 0.00 (0.00) 0.01 (0.09) 0.00 (0.00) 0.01 (0.92) stress 0.67 (0.61) 0.47 (0.00) 0.70 (0.61) 0.43 (0.61)**Attention-interaction approach 0.27 (0.52) 0.32 (0.59) 0.26 (0.49) 0.34 (0.61) stress 2.90 (1.90) 2.68 (1.38) 3.00 (1.51) 2.61 (1.46)IBA total scores approach 2.73 (1.48) 3.69 (1.85)** 2.82 (1.69) 3.82 (1.79)** stress 12.73 (3.07) 11.87 (2.87) 13.00(3.02) 11.61 (2.74)**

T-test, *P<0.05, **P<0.01

Table 3. Infant Behavioral Assessment (IBA): Effect Size (ES) of change in all VLBW infants

and in in infants with oxygen dependency ≥28 days, between 0 and 6 months corrected

age

IBA scores

ES all interventionInfants (n=83)

ES all control Infants (n=74)

ES interventionInfants with

O2 ≥28 days (n=33)

ES controlInfants with

O2 ≥28 days (n=14)

Autonomic approach + 1.85 + 0.62 +2.54 + 1.20 stress - 2.71 - 2.26 - 3.61 - 2.23Motor approach + 4.14 + 3.11 + 4.19 + 2.80 stress - 3.37 - 3.06 - 3.49 - 2.18State approach n.a. n.a. n.a. n.a. stress - 0.80 - 0.67 - 1.10 - 1.03Attention-interaction approach + 6.16 + 5.48 + 7.70 + 6.49 stress - 1.66 - 1.67 - 2.23 - 1.59IBA total scores approach + 6.81 + 5.51 + 7.71 + 5.72 stress - 3.62 - 3.54 - 4.32 - 2.73

n.a. = not applicable.



2

Discussion

This study aimed to determine the reliability, sensitivity and responsiveness of the IBA

to evaluate neurobehavioral organization in very preterm-born infants. Our data show

that the reliability of the IBA in the three categories of communication (approach, self-

regulation and stress) is moderate to good, and the item-by-item percentage agreement

of the IBA was good to excellent. Disagreement occurred most often in motor items such

as ‘stilling’, ‘hands resting’, ‘toe grasp’ and ‘squirm’. ‘Stilling’ is defined as the cessation

of movement of the trunk and extremities in anticipation, while the infant expresses

invested attention in an object, person or sound in the environment. ‘Squirm’ is defined as

writhing or wriggling, agitated movements of the trunk and/or extremities. Differences

in scoring may occur when the infant displays the behavior for a very short moment, or

as part of another movement. Adding a time component to the definitions of some of

these items may further enhance inter-observer agreement. Although some refinement

of the IBA definitions may be needed, the scores indicate an acceptable consistency with

which different observers can create the same analyses of infant behavior with the IBA.

The sensitivity of the IBA is demonstrated by clear differentiations in neurobehavioral

organization between very preterm infants with or without perinatal risk factors. In

particular, infants with oxygen dependency >28 days showed less organization, illustrated

by less approach and more stress. Apart from a more fragile autonomic system, these

infants demonstrated less motor control and displayed more negative emotions or hyper-

alertness. Infants born with a GA ≤28 weeks were discriminated by their more fragile

autonomic system (i.e. less respiratory or visceral stability and more tremor or startle)

and overall less approach behavior, indicating a declined ability to process information

or to engage in interactions. It appears that the outcomes of IBA observations regarding

infants with oxygen dependency and young GA reflect those found in studies using

hands-on neonatal neurobehavioral assessments, confirming that engaging a preterm

infant in a normal caregiving interaction (in this case the changing of a diaper) may risk

instability in the autonomic and motor system.17–19

Large responsiveness was found on all scores of the IBA, in both the total groups and

in the subgroups of oxygen dependent infants over a 6-month period, except for state

stress in the total group, which was moderate responsive. This last finding is probably

due to the standardization of the test, which required an awake state at the start of the

observation. The subsystems show that, in all infant groups, the largest changes take place

in the attention⁄interaction system, which is in line with the infant’s early development,

during which the infant gradually interacts with and explores his environment more.

Consistent with the improved developmental outcomes of the intervention infants in

our trial,8 the IBA measured a larger change in the intervention infants’ neurobehavioral

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36 | Chapter 2

competence (as the balance between approach and stress). In our trial, the risk

factor oxygen dependency ≥28 days was found to have a significant influence on the

outcomes.8–10 In line with these findings, the IBA also measured the largest change in

neurobehavioral competence in these high-risk intervention infants compared with

the total randomized groups and the high-risk control group. High-risk control infants

showed more change in approach over time than the total control group. This may point

at neurobehavioral recovery, which is normally particularly the case in infants with most

severe illnesses. However, the high-risk control infants’ resilience was not accompanied

with less stress, which may be at the cost of the infants’ information processing, and/or

their energy and health.

The results from this study support the validity of the IBA to monitor and guide

very preterm infants’ neurobehavioral organization and to evaluate intervention

to provide a more holistic picture of the infant.20–22 The ability of the IBA to support

the infant’s neurobehavioral organization during interactions from minute to minute

distinguishes the instrument from other neurobehavioral assessments at infant age that

provide us with a score but are not directly related to the actual situation in which

the caregiver or interventionist can do something for the child. Supporting the infant’s

self-regulatory competence to approach and respond to environmental information and

to diminish stress is currently seen as an important element in early intervention for

infants at biological and/or social risk.23–25 A behavioral analysis of the child’s individual

expectations, like the IBA, might be basic for effective neurobehavioral intervention.

Moreover, the IBA may have been crucial for the positive results we found in our RCT

in very preterm infants.7–10 It gives the interventionist a better insight in the infant’s

proximal developmental goals or underlying problem areas and may contribute to the

professionals’ understanding and valuation of the self-regulatory and adaptive processes

that precede skills or needs.5,6 This strengthens the confidence that the interventionist

can timely target areas that need specific support, but also what the infant does well

and needs less support and/or more challenge. The ability of the IBA to incorporate the

infants’ behaviors to approach information and to regulate themselves has the potential

to focus the intervention more positively on ways parents can support and foster their

child’s strengths, which may contribute to a satisfying parent-infant relationship.26,27

Also some limitations of this study should be noted. Research use of the IBA requires a

careful creation of the sample interaction for each specific infant group and/or age, and

our results may not be representative for other groups, ages or circumstances. We found

in preparatory studies that a 2-min interaction shows enough variability in behavior if

the challenge is well chosen. If the interaction takes 5 minutes, the child often shows a

continuation of the same behaviors or the infant may give up. However, the standardized

IBA ‘observation windows’ we used for this study provide a relatively short impression of



2

the infant’s neurobehavioral organization, which may not be representative of the total

interaction. Therefore, IBA observations should not be used as a level of performance, in

isolation from other measures.

We conclude that the IBA is a reliable and valid tool to evaluate and support

neurobehavioral organization in very preterm infants. Additional validation of the IBA

in different infant populations at different ages is warranted.

Acknowledgements

We sincerely thank Rodd Hedlund for the inspiring training sessions and his support.

The study was supported by grants from the Innovatiefonds Zorgverzekeraars (project

no. 576) and ZonMw (Zorg Onderzoek Nederland, project no. 62200032). The trial

from which the data for this study are drawn is registered with controlled-trials.com

ISRCTN65503576.

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38 | Chapter 2

References

1. Hedlund R, Tatarka M. (1986) The Infant Behavioral Assessment. Available at: http://www.ibaip.org. Accessed on July 10, 2011.

2. Als H. NIDCAP-observation sheet. Boston, MA: NIDCAP Federation International, 2001, 2006, 1981.

3. Als H. Manual for the naturalistic observation of newborn behavior. Boston, MA: NIDCAP Federation International, 2001, 2006, 1981, 1984, 1995.

4. Als H. Toward a synactive theory of development: promise for the assessment of Infant individuality. Infant Ment Health J 1982;3:229–243.

5. Hedlund R. (1998) The Infant Behavioral Assessment and Intervention Program. Available at: http://www.ibaip.org. Accessed on July 10, 2011.

6. Hedlund R. (1998).The neurobehavioral curriculum for early intervention. Available at: http://www.ibaip.org. Accessed on July 10, 2011.

7. Meijssen D, Wolf M-J, Koldewijn K, et al. The effect of the Infant Behavioral Assessment and Intervention Program on mother-infant interaction after very preterm birth. J Child Psychol Psychiatry 2010; 51:1287–1295.

8. Koldewijn K, Wolf MJ, van Wassenaer A, et al. The Infant Behavioral Assessment and Intervention Program for very low birth weight infants at 6 months corrected age. J Pediatr 2009;154:33–38.

9. Koldewijn K, van Wassenaer A, Wolf MJ, et al. A neurobehavioral intervention and assessment program in very low birth weight infants: outcome at 24 months. J Pediatr 2010;156:359–365.

10. Verkerk G, Jeukens-Visser M, Koldewijn K, et al. The Infant Behavioral Assessment and Intervention Program in very low birth weight infants improves independency in mobility in daily activities at preschool age. J Pediatr 2011;159:933-938.

11. Wolf MJ, Koldewijn K, Beelen A, Smit B, Hedlund R, de Groot IJ. Neurobehavioral and developmental profile of very low birth weight preterm infants in early infancy. Acta Paediatr 2002;91:930–938.

12. Koldewijn K, Wolf MJ, van Wassenaer A, Beelen A, de Groot IJ, Hedlund R. The Infant Behavioral Assessment and Intervention Program to support preterm infants after hospital discharge: a pilot study. Dev Med Child Neuro 2005;47:105–112.

13. Van der Meulen BF, Ruiter SAJ, Lutje Spelberg HC, Smrkovsky M. Bayley scales of Infant Development-II, Netherlands version. Lisse: Swets Test Publishers, 2002.

14. Dubowitz L, Mercuri E, Dubowitz V. An optimal score for the neurological examination of the term infant. J Pediatr 1998;133:406–416.

15. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33:159–174.

16. Cohen J. Statistical power analyses for the behavioral sciences. 2nd ed. New York: Academic Press, 1977.

17. Brown N, Doyle L, Bear M, Inder T. Alterations in neurobehavior at term reflect differing perinatal exposures in very preterm infants. Pediatrics 2006;118:2461–2471.

18. Mouradian L, Als H, Coster W. Neurobehavioral functioning of healthy preterm infants of varying gestational ages. J Dev Behav Pediatr 2000;21:408–416.

19. Huppi PS, Schuknecht B, Boesch C, Bossi E, Felblinger J, Fusch C, et al. Structural and neurobehavioural delay in postnatal brain development of preterm infants. Pediatr Res 1996;39:895–901.



2

20. Saigal S, Rosenbaum P. What matters in the long term: reflections on the context of adult outcomes versus detailed measures in childhood. Semin Fetal Neonatal Med 2007;12:415–422.

21. Msall ME, Park JJ. The spectrum of behavioral outcomes after extreme prematurity: regulatory, attention, social, and adaptive dimensions. Semin Perinatol 2008;32:42–50.

22. Robertson CMT, Watt M-J, Dinu IA. Outcomes for the extremely premature infant: what is new? and where are we going? Pediatr Neurol 2009;40:189–196.

23. Shonkoff JP, Phillips DA. Acquiring self-regulation. In: Shonkhoff JP, Phillips DA, editors. From neurons to neighbourhoods: the science of early childhood development. 2nd ed. Washington, DC: National Academy Press, 2001:93–123.

24. Shonkoff JP, Boyce WT, McEwan BS. Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. JAMA 2009;301:2252–2259.

25. Msall ME. Optimizing early development and understanding trajectories of resiliency after extreme prematurity. Pediatrics 2009;124:387–390.

26. Dunst CJ. Revisiting ‘Rethinking Early Intervention’. Topics Early Child Spec Educ 2000;20:95–104.

27. Spittle AJ, Orton J, Doyle LW, Boyd RN. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev 2007;2: CD005495.

Chapter 3

Comparing two motor assessment tools to

evaluate neurobehavioral intervention effects in

very low birth weight infants at 1 year

Janeline W.P. Van Hus, Martine Jeukens-Visser, Karen Koldewijn,

Loekie Van Sonderen, Joke H. Kok, Frans Nollet, Aleid G. Van Wassenaer-Leemhuis.

Physical Therapy 2013;93:1475-1483

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42 | Chapter 3

Abstract

Background. Infants with very low birth weight (VLBW) are at increased risk for motor

deficits, which may be reduced by early intervention programs. For detection of motor

deficits, and to monitor intervention, different assessment tools are available. It is

important to choose tools that are sensitive to evaluate the efficacy of intervention on

motor outcome.

Aim. The purpose of this study was to compare the Alberta Infant Motor Scale

(AIMS) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant

Development-Dutch Second Edition (BSID-II-NL) in their ability to evaluate effects of an

early intervention, provided by pediatric physical therapists, on motor development in

infants with VLBW at 12 months corrected age (CA).

Design. This was a secondary study in which data collected from a randomized controlled

trial (RCT) were used.

Methods. At 12 months CA, 116 of 176 infants with VLBW, participating in a RCT on the

effect of the Infant Behavioral Assessment and Intervention Program, were assessed with

both the AIMS and the PDI. Intervention effects on the AIMS and PDI were compared.

Results. Corrected for baseline differences, significant intervention effects were found

for AIMS and PDI scores. The highest effect size was for the AIMS subscale sit. A significant

reduction of abnormal motor development in the intervention group was only found

with the AIMS.

Limitations. No Dutch norms are available for the AIMS.

Conclusion. The responsiveness of the AIMS to detect intervention effects was better

than the PDI. Therefore, caution is recommend in monitoring infants with VLBW only

with the PDI and the use of both the AIMS and the BSID is advised when evaluating

intervention effects on motor development at 12 months CA.


Evaluating efficacy of intervention on motor outcome | 43

3

Introduction

Infants with very low birth weight (VLBW) have more motor deficits compared to their

full-term counterparts, and their motor deficits persist throughout childhood.1 Some

studies have demonstrated poor quality of movements, low postural control and atypical

postures of VLBW infants in their first year of life.2,3 Therefore, motor development is

an important domain to follow-up in these infants. In 2006, the American Academy of

Pediatrics published guidelines for the follow-up of preterm infants and recommended

that all VLBW infants should have a structured, age-appropriate neuromotor examination

at least twice during the first year of life.4 However, no recommendations for specific

instruments were made.

Until recently, there was little evidence of an effect of early intervention programs

on motor outcome in VLBW infants.5 A systematic review of neuromotor assessments6

concluded that large-scale randomized controlled trials (RCTs) of interventions are

needed, as well as assessment tools that are sensitive enough to measure change in

motor performance, in order to evaluate the efficacy of the intervention programs in the

first year of life. The use of more than one assessment tool is recommended to ensure

that one has appropriate predictive, discriminative, and evaluative assesments.6

Between 2004 and 2007, a multicenter RCT7 was designed and conducted by pediatric

physical therapists to evaluate the effectiveness of the Infant Behavioral Assessment and

Intervention Program© (IBAIP)8 in VLBW infants. The instrument used to measure the

primary outcome at 6 and 24 months corrected age (CA) was the Bayley Scales of Infant

Development - Dutch second edition (BSID-II-NL).9 At both time points, an intervention

effect was found on the motor domain.7,10

At 12 months CA, motor outcome was measured using the Psychomotor

Developmental Index (PDI) of the BSID-II-NL, and in a large subset of infants participating

in the trial, the Alberta Infant Motor Scale (AIMS) was also used to measure motor

outcome.11 The AIMS was added to the assessment protocol, because information about

possible overestimation of the PDI12 became apparent when 12-month follow-up was

in progress. The AIMS demonstrated the best psychometric properties in a systematic

review of motor assessments for preterm infants.6 The BSID-II-NL is moderately reliable

and valid according to studies on the instrument’s psychometric qualities but it has low

reliability until the age of 12 months.12,13 The test construction of the AIMS is based on

the dynamical systems theory of motor development,11,14 whereas the PDI is based on the

traditional neuromaturational concept.9

The neuromaturational theory proposes that changes in gross motor skills during

infancy result only from the neurological maturation of the central nervous system

(CNS). The dynamic motor theory considers the CNS as one subsystem of many that

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44 | Chapter 3

dynamically interacts to develop movements. Other elements that explain movement

changes are the infant’s biomechanical and psychological factor and the nature of the

task or environment.11 Overall, the AIMS is considered to have good validity and high

reliability and is able to detect subtle changes in movement quality.11,14,15 Responsiveness

or sensitivity to change, to our knowledge, has not been documented.

The data of both concurrent assessments enabled evaluation of intervention effects

on the intermediate time point of 12 months, in the light of the above mentioned need

for sensitive assessment tools that measure change in motor performance. The purpose

of this study was to compare the AIMS and the PDI of the BSID-II-NL in their ability to

evaluate the effects of an early neurobehavioral intervention program, the IBAIP, on

motor development in VLBW infants at 12 months CA.

Methods

Participants and Procedure

The study population consisted of VLBW infants of 12 months CA participating in a

RCT7 assessing the effect of a neurobehavioral intervention program, the IBAIP.8 Two

level III hospitals with neonatal intensive care unit facilities and all 5 city hospitals in

Amsterdam, the Netherlands, participated in this RCT. After recruitment, 176 infants

with a gestational age (GA) <32 weeks and/or a birth weight <1500 gram were included.

Exclusion criteria were severe congenital abnormalities of the infant, severe physical or

mental illness/problems of the mother, non-native families for whom an interpreter could

not be arranged, and participating in other trials on post discharge management. After

computer-generated randomization, stratified for GA (< and ≥30 weeks) and recruitment

site, with multiplets assigned to the same group, 86 participants were assigned to the

intervention group and 90 to the control group. The study flow diagram is presented in

Figure 1.

The intervention started a few days before discharge. As at that point in time neither

the AIMS nor the PDI are applicable, the standardized Infant Behavioral Assessment©16

(IBA) was administered, between 35-38 weeks postmenstrual age. The IBA systematically

observes and interprets 113 infant communicative behaviors that are categorized

according to four subsystems: the autonomic system, the motor system, the state system,

and the attention/interaction system. Within each of the four subsystems, the behaviors

are interpreted as approach (stable/engagement), self-regulatory, or stress (unstable/

disengagement) behaviors. In agreement with the higher biological risk of the IBAIP

group, this assessment showed7 that, at baseline, infants in the intervention group

showed significantly less interaction and more stress.7



3

Figure 1. Study flow diagram

315

eligible participants

86 intervention infants

Follow up at 12 months 84 withdrawn (1)

moved abroad (1)

BSID-II PDI 83 AIMS 58

90 control infants

died before discharge (1)

176

randomized

Follow up at 6 months 85 withdrawn (1), lost in follow up (3)

BSID-II PDI 83

Follow up at 12 months 79 withdrawn (2), lost in follow up (1)

died (1), moved abroad (2)

BSID-II PDI 77 AIMS 58

Follow up at 24 months 83 moved abroad (1)

BSID-II PDI 75

Follow up at 24 months 78 lost in follow up (1)

BSID-II PDI 74

Follow up at 6 months 86 BSID-II PDI 86

139 excluded

refused to participate (38) died (11) child factors (12)

language reasons (11) parental factors (12)

older brother/sister in trail (3) participation in other trail (52)

The intervention period ended at 6 months CA. At 12 months CA, 6 months after

the intervention had ended, pediatric and developmental assessments were performed

during one visit at the follow-up clinic. First, the standard clinical neurological

examination and the AIMS were performed by one of three experienced pediatricians.

R1R2R3R4R5R6R7R8R9


46 | Chapter 3

Subsequently, one of two developmental psychologists administered the BSID-II-NL. The

visit lasted about 2 hours.

The AIMS was added to the assessment protocol 2 months after the start of the follow-

up at 12 months CA. Therefore, not all infants included in the original RCT were assessed

with the AIMS, and those not assessed with the AIMS were excluded from this study.

Although no interrater reliability was calculated, all assessors were trained according

to the standardized instructions of both tests and were blinded for group assignment.

The infants and the parents in the intervention group received 1 intervention session

shortly before discharge and 6 to 8 one-hour sessions at home from an IBAIP-trained

pediatric physical therapist. The control group received standard care and was referred

to a non-IBAIP-trained physical therapist if deemed necessary by the pediatrician. Written

informed consent was obtained from the parents.

Measurements

Two standardized instruments documented the infants’ motor development. The AIMS11

is a measure of infant gross motor development. It is designed to measure motor skills

from term age to 18 months of age. The test consists of 58 items divided into 4 subscales:

prone, supine, sit, and stand. In each item, the qualitative aspects of the movement

is specifically described in terms of weight-bearing surface of the body, the posture

necessary to achieve the gross motor skill and the antigravity or involuntary movement

performed by the infant in the position. It has been set as the norm on 2,202 infants born

in the province of Alberta, Canada. Raw total scores and subscale score can be converted

to centile ranks and compared with the ranks of age-equivalent peers. Mildly delayed

motor development on the AIMS is defined as a total score below the 10th percentile,

and abnormal motor development as a score below the 5th percentile. The AIMS can be

easily administered in clinical settings; requires minimal handling, and can be completed

in 20 minutes.

The BSID-II-NL9 is used to assess the mental and psychomotor development of children

aged 1 to 42 months. It consists of mental, behavioral and psychomotor scales. Because

of the aim of this article, only the psychomotor scale is described here. The 111 items

of the psychomotor scale measure fine and gross motor skills. Depending on the age

and developmental level of the infant, an age-appropriate set of items is administered.

Raw scores can be converted in the PDI with, in the population with normal motor

development, a mean (SD) of 100 (15). Mildly delayed motor development is defined

as <85 points (-1 SD) and an abnormal motor development as <70 points (-2 SD). The

standardization was based on the test results of 1909 Dutch children and set into Dutch

norms in 2002. It takes about 45 minutes to administer the PDI.



3

The Infant Behavioral Assessment and Intervention Program

The IBAIP8 is a neurobehavioral intervention program. To attend the IBAIP training and

become certified, clinical experience with newborns or young infants and knowledge

of infant development and standardized testing are required. The IBAIP, therefore, is

accessible for pediatric physical therapists. The IBAIP aims to support the infant’s self-

regulatory competence and multiple developmental functions via responsive parent-

infant interactions. In practice, the interventionist teaches the parent to recognize and

interpret the three different kinds of communicative behaviors of their infant in daily

life activities, as approach behaviors, self-regulatory behaviors or stress behaviors to

promote interactions that match to the infants’ needs.

Facilitation strategies are offered to best support the infant’s neurodevelopmental

progression and self-regulatory competence. As a result, the infant is able to interact

and explore while maintaining stable physiological and behavioral functioning. The

facilitation strategies address environmental facilitation (eg. visual and auditory input),

handling and positioning (eg. the infant’s position in supine or prone), and cue-matched

facilitation (eg. hand to mouth, foot bracing, or hands to midline). Thus, the program

supports the infant’s growth, the infant’s motivation to explore, and the possibility to

learn from information. For more detailed information about the content of the IBAIP,

we refer to Hedlund8and Hedlund and Tatarka.16

Data Analysis

Data were analyzed using the SPSS computer program, version 16.0 (SPSS Inc, Chicago,

Illinois). Differences in sociodemographic and perinatal characteristics between

participants and nonparticipants and motor outcomes of the AIMS and PDI between

participants and between intervention and control groups, were analyzed using the

independent-samples t test and the Chi-squared test, when appropriate. The Pearson

(r) correlation coefficient was used to assess the relationship between the raw scores

of the PDI and the AIMS total and subscale scores. Multiple linear regression analyses

were used to assess the effect of the intervention on the PDI and AIMS total scores and

subscale scores.

We adjusted scores for the following variables that differed at baseline: IBA approach

and stress behavior, gender, oxygen therapy ≥28 days, surfactant treatment, and

continuous positive airway pressure (CPAP). The adjusted scores were included in the

linear regression model as covariates because no collinearity among these factors was

found. An α level of 0.05 was considered for all tests of significance.

Effect sizes (ESs) were calculated as the adjusted mean difference between the

intervention and control groups divided by the standard deviation of the total group.

To interpret the ES, we used Cohen’s criteria: ≥0.2 = small; ≥0.5 = moderate; ≥0.8 = large

effect.17

R1R2R3R4R5R6R7R8R9


48 | Chapter 3

To compare motor outcome between the intervention and control groups, binary

logistic regression was performed, adjusted for baseline differences, with as dependent

variables the AIMS and PDI outcomes (normal versus mildly abnormal motor development),

and odds ratios (ORs) were calculated.

Results

Sociodemographic and perinatal factors

At 12 months CA, 116 out of 176 infants participating in the RCT were assessed with the

PDI and the AIMS. They were equally divided between the intervention group (n = 58)

and control group (n = 58). Of the 60 infants who formed no part of this study, 47 infants

were only assessed with the PDI and 13 infants did not participate in the assessment at

12 months CA. The participants (n = 116) did not differ from the nonparticipants (n = 60)

with respect to sociodemographic and perinatal factors, except for 4 factors. Compared

with the nonparticipants, the participants had fewer approach behaviors and more stress

behaviors, more low educated fathers (46.5% versus 26.3%, P = 0.011), less artificially

ventilated infants (37.1% versus 53.3%, P = 0.039), a lower occurrence of ventricular

dilation (1.7% versus 8.3%, P = 0.033) and fewer septic periods (44.0% versus 60.0%,

P = 0.044). A description of the sociodemographic and perinatal factors in the intervention

and control groups is presented in Table 1.

At baseline, the infants in the intervention group showed more stress behaviors

and fewer approach behaviors, as measured with the IBA. In accordance with findings

at 6 and 24 months7,10 and despite randomization, significantly more infants of the

intervention group received respiratory therapy as indicated by surfactant treatment,

CPAP, and oxygen therapy ≥28 days than in the control group. In addition, there were

significantly more boys in the intervention group. Because of this imbalance between

the two groups, we adjusted the outcomes for the IBA at baseline and these perinatal

factors.



3

Table 1. Sociodemographic and perinatal characteristics of the study participants

Characteristics Intervention(n=58)

Control(n=58) P

Social background factorsSingle- parent family, n (%) 9 (15.5) 5 (8.6) .254Maternal age at date birth (y), mean (SD) 31.7 (5.0) 32.2 (5.0) .642Paternal age at date birth (y), mean (SD) 36.1 (7.4) 35.7 (6.0) .335Mother born in the Netherlands, n (%) 33 (56.9) 38 (65.5) .341Father born in the Netherlands, n (%) 34 (58.6) 35 (60.3) .850Maternal education low, n (%) 26 (44.8) 23 (39.7) .573Paternal education low, n (%) 29 (50.0) 24 (41.4) .265Perinatal factorsGestational age (weeks), mean (SD) 29. 8 (2.1) 29.9 (2.0) .440Gestational age <28 weeks, n (%) 12 (20.8) 6 (10.3) .124Birth weight (g), mean (SD) 1248 (338.6) 1315 (317.3) .267Small for gestational age†, n (%) 15 (12.9) 8 (6.9) .103Sex: male, n (%) 37(63.8) 26(44.8) .040*Twins/Triplets, n (%) 16 (27.6) / 7 (12.1) 15 (25.9) / 1 (1.7) .075Antenatal steroid use, n (%) 41 (70.7) 42 (72.4) .833APGAR score, at 5 min, mean (SD) 8.5 (1.7) 8.6 (1.4) .765Surfactant, n (%) 21 (36.2) 11 (19.0) .038*Artificial ventilation, n (%) 24 (41.4) 19 (32.8) .336CPAP, n (%) 51 (87.9) 40 (69.0) .013*Oxygen support ≥28 days pma, n (%) 22 (37.9) 10 (17.2) .013*Indomethacin use, n (%) 12 (20.7) 5 (8.6) .066Septic periods before discharge, n (%) 30 (51.7) 21 (36.2) .092Intraventricular hemorrhage ‡

grade 1, 2/3, 4, n (%) 10 (17.2) / 3 (5.2) 8 (13.8) / 2 (3.4) .859Periventricular leucomalacia§, n (%) 8 (13.8) 6 (10.3) .569At dischargeIBA total Approach, mean (SD) 3.1 (1.7) 3.9 (1.8) .005*IBA total Regulation, mean (SD) 12.4 (3.3) 12.7 (3.1) .500IBA total Stress, mean (SD) 12.4 (3.3) 11.4 (2.6) .003*Length of hospitalization (d), mean (SD) 57 (29.4) 49 (22.1) .100Weight (g), mean (SD) 2420 (430.5) 2339 (410.9) .297Oxygen supply at discharge, n (%) 4 (6.9) 2 (3.4) .402

Differences in mean scores and proportions between the groups are analyzed using t-tests or χ2

tests. CPAP=continuous positive airway pressure. IBA=Infant Behavioral Assessment. PMA=postmentrual age.* p <.05. †Small for gestational age was defined as >1 SD below mean Dutch reference data.‡IVH defined according to Papile.§ Periventricular leucomalacia is defined according to de Vries.

R1R2R3R4R5R6R7R8R9


50 | Chapter 3

Motor outcomes and intervention effects at 12 months CA

The mean corrected test age at motor assessments was 12 months and 1 week. The total

group of 116 VLBW infants had a mean (SD) AIMS total score of 48.1(8.6) and a mean

(SD) PDI of 99.8 (15.0). Of the 116 VLBW infants, abnormal motor development was

determined in 20.7% of the infants based on the AIMS versus 2.6% based on the PDI.

Mildly abnormal motor development was determined in 31.9% of the infants using the

AIMS versus 8.6% using the PDI. The PDI correlated significantly with the AIMS total

score (r = 0.726, P <0.001) and with the AIMS subscales supine (r = 0.412, P <0.001), prone

(r = 0.626, P <0.001), sit (r = 0.582, P <0.001) and with the subscale stand (r = 0.751, P

<0.001).

Table 2 shows the motor outcomes in the intervention and control groups. The infants in

the intervention group had significant higher AIMS total and subscale sit scores than the

infants in the control group. After adjustment for the baseline differences, a significant

intervention effect was found on the AIMS total score and all AIMS subscale scores and

also on the PDI. The AIMS total score and the subscale scores supine and sit had the

largest ESs and were moderate according to Cohen’s criteria. The ES of the PDI was small.

The rates of (mildly) abnormal motor outcome scores in both tests are presented in Table

3. The AIMS classified 13.8% of the infants in the IBAIP group as having an abnormal

motor development versus 27.6% of the infants in the control group (P = 0.071). Adjusted

for the baseline difference, the OR for abnormal motor development on the AIMS was

statistically significant (OR = 0.17, P = 0.012, 95% confidence Interval (CI) = 0.04 – 0.67).

The PDI classified 1.8% of the infants in the IBAIP group as having an abnormal motor

development versus 3.5% of the infants in the control group (P = 0.566). The OR for

abnormal motor development on the PDI was not significant (OR = 0.21, P = 0.266, 95%

CI = 0.01 – 3.30).



3

Tab

le 2

. Co

mp

aris

on

of

ou

tco

mes

on

th

e A

IMS

and

th

e PD

I of

the

BSI

D-I

I-N

L b

etw

een

inte

rven

tio

n g

rou

p a

nd

co

ntr

ol g

rou

p

Inte

rven

tio

n(n

=58

)m

ean

(SD

)

Co

ntr

ol

(n=

58)

mea

n (

SD)

Mea

n

dif

f.P1

Inte

rven

tio

n(n

=58

)A

dj.

mea

n (

SE)

Co

ntr

ol

(n=

58)

Ad

j. m

ean

(SE

)

Ad

j. m

ean

dif

f.P2

Effe

ctSi

ze

AIM

S

Tota

l sco

re49

.8 (

7.0)

46.4

(9.

8)3.

4.0

31*

50.6

(1.

0)44

.4 (

1.1)

5.7

.000

*0.

72

Pro

ne

19.1

(3.

1)18

.1 (

4.1)

1.0

.171

19.3

(0.

5)17

.7 (

0.5)

1.7

.024

*0.

44

Sup

ine

9.0

(0.8

)8.

7 (0

.8)

0.3

.079

9.1

(0.1

)8.

6 (0

.1)

0.5

.002

*0.

59

Sit

11.4

(1.

4)10

.6 (

2.3)

0.8

.031

*11

.5 (

0.3)

10.3

(0.

3)1.

2.0

01*

0.64

St

and

9.

9 (3

.7)

9.1

(4.0

)0.

8.2

6110

.1 (

0.5)

8.6

(0.5

)1.

5.0

39*

0.39

BSI

D-I

I-N

L

PDI

102.

2 (1

5.0)

97.4

(14

.8)

4.8

.083

102.

8 (2

.0)

96.5

(2.

0)6.

3.0

32*

0.42

Dif

fere

nce

s in

mea

n s

core

s ar

e an

alyz

ed u

sin

g t

-tes

ts. M

ult

iple

lin

ear

reg

ress

ion

an

alys

es w

ere

use

d t

o a

sses

s th

e ef

fect

of

the

inte

rven

tio

n o

n t

he

dev

elo

pm

enta

l sco

res,

ad

just

ed f

or

stan

dar

diz

ed In

fan

t B

ehav

iora

l Ass

essm

ent

app

roac

h a

nd

str

ess

beh

avio

r at

bas

elin

e, s

urf

acta

nt,

O2≥

28d

ays,

co

nti

nu

ou

s p

osi

tive

air

way

pre

ssu

re, a

nd

gen

der

. AIM

S=A

lber

ta In

fan

t M

oto

r Sc

ale.

PD

I=Ps

ych

om

oto

r d

evel

op

men

tal I

nd

ex.

BSI

D-I

I-N

L=B

ayle

y Sc

ales

of

Infa

nt

Dev

elo

pm

ent-

seco

nd

Du

tch

ver

sio

n.

Mea

n d

iff.

=m

ean

dif

fere

nce

. A

dj.=

Ad

just

ed.

SD=

stan

dar

d d

evia

tio

n.

SE=

stan

dar

d e

rro

r. P1 =

P v

alu

e u

nco

rrec

ted

. P2

= P

val

ue

corr

ecte

d. *

P<

0.05

.

Tab

le 3

. Rat

es o

f ab

no

rmal

ou

tco

me

on

th

e A

IMS

and

th

e PD

I of

the

BSI

D-I

I-N

L in

inte

rven

tio

n g

rou

p a

nd

co

ntr

ol g

rou

p

Inte

rven

tio

nG

rou

pn

(%

)

Co

ntr

ol

Gro

up

n (

%)

Un

adju

sted

OR

(95

% C

I)P1

Ad

just

edO

R (

95%

CI)

P2

AIM

S

Mild

ly a

bn

orm

al (

<P1

0)14

(24

.1)

23 (

39.7

)0.

48 (

0.22

-1.0

8).0

750.

24 (

0.09

-0.6

8).0

08*

A

bn

orm

al (

<P5

)8

(13.

8)16

(27

.6)

0.42

(0.

16-1

.08)

.071

0.17

(0.

04-0

.67)

.012

*PD

I (B

SID

-II-

NL)

M

ildly

ab

no

rmal

(<

85 p

oin

ts)

4 (6

.9)

6 (1

0.3)

0.59

(0.

18-1

.92)

.381

0.46

(0.

12-1

.73)

.252

A

bn

orm

al (

<70

po

ints

)1

(1.8

)2

(3.5

)0.

49 (

0.43

-5.5

7).5

660.

21 (

0.01

-3.3

0).2

66

Mu

ltip

le lo

gis

tic

reg

ress

ion

an

alys

es w

ere

use

d t

o d

eter

min

e th

e in

terv

enti

on

eff

ect

on

th

e te

st o

utc

om

es n

orm

al v

ersu

s ab

no

rmal

, ad

just

ed f

or

stan

dar

diz

ed In

fan

t B

ehav

iora

l Ass

essm

ent

app

roac

h a

nd

str

ess

beh

avio

r at

bas

elin

e, s

urf

acta

nt,

O2≥

28d

ays

con

tin

uo

us

po

siti

ve a

irw

ay p

ress

ure

, an

d g

end

er. A

IMS=

Alb

erta

Infa

nt

Mo

tor

Scal

e. P

DI=

Psyc

ho

mo

tor

dev

elo

pm

enta

l In

dex

.B

SID

-II-

NL=

Bay

ley

Scal

es o

f In

fan

t D

evel

op

men

t-se

con

d D

utc

h v

ersi

on

. P1=

P v

alu

e u

nco

rrec

ted

. P2

= P

val

ue

corr

ecte

d.

* P<

0.05

. OR

=O

dd

s ra

tio

. CI=

con

fid

ence

inte

rval

.

R1R2R3R4R5R6R7R8R9


52 | Chapter 3

Discussion

This study demonstrates how two motor assessment tools, the AIMS and the PDI, differ

in evaluating effects of an early intervention on motor development in VLBW infants. On

both tests, we found intervention effects. However, the AIMS detected more and more

specific intervention effects than the PDI at 12 months CA. Significantly more infants had

an abnormal motor score according to the AIMS norms than according to the PDI norms.

In addition, a significant reduction of abnormal motor outcome in the intervention

group was found with the AIMS but not with the PDI.

Using two instruments with different test constructs enabled the evaluation

of different aspects of motor development. The PDI assesses gross and fine motor

development and has the advantage of a large age range (1-42 months) during which it

can be repetitively used. A limitation of the PDI is an uneven distribution of the different

motor skill items. For 11 out of 15 items, the standing position is required at the age of 12

months, whereas only 2 items are assessed in sitting position and another two in prone

position.9 The AIMS has the advantage of assessing motor development in 4 positions

(supine, prone, sit and stand), providing gross motor subscales, and incorporates other

developmental elements like the gravitational position of the infant, weight bearing and

postural alignment, but lacks the fine motor skills. VLBW infants are known to experience

difficulties in these qualitative aspects of motor development, such as reduced active

flexion power and discrepancies between the active muscle power and passive muscle

tone.18,19 The latter influences the capability in independent sitting.3 The assessment in 4

positions may explain the reason that the AIMS defines a higher proportion of infants as

mildly abnormal or abnormal in VLBW children than the PDI.

Our mean PDI scores are comparable with those of Westera et al,12 who also found a

relative high score (100.5) in a large group (n = 207) VLBW infants at 12 months CA. This

finding supports the reports on overestimation of the PDI in VLBW infants at 12 months

CA. Indeed, the rates of abnormal motor development were lower using the PDI, than

using the AIMS. VLBW infants’ experience difficulties with items that encompass trunk

control and trunk rotation and tend to compensate with hyperextension.2,3 Therefore,

they have fewer problems with items in standing position then in sitting position or

with making transits in or out of sitting or supine position. Using the AIMS, there were

significantly fewer infants with abnormal motor development in the intervention group.

No such effect was found with the PDI. This finding adds to our conclusion that the

responsiveness of the AIMS to detect an intervention effect was better than the PDI.

In this study, positive effects were found on all AIMS subscales, especially on the

subscales sit and supine. ESs on these subscales can be useful to elucidate specific effects

of the intervention on the motor system. An ES on the subscales sit and supine suggests



3

that the neurobehavioral intervention enhanced the infants’ postural control. The IBAIP

aims to support self-regulation. The self-regulatory strategies involve the motor system

and focus on midline orientation, which may have helped to gain more control over

posture and movements, and thus improved development in supine and sitting posture.

These self-regulatory strategies are of clinical relevance, since postural control, a basic

ingredient for motor development, often is described as one of the specific motor

problems in preterm infants.2,3

We expected positive intervention effects on motor outcomes at 12 months CA

because previous significant intervention effects were found with the PDI at 6 and 24

months CA.7,10 At 12 months of age, the positive intervention effects were found even

in this subset (71.2%) of the RCT. The reason for this reduction was that follow-up was

already in progress, when the AIMS was added to the protocol.

The AIMS total score correlated less with the PDI score in our study (r = 0.73, P <0.001)

compared to other publications (r = 0.90 and r = 0.89, P <0.01).13,14 The discrepancies may

be due to the use of the Dutch version of the BSID-II or methodological differences such

as the number of assessed infants at 12 months CA. In our study, we assessed 116 infants

and other studies evaluated 45 and 48 infants.13,14 To our knowledge, no correlation

values between the subscales of the AIMS and the PDI have been described so far. Not

surprisingly, the strongest correlation was between the PDI and the AIMS subscale stand

because, as mentioned above, for 11 out of 15 items on the PDI at the age of 12 months,

the standing position is required.

A significant limitation of this study is that no interrater reliability was calculated

for the raters who scored the AIMS and the BSID-II-NL. We can report that the three

assessors of the AIMS and two assessors of the BSID-II-NL were trained according to the

standardized instructions of both tests. However, reliability between raters still remains

a limitation. Therefore, our findings should be cautiously generalized.

The relevance of adding the AIMS to Bayley Scales of Infant Developmental (BSID)

assessments is supported by growing concerns about the high scores of the third edition

of the BSID20 in high risk populations.21-23 This new edition of the BSID will be available for

Dutch children in 2014. The BSID-III separates the psychomotor scale in a fine and a gross

motor scale but in comparison with the second edition, the gross motor assessment items

are only assessed in standing position at the age of 12 months. Because the abilities in

which VLBW infants’ experience difficulties, such as trunk control and trunk rotation, are

underrepresented in both the BSID-II and the BSID-III, the current results using the BSID-II

- AIMS comparison are also applicable for the Bayley III. Further research is warranted to

explore the correlation between the outcomes of the AIMS and motor scale of the BSID-

III, as well as between AIMS scores during infancy and motor outcomes at school age.

R1R2R3R4R5R6R7R8R9


54 | Chapter 3

Conclusion

This study demonstrates that both the AIMS and the PDI of the BSID-II-NL are able to

evaluate the effect of early neurobehavioral intervention on motor development in

VLBW infants at 12 months CA. However, the responsiveness of the AIMS to detect an

effect of this intervention was better than the PDI. Effects on the AIMS subscales sit and

supine pointed toward improved postural control due to the intervention. In line with

recent publications, we recommend caution with monitoring VLBW infants only with

the PDI and advise to use both the AIMS and the PDI to evaluate intervention effects on

motor development at 12 months CA.

Acknowledgements

The study was approved by the Medical Ethics Committees of the two level-III hospitals

and all 5 city hospitals in Amsterdam, the Netherlands. The study was supported by

grants from the Innovatiefonds Zorgverzekeraars (project no. 576) and ZonMw (Zorg

Onderzoek Nederland, project no. 62200032). The trial from which the data for this

study are drawn is registered with controlled-trials.com ISRCTN65503576.



3

References

1. De Kieviet JF, Piek JP, Aarnoudse-Moens CS et al. Motor development in very preterm and very low-birth-weight children from birth to adolescence. JAMA 2009;302:2235-2242.

2. Pin TW, Darrer T, Eldrigde B et al. Motor development from 4 to 8 months corrected age in infants born at or less than 29 weeks’ gestation. Dev Med Child Neurol 2009;51:739-745.

3. De Groot L, Hopkins B, Touwen BC. Muscle power, sitting unsupported and trunk rotation in preterm infants. Early Hum Dev 1995;43:37-46.

4. Wang JC, McGlynn A, Brook RH et al. Quality of care indicators for the neurodevelop-mental follow-up of very low birth weight children: Results of an expert process. J Pediatr 2006;117:2080-2092.

5. Spittle A, Orton J, Doyle LW et al. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants Cochrane Database Syst Rev 2007;18:CD005495.

6. Spittle AJ, Doyle WL, Boyd RN. A systematic review of the clinimetric properties of neuromotor assessments for preterm infants during the first year of life. Dev Med Child Neurol 2008;50:254-266.

7. Koldewijn K, Wolf MJ, Van Wassenaer AG et al. The Infant Behavioral Assessment and Intervention Program for very low birth weight infants at 6 months corrected age. J Pediatr 2009;154:33-38.

8. Hedlund R. The infant Behavioral Assessment and Intervention program.1998. Available from: http://www.ibaip.org. Accessed February 15, 2012.

9. Van der Meulen BF, Ruiter SAJ, Lutje Spelberg HC et al. BSID-II- NL. Dutch Manual. Lisse: Swets Test Publishers; 2002.

10. Koldewijn K, Van Wassenaer AG, Wolf MJ et al. A neurobehavioral intervention and assessment program in very low birth weight infants: outcome at 24 months. J Pediatr 2010;156:359-365.


12. Westera JJ, Houtzager BA, Overdiek B et al. Applying Dutch and US versions of the BSID-II in Dutch children born preterm leads to different outcomes. Dev Med Child Neurol 2008;50:445-449.

13. Ruiter SAJ, Lutje Spelberg HC, van der Meulen BF et al. The BSID-II-NL: construction, standardization, and instrumental utility. D J Psychol 2008;64:15-40.

14. Jeng SF, Yau KI, Cheb LC, Hsiao SF. Alberta Infant Motor Scale: reliability and validity when used on preterm infants in Taiwan. Phys Ther 2000;80:168-178.

15. Almeida KM, Dutra MV, Mello RR et al. Concurrent validity and reliability of the Alberta Infant Motor Scale in premature infants. J Pediatr (Rio J) 2008;84:442-448.

16. Hedlund R. Tatarka M. The infant Behavioral Assessment. 1988. Available from: http://www.ibaip.org. Accessed February 15, 2012.

17. Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, NJ: Lawrence Erlbaum Associaties;1988.

18. Dewey D, Creighton DE, Heath JA et al. Assessment of Developmental Coordination Disorder in children born with extremely low birth weights. Dev Neuropsy 2011;36:42-46.

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56 | Chapter 3

19. De Groot L, Van De Hoek AM, Hopkins B, Touwen BC. Development of relationship between active and passive muscle power in preterms after term age. Neuropediatrics 1992;23:298-305.

20. Bayley N. Bayley scale of infant and toddler development, 3rd edition. San Antonio (TX): Harcourt Assessment; 2006.

21. Moore T, Johnson S, Haider S, Hennessy E, Marlow N. Relationship between test scores using the second and third editions of the Bayley scales in extremely preterm children. J Pediatr 2012;100:553-558.

22. Anderson PJ, De Luca CR, Hutchinson E, Roberts G, Doyle LW. Underestimation of developmental delay by the new Bayley-III scale. Arch Pediatr Adolesc Med 2010;164:352-356.

23. Vohr BR, Stephens BE, Higgins RD et al. Are outcomes of extremely preterm infants improving? Impact of Bayley assessment on outcomes. J Pediatr 2012;161:222-228.

Chapter 4

Motor impairment in very preterm-born

children: Links with other developmental

deficits at 5 years of age

Janeline W.P. Van Hus, Eva S. Potharst, Martine Jeukens-Visser,

Joke H. Kok, Aleid G. Van Wassenaer-Leemhuis

Developmental Medicine and Child Neurology 2014;56;587-594

Chapter 4

Motor impairment in very preterm-born

children: Links with other developmental

deficits at 5 years of age

Janeline W.P. Van Hus, Eva S. Potharst, Martine Jeukens-Visser,

Joke H. Kok, Aleid G. Van Wassenaer-Leemhuis

Developmental Medicine and Child Neurology 2014;56;587-594

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58 | Chapter 4

Abstract

Aim. To elucidate the relation between motor impairment and other developmental

deficits in very preterm-born children without disabling cerebral palsy and term-born

comparison children at 5 years of (corrected) age.

Methods. In a prospective cohort study, 165 children (81 very preterm-born and 84

term-born) were assessed with the Movement Assessment Battery for Children-2nd

edition, Touwen’s neurological examination, the Wechsler Preschool and Primary

Scale of Intelligence, processing speed and visuomotor coordination tasks of the

Amsterdam Neuropsychological Tasks, and the Strengths and Difficulties Questionnaire.

Results. Motor impairment (≤15th centile) occurred in 32% of the very preterm-born

children compared with 11% of their term-born peers (P = 0.001). Of the very preterm-

born children with motor impairment, 58% had complex minor neurological dysfunctions,

54% had low IQ, 69% had slow processing speed, 58% had visuomotor coordination

problems and 27%, 50% and 46% had conduct, emotional and hyperactivity problems

respectively. Neurological outcome (odds ratio (OR) = 41.7, 95% CI 7.5-232.5) and full-

scale IQ (OR = 7.3, 95% CI 1.9-27.3) were significantly and independently associated with

motor impairment. Processing speed (OR = 4.6, 95% CI 1.8-11.6) and attention (OR = 3.2,

95% CI 1.3-7.9) were additional variables associated with impaired manual dexterity.

These four developmental deficits mediated the relation between preterm birth and

motor impairment.

Conclusion. Complex minor neurological dysfunctions, low IQ, slow processing speed

and hyperactivity/inattention should be taken into account when very preterm-born

children are referred for motor impairment.


Motor impairments and other deficits in preterm children | 59

4

Introduction

Deficits on multiple developmental domains occur more often in very preterm-born

children (<30 weeks’ gestation and/or birth weights <1000 g) than in term-born

children.1 Owing to improved neonatal intensive care, the rate of cerebral palsy (CP) in

very preterm-born children has dropped to approximately 5%.2 However, preterm birth

is still associated with significant motor impairment persisting throughout childhood.3

In several studies motor impairment is found in about 30 to 40% of very preterm-born

children at 5 years of age.1,4-6

Impaired motor development early in life may affect children’s ability to explore their

environment and gain experiences, which may in turn result in later cognitive delay,

intellectual disabilities or behavioral problems.7-9 In an earlier study on very preterm-

born children at age 5, we described that, in addition to motor impairment occurring in

30%, minor neurological dysfunction (MND) occurred in 45%, cognitive problems in 39%

and behaviour problems in 27%.1

Spittle et al.10 found that white matter abnormalities in very preterm-born children

predict motor impairment at 5 years of age. Because white matter injury occurs in various

areas of the brain,11 and is often accompanied by damage of the grey matter, corpus

callosum, and cerebellum,12 it is not surprising that, apart from motor impairment,

there is also a high frequency of deficits in other domains. Furthermore, Diamond’s13

overview of studies indicated a close functional relation between motor and cognitive

development.

Diffuse white matter loss may also be responsible for processing speed decrements

in very preterm-born adolescents.14 Processing speed, the basic speed at which the brain

processes information, is thought to underlie academic attainments, executive function

and behavior,15 but not much is known about the relation between processing speed and

motor function in very preterm-born children. The extent to which motor impairment in

very preterm-born children is associated with other deficits is unclear. This information

would be of interest from the causal point of view but also in the light of treatment.

Assuming that very preterm-born children have more motor impairment and other

developmental deficits than term-born children, we hypothesize that: (1) especially in

very preterm-born children with motor impairment, deficits in neurological outcome,

cognition, visuomotor coordination, processing speed and behavior are frequently

found; (2) other developmental deficits may, in part, mediate the higher occurrence of

motor deficits in very preterm-born children.

Therefore we studied; (1) the frequency of motor impairment in very preterm-born

children without disabling CP and in term-born children at 5 years of (corrected) age; (2)

the frequency of abnormal neurological outcome and deficits in cognition, processing

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60 | Chapter 4

speed, visuomotor coordination and behavior in very preterm-born and term-born

children and in very preterm-born children with and without motor impairment at 5 years

of (corrected) age; (3) the association of motor impairment with these developmental

deficits and (4) whether these developmental deficits mediate the relation between

preterm birth and motor impairment.

Methods

Participants

Two groups of children participated in the study, the very preterm-born group (children

born <30 weeks’ gestation and/or with birth weight <1000 g) and the comparison group

(children born after 37 weeks’ gestation and with birth weight >2500 grams). Participants

in the very preterm-born group were recruited from a single centre prospective cohort

study as part of the follow-up program of the Emma’s Children’s Hospital/Academic

Medical Centre, Amsterdam, the Netherlands.1 Children in the comparison group were

recruited from the school or social network of the very preterm-born group or via

mainstream schools in the neighbourhood of our hospital. The very preterm-born group

reached the corrected age of five years between December 2007 and June 2009. The

children in the comparison group reached the age of five years in the same time period.

Inclusion criteria of the very preterm-born group were (1) hospitalization in our neonatal

intensive care unit; (2) participation at least once in our neonatal follow-up program,

and (3) resident in the Netherlands. Exclusion criteria were: (1) participation in other

studies (because of the use of different instruments and different timing of follow up);

(2) a genetic syndrome; or (3) unable to participate in an intelligence test due to the

extent of their disability. The exclusion criterion of the comparison group was a planned

or current referral for learning or behavioral problems.

Procedures

The assessment protocol was similar for both groups. Two appointments were made at

the (corrected) age of 5 years at the Academic Medical Centre in Amsterdam. At the first

appointment, the child’s intelligence and visuomotor coordination were assessed by a

trained psychologist. At the second visit, within 3 months after the first visit, motor and

neurological tests were performed by a trained pediatrician or pediatric physical therapist

and focused attention and processing speed were assessed by the trained psychologist.

The investigators were not blind for birth status. Parents and teachers were asked to fill

in a questionnaire regarding the behavior of the child. Informed consent to participate

in the study was obtained from the parents and the Medical Ethical Committee of the

hospital approved the study. Perinatal and sociodemographic characteristics were taken



4

from the medical records, including education level and country of birth of the mother

as variables reflecting social-economic status (SES) because of a possible association

between low SES and cognition.

Measurements

Movement Assessment Battery for Children second edition (MABC-2)

The MABC-216 is a standardized and normative referenced test, designed to identify

impairment of motor functions in children aged 3 to 16 years. Motor outcomes were

calculated using the age band 3 to 6 years. Within this age band eight tasks (items) are

grouped under three components: manual dexterity, aiming and catching and balance.

Raw scores of the three components and the total test (the sum of all eight items) are

converted to standard scores. Reference means (SD) for the total test and component

standard scores are 10 (3). A standard score of less than 7 reflects performances no

greater than the 15th centile and is regarded as motor impairment.

The neurological examination according to Touwen

The neurological examination according to Touwen17 is a standardized and age-specific

examination to assess the neurological condition of a child between 4 and 12 years old

and pays special attention to MND. It addresses eight functional clusters: posture, reflexes,

involuntary and associated movements, coordination problems, fine manipulation

disability, sensory deficits and cranial nerve dysfunctions. Because children with disabling

CP were excluded in this study, neurological outcome was considered abnormal if there

was either complex MND or non-disabling CP.

Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL)

Intelligence was assessed using the WPPSI-III-NL.18 The seven core subtests were

administered. The Full scale intelligence quotient (IQ) was calculated. Reference mean

(SD) is 100 (15). The Full scale IQ was considered abnormal if it was more than 1 SD below

the mean (<85 points).

Baseline Speed task of the Amsterdam Neuropsychological Tasks (ANT)

Processing speed and consistency of speed were measured using the Baseline Speed task

of the ANT.19 This task requires children to react as fast and as accurately as possible to

simple stimuli by hitting a large button. The dependent measure was processing speed,

the time a child needed to process the information and generate a motor response.

Scores were considered abnormal if they were more than 1 SD above the mean of the

comparison group. The outcomes of the left and the right hand were combined.

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62 | Chapter 4

Tracking/Pursuit tasks of the Amsterdam Neuropsychological Tasks (ANT)

Visuomotor coordination was measured using the Tracking and Pursuit tasks of the ANT.19

The tracking task requires the child to trace a circle with a mouse cursor. The pursuit

task requires tracking a randomly moving target with a mouse cursor. The dependent

measure was the distance between the cursor and the circle or target. Scores were

considered abnormal if they were more than 1 SD above the mean of the comparison

group. The outcomes of the left and the right hand were combined.

Strengths and Difficulties Questionnaire (SDQ)

This behavior questionnaire has five subscales each consisting of five items, and a

total difficulty score.20 For this study, the “conduct”, “emotional”, and “hyperactivity/

inattention” subscales were assessed, using both parents and teacher form. According to

the test manual, a score was classified abnormal if it was above the 80th centile of the

norm score.

Statistical Analysis

Data analyses were performed using the computer program SPSS version 20.0 (IBM SPSS

Statistics, IBM Corporation, NY, USA). Differences in sociodemographic and perinatal

characteristics and the frequency of (abnormal) test outcomes between the very preterm-

born and comparison groups and between the very preterm-born and term-born children

with and without motor impairment were analyzed using the independent-samples

T-test and the Chi squared test, as appropriate. Two-sided P values <0.05 were considered

statistically significant.

To investigate the association between motor impairment and other developmental

deficits, four binary logistic regression analyses were performed with dependent

variables normal versus abnormal outcome (>15th centile versus ≤15th centile) on

the total score of the MABC-2 and the three components. Odds ratios (ORs) and 95%

confidence intervals (CIs) were calculated. The model consisted of two blocks; the first

block contained the variable birth status (preterm/term) and the variables that differed

between the groups. All variables were entered to the model at the same time. The

second block contained the dichotomous variables (normal/abnormal): neurological

outcome, full scale IQ, processing speed, tracking and pursuit, conduct, emotional and

hyperactivity\inattention behavior problems. The variables in the second block were via

a forward stepwise procedure added to the model when the variables had a P value of

0.05. To derive the robustness of the 95% confidence intervals vested through stepwise

logistic regression, additional bootstrapping analyses for the estimated regression

coefficient b were done.



4

Subsequently a mediation model was tested to analyse the extent to which these

developmental deficits mediate the association between preterm birth and total motor

impairment, and between preterm birth and impaired manual dexterity. Univariate

binary logistic regression analyses were performed for the different pathways. The

potential mediators were entered separately to the mediation model, combined with

the variables that differed between the groups. The Sobel-technique,21,22 was performed

to address whether the effect of birth status on motor impairment was significantly

reduced by including a potential mediator.

Results

One hundred thirty-eight very preterm-born children fulfilled our inclusion criteria.

Twenty-three children were excluded: 16 participated in another study, 4 were unable

to participate due to the extent of their disability, and 3 had a genetic syndrome. Eleven

children were lost to follow-up. Participating children (n = 104) differed only from non-

participants (n = 34) in the proportion of children who were part of twins (27% and

77% respectively, P <0.001). The 95 participating term-born children were recruited from

schools attended by very preterm-born children (n = 63), were friends (n = 14) or family

(n = 1) of very preterm-born children or were from schools in the neighborhood of our

hospital (n = 17).

Nineteen very preterm-born children were excluded because motor functioning was

assessed using a different version of the MABC (1st edition) and 4 very preterm-born

children and 11 term-born children were excluded because motor functioning was not

addressed due to no show or logistical problems.

One hundred and sixty-five children (81 very preterm-born and 84 term-born)

remained in the present study. Non-participating very preterm-born children (n = 23) did

not differ from the participants (n = 104) with respect to sociodemographic and perinatal

factors.

The sociodemographic factors did not differ between the very preterm-born and

comparison group except for two factors: the very preterm-born group comprised more

parents born outside the Netherlands (mother’s P = 0,011, father’s P = 0.005) and more

low educated mothers (P = 0.002) (Table 1). The countries/regions of maternal origin

were Suriname, Turkey, Morocco and West-Africa. In our analyses we corrected for low

educated mothers and mothers not born in the Netherlands. No correction for fathers

born outside the Netherlands was done because of the high correlation with the mothers

(Pearson’s r = 0.839).

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64 | Chapter 4

Table 1. Perinatal and social background characteristics of very preterm-born and

comparison children

Characteristics Very preterm-born group (n=81)

Comparison group (n=84) p

Perinatal characteristics Gestational age (wk), mean (SD) 28.7 (1.5) 40.0 (1.7) .000 Birth weight (g), mean (SD) 1078.7 (264.2) 3448.1 (511.9) .000 Gender: male, n (%) 40 (49.4) 34 (40.5) .250 Part of a multiplet, n (%) 24 (29.6) 3 (3.6) .000 Small for gestational age, n (%) 25 (30.9) - Surfactant, n (%) 38 (46.9) - Inotropics, n (%) 20 (24.7) - Postnatal dexamethason, n (%) 3 (3.7) - Indomethacin for patent ductus, n (%) 25 (30.9) - Requiring ventilation, n (%) 47 (58.0) - CPAP (d), n (%) 17.0 (14.1) - Oxygen support ≥28 days, n (%) 27 (33.3) - Oxygen support at 36 weeks, n (%) 13 (16.0) - Sepsis, n (%) 22 (27.2) - Necrotizing enter colitis, stage 2, n (%) 2 (2.5) - Subependymal hemorrhage, n (%) 18 (22.2) - IVH*, n (%) 6 (7.4) - IVH grade 2, n (%) 3 (3.7) - IVH grade 3, n (%) 3 (3.7) - PVL 1**, n (%) 3 (3.7) - Post hemorrhagic hydrocephalus***, n (%) 4 (4.9) -Social background characteristics Age infant at test date (y), mean (SD) 5.18 (0.2) 5.19 (0.1) .614 Maternal age at date birth (y), mean (SD) 31 (6.0) 31 (4.0) .88 Paternal age at date birth (y), mean (SD) 34 (7.0) 34 (5.0) .99 Mother not born in the Netherlands, n (%) 21 (25.9) 9 (10.7) .011 Father not born in the Netherlands, n (%) n = 81/81

19 (25.0)n = 82/84

7 (8.4) .005 Maternal low education****, n (%) n = 79/81

21 (26.6)n = 84/84

7 (8.3).002

Paternal low education, n (%) n = 73/8122 (30.1)

n = 81/8416 (19.8) .136

Data are presented as n (%) or as M ± SD. Differences in mean scores and proportions between the groups were analyzed using t-tests or χ2 tests. - , not applicable.*IVH=intraventricular haemorrhage defined according to Papile.**PVL=periventricular leukomalacia defined according to de Vries. There were no cases of PVL 2-4. ***Hydrocephalus defined as 4 mm >p97 of Levene curves.****Low education defined as <6 years post elementary schooling.



4

Test outcomes

A significant difference in motor impairment was found between the very preterm-

born (32.1%) and the comparison group (10.7%), (P = 0.001) (Table 2). On the MABC-

2 components, significant differences between the groups were found on manual

dexterity (very preterm-born 69.4% vs comparison group 30.6%, P = 0.006). No significant

differences were found on balance (very preterm-born 18.5% vs comparison group 9.5%,

P = 0.095) and aiming and catching (very preterm-born 25.9% vs comparison group

23.8%, P = 0.753).

Significant differences between both groups were found on all other tests at the

disadvantage of the very preterm-born group (Table 2). Within the very preterm-born

group, children with motor impairment had significantly more complex MND, low

IQ, slow processing speed, and abnormal visuomotor coordination than children with

normal motor outcome. Behavioral problems were comparable between very preterm-

born children with and without motor impairment (Table 2). Within the comparison

group, no significant differences between children with and without motor impairment

were found (Table 2).

In the 26 very preterm-born children with motor impairment, motor impairment

always co-occurred with one or more other abnormal test outcomes, whereas in 4 of

the 9 term-born children with motor impairment all other test outcomes were normal.

Moreover, 18 very preterm-born children with motor impairment had abnormal outcomes

on three through five different developmental tests, whereas this did not occur in term-

born children with motor impairment.

Multivariate associations and mediation effects

We investigated which of the other deficits were most associated with motor impairment,

taking preterm birth status into account and correcting for low educated mothers and

mothers not born in The Netherlands. Motor impairment (total score) and an abnormal

score on the component manual dexterity were significantly associated with preterm

birth. For impaired aiming and catching and balance, no significant association with

preterm birth was found (Table 3). The significant association between preterm birth

status and motor impairment (total score) and impaired manual dexterity disappeared

when other developmental deficits were entered into the model. Motor impairment

was significantly associated with complex MND (OR = 41.7, 95% CI 7.5-232.5) and low IQ

(OR = 7.3, 95% CI 1.9-27.3). Impaired manual dexterity was significantly associated with

low IQ (OR = 4.5, 95% CI 1.4-14.8), slow processing speed (OR = 4.6, 95% CI 1.8-11.6) and

hyperactivity/inattention (OR = 3.2, 95% CI 1.3-7.9).

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66 | Chapter 4

Tab

le 2

. Co

mp

aris

on

of

mu

lti-

do

mai

n o

utc

om

es b

etw

een

ver

y p

rete

rm-b

orn

(VPT

) an

d c

om

par

iso

n g

rou

ps,

an

d b

etw

een

VPT

ch

ildre

n

wit

h a

nd

wit

ho

ut

mo

tor

imp

airm

ent

VP

gro

up

(n=

81)

Co

mp

aris

on

gro

up

(n=

84)

P1

VPT

gro

up

MA

BC

≤p15

(n=

26)

VPT

gro

up

MA

BC

>p

15(n

=55

)P2

Co

mp

aris

on

gro

up

MA

BC

≤p15

(n=

9)

Co

mp

aris

on

g

rou

pM

AB

C>

p15

(n=

75)

P3

Mo

tor

dev

elo

pm

ent

(MA

BC

-2):

To

tal t

est,

mea

n (

SD)

8.37

(3.

3)10

.04

(2.6

).0

00-

--

--

- M

anu

al d

exte

rity

, mea

n (

SD)

8.02

(3.

1)9.

77 (

2.4)

.000

--

--

--

Aim

ing

an

d c

atch

ing

, mea

n (

SD)

8.35

(3.

5)9.

17 (

3.3)

.120

--

--

--

Bal

ance

, mea

n (

SD)

9.59

(3.

6)11

.32

(3.2

).0

01-

--

--

- A

bn

orm

al M

AB

C-2

, n (

%)

26 (

32.1

)9

(10.

7).0

01-

--

--

-N

euro

log

ical

exa

min

atio

n (

Tou

wen

): N

orm

al, n

(%

)42

(51

.9)

71 (

84.5

).0

00-

--

--

- C

om

ple

x M

ND

/no

n-d

isab

ling

CP*

, n (

%)

18 (

22.2

)2

(2.4

).0

0015

(57

.7)

3 (5

.5)

.000

2(22

.2)

0 (0

0.0)

.246

Inte

llig

ence

(W

PPSI

-III-

NL)

: F

ull

scal

e IQ

, mea

n (

SD)

92.0

9 (1

7.5)

103.

39 (

11.4

).0

00-

--

Fu

ll sc

ale

IQ <

85

po

ints

, n (

%)

21 (

25.9

)2

(2.4

).0

0014

(53

.8)

7 (1

2.7)

.000

1 (1

1.1)

1 (1

.3)

.069

Pro

cess

ing

sp

eed

(A

NT)

: B

asel

ine

Spee

d r

eact

ion

tim

e, m

ean

(SD

)67

7.28

(19

1.8)

575.

54 (

108.

7).0

00-

--

Ab

no

rmal

, n (

%)

29 (

35.8

)12

(14

.3)

.002

18 (

69.2

)11

(20

.0)

.000

1 (1

1.1)

11 (

14.9

).7

62V

isu

om

oto

r co

ord

inat

ion

(A

NT)

: T

rack

ing

dis

tan

ce, m

ean

(SD

)

13

.3 (

5.9)

10.6

5 (3

.3)

.001

--

- A

bn

orm

al T

rack

ing

, n (

%)

27 (

33.3

)13

(15

.5)

.006

17 (

65.4

)10

(18

.2)

.000

0 (0

0.0)

13 (

17.3

).1

71 P

urs

uit

dis

tan

ce, m

ean

(SD

)

7.

91 (

4.9)

5.64

(2.

2).0

00-

--

Ab

no

rmal

Pu

rsu

it, n

(%

)24

(29

.6)

11 (

13.1

).0

0713

(50

.0)

11 (

20.0

).0

021

(11.

1)10

(13

.3)

.852

Beh

avio

r (S

DQ

): C

on

du

ct p

rob

lem

s, n

(%

)18

(22

.2)

10 (

11.9

).0

787

(26.

9)11

(20

.0)

.484

1 (1

1.1)

9 (1

2.0)

.938

Em

oti

on

al s

ymp

tom

s, n

(%

) 30

(37

.0)

13 (

15.5

).0

0213

(50

.0)

17 (

30.9

).0

970

(00.

0)13

(17

.3)

.174

Hyp

erac

tivi

ty/in

atte

nti

on

pro

ble

ms,

n (

%)

32 (

39.5

)13

(15

.5)

.001

12 (

46.2

)20

(36

.4)

.400

3 (3

3.3)

10 (

13.3

).1

17

Dif

fere

nce

s in

pro

po

rtio

ns

and

mea

n s

core

s b

etw

een

th

e g

rou

ps

are

anal

yzed

usi

ng

χ2 te

sts,

t-t

est

or

Ind

epen

den

t sa

mp

le T

-tes

t.

P1 =p

val

ue

bet

wee

n V

PT a

nd

co

ntr

ol g

rou

p. P

2 =

p v

alu

e V

PT g

rou

p w

ith

an

d w

ith

ou

t m

oto

r im

pai

rmen

t.P3

= p

val

ue

com

par

iso

n g

rou

p w

ith

an

d w

ith

ou

t m

oto

r im

pai

rmen

t. M

AB

C≤p

15 =

≤15

th c

enti

le =

ab

no

rmal

.*I

n t

he

18 V

PT c

ases

wit

h a

bn

orm

al n

euro

log

ical

ou

tco

me,

16

had

co

mp

lex

MN

D a

nd

2 n

on

-dis

ablin

g C

P. B

oth

ter

m-b

orn

ch

ildre

n h

ad c

om

ple

x M

ND

.



4

Table 3. Associations with motor impairment in total group

Dependent variables

Independent variables b 95% CIfor b

p Exp(B)

95% CIfor Exp(B)

MABC-2: Total score ≤ p15

Block 1: Preterm/termBlock 2: Preterm/term Complex MND1

IQ<85 points

1.321

0.1713.7301.987

0.6 - 2.4

-1.2 - 1.52.5 - 23.80.6 - 4.0

0.002

0.7560.0010.001

3.7

1.241.77.3

1.6 - 8.9

0.4 - 3.67.5 - 232.51.9 - 27.3

MABC-2: Manual Dexterity

Block 1: Preterm/termBlock 2: Preterm/term IQ<85 points Slow processing speed Hyperactivity/inattention

0.996

0.1781.5081.5231.151

0.2 - 2.0

-0.8 - 1.30.3 - 3.30.6 - 2.70.2 - 2.2

0.015

0.7270.0130.0010.014

2.7

1.24.54.63.2

1.2 - 6.2

0.5 - 3.21.4 - 14.81.8 - 11.61.3 - 7.9

MABC-2: Aim & Catch

Block 1: Preterm/termBlock 2: Preterm/term Complex MND

0.178

-0.2271.713

-0.6 - 0.9

-1.2 - 0.60.5 - 3.2

0.618

0.5790.002

1.2

0.85.5

0.6 - 2.5

0.4 - 1.81.8 - 16.9

MABC-2: Balance

Block 1: Preterm/termBlock 2: Preterm/term Complex MND IQ<85 points

0.662

-0.6412.4531.581

-0.3 - 1.8

-2.5 - 0.81.1 - 4.90.0 - 3.4

0.187

0.3330.0010.011

1.9

0.69.65.0

0.7 - 4.9

0.2 - 2.12.6 - 35.41.4 - 17.5

Associations between motor impairment and other developmental deficits analyzed using 4 binary logistic regressions. Data are presented as b (regression coefficient) and bootstrapped confidence intervals for b, p values, Exp(B) (odds ratio) and confidence intervals for Exp(B).Outcomes were adjusted for low educated mothers and mothers not born in the Netherlands.1Complex MND = Complex Minor Neurological Dysfunction.

In the mediation model (Figure 1) the effect of preterm birth on motor impairment,

the direct pathway, became non-significant after controlling for the effects of the indirect

pathway (Table 4). The association between preterm birth and motor impairment was

mediated by complex MND and low IQ. The effect of preterm birth on impaired manual

dexterity was mediated by low IQ, slow processing speed, and hyperactivity/inattention

(Table 4). In addition, Sobel’s (Z) test achieved significance (Z: P <0.05), indicating a

significant mediation between birth status and motor impairment and between birth

status and impaired manual dexterity (Table 4).

R1R2R3R4R5R6R7R8R9


68 | Chapter 4

Tab

le 4

. Res

ult

s o

f m

edia

tio

n a

nal

ysis

fo

r m

oto

r im

pai

rmen

t in

ver

y p

rete

rm-b

orn

ch

ildre

n.

Pa

th A

Path

BPa

th C

Tes

t o

f m

edia

tio

nPa

th C

(a

dju

sted

fo

r in

dir

ect

pat

h)

Mo

tor

imp

airm

ent

(to

tal)

a (S

a)p

b (

Sb)

pc

(Sc)

pZ

pc

(Sc)

p

Co

mp

lex

MN

D3.

067

(1.0

5)0.

004

4.06

1 (0

.82)

0.00

01.

321

(0.4

4)0.

003

2.52

0.01

10.

591

(0.5

1)0.

248

IQ

<85

po

ints

2.38

1(0.

78)

0.00

22.

412

(0.5

4)0.

000

1.32

1 (0

.44)

0.00

32.

520.

012

0.88

0 (0

.47)

0.06

5 Im

pai

red

man

ual

dex

teri

ty

IQ <

85 p

oin

ts2.

381(

0.78

)0.

002

2.30

5 (0

.53)

0.00

00.

996

(0.4

2)0.

018

2.50

0.01

20.

529

(0.4

6)0.

252

Sl

ow

pro

cess

ing

sp

eed

0.99

3 (0

.41)

0.01

51.

884

(0.4

2)0.

000

0.99

6 (0

.42)

0.01

82.

130.

033

0.73

1 (0

.45)

0.10

3

Hyp

erac

tivi

ty/in

atte

nti

on

1.21

7 (0

.39)

0.00

21.

379

(0.4

1)0.

001

0.99

6 (0

.42)

0.01

82.

190.

022

0.73

3 (0

.44)

0.09

6

Path

A: e

ffec

t o

f p

rem

atu

rity

on

th

e m

edia

tors

: co

mp

lex

MN

D/ I

Q <

85 p

oin

ts/ s

low

pro

cess

ing

sp

eed

/ hyp

erac

tivi

ty/in

atte

nti

on

.Pa

th B

: eff

ect

of

the

med

iato

rs o

n m

oto

r im

pai

rmen

t/im

pai

red

man

ual

dex

teri

ty.

Path

C: e

ffec

t o

f p

rem

atu

rity

on

mo

tor

imp

airm

ent/

imp

aire

d m

anu

al d

exte

rity

.Pa

th C

(ad

just

ed f

or

ind

irec

t p

ath

): e

ffec

t o

f p

rem

atu

rity

on

mo

tor

imp

airm

ent/

imp

aire

d m

anu

al d

exte

rity

ad

just

ed f

or

ind

irec

t p

ath

via

pat

h A

an

d p

ath

B.

a,b

,c: u

nst

and

ard

ized

pat

h c

oef

fici

ents

. Sa,

Sb,S

c: s

tan

dar

d e

rro

rs o

f th

e p

ath

co

effi

cien

ts.

All

ou

tco

mes

are

co

rrec

ted

fo

r lo

w e

du

cati

on

mo

ther

s an

d m

oth

ers

no

t b

orn

in t

he

Net

her

lan

ds.



4

Figure 1. Model of direct (path C) and indirect (path A and B) effects of preterm birth on motor impairment, corrected for low-educated mothers and mothers not born in the Netherlands

Path A: effect of prematurity on the mediators: complex MND/ IQ <85 points/ slow processing speed/ hyperactivity/inattention. Path B: effect of the mediators on motor impairment/impaired manual dexterity. Path C: effect of prematurity on motor impairment/impaired manual dexterity. Path C (adjusted for indirect path): effect of prematurity on motor impairment/impaired manual dexterity adjusted for indirect path via path A and path B. a,b,c: unstandardized path coefficients. Sa,Sb,Sc: standard errors of the path coefficients. All outcomes are corrected for low education mothers and mothers not born in the Netherlands.

IQ <85 points Complex MND

Slow processing speed Hyperactivity/inattention

Preterm birth maturity

Motor impairment Direct effect

Path C

Path B Path A

Indirect effect

Figure 1. Model of direct (path C) and indirect (path A and B) effects of preterm birth on motor impairment, corrected for low-educated mothers and mothers not born in the Netherlands

Path A: effect of prematurity on the mediators: complex MND/ IQ <85 points/ slow processing speed/ hyperactivity/inattention.Path B: effect of the mediators on motor impairment/impaired manual dexterity.Path C: effect of prematurity on motor impairment/impaired manual dexterity.Path C (adjusted for indirect path): effect of prematurity on motor impairment/impaired manual dexterity adjusted for indirect path via path A and path B. a,b,c: unstandardized path coefficients. Sa,Sb,Sc: standard errors of the path coefficients.All outcomes are corrected for low education mothers and mothers not born in the Netherlands.

Discussion

Our study confirms the high frequency of both motor impairment and deficits in other

developmental domains in very preterm-born children at 5 years’ corrected age. The

motor impairment rate (32.1%) was comparable to an earlier Dutch study on very

preterm-born children,4 but also to studies from other countries.5,6 Contrary to the other

studies in which problems on all MABC components were described, we found especially

worse outcomes on manual dexterity and balance and less on aiming and catching. This

might be due to the fact that our comparison group had a standard score of 9 in aiming

and catching, which is lower than the reference mean of 10.

Very preterm-born children with motor impairment had a substantial higher rate

of other abnormal test outcomes than very preterm-born children without motor

impairment. The frequency of complex MND, low intelligence, slow processing speed,

and visuomotor coordination problems occurred in more than 50% of the very preterm-

born children with motor impairment. We defined motor impairments as ≤15th centile

on the MABC-2, including children with mild-moderate motor impairment, because

R1R2R3R4R5R6R7R8R9


70 | Chapter 4

research has suggested that very preterm-born children whose scores fall between the

6th and 15th centile are at significant risk for associated problems in learning, attention

and psychosocial adjustment.23 Indeed, this mildly to moderately impaired motor group,

had a worse developmental profile. These impairments may co-occur because of the

possible underlying white matter damage, causing multiple impairments.10,11

Although the very preterm-born children had significantly more motor impairments

than term-born children, this difference disappeared when other developmental deficits

were also taken into account in the analyses. Complex MND and low intelligence were

found to mediate between preterm birth and motor impairment. Low intelligence,

slow processing speed and hyperactivity/inattention played a mediating role between

preterm birth and manual dexterity problems.

Complex MND can be considered as a distinct form of perinatally acquired brain

dysfunction, which is likely associated with the cortico-striato-thalamo-cortical and

cerebello-thalamo-cortical pathways.24 According to Volpe,11 these are the circuitries

that are often damaged in very preterm-born children. They play a role in sensorimotor

aspects of motor programming, movement planning, programme selection and motor

memory and in cognitive tasks. In line with this, Diamond13 described the interrelation

between cognition and motor performance, and the brain areas involved with both

functions simultaneously, namely the dorsolateral prefrontal cortex, the cerebellum and

the caudate nucleus. Damage to those circuitries can result in both cognitive and motor

impairment.

In addition to the simultaneous involvement of brain structures in cognition and

motor performance, the assessment of motor abilities also includes functions other

than motor performance and these are tested in part as well. Although the MABC-2

is an effective test in identifying motor impairment in the high-risk population of

very preterm-born children,25 cognition, speed, motor planning, spatial precision and

behavioral adaptation to the test-situation are also required for normal outcome. In

general, it is almost impossible to measure one developmental domain without tapping

into other integrated functions.

Although all very preterm-born children with motor impairment also had deficits in

other developmental domains, this was not true for the term-born children with motor

impairment. In the comparison group 45% of children with motor impairment had no

additional deficits. In term-born children, the cause of motor impairment might be

restricted or more isolated.

We found a high frequency of behavioral problems in the very preterm-born group

irrespective of motor impairment. Nevertheless, hyperactivity/inattention was associated

with impairments in manual dexterity. The relation between manual dexterity and

attention has been described in children with attention-deficit-hyperactivity disorder



4

(ADHD).26 Furthermore, it is known that very preterm-born children have an increased

risk for this disorder.27

Of the very preterm-born children with motor impairment, 69% had problems with

processing speed. Several studies showed that processing speed is a basic key ability

underlying deficits in intelligence in very preterm-born children,14,15,28,29 linking reduction

of white matter integrity to slow processing speed. We hypothesize that processing

speed also plays an important role in motor performance, especially when motor skills

become more complex at age 5. Indeed in our study, processing speed was associated

with, in particular, manual dexterity.

Problems in visuomotor coordination were found in respectively 65% (tracking task)

and 50% (pursuit task) of the very preterm-born children with motor impairment. This

may be caused by cerebellar damage, by attention difficulties arising from damage to

the prefrontal cortex, or alternatively by an impaired ability to process and comprehend

the visual input.30 In our multivariate model however, these visuomotor skills were not

associated anymore with motor impairment.

A study limitation was the fact that the investigators were not blinded to birth status.

However, highly standardized testing rules were followed in all children, in order to reduce

this shortcoming. Further, we included term-born children free from planned or current

referral for learning or behavioral problems. A non-selected group of term-born peers

might have led to different results. We did not study the effect of neonatal morbidities

further, because our focus was the comparison between term and very preterm-born

children. Bonifacio et al31 showed that brain injury and neonatal co-morbidities, and

not prematurity per se, are associated with abnormal brain development of brain

microstructure, suggesting that, especially preterm infants with these morbidities are at

risk of motor problems.

Because motor outcome was the main topic of our paper, we did not study how

motor outcome might mediate other deficits. Thus our results focus on interrelations,

which of course can be bidirectional.

Using a broad assessment on different developmental domains is a study strength.

It is also important from the clinical point of view as those treating very preterm-born

children with motor impairment should be aware of the interrelation of problems in

other developmental domains.

Conclusion

In the absence of disabling CP, motor impairment occurs more frequently in very preterm-

born than in term-born children at 5 years of (corrected) age. Very preterm-born children

with motor impairment more often have complex MND and impairments in cognition,

R1R2R3R4R5R6R7R8R9


72 | Chapter 4

processing speed and visuomotor coordination than very preterm-born children without

motor impairment, however behavior problems are comparable for both groups.

Complex MND, low intelligence, slow processing speed and hyperactivity/inattention

mediate the association between preterm birth and motor impairment. These deficits

should be taken into account when very preterm-born children with motor impairment

are referred for intervention.



4

References

1. Potharst ES, van Wassenaer AG, Houtzager BA, van Hus JW, Last BF, Kok JH. High incidence of multi-domain disabilities in very preterm children at five years of age. J Pediatr 2011;159:79-85.

2. Hack M, Costello DW. Trends in the rates of cerebral palsy associated with neonatal intensive care of preterm children. Clin Obstet Gynecol 2008;51:763-774.

3. de Kieviet JF, Piek JP, Aarnoudse-Moens CS, Oosterlaan J. Motor development in very preterm and very low-birth weight children from birth to adolescence: a meta-analysis. JAMA 2009;302:2235-2242.

4. de Kleine MJ, den Ouden AL, Kollee LA et al. Development and evaluation of a follow up assessment of preterm infants at 5 years of age. Arch Dis Child 2003;88:870-875.

5. Howe TH, Sheu CF, Wang TN, Hsu YW, Wang LW. Neuromotor outcomes in children with very low birth weight at 5 years of age. Am J Phys Med Rehabil 2011;90:667-680.

6. Zwicker JG, Yoon SW, Mackay M, Petrie-Thomas J, Rogers M, Synnes AR. Perinatal and neonatal predictors of evelopmental coordination disorder in very low birthweight children. Arch Dis Child 2013;98:118-122.

7. National scientific council on the developing child. The timing and quality of early experiences combine to shape brain architecture. Working paper 5, 2007. Retrieved April 2013 from Center on the Developing Child, Harvard University, www.developingchild.net.

8. National scientific council on the developing child. Early experiences can alter gene expression and affect long-term development. Working paper 10, 2010. Retrieved April 2013 from Center on the Developing Child, Harvard University, www.developingchild.net.

9. Piek JP, Dawson L, Smith LM, Gasson N. The role of early fine and gross motor development on later motor and cognitive ability. Hun Mov Sci 2008;27:668-681.

10. Spittle AJ, Cheong J, Doyle LW et al. Neonatal white matter abnormality predicts childhood motor impairment in very preterm children. Dev Med Child Neurol 2011;53:1000-1006.

11. Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009;8:110-24.

12. de Kieviet JF, Zoetebier L, van Elburg RM, Vermeulen RJ, Oosterlaan J. Brain development of very preterm and very low-birthweight children in childhood and adolescence: a meta-analysis. Dev Med Child Neurol 2012;54:313-323.

13. Diamond A. Close interrelation of motor develoment and cognitive development and of the cerebellum and prefrontal cortex. Child Dev. 2000;71:44-56.

14. Soria-Pastor S, Gimenez M, Narberhaus A et al. Patterns of cerbral white matter damage and cognitive impairment in adolescents born very preterm. Int J. Dev Neurosc 2008:26:647-654.

15. Mulder H, Pitchford NJ, Marlow N. Processing Speed Mediates Executive Function Difficulties in Very Preterm Children in Middle Childhood. J Int Neuropsychol Soc 2011;28:1-10.

16. Henderson SE, Sugden DA, Barnett AL. Movement Assessment Battery for Children - second edition (MovementABC-2); Examiner’s manual. London: Harcourt Assessment. 2007.

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74 | Chapter 4

17. Touwen BCL. Examination of the child with minor neurological dysfunction, second edition. Philadelphia: Lippencott. 1979.

18. Hendriksen J, Hurks P. WPPSI-III-NL. Wechsler preschool and primary scale of intelligences, 3rd edition, Nederlandse bewerking. Amsterdam; Pearson Assessment and Information BV. 2009.

19. De Sonneville MJL. Computerbaded Amsterdam Neuropsychological Test battery (ANT). Lisse, Swets 1999.

20. Goodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry 1997;38:581-586.

21. MacKinnon, D. P., & Dwyer, J. H. (1993). Estimating mediated effects in prevention studies. Eval Rev 1993;17:144-158.

22. Sobel, M. E. (1982). Asymptotic intervals for indirect effects in structural equations models. In S. Leinhart (Ed.), Sociological methodology 1982 (pp.290-312). San Francisco: Jossey-Bass.

23. Dewey D, Kaplan BJ, Crawford SG, Wilson BN. Developmental coordination disorder: Associated problems in attention, learning, and psychosocial adjustment. Hum Mov Sci 2002:21:905-18.

24. Hadders-Algra M. Two distinct forms of minor neurological dysfunction: perspectives emerging from a review of data of the Groningen Perinatal Project. Dev Med Child Neurol 2002;44:561-571.

25. Dewey D, Creighton DE, Heath JA, et al. Assessment of developmental coordination disorder in children born with extremely low birth weights. Dev Neuropsychol 2011;36:42-56.

26. Schoemaker MM, Ketelaars CE, van Zonneveld M, Minderaa RB, Mulder T. Deficits in motor control processes involved in production of graphic movements of children with attention-deficit-hyperactivity disorder. Dev Med Child Neurol 2005;47:390-395.

27. Lindstrom K, Lindblad F, Hjern A. Preterm birth and attention-deficit/hyperactivity disorder in schoolchildren. Pediatrics 2011;127:858-865.

28. de kieviet JF, van Elburg RM, Lafeber HN, Oosterlaan J. Attention problems of very Preterm Children Compared with Age-Matched Term Controls at School-Age. J Pediatr 2012;161:824-829.

29. Rose SA, Feldman JF, Jankowski JJ. Modeling a cascade of effects: the role of speed and executive functioning in preterm/full-term differences in academic achievement. Dev Sci 2011;14:1161-1175.

30. Goyen TA, Lui K, Woods R. Visual-motor, visual-perceptual, and fine motor outcomes in very-low-birthweight children at 5 years. Dev Med Child Neurol 1998;40:76-81.

31. Bonifacio SL, Glas HC, Chau V, Berman JI, Xu D, Brant R et al. Extreme premature birth is not associated with impaired development of brain microstructure. J Pediatr 2010;157:726-732.

Chapter 5

Sustained developmental effects of the

Infant Behavioral Assessment and Intervention

Program in very low birth weight infants at

5.5 years


Christiaan J.A. Geldof, Joke H. Kok, Frans Nollet, Aleid G. Van Wassenaer-Leemhuis.

Journal of Pediatrics 2013;163:1112-1119

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76 | Chapter 5

Abstract

Aim. To evaluate the effect of the Infant Behavioral Assessment and Intervention

Program© (IBAIP) in very low birth weight (VLBW) infants on cognitive, neuromotor, and

behavioral development at 5.5 years corrected age (CA).

Methods. In a randomized controlled trial, 86 VLBW infants received post discharge IBAIP

intervention until 6 months CA, and 90 VLBW infants received standard care. At 5.5 years

CA, cognitive and motor development, and visual-motor integration were assessed with

the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL), the Movement

Assessment Battery for Children second edition (MABC-2), and the Developmental Test

of Visual Motor Integration (VMI). Neurological conditions were assessed with the

neurological examination according to Touwen, and behavior with the Strengths and

Difficulties Questionnaire (SDQ).

Results. At 5.5 years CA, 69 children in the intervention and 67 children in the control

group participated (response rate 77.3%). Verbal and performance IQ-scores <85 occurred

significantly less often in the intervention than in the control group (17.9% vs 33.3%, P =

0.041, and 7.5% vs 21.2%, P = 0.023, respectively). After adjustment for differences, the

odds ratio for performance IQ was significant: 0.24, 95% CI: 0.06-0.95. Adjusted mean

scores on WPPSI-III-NL subtasks block design and vocabulary, the MABC-2 component

aiming and catching and the VMI were significantly better in the intervention group. No

intervention effect was found on the SDQ.

Conclusion. The IBAIP leads, 5 years after the early neurobehavioral intervention, to

improvements on performance IQ, ball skills and visual-motor integration at 5.5 years

CA.


Effects of the IBAIP at 5.5 years | 77

5

Introduction

In response to the high rate of neurodevelopmental problems, which persist throughout

childhood in very low birth weight (VLBW) infants,1-3 various early intervention programs

have been developed. The aim of these programs is the prevention of cognitive, motor

and behavioral impairments in preterm infants. A Cochrane meta-analysis on the effect

of post discharge early intervention programs for preterm infants found a positive

influence on cognitive and motor outcome during infancy, with the cognitive benefits

persisting till the age of 5 years.4 It is suggested that programs that focus on parent-

infant relationships along with infant development may have the greatest impact.5

However, there are few long-term outcomes of randomized controlled trials (RCTs)

involving multidimensional interventions.

The Infant Behavioral Assessment and Intervention Program© (IBAIP)6 is an early

intervention program that focuses on environmental, behavioral and early developmental

factors. The aim is to support the infant’s self-regulatory competence and multiple

developmental functions via responsive parent-infant interactions. Between 2004 and

2007, a multicenter RCT was conducted to compare the effects of the IBAIP to standard

follow-up care, with respect to cognitive and motor development, infants’ behavioral

regulation, the well-being of the parents, and parent-infant interaction.7 Results of

this study included improved mental, motor, and behavioral development and mother–

infant interaction at 6 months corrected age (CA),7,8 improved motor development at 24

months CA9 and improved independency in mobility at 44 months CA10 in favor of the

parents and infants who received the IBAIP intervention.

The aim of the current study was to evaluate the effect of the IBAIP in VLBW children

on cognitive, neuromotor, and behavioral development at 5.5 years CA.

Methods

The study population consisted of VLBW children participating in a multicenter RCT

on the effect of the IBAIP in Amsterdam, The Netherlands.7 In this RCT, 176 infants of

gestational age (GA) <32 weeks and/or birth weight <1500 gram were included. Exclusion

criteria were severe congenital abnormalities of the infant, severe physical or mental

illness/problems of the mother, non-Dutch-speaking families for whom an interpreter

could not be arranged, and participating in other trials on post discharge management.

Written informed consent was obtained from the parents before the onset of the study.

After computer-generated randomization, stratified for GA (< and ≥30 weeks) and

recruitment site, with multiplets assigned to the same group, 86 infants were assigned

to the intervention group and 90 to the control group. The infants and the parents in

R1R2R3R4R5R6R7R8R9


78 | Chapter 5

the intervention group received 1 intervention session shortly before discharge and 6

to 8 sessions at home from an IBAIP-trained pediatric physical therapist up to 6 months

CA. The control group received standard care and was referred to a non IBAIP-trained

physical therapist if deemed necessary by the pediatrician.

The IBAIP 6 is a neurobehavioral intervention program based on the same theory as

the Newborn Individualized Developmental Care and Assessment Program (NIDCAP).11

The IBAIP-trained interventionist assists the parents to affectively and responsively

interact with their child, through natural observations of the infant’s behavior. The

interventionist evaluates the infant’s neurobehavioral organization and self-regulatory

competence, within the context of the environment, and facilitation strategies may

be offered to best support the infant’s neurodevelopmental progression and self-

regulation. The facilitation strategies address environmental facilitation (eg. visual and

auditory input), handling and positioning (eg. the infant’s position in supine or prone),

and cue-matched facilitation (eg. hand to mouth, foot bracing, or hands to midline). The

IBAIP aims to provide ample opportunities for the infant to actively process and explore

information, while at the same time maintaining stable physiological and behavioral

functioning. Thus, the program supports the infant’s growth, the infant’s motivation to

explore, and the possibility to learn from information. For more detailed information

about the content of the IBAIP, we refer to the internet and earlier publications.6-10

Assessment Procedure

Two months before their child would reach the age of 5.5 year CA, between 2009 and

2011, an invitation letter was sent to the parents of all children that participated in the

RCT. Upon positive reaction, an appointment for the follow up assessments was scheduled.

Non-responders were reminded about the study. The medical Ethics Committee of the

Academic Medical Center, Amsterdam approved the follow-up study. The pediatric and

developmental assessments were performed at the follow-up clinic of the Academic

Medical Center in Amsterdam. Cognitive abilities were assessed by a psychologist (CG),

motor development, visual-motor integration and, neurologic functions were assessed by

a pediatric physical therapist (JVH). The investigators were blinded for group assignment.

While their child was fulfilling the developmental assessments, the parents were asked

to fill out a questionnaire regarding the behavior of their child. Sociodemographic data,

school performances and the need for mental and/or paramedical support at 5.5 years

CA were obtained by interview of the parents.

Perinatal risk factors were taken from the medical records at discharge. Severe

cranial ultrasound abnormalities were defined as the existence of an intraventricular

hemorrhage grade 3 or 4, or periventricular leucomalacia grade 3 or/and ventricular

dilation. Bronchopulmonary dysplasia was defined when the infant was oxygen



5

dependent ≥ 28 days.12 Small for GA was defined as >1 SD below mean Dutch reference

data for birth weight in relation to GA.

Assessment Instruments

Cognitive and neuromotor development were assessed with a set of standardized tests

consisting of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL),13

the Movement Assessment Battery for Children second edition (MABC-2),14 and the

Developmental Test of Visual Motor Integration (VMI).15 Neurological conditions were

assessed with the neurological examination according to Touwen16 and behavior with

the Strengths and Difficulties Questionnaire (SDQ).17

The Dutch translation of the WPPSI-III-NL was used. The full scale IQ, performance IQ,

verbal IQ, and processing speed quotient were calculated. Reference means (SD) for the

IQ indices are 100 (15). The test consists of 8 core subtests with a mean (SD) of 10 (3). The

IQ was considered abnormal if more than 1 SD (<85 points) below the mean.

The MABC-2 focuses on the identification of impairments of motor function. Motor

outcomes were calculated using the age band 3 till 6 years. Within this age band 8 tasks

(items) are grouped under 3 components: manual dexterity, aiming and catching and

balance. Raw scores of the 3 components and the total test (the sum of all 8 items) are

converted to standard scores. Reference means (SD) for the total test and component

standard scores are 10 (3). A standard score of <7 reflects performances ≤15th centile and

is regarded as mild to severe motor impairment.

The VMI test (24 geometric forms, increasing in difficulty, that need to be copied

using paper and pencil) assesses the integration of visual–perceptual processing and

fine motor skills. Supplementary, the visual perception test, and the motor coordination

test were administered as a means to compare the visual-motor integration results with

relatively pure visual and motor performance. Raw scores are standardized for age and

have a mean (SD) of 100 (15). A standard score <85 points (<1 SD) was regarded as

abnormal.

The neurological examination according to Touwen pays special attention to minor

neurological dysfunction (MND). It addresses eight functional clusters. Neurological

development was classified as normal when no deviant cluster or one or two clusters

of dysfunction (simple MND) were present and, as abnormal when there were three or

more clusters of dysfunction (complex MND) or when cerebral palsy was present.

The SDQ parents form is a parental behavioral screening questionnaire that has

a total difficulty score, and five subscales consisting of five items each: hyperactivity/

inattention, conduct problems, peer problems, emotional symptoms and prosocial

behavior. According to the test manual, a score is abnormal if higher than the 80th

percentile for the parents outcome. An abnormal total difficulty score is a score ≥17

points.

R1R2R3R4R5R6R7R8R9


80 | Chapter 5

Statistical analysis

Data were analyzed using the computer program SPSS version 16.0 (SPSS Inc, Chicago,

Illinois). Univariate analyses (t tests and χ2 tests) were carried out to study differences in

perinatal and sociodemographic characteristics between the intervention and control

group and between participants and nonparticipants. A two-sided power calculation

was performed using the nQuery version 7.0 computer program (nQuery Advisor, Los

Angeles, California). When appropriate, t tests and χ2 tests were used to compare mean

test outcomes or proportions of children with abnormal scores between the groups.

Multiple logistic regression analyses were used to determine the intervention effect

on normal vs abnormal test outcomes. Multiple linear regression analyses were used to

assess the effect of the intervention on the WPPSI-III-NL, the MABC-2, the VMI and the

SDQ. Perinatal variables and sociodemographic variables at 5.5 years CA that differed

at baseline or are known from literature to affect long-term outcome were included in

the model as covariates. The variables included were use of surfactant, oxygen support

≥28 days, indomethacin use, septic periods, GA <28 weeks, small for GA, severe cranial

ultrasound abnormality, low maternal education, first language not Dutch, and gender.

An α level of 0.05 was considered significant for above mentioned tests. Effect sizes

(ES) were calculated as the adjusted mean difference between the intervention and

control group divided by the SD of the total group. To interpret the effect size we used

Cohen’s criteria: ≥0.2 = small; ≥0.5 = moderate; ≥0.8 = large effect.18 Because twins and

triplets were assigned to the same group, and this could have biased the outcomes, we

repeated the analyses with only 1, randomly chosen, multiplet member.

Results

Of the 176 children participating in the RCT, 136 were available for follow-up at the

CA of 5.5 years. The response rate was 80.2% (n = 69) in the intervention group and

74.4% (n = 67) in the control group. The mean (SD) CA at the assessment time point was

5.5 years (0.1). The sample size was calculated originally with 90% power to detect a

difference of 0.5 SD in Bayley Scales of Infant Development, Second Edition scores at 6

and 24 months with an α level of 0.05. With our sample size at 5.5 years, we calculated

a power of 82%, to detect a difference of 0.5 SD between the intervention and control

group on the WPPSI-III-NL and MABC-2, with an α level of 0.05.

The patient flow of the study until 5.5 years CA is shown in Figure 1, including reasons

for not participating. The participants (n = 136) did not differ from the nonparticipants

(n = 40) with respect to sociodemographic and perinatal factors, except that mothers

of participants were significantly more often born in the Netherlands than those of

nonparticipants (59.6% vs 45.0%, P = 0.003).



5

Figure 1. Study flow diagram

R1R2R3R4R5R6R7R8R9


82 | Chapter 5

Table 1. Sociodemographic and perinatal characteristics

Characteristics Intervention(n=69)

Control (n=67) P value

Social background factors Family status 2 parent(s), n (%) 50(47.6) 53(79.1) .366 Maternal age at date birth (y), mean (SD) 32.9 (5.3) 31.6 (5.7) .201 Paternal age at date birth (y), mean (SD) 36.1 (7.4) 35.7 (6.6) .739 Mother born in the Netherlands, n (%) 43 (62.3) 38 (56.7) .506 Father born in the Netherlands, n (%) 44 (63.8) 36 (53.7) .455 First language not Dutch, n (%) 5 (7.2) 16 (23.9) .007* Maternal education low, n (%) 20 (29.0) 27 (40.3) .165 Paternal education low, n (%) 28 (41.8) 27 (40.3) .861Perinatal factors Gestational age (weeks), mean (SD) 29.5 (2.2) 30.0 (2.1) .168 Gestational age <28 weeks, n (%) 21 (30.4) 15 (22.4) .288 Birth weight (g), mean (SD) 1220.8 (347.5) 1304.8 (327.8) .150 Small for gestational age**, n (%) 18 (26.1) 11(16.4) .169 Sex: male, n (%) 38(55.1) 28(41.8) .121 Multiple birth, n (%) 19 (27.5) 21(31.3) .626 Antenatal steroid use, n (%) 51 (73.9) 49 (73.1) .918 APGAR score, at 5 min, mean (SD) 8.5 (1.5) 8.5 (1.5) .908 Surfactant, n (%) 27 (39.1) 15 (22.4) .035* Artificial ventilation, n (%) 35 (50.7) 25 (37.3) .115 CPAP, n (%) 61 (88.4) 47 (70.1) .008* Oxygen support ≥28 days pma, n (%) 29 (42.0) 13 (19.4) .004* Oxygen support at 36 weeks pma, n (%) 20 (29.0) 7 (10.4) .007* Postnatal steroid use, n (%) 4 (5.8) 2 (3.0) .425 Indomethacin use, n (%) 16(23.2) 6 (9.0) .024* Septic periods before discharge, n (%) 43 (62.3) 25 (37.3) .022* Necrotizing enterocolitis, n (%) 3 (4.3) 1 (1.5) .324 IVH*** grade 1, 2/3, 4, n (%) 11(16.0)/ 5 (7.2) 8 (11.9)/ 3 (4.5) .213 PVL**** grade 1/2, 3, n (%) 5(7.2)/0 (0) 7(10.4)/2 (3.0) .523 Ventricular dilatation, n (%) 2 (2.9) 3 (4.5) .625 Severe abnormal cranial ultrasound*****, n (%) 7 (10.1) 4 (6.0) .372

At discharge Length of hospitalization (d), mean (SD) 59.7 (29.1) 51.3 (25.9) .078 Breast milk at discharge, n (%) 29 (42.0) 37 (55.2) .124

Data are presented as n (%) or as M ± SD. Differences in mean scores and proportions between the groups are analyzed using t-tests or χ2 tests. CPAP=continuous positive airway pressure, pma=postmenstrual age. * p <0.05. ** Small for gestational age was defined as >1 SD below mean Dutch reference data.*** IVH=intraventricular hemorrhage defined according to Papile.**** PVL=periventricular leucomalacia defined according to de Vries.***** Severe abnormal cranial ultrasound was defined as IVH 3 or 4, PVL 3 and ventricular dilation.



5

Tab

le 2

. Rat

es o

f co

gn

itiv

e, n

euro

mo

tor

and

beh

avio

ral i

mp

airm

ent

in in

terv

enti

on

(IB

AIP

) an

d c

on

tro

l gro

up

Inte

rven

tio

nG

rou

pn

(%

)

Co

ntr

ol

Gro

up

n (

%)

Un

adju

sted

OR

(95

% C

I)P1

Ad

just

edO

R (

95%

CI)

P2

WPP

SI-I

II-N

L† : V

erb

al IQ

(<

85 p

oin

ts)

12 (

17.9

)22

(33

.3)

0.45

(0.

20-0

.98)

.041

*0.

34 (

0.11

-1.0

4).0

59 P

erfo

rman

ce IQ

(<

85 p

oin

ts)

5 (7

.5)

14 (

21.2

)0.

30 (

0.10

-0.8

9).0

23*

0.24

(0.

06-0

.95)

.043

* P

roce

ssin

g S

pee

d Q

(<

85 p

oin

ts)

13(1

9.4)

13(2

2.8)

0.35

(0.

36-2

.01)

.706

0.57

(0.

21-1

.57)

.278

Fu

ll sc

ale

IQ (

<85

po

ints

)11

(16.

9)16

(24

.6)

0.60

(0.

25-1

.42)

.243

0.56

(0.

17-1

.86)

.341

MA

BC

-2:

Mo

tor

imp

airm

ent

(≤p

15)

22 (

31.9

)16

(23

.9)

1.49

(0.

70-3

.18)

.298

1.10

(0.

45-2

.61)

.854

Neu

rolo

gic

al e

xam

inat

ion

: C

om

ple

x M

ND

an

d C

P24

(34

.8)

15 (

22.4

)1.

85 (

0.87

-3.9

5).1

101.

00 (

0.39

-2.6

0).9

93V

MI:

Vis

ual

Mo

tor

Inte

gra

tio

n (

<85

po

ints

)8

(11.

6)6

(9.0

)1.

33 (

0.44

-4.0

7).6

131.

03 (

0.29

-3.6

9).9

69SD

Q p

aren

ts f

orm

‡ : T

ota

l pro

ble

m s

core

(≤1

7 p

oin

ts)

7 (1

0.8)

7 (1

0.8)

1.00

(0.

33-3

.03)

1.00

01.

56 (

0.39

-6.2

5).5

35

Mu

ltip

le l

og

isti

c re

gre

ssio

n a

nal

yses

wer

e u

sed

to

det

erm

ine

the

inte

rven

tio

n e

ffec

t o

n t

he

test

ou

tco

mes

no

rmal

ver

sus

abn

orm

al,

un

adju

sted

an

d a

dju

sted

fo

r su

rfac

tan

t, in

do

met

hac

in, O

2≥28

day

s, s

epti

c p

erio

ds,

firs

t la

ng

uag

e n

ot

Du

tch

, ges

tati

on

al a

ge

<28

wee

ks, s

mal

l fo

r g

esta

tio

nal

ag

e, s

ever

e ab

no

rmal

ult

raso

un

d, l

ow

mat

ern

al e

du

cati

on

an

d g

end

er. P

1 =

P v

alu

e u

nco

rrec

ted

. P 2 =

P v

alu

e co

rrec

ted

. * P

< 0

.05.

R1R2R3R4R5R6R7R8R9


84 | Chapter 5

Despite random assignment, there were some significant differences in pre-

randomization perinatal characteristics between the intervention and control group

(Table 1). More infants in the intervention group received respiratory therapy (i.e.

surfactant treatment, continuous positive airway pressure (CPAP) and oxygen therapy

≥28 days and at 36 weeks post menstrual age). In addition, occurrence of septic periods

and need for indomethacin was higher in the intervention group. The main language at

home was non-Dutch in more families in the control group at 5.5 years CA.

Outcomes

Table 2 presents the rates of cognitive, neuromotor and behavioral impairment in the

intervention (IBAIP) and control group. Impairment in verbal IQ and performance IQ

occurred significantly less often in the intervention group. After adjustment for risk

factors, the odds ratio (OR) for performance IQ was 0.24 and remained significant. Motor

impairment, abnormal visual-motor integration and abnormal neurological examination

were not significant different between the groups before and after adjustment.

The outcomes of the development assessments and behavior are presented in table 3.

Univariate analyses showed significant differences between the intervention and control

group on the WPPSI-III-NL core subtests block design and vocabulary. After adjustment

for risk factors, significant intervention effects were found on the WPPSI-III-NL core

subtests block design and vocabulary, on the MABC-2 component aiming and catching,

and on the VMI.

All effect sizes were small; on aiming and catching 0.44, on block design 0.40, on

vocabulary 0.41 and on the VMI 0.37. There were no significant differences between the

groups with respect to behavioral outcomes.

Results were similar when the analyses were repeated with only 1, randomly chosen,

child per family, in the case of multiplets, to explore a possible nesting effect.

The need for psychological support by a psychologist, psychiatrist and/or social worker

in the families in the intervention and control group, was comparable, 8 (11.6%) vs 6

(9.0%), as was the need for child paramedical support (pediatric physical therapy and/or

occupational therapy and/or speech therapy), 20 (30.0%) vs 22 (32.8%). Grade retention

occurred in 18 (26.1%) children in the intervention group vs 15 (22.4%) children in the

control group (non-significant). Need for special school education occurred in 5 (7.2%)

children in the intervention group vs 9 (13.4%) children in the control group (non-

significant).



5

Tab

le 3

. Co

mp

aris

on

of

ou

tco

mes

fo

r d

evel

op

men

t an

d b

ehav

ior

bet

wee

n in

terv

enti

on

(IB

AIP

) an

d c

on

tro

l ch

ildre

n

Inte

rven

tio

n(n

=69

)m

ean

(SD

)

Co

ntr

ol

(n

=67

)m

ean

(SD

)P1

Inte

rven

tio

n(n

=69

)A

dju

sted

mea

n (

SE)

Co

ntr

ol

(n=

67)

Ad

just

ed m

ean

(SE

)P2

WPP

SI-I

II-N

L† : B

lock

des

ign

9.87

(2.

9)8.

71 (

3.0)

.025

*9.

89 (

0.4)

8.69

(0.

4).0

26*

In

form

atio

n9.

24 (

3.4)

8.58

(3.

6).2

769.

17 (

0.4)

8.64

(0.

4).3

57 M

atri

x re

aso

nin

g9.

94 (

2.8)

9.25

(2.

7).1

529.

96 (

0.4)

9.23

(0.

3).1

64 V

oca

bu

lary

10.4

2 (2

.9)

9.24

(2.

6).0

14*

10.3

8 (0

.3)

9.28

(0.

3).0

16*

Pic

ture

co

nce

pt

9.88

(2.

8)9.

69 (

3.1)

.729

9.75

(0.

4)9.

83(0

.4)

.888

Sym

bo

ol s

earc

h9.

65 (

3.8)

9.27

(3.

7).5

819.

81 (

0.5)

9.10

(0.

5).3

28 W

ord

rea

son

ing

8.95

(2.

7)8.

48 (

3.4)

.402

8.97

(0.

3)8.

46 (

0.3)

.313

Co

din

g9.

43 (

2.9)

9.76

(3.

2).5

549.

77(0

.4)

9.37

(0.

4).4

55 V

erb

al IQ

97.2

5 (1

5.9)

93.1

5 (1

6.9)

.152

96.9

7 (1

.8)

93.4

4 (1

.8)

.179

Per

form

ance

IQ99

.51

(14.

4)95

.03

(15.

0).0

8299

.23

(1.8

)95

.32

(1.8

).1

47 P

roce

ssin

g S

pee

d Q

97.3

1 (1

7.5)

98.6

3 (1

7.4)

.677

98.6

8 (2

.2)

97.0

7 (2

.3)

.630

Fu

ll sc

ale

IQ97

.70

(15.

6)94

.25

(15.

8).2

0897

.46

(1.8

)94

.48

(1.9

).2

79M

AB

C-2

: T

ota

l tes

t sc

ore

8.64

(3.

8)8.

76 (

3.5)

.843

9.06

(0.

4)8.

33 (

0.4)

.252

Man

ual

dex

teri

ty

8.96

(3.

3)9.

39 (

3.6)

.464

9.37

(0.

4)8.

96 (

0.4)

.493

Aim

ing

an

d c

atch

ing

9.09

(3.

5)8.

33 (

3.3)

.189

9.46

(0.

4)7.

94 (

0.4)

.014

* B

alan

ce

8.75

(4.

0)9.

31 (

3.9)

.406

9.08

(0.

5)8.

98 (

0.5)

.893

VM

I: V

isu

al M

oto

r In

teg

rati

on

99

.49

(18.

8)96

.67

(21.

4).4

1410

1.78

(2.

2)94

.32

(2.3

).0

27*

Vis

ual

Per

cep

tio

n10

0.93

(22

.9)

100.

63 (

24.0

).9

4110

1.67

(2.

9)99

.86

(3.0

).6

73 M

oto

r C

oo

rdin

atio

n92

.07

(21.

9)93

.21

(23.

8).7

72 9

4.93

(2.

5)90

.27

(2.5

).2

10SD

Q p

aren

ts f

orm

‡ : T

ota

l pro

ble

m s

core

8.28

(5.

9)8.

86 (

5.3)

.556

8.46

(0.

7)8.

68 (

0.7)

.836

Dif

fere

nce

s in

mea

n s

core

s ar

e an

alyz

ed u

sin

g t

-tes

ts.

Mu

ltip

le l

inea

r re

gre

ssio

n a

nal

yses

wer

e u

sed

to

ass

ess

the

effe

ct o

f th

e in

terv

enti

on

on

th

e d

evel

op

men

tal

sco

res,

ad

just

ed f

or

surf

acta

nt,

in

do

met

hac

in,

O2≥

28d

ays,

sep

tic

per

iod

s, fi

rst

lan

gu

age

no

t D

utc

h,

GA

<28

wee

ks,

smal

l fo

r G

A, s

ever

e ab

no

rmal

ult

raso

un

d, l

ow

mat

ern

al e

du

cati

on

an

d g

end

er. P

1 =

P v

alu

e u

nco

rrec

ted

. P 2 =

P v

alu

e co

rrec

ted

. * P

< 0

.05.

† In

terv

enti

on

g

rou

p n

= 6

7 o

n W

PPSI

Ver

bal

IQ, P

erfo

rman

ce IQ

an

d F

ull

scal

e IQ

an

d n

= 6

5 o

n P

roce

ssin

g S

pee

d Q

; Co

ntr

ol g

rou

p n

= 6

6 o

n W

PPSI

Ver

bal

IQ,

Perf

orm

ance

IQ, n

= 5

7 o

n P

roce

ssin

g S

pee

d Q

an

d n

= 6

5 o

n F

ull

scal

e IQ

. ‡ In

terv

enti

on

an

d c

on

tro

l gro

up

n =

65.

R1R2R3R4R5R6R7R8R9


86 | Chapter 5

Discussion

The present study was performed to evaluate the effect of the IBAIP on cognitive,

neuromotor, and behavioral outcomes in VLBW children at 5.5 years CA. We found

that, 5 years after completion of the intervention, the IBAIP improved the children’s

performance IQ, motor skills with respect to handling a ball and visual-motor integration.

Because biological risk factors, which are associated with worse development,

occurred more often in the intervention group, all earlier and current results were based

on analyses correcting for these imbalances. The higher biological vulnerability of the

children in the intervention group was confirmed by a higher occurrence of complex

MND in this group. Complex MND can be considered as a distinct form of perinatally

acquired brain dysfunction.19

The intervention effect found on the rate of impairment in verbal IQ was not

significant after adjustment, which may be explained by the fact that in more families in

the control group the first language was non-Dutch.

The finding of the present study are in agreement with results of a systematic review

by Orton et al,20 showing that early developmental interventions have a positive effect

on preterm infants’ cognitive development at 3-5 years. Our study, however, showed a

different pattern in outcomes than other studies. Following mental, motor and behavioral

improvements in the intervention group directly after conclusion of the intervention at

6 months,7 a sustained effect on motor development could be demonstrated at 24 and

44 months9,10 and 5.5 years. Effects in the cognitive domain, however, were found after

5 years.

The Norwegian modified Mother-Infant Transaction Program (MITP),21 like the IBAIP

anchored in the NIDCAP model of development, also found positive results on IQ at 5

years of age, which were already visible as non-significant cognitive improvements at 3

years CA.

The British Avon Premature Infant Project (APIP),22 based on a different concept,

investigating effects of either developmental education or parent advisor program,

reported small cognitive benefits at 2 years of age, but these improvements were

washed out at age 5. It remains speculative whether the delayed cognitive intervention

effect results from insufficient sensitivity of measurements to reveal subtle differences

in cognition at earlier age or is related to the maturation process of the involved brain

areas. Aspects of mental function are carried out by different hierarchies of neural

circuits in the brain, maturing at different times in a child’s life. Synapse formation of

higher cognitive capacities begin to mature by age 3 years.23

In a recent review Guralnick,24 states that positive cognitive outcomes after early

intervention could be understood in terms of improvements in developmental pathways



5

associated with parental sensitive-responsiveness and child participation. These parent-

child transaction processes provide the continuity necessary to maintain an optimal

development environment for the child to grow up. The recent results from the MITP and

IBAIP seem to confirm this and strengthen the expectation that optimizing early parent-

child transaction processes after discharge from hospital may be important ingredients

for sustained intervention effects.

Our results can also be compared to NIDCAP, which improves parental sensitive

responsiveness and the child’s self regulation during hospital stay. An 8-year follow-

up NIDCAP study yielded results comparable to ours, showing that the 11 children that

received NIDCAP intervention, had a better performance IQ (although not statistically

significant), and significantly better spatial and visual abilities as compared with 11

control children.25

Improvements on performance IQ, ball skills, and visual-motor integration as found in

our study, all involve visual-spatial abilities and motor responses, and functionally overlap

to a large extend. The most common form of brain injury affecting children born very

preterm consists of diffuse white matter abnormalities, which are related to executive

functions, visual-spatial and motor impairments 26,27 This seems to point to the strengths

of NIDCAP and IBAIP to affect those brain structures that are most vulnerable in preterm

born infants. We did not perform magnetic resonance imaging, but in a recent study on

the effects of NIDCAP on brain function and structure at 9 months of age, especially less

pervasive aberrant connectivity was found.28

We hypothesize that the outcomes in our study may be the result of the early positive

and scaffolding neurobehavioral support that parents who received IBAIP offered their

child at a sensitive period of the involved brain areas, regarding the development of

self-regulation and motor control.23 Scaffolding support implies the process where the

adult continuously adjusts his/her interactions to the infant’s changing needs for support

over time.5 If the degree and intensity of the support and/or tasks are well attuned

to the infant’s neurobehavioral competence, it may help the child to self-regulate, in

other words, to organize his behavior in order to gain control over his own body and

the world around him. By improving self-regulatory competencies as well as providing

the environmental and task activities that the infant expects and can handle, the IBAIP

enhances the infants’ information processing and abilities to explore.

Improving early self-regulation affects, besides cognitive development, also the motor

system as it enhances midline orientation which strengthens the child’s control over

posture and movements. Improvement of the ability of the sensory system to estimate

the state of the body and the world around it (motor control)29 and better visual-spatial

processing30 might be the associated underlying mechanisms that account for the motor

improvements we found in this and also previous reports.

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88 | Chapter 5

A limitation inherent to follow-up studies is an attrition bias. The response rate was

80.2% in the intervention group and 74.4% in the control group. A difference with

other early developmental intervention studies is our urban population with a strong

multicultural composition, which is more difficult to reach. Nevertheless, we had enough

power to find possible differences between the intervention and the control group.

No significant intervention effect was found on behavior. In both groups, 10.8% of

the parents reported behavior difficulties in their children. This is low compared to the

earlier mentioned Dutch study3 on difficulties of VLBW infants in multiple domains, where

26.2% of the parents of VLBW children at 5 years CA reported behavior difficulties. This

may be due to a difference in inclusion criteria of the children (<30 weeks‘ gestation or

<1000 gram). Moreover, we did not use the teachers’ form of the SDQ, which may have

led to an incomplete representation of this domain.

In summary, the IBAIP leads to sustained improvements in development at the CA

of 5.5 years. These improvements were found on performance IQ, ball skills and visual-

motor integration. Strengthening the parental sensitive-responsiveness and the child’s

self-regulation possibly underlie these sustained intervention effects.

Acknowledgements

We thank all the participating parents and children, and M.J. Wolf for her assistance in

the design of this study and L. van Sonderen for her support during data collection.

The study was approved by the Medical Ethics Committees of the two level-III hospitals

and all 5 city hospitals in Amsterdam, the Netherlands. The study was supported by

grants from the Innovatiefonds Zorgverzekeraars (project no. 576) and ZonMw (Zorg

Onderzoek Nederland, project no. 62200032).

The trial was registered with controlled-trials.com (ISRCTN65503576).



5

References




4. Spittle AJ, Orton J, Anderson PJ, Boyd RN, Doyle LW. Early Developmental Intervention Programs to improve cognitive and motor outcomes for preterm infants-an updated Cochrane review. Abstract E-PAS 2012:4527.438

5. Spittle AJ, Orton J, Doyle LW, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev 2007:CD005495.

6. Hedlund R. The Infant Behavioral Assessment and Intervention Program©. 1998. Washington Research Institute, Seatle. Available from: http://www.ibaip.org. Accessed Jan 12, 2012.


8. Meijssen D, Wolf MJ, Koldewijn K et al. The effect of the Infant Behavioral Assessment and Intervention Program on mother-infant interaction after very preterm birth. J Child Psychol Psychiatry 2010;51:1287-1295.

9. Koldewijn K, van Wassenaer A Wolf MJ et al. A neurobehavioral intervention and assessment program in very low birth weight infants: outcome at 24 months. J Pediatr 2010;156:359-365.

10. Verkerk G, Jeukens-Visser M, Koldewijn K et al. Infant behavioral assessment and intervention program in very low birth weight infants improves independency in mobility at preschool age. J Pediatr 2011;159:933-938.

11. Als H, Gilkerson L. The role of relationship-based developmentally supportive newborn intensice care in strengthening outcom of preterm infants. Semin Perinatol 1997;21:178-189.

12. Jobe AL, Bancalari E. Bronchopulmonary dysplasia. NICHD/NHLBI/ORD Workshop Summary. Am J Respir Crit Care Med 2001;163:1723-1729.

13. Hendrikson J, Hurks P. WPPSI-III-NL. Wechsler preschool and primary scale of intellingences. 3rd edition, Dutch version. Amsterdam: Pearon Assessment and Information BV; 2009.

14. Henderson SE, Sugden DA, Barnett AL. Movement Assessment Battery for Children - 2nd edition (Movement ABC-2); Examiner’s manual. London: Harcourt Assessment; 2007.

15. Beery KE, Beery NA. The Beery-Buktenica developmental Test of Visual-Motor Integration, Beery VMI. Administration, Scoring, and Teaching Manual, 5th edition. Minneapolis: NCS Pearson Inc.; 2004.

16. Touwen BCL. Examination of the child with minor neurological dysfunction, second edition.Philadelphia: Lippencott; 1979.

17. Goodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry 1997;38:581-586.

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18. Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988.

19. Hadders-Algra M. Two distict forms of minor neurlogical dysfunction: perspectives emerging from a review of data of the Grongingen Perinatal Project. Dev Med Child Neurol 2002;44:561-571.

20. Orton J, Spittle A, Doyle L, Anderson P, Boyd R. Do early intervention programmes improve cognitive and motor outcomes for preterm infants after discharge? A systematic review. Dev Med Child Neurol 2009;51:851-859.

21. Nordhov SM, Ronning JA, Dahl LB, Ulvund SE, Tunby J, Kaaresen PI. Early intervention improves cognitive outcomes for preterm infants: randomized controlled trial. Pediatrics 2010;126:e1088-e1094.

22. Johnson S, Ring W, Anderson P, Marlow N. Randomised trial of parental support for families with very preterm children: outcome at 5 years. Arch Dis Child 2005;90:909-915.

23. National Scientific Council on the Developing Child at Harvard University (2007).The timing and qualtity of early experiences combine in shape brain architecture. Working paper #5. Retrieved May 2012, from http://www.developingchild.net.


25. McAnulty GB, Butler SC, Bernstein JH, Als H, Duffy FH, Zurakowski D. Effects of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) at age 8 years: preliminary data. Clin Pediatr 2010;49:258-270.

26. Clark CAC, Woodward LJ. Neonatal cerebral abnormalities and later verbal and visuospatial working memory abilities of children born very preterm. Dev neuropsychology 2010;35:622-642.

27. Spittle AJ, Cheong J, Doyle LW, Roberts G, Lee KJ, Lim J, et al. Neonatal white matter abnormality predicts childhood motor impairment in very preterm children. Dev Med Child Neurol 2011;53:1000-1006.

28. Als H, Duffy FH, McAnulty G, Butler SC, Lightbody L, Kosta S et al. NIDCAP improves brain function and structure in preterm infants with severe intrauterine growth restriction. J Perinatol 2012;32:797-803.

29. Shadmehr R, Smith MA, Krakauer JW. Error correction, sensory prediction, and adaptation in motor control. Annu Rev Neurosci 2010;33:89-108.

30. Kravitz DJ, Saleem KS, Baker CI, Mishkin M. A new neural framework for visuospatial processing. Nat Rev Neurosci 2011;12:217-230.

Chapter 6

Longitudinal developmental effects

of the IBAIP in very preterm-born infants


Rebecca Holman, Joke H. Kok, Frans Nollet, Aleid G. Van Wassenaer-Leemhuis

Submitted

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92 | Chapter 6

Abstract

Background and aim: Very preterm-born and very low birth weight (VLBW) infants

are at risk of developmental problems. Therefore, early interventions are needed. The

Infant Behavioral Assessment and Intervention Program© (IBAIP) improved development

in VLBW infants at separate time-points. Our objective was to investigate longitudinal

intervention effects of the IBAIP in VLBW infants on neurodevelopment up to and

including 5.5 years of corrected age (CA).

Methods: In a randomized controlled trial, 86 VLBW infants received the IBAIP and

90 VLBW infants received standard care. At 6, 12, and 24 months CA, cognitive and

motor development was assessed with the Bayley Scales of Infant Development. At 5.5

years CA the Wechsler Preschool and Primary Scale of Intelligence and the Movement

Assessment Battery for Children were used. Longitudinal data were analyzed with linear

mixed models in the total group and three subgroups, using Z-scores generated from

raw cognitive and motor scores.

Results: A significant longitudinal intervention effect (0.4SD) on motor development was

found (P = 0.006), but not on cognitive development (P = 0.063). In the subgroup “VLBW

children with bronchopulmonary dysplasia (BPD)” significant longitudinal intervention

effects were found for both cognitive (effect = 0.7SD; P = 0.019) and motor (effect =

0.9SD; P = 0.026) outcome. Maternal education hardly influenced intervention effects

over time, but in children with combined biological and social risks an intervention effect

of 0.8SD was found on cognitive development (P = 0.044).

Conclusion: The IBAIP leads to long-term improvements on motor development in VLBW

infants. Particularly VLBW children with BPD benefit from the intervention, both on the

cognitive and motor domains.


Longitudinal effects of the IBAIP | 93

6

Introduction

Improved and technologically more advanced care increased the survival rate of premature

and sick neonates1 and decreased the incidence of severe handicaps like cerebral palsy.2

However, mild cognitive, motor and behavioral problems, with prevalence’s of up to

50 to 75%, are the dominant developmental deficits reported in infants born before

32 weeks’ gestation and/or birth weight less than 1500 gram. These deficits tend to co-

occur and persist throughout childhood.3,4,5 Biological risk factors, such as brain injuries,

bronchopulmonary dysplasia (BPD), and social risk factors, such as low level of parental

education, and poor parent-infant relationships, have been associated with poor

neurodevelopmental outcome.6,7

In response to these outcomes, focus of outcome research in NICU-graduates has

shifted from mortality and morbidity to healthy survival, and inspired health care

professionals to develop evidence-based early intervention programs. A recent meta-

analysis concluded that programs focusing on sensitive and responsive parenting, along

with infant development, have the greatest impact on improvement in developmental

outcomes.8

In a randomized controlled trial (RTC), we have evaluated the effects of an early

intervention program, the Infant Behavioral Assessment and Intervention Program©

(IBAIP)9 on neurodevelopment in infants with a gestational age <32 weeks and/or birth

weight <1500 gram, in short, very low birth weight (VLBW) infants. Cross-sectional data-

analyses revealed significant and clinically relevant intervention effects on cognitive

development at 6 months and 5.5 years corrected age (CA), and on motor development

at 6, 12 and 24 months and 5.5 years CA.10-13 Moreover, subgroup analyses indicated

improved developmental outcomes in extra vulnerable VLBW infants, such as infants

with BPD.13

Effects of RCTs involving early intervention in VLBW infants are generally described

for each follow-up age without studying longitudinal effects over time. As this approach

is insensitive to individual developmental changes over time, mean outcomes of the

study groups may not be representative for the patterns of individual outcomes.14,15 To

our knowledge no longitudinal data-analysis of early intervention studies, based on

individual developmental outcomes over time, has been described. Therefore, our aim

in this study is to evaluate the effects of the IBAIP in VLBW infants on cognitive and

motor development from 6 months up to and including 5.5 years CA, using longitudinal

data-analysis. Also, we present longitudinal intervention effects on subgroups of VLBW

infants with BPD, with low maternal education (LME) and with multiple biological and

social risks (MR).

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94 | Chapter 6

Methods

Participants

The original RCT10 evaluated the effectiveness of the IBAIP in VLBW infants at 6, 12 and

24 months CA between 2004 and 2007. Two level-III hospitals with neonatal intensive

care unit facilities and 5 general hospitals in Amsterdam, the Netherlands, participated

in the study. The Medical Ethics Committees of all hospitals involved approved the study

design. A follow-up study was performed at 5.5 years CA between 2009 and 2011 and was

approved by the Medical Ethics Committee of the Academic Medical Center, Amsterdam.

All infants with a gestational age <32 weeks and/or birth weight <1500 gram, were

eligible for the trial. We excluded infants with severe congenital abnormalities, infants

whose mother had severe physical or mental illness, infants from non-Dutch-speaking

families for whom an interpreter could not be arranged, and infants participating in

other post discharge trials. Infants were randomized to IBAIP or control groups using

a computer based procedure, which stratified for gestational age (< and ≥30 weeks)

and recruitment site. The infants and parents in the IBAIP group received 1 intervention

session shortly before discharge and 6 to 8 sessions at home from an IBAIP-trained

pediatric physical therapist up to 6 months CA. The control group received standard care.

Early intervention program

The IBAIP is a preventive neurobehavioral intervention program which addresses the

infant and parents. It is primarily based on the synactive model of neonatal behavioral

organization.17 The IBAIP, focusing on environmental, behavioral and early developmental

factors, aims to support the infant’s self-regulatory competence and multiple

developmental functions via responsive parent-infant interactions. The interventionist

supports the parents to interact sensitively and responsively with their infant, by observing

the infant’s behavior. The intervention is guided by the Infant Behavioral Assessment©

(IBA).18 The IBA is an observational tool that systematically observes and interprets 113

infant communicative behaviors that are categorized according to four subsystems: the

autonomic, motor, state and attention/interaction system. Within each subsystem, the

behaviors are interpreted as approach (stable/engagement), self-regulation, or stress

(unstable/disengagement) behaviors. Facilitation strategies may be offered to best

support the infant’s neurodevelopmental progression and self-regulation, within the

context of the environment. Thus, the IBAIP aims to provide ample opportunities for the

infant to actively process and explore information, while at the same time maintaining

stable physiological and behavioral functioning.



6

Assessment Procedure

The neurodevelopmental assessments took place between 2004 and 2011, at 6, 12, 24

and 5.5 years CA. The assessors were blinded to study group assignment. Perinatal factors

were extracted from the children’s medical records at discharge. Cranial ultrasound

abnormalities were defined as the existence of intraventricular hemorrhage (grade

III to IV), periventricular leucomalacia (grade I to IV), or ventricular dilation for which

treatment was needed. BPD was defined as oxygen dependency at ≥28 days.16 A multiple

risk (MR) factor was composed to explore potential effects of biological and social risk

factors, including low maternal education as social risk and abnormal cranial ultrasound

or BPD as biological risks.

Mothers were defined as having a low level of education if they had received less

than four years of post-elementary schooling.

Assessment Instruments

At 6, 12 and 24 months CA, cognitive and motor development were assessed using

the mental and psychomotor scale of the Bayley Scales of Infant Development, Dutch

second edition (BSID-II-NL).19 The mental scale consists of 178 items with regards to

visual and additive information processing, eye-hand coordination, imitation, language

development, memory, and problem resolution. The 111 items of the psychomotor scale

measure fine and gross motor skills.

Cognitive development at 5.5 years CA was assessed using the Wechsler Preschool

and Primary Scale of Intelligence, Dutch third edition (WPPSI-III-NL).20 All core subtests

were administered. The sum of all composite scores and full scale intelligence quotient

were calculated.

Motor development at 5.5 years CA was assessed using the Movement Assessment

Battery for Children; second edition (MABC-2).21 Within the 3 to 6 years age band, 8 tasks

are grouped under 3 components: manual dexterity, aiming and catching and balance.

In order to facilitate comparison among cognitive and motor developmental

assessments across time-points and instruments, we performed our analyses using age

standardized Z-scores generated from the total raw scores of the above mentioned

assessment instruments.

Statistical Analyses

Univariate analyses (t-tests and χ2 tests) were performed to compare the perinatal and

sociodemographic characteristics of the IBAIP and control group. A propensity score

approach was used to adjust for group differences.22 For each infant, the propensity

score was calculated using a binary logistic regression analysis with dependent

variable group allocation (IBAIP or control). The independent variables in this analysis

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96 | Chapter 6

were: gender; gestational age less than ≤28 weeks; small for gestational age; use of

Indomethacin; Surfactant; continuous positive airway pressure; septic periods; abnormal

cranial ultrasound; and mother’s first language (Dutch, not Dutch). The variables BPD,

LME and MR were not included in the propensity score, as we assessed longitudinal

outcome according to these three risk factors separately.

Univariate analyses of variance (ANOVA) were performed to obtain adjusted means

for the cognitive and motor raw and z-scores for the IBAIP and control groups at each

time point.

Two linear mixed models were built to evaluate the longitudinal effects of the

intervention on cognitive and motor development separately, adjusted for the propensity

score, BPD, LME, and MR. Each model consisted of 6 steps. In Step 1, an empty model was

fitted with all the infants and a repeated measures covariance matrix of the type Toepliz

to the cognitive or motor data. In Step 2, the time-point (6, 12, 24 months or 5.5 years)

was added as a categorical fixed effect. In Step 3, the propensity score was added as a

fixed effect. In Step 4, three variables: BPD; LME; and MR were added as fixed effects

simultaneously. In Step 5, we entered the study group (IBAIP or control) into the model.

In Step 6, an interaction term between study group and time was added.

To evaluate the effect of the IBAIP in subgroups, we used the same modeling

strategy but with stratification according to BPD, LME and MR factors and omitting Step

4. The fit of the model in the different steps was assessed using Akaike’s Information

Criterion (AIC) in the smaller-is-better form. A P value of less than 0.05 was considered as

statistically significant and effect sizes between 0.2 and 0.5 as small, between 0.5 and 0.8

as moderate and above 0.8 as large.23 All statistical analysis were carried out using SPSS

computer program, version 20.0 (SPSS Inc, Chicago, Illinois).

Results

Of the 315 VLBW infants born during the inclusion period, 176 infants were included in

the study: 86 infants in the IBAIP group and 90 infants in de control group. The study

flow diagram shows the course in time of the number of participants, the reasons for

not participating, and assessment instruments used at each time point (Figure 1). The

response rate at 6, 12, 24 months and 5.5 years CA was respectively 100%, 98%, 97%

and 80% in the IBAIP group and in the control group respectively 94%, 88%, 87% and

74%. Despite random assignment, there were some significant differences in perinatal

characteristics at baseline between the IBAIP and control group (Table 1). More infants in

the IBAIP group than in the control group received Indomethacin and had a gestational

age <28 weeks. In addition, the infants in the IBAIP group had more septic episodes,

were oxygen dependent for a longer period and were longer hospitalized.



6

Figure 1. Study flow diagramFigure 1. Study flow diagram

315 eligible participants

176 randomized

139 excluded Refused to participate (38) Died (11) Language reasons (11) Child factors (12) Parental factors (12) Older brother/sister in trial (3) Participation in other trial (52)

90 control infants Died before discharge (1)

Follow-up 6 months: 86

BSID-II: MDI 86, PDI 86


Died (1), withdrawn (1), lost to follow-up (3)



Withdrawn (1), living abroad (1)



Withdrawn (1), living abroad (2)



Died (2), withdrawn (3), living abroad (2), lost to follow-up (4)



Died (2), withdrawn (3), living abroad (2), lost to follow-up (5)


86 intervention infants

Follow-up 5.5 years: 69

Withdrawn (5), moved abroad (2), lost to follow-up (10)

WPPSI-III: 67, MABC-2: 69

Follow-up 5.5 years: 67

Died (2), withdrawn (10), moved abroad (1), lost to follow-up (10)

WPPSI-III: 66, MABC-2: 67

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98 | Chapter 6

Table 1. Perinatal and sociodemographic characteristics

IBAIP (n=86)

Control (n=90) P

Perinatal factorsMale / female, n (%) 50 (58.1) / 36 (41.9) 41 (45.6) / 49 (54.4) .095Multiple birth, n (%) 27 (31.4) 26 (28.9) .750Birth weight in g, mean (SD) 1242 (332) 1306 (318) .200Gestational age in weeks, mean (SD) 29.6 (2.2) 30.0 (2.2) .300Gestational age <28 weeks, n (%) 21 (24.4) 11 (12.2) .040*Small for gestational age**, n (%) 23 (26.7) 17 (18.9) .229Artificial ventilation, n (%) 43 (50.0) 32 (35.6) .060Surfactant, n(%) 34 (39.5) 16 (17.7) .005*CPAP, n (%) 75(87.2) 65 (72.2) .008*BPD, n (%) 34 (39.5) 18 (20.0) .005*Septic periods before discharge, n (%) 52 (60.0) 35 (38.9) .030*Necrotizing enterocolitis, % 4 (4.7) 1 (1.1) .160IVH grade 1-4***, n (%) 21 (24.4) 14 (15.6) .890PVL grade 1-3****, n (%) 12 (14.0) 10 (11.1) .430Ventricular dilatation, n (%) 3 (34.9) 4 (44.4) .750Abnormal ultrasound, n (%)***** 31(36.0) 26 (28.9) .390Indomethacin use, n (%) 18 (20.9) 7 (7.8) .014*ROP grade ≥3, n (%) 4 (4.7) 1 (1.1) .160Length stay hospital in days, mean (SD) 55.4 (25.9) 47.6 (21.7) .030*Sociodemographic factorsMaternal age in y, mean (SD) 32.4 (5.4) 32.0 (5.2) .790Family status of 2 parents, n (%) 70 (81.4) 82 (91.1) .060First language not Dutch, n (%) 28 (32.6) 39 (43.3) .110Mother with job, n (%) 63 (73.3) 53 (61) .840Low maternal education, n (%) 30 (34.9) 38 (40.2) .318Multiple risk, n (%)****** 25 (14.2) 14 (8.0) .072Mean age assessments 6 months, mean (SD) in days 183 (8.0) 185 (8.5) .41612 months, mean (SD) in days 372 (14.4) 372 (11.6) .90124 months, mean (SD) in days 738 (18.1) 740 (17.9) .4365.5 years, mean (SD) in years 5.5 (0.1) 5.5 (0.1) .320

Differences in mean scores and proportions between the groups are analyzed using t-tests or χ2

tests. * p <.05. ** Small for gestational age was defined as >1 SD below mean Dutch reference data.***IVH = Intraventricular haemorrhage, grade defined according to Papile.**** PVL = Periventricular leucomalacie defined according to de Vries. ******Multiple risk was defined as children with low maternal education and BPD/abnormal ultrasound.******Abnormal ultrasound was defined as IVH grade 3-4, PVL and ventricular dilation. ROP = Retinopathy for prematurity.



6

Outcomes on cognitive development

Outcomes on cognitive development at 6, 12, and 24 months and 5.5 years CA and over

time are reported in Table 2. Adjusted mean cognitive outcomes of the raw and Z-scores

are presented in Table 2A. At all time-points, the IBAIP group had higher scores than the

control group. Linear mixed models for repeated measures analyses (Table 2B) showed

a non-significant intervention effect on cognitive development in the total group over

time (P = 0.063). A non-significant and small difference in adjusted Z-scores of 0.2 SD in

favor of the IBAIP group was found. The intervention-time interaction was not significant

(P = 0.142), which implies that the intervention effect on cognitive development did not

increase or decrease over time (Figure 2A). Linear mixed models analyses in the subgroups

(Table 2B) showed a significant intervention effect in infants with BPD (P = 0.019) and

with MR (P = 0.044), with a moderate difference in adjusted Z-scores of respectively

0.7 SD and 0.8 SD (Figure 2B, 2D). No significant intervention effect was found in the

subgroup LME (Figure 2C).

Outcomes on motor development

Adjusted mean motor outcomes of the raw and Z-scores are presented in Table 2A. At all

time-points the IBAIP group scored higher than the control group. Linear mixed models

for repeated measures analyses showed a significant intervention effect on motor

development over time (P = 0.006) (Table 2B). The moderate difference in adjusted

Z-scores was 0.4 SD in favor of the IBAIP group. The intervention-time interaction was not

significant (P = 0.484) which implies that the intervention effect on motor development

did not increase or decrease over time (Figure 2E). Linear mixed models analyses in the

subgroups (Table 2B) showed a significant intervention effect in infants with BPD (large

effect size of 0.9SD, P = 0.014) (Figure 2F) and with high maternal education (small effect

size of 0.4SD, P = 0.012) (Figure 2G). In the groups with or without MR, similar small

effect sizes (0.369) were found but the effect was only significant in the group without

MR (Figure 2H).

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100 | Chapter 6

Figure 2. Linear mixed model comparisons

Linear mixed models were built to assess longitudinal cognitive (2A,B,C,D) and motor (2E,F,G,H) developmental outcome in total group (2A,E) and in the subgroups.Intervention = children who received the IBAIP intervention. Control = children who received standard care.Subgroup BPD = children with or without (= no) bronchopulmonary dysplasia.Subgroup LME = children with or without (= no) mothers with low education.Subgroup MR = children with or without (= no) multiple risk.



6

Table 2 Longitudinal comparison of cognitive and motor development

2A Cognitive and motor outcomes per time-point

6 months 12 months 24 months 5.5 years

Adj. mean ± SE Adj. mean ± SE Adj. mean ± SE Adj. mean ± SECognitive raw scoresIBAIP 59.49 ±0.61 83.90 ±0.68 126.5 ±1.44 97.04 ±2.00Control 57.43 ±0.63 83.30 ±0.71 125.9 ±1.50 94.90 ±2.00Motor raw scoresIBAIP 35.60 ±0.46 60.00 ±0.61 82.00 ±0.61 73.30 ±2.3Control 33.40 ±0.47 58.70 ±0.64 80.20 ±0.62 68.90 ±2.3Cognitive Z-scoresIBAIP 0.18 ±0.11 0.05 ±0.11 0.02 ±0.12 0.07 ±0.13Control -0.19 ±0.11 -0.05 ±0.12 -0.02 ±0.12 -0.07 ±0.13Motor Z-scoresIBAIP 0.24 ±0.11 0.12 ±0.11 0.15 ±0.13 0.12 ±0.12Control -0.25 ±0.11 -0.12 ±0.11 -0.28 ±0.13 -0.12 ±0.13

2B Linear Mixed Model comparisons

Groupn=176

Time*

GroupBPDn=52

No BPDn=124

LMEn=68

No LMEn=108

MRn=39

No MRn=137

CognitionEstimateEffect size 0.223 - 0.681 0.071 0.095 0.265 0.770 0.106P value 0.063 0.142 0.019 0.584 0.650 0.092 0.044 0.390MotorEstimateEffect size 0.355 - 0.896 0.142 0.213 0.419 0.369 0.369P value 0.006 0.484 0.014 0.195 0.470 0.012 0.268 0.009

Univariate Analysis of Variance were used for adjusted (Adj.) mean ± standard error (SE) cognitive and motor developmental raw and Z-score (Table 2A), Adjusted for propensity score and O2≥28days, maternal low education and multiple risk factors. Linear mixed models were built to assess longitudinal cognitive and motor developmental outcome in total group and in the subgroups (Table 2B). BPD = bronchopulmonary dysplasia, LME = low maternal education, MR = multiple risk.

Discussion

The present paper describes the longitudinal intervention effects of the IBAIP on

development of VLBW infants from 6 months up to and including 5.5 years of corrected

age. This longitudinal data-analysis study demonstrates that the IBAIP leads to stable

improvements of motor development over 5.5 years. Contrary to this clear effect on

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102 | Chapter 6

motor development, the longitudinal intervention effect on cognitive development was

non-significant and had a small effect size. But in the subgroup of VLBW infants with

BPD both cognitive and motor development was improved over time in IBAIP children.

The VLBW infants with BPD benefitted most from the early intervention.

The motor gains acquired at 6 months CA, when the intervention ended, were

preserved over at least 5 years’ time. This stable main effect on motor outcome over time

seems to confirm that early experiences during sensitive periods of brain development

play an important role in shaping the capacities of the brain and affect long-term

development.24

Despite literature suggesting that cognitive and motor development are interrelated

and improved motor development may lead to improved cognitive development,25 no

longitudinal effect on cognitive development was found. Neither was any interaction

with time found. At 5.5 years performance IQ was improved in the IBAIP group13 and

not total IQ and thus a cognitive gain might have been missed because only total

cognitive scores were used in our mixed models. At the age of 6, 12 and 24 months, the

BSID-II cognitive assessment does not have a verbal or performance separation. These

cognitive abilities may not be present before age 3, when aspects of cognitive function

start maturing. Alternatively, an age specific intervention aiming at both verbal and

performance abilities of cognitive development, may be necessary during the sensitive

period of the brain for cognitive development.26 Another possibility is that improvements

of overall IQ are not yet present and will be in due time.

By adding the perinatal factors into the models and especially studying the most

prominent biological (we chose BPD), social (LME) and combined biological and social

risk (MR) factors in three subgroups, we hypothesized, based on an earlier study,13 to find

significant intervention effects in high risk subgroups. Indeed infants with BPD benefitted

from the intervention, both on cognitive and motor development. BPD affects as much

as 35% of the VLBW infants27 and is associated with white matter abnormalities in the

brain which have a negative influence on self-regulation and neurodevelopment in these

infants.28,29 Also difficulties in gaining homeostatic, postural and state control due to the

breathing problems may play a role. These problems makes them particularly vulnerable

to stress and obtaining a responsive parent-infant relationship is more difficult which, in

return, may hinder their environmental explorations. The focus of the IBAIP to support

responsive parent-infant interactions and infants’ self-regulation may be especially

helpful for infants with BPD, as it may facilitate their postural control and exploratory

activities without stress.

LME is associated with worse developmental, especially cognitive outcome.30 We did

not find intervention effects in this subgroup, however. Few studies have investigated

the association between maternal education, parenting stress and responsive mother-



6

infant interactions. Mothers with low education are known to experience more stress

and the stress decrease over time.31 They may be less available, and may have a lower

quality of interactions with their child.32,33 The intervention effect on motor outcome

which we found in VLBW infants with high educated mothers and the failure to do so

in infants with LME, demonstrates how important it is to design interventions, focusing

especially on supporting parent-infant interaction in social risk groups and its influence

on effectiveness of early intervention and child development. Recently researchers

stressed the need to strengthen the resources and self-regulatory capabilities of the

parents, so that they can better support their children.34

A large intervention effect was found in VLBW infants with MR on cognitive

development. The effects in this subgroup should however be interpreted with caution,

because the parameter estimates were similar in both groups with or without MR and

did not differ from the total group and therefore were attributed to low power.

As far as we know, no longitudinal data-analyses in early intervention studies in

VLBW infants have been published. The mixed model approach has several advantages

over cross sectional analyses repeated at different time-points. Taylor et al35 describes

that this approach incorporates estimates of intra-individual relations across repeated

assessments and, thus, is a sensitive method for assessing alterations. Additional

advantages are that assessments do not have to be equally spaced in time, and that

maximum likelihood methods allow incomplete longitudinal data to be considered in

estimating model effects. Further, risk factors can be included, allowing assessment of

the concurrent influences of these factors on outcomes, like we did in our subgroups.

There are no comprehensive cognitive or motor developmental tests that can

be applied from infancy to childhood and therefore different instruments had to be

combined in this longitudinal data analysis. The BSID19 is considered as the best measure

for the assessment for infants from the age of 1 to 42 months. For children beyond

age 42 months, the WPPSI20 and MABC-221 are the most common and extensively used

measurements to assess cognitive or motor development respectively. In order to

facilitate comparison among the different tests we used standardized Z-scores generated

from the raw scores. An increase or decrease of the infant’s development can therefore

not be read from our graphs. However, the effect of the intervention on cognitive and

motor development is obvious and remained stable over time.

Strengths of this study included the relatively large sample size of VLBW infants,

high response rate over time, the use of multiple standardized, norm-referenced method

measurements approach to the assessment of cognitive and motor development and the

use of repeated measures over time.

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104 | Chapter 6

Conclusion

This longitudinal data analysis study demonstrates that the IBAIP leads to improvements

on motor development in VLBW children over time. Particularly VLBW children with

BPD benefit from the intervention, both on the cognitive and motor domains.

Strengthening the parental sensitive-responsiveness and the child’s self-regulation in

an early and sensitive period of brain development, possibly underlie the sustained

neurodevelopmental improvements.



6

References

1. Richardson DK, Gray JE, Gortmaker SL, Goldmann DA, Pursley DM, McCormick MK. Declining severity adjusted mortality: evidence or improving neonatal intensive care. Pediatrics 1998;102:893-899.

2. Platt MJ, Cans C, Johnson A et al. Trends in cerebral palsy among infants of very low birth weight (>1500 g) or born prematurely (<32 weeks) in 16 European centers; a database study. Lancet 2007;369:43-50.




6. Short EJ, Klein NK, Lewis BA et al. Cognitive and academic consequences of Bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. Pediatrics 2003:112:359-366.

7. Potijk MR, Kerstens JM, Bos AF et al. Developmental delay in moderately preterm born children with low socio-economic status: Risk multiply. J. Pediatr 2013;163: 1289-1295.

8. Spittle AJ, Orton J, Doyle LW, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev. 2007:CD005495.

9. Hedlund R (1998). The Infant Behavioral Assessment and Intervention Program.© Available from: http://www.ibaip.org. Accessed Jan 12, 2012.


11. Van Hus JWP, Jeukens-Visser M, Koldewijn K et al. Sustained developmental effects of the Infant Behavioral Assessment and Intervention Program in very low birth weight infants at 5.5 years corrected age. J. Pediatr 2013;162:1112-1119.

12. Van Hus JWP, Jeukens-Visser M, Koldewijn K et al. Comparing two motor assessment toolsto evaluate neurobehavioral intervention effects in infants with very low birth weight at 1 year. Phys Ther 2013;93:1475-1483.


14. Karmiloff-SmithA. Neuroimaging of developing brain: Taking “developing” seriously. Hum Brain Mapp 2010;31:934-941.

15. Sadeghi N, Prastwaw M, Fletcher PT, Wolff J, Gilmore JH, Gertig G. Regional Characterizan of ligitudinatl DT-MRI to study white matter maturation of the early developing brain. NeuroImage 2012;68:236-247.

16. Jobe AL, Bancalari E. Bronchopulmonary dysplasia. Workshop Summary. Am J Respir Crit Care Med 2001;163:1723-1729.

17. Als H. A synactive model of neonatal behavioral organization. Phys Occup Ther Pediatr 1986;6:3-55.

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106 | Chapter 6

18. Hedlund R, Tatarka M (1986,1998). The Infant Behavioral Assessment.© Available from: http://www.ibaip.org. Accessed February 15, 2012.

19. Van der Meulen BF, Ruiter SAJ, Lutje Spelberg HC et al. The Bayley Scales of Infant Development – Second edition, Dutch Manual (BSID-II- NL). Lisse: Swets Test Publishers; 2002.

20. Hendrikson J, Hurks P. WPPSI-III-NL. Wechsler preschool and primary scale of intellingences. 3rd edition, Dutch version. Amsterdam: Pearon Assessment and Information BV; 2009.

21. Henderson SE, Sugden DA, Barnett AL. Movement Assessment Battery for Children – 2nd

edition (Movement ABC-2); Examiner’s manual. London: Harcourt Assessment 2007.

22. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41–55.

23. Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988.

24. Scientific Council on the Developing Child at Harvard University (2007). Early experiences can alter gene expression and affect long-term development. Working paper #10. Retrieved Jan 2014, from http://www.developingchild.net.

25. Diamond A. Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex. Child Development 2000;71:44-56.

26. Scientific Council on the Developing Child at Harvard University (2007). The timing and quality of early experiences combine to shape brain architecture. Working paper #5. Retrieved Jan 2014, from http://www.developingchild.net.

27. Smith VC, Zumanick JAF, Cormick MC et al. Trend in severe bronchopulmonary dysplasia rates between 1994 and 2000. J Pediatr 2005;146:469- 473.

28. Majnemer A, Riley P, Shevell M, Greenstone H, Coates AL. Bronchopulmonary dysplasia increases risk for later neurological and motor sequelae in preterm survivors. Dev Med Child Neuro 2000;42:53-60.

29. Clark CAC, Woodward LJ, Horwood LJ, Moor S. Development of emotional and Behavioral regulation in children born extremely preterm and very preterm: biological and social influences. Child Development 2008;79:1444-1462.

30. Rodrigues MC, Mello RR, Silva KS, Carvalho ML. Risk factors for cognitive impairment in school-age children born preterm, application of a hierarchical model. Arq Neuropsquiatr 2010;70:583-589.

31. Spinelli M, Poehlmann J, Bolt D. Predictors of parenting stress trajectories in premature infant-mother dyads. J Fam Psychol 2013;6:873-883.

32. Potharst ES, Schuengel C, Last BF, Van Wassenaer-Leemhuis AG, Kok JH, Houtzager BA. Difference in mother-child interaction between preterm and term born preschoolers with and without disabilities. Acta Pead 2012;101:597-608.

33. Walker LO, Crain H, Thompson E. Mothering behavior an maternal role attainment during the postpartum period. Nursing Research1986;35:352-355.

34. Shonkoff JP, Fisher PA. Rethinking evidence based pratice and two-generation programs to create the future of early childhood policy. Dev psychopathol 2013;25:1635-1653.

35. Taylor HG, Nori MM, Klein N, Hack M. Longitudinal outcomes of very low birth weight: Neuropsychological findings. JINS 2004;10:149-163.

Chapter 7

General discussion

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108 | Chapter 7


General discussion | 109

7

Very preterm birth has adverse effects on the normal maturational process of the brain,

which consequently may result in neurodevelopmental deficits in VLBW infants. These

deficits often co-occur and persist throughout childhood.1-4

The general aim of this thesis was to expand the knowledge on long-term effects

of an early intervention program for very preterm-born children, to provide optimal


The Infant Behavioral Assessment and Intervention Program© (IBAIP) is an early

intervention program, aiming to prevent developmental deficits in VLBW infants by

supporting both the infant’s competence to self-regulate and the parental sensitive-

responsiveness.5 Between 2004 and 2007 a multicenter randomized controlled trial (RCT)

was carried out to compare the effects of the IBAIP to standard care at 6 and 24 months

CA.6,7 A follow-up study between 2007 and 2009, evaluated the effects of the IBAIP at

the preschool age of 44 months.8 In a second follow-up study, between 2009-2011, the

effects of the IBAIP at early school age (5.5 years CA) were evaluated.

The specific objectives in this thesis were:

- To investigate the clinimetric properties of the Infant Behavior

Assessment (IBA) in order to evaluate neurobehavioral organization

In VLBW infants (Chapter 2).

- To compare two motor assessment instruments, the Alberta Infant Motor

Scale (AIMS) and the psychomotor scale (PDI) of the second Dutch edition

of Bayley Scales of Infant Development (BSID-II-NL) in their ability to

detect intervention effects at 12 months CA (Chapter 3).

- To elucidate the relation between motor impairment and other

developmental deficits in very preterm-born children and term-born

children at 5 years of age (Chapter 4).

- To evaluate the effect of the IBAIP on cognitive, motor, and behavioral

development in VLBW infants at 5.5 years CA and longitudinally from 6 months up to

and including 5.5 years CA (Chapter 5 and 6).

In this concluding chapter, the main findings of the 5 presented studies are discussed

and issues concerning the methodology are critically reviewed. Clinical implications and

suggestions for further research conclude this final chapter.

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110 | Chapter 7

Main findings of the study

Developmental assessment instruments

The IBA is a measurement tool assessing self-regulation in infants from term age to 9

months CA.9 Because the IBA is primarily intended to be used in a qualitative manner,

in conjunction with the IBAIP, the clinimetric properties of the IBA needed to be further

investigated, by determining its reliability, sensitivity and responsiveness to evaluate

neurobehavioral organization (i.e. self-regulation).

In Chapter 2, we showed that the reliability, sensitivity and responsiveness of the

IBA are satisfactory to good to evaluate neurobehavioral organization in VLBW

infants. The inter-observer reliability of the IBA was moderate to good and the item-

by-item percentage agreement was good to excellent. The sensitivity of the IBA was

demonstrated by clear and expected differentiations in neurobehavioral organization

between VLBW infant with or without biological high risk factors (gestational age ≤28

weeks or bronchopulmonary dysplasia (BPD)) at 35-38 weeks postmenstrual age. Large

responsiveness was found on all scores of the IBA in both the intervention and control

groups and in the BPD high-risk subgroups over a 6-month period.

Because of the fact that the IBA give insight in how to support the infant’s self-

regulation during interactions from minute to minute, distinguishes the instrument

from other neurobehavioral assessments at infant age. Those instruments provide a

degree of self-regulation but not an entry for support. Supporting the infants’ self-

regulatory competence to approach and respond to environmental information and

to diminish stress is currently seen as an important element in early intervention for

infants at biological and/or social risk.10,11 A behavioral analysis of the child’s individual

expectations, like the IBA, might be the basis for effective neurobehavioral intervention.

Moreover, neurobehavioral analyses may have been crucial for the positive results we

found in our RCT in VLBW infants, as it was the basis for intervention. Complementary use

of a neurobehavioral analyses instrument to neurological and developmental measures

provides a more comprehensive picture of the infants’ development.

In the light of the need for sensitive assessment tools that measure changes in infant

development, we demonstrated that two motor assessment tools differ in evaluating

neurobehavioral intervention effects in VLBW infants at 12 months CA (Chapter 3).

Both the AIMS12 and PDI of the BSID-II-NL13 found intervention effects in VLBW infants

at 12 months CA. However, a reduction of abnormal motor development was reflected

only on the AIMS, and the responsiveness of the AIMS to detect intervention effects was

better than that of the PDI. The AIMS classified 13.8% of the infants in the intervention



7

group as having an abnormal motor development versus 27.6% of the infants in the

control group, while the PDI classified 1.8% versus 3.5% respectively. The failure to detect

motor disturbances at early age may be due to the lack of sensitive measures at that age,

and may be one of the reasons for the apparent increase in developmental problems

with increasing age in VLBW infants. Therefore, caution is recommended in monitoring

VLBW infants only with the PDI, and the additional use of the AIMS is advised when

evaluating intervention effects on motor development at 12 months CA.

Further, we showed that the AIMS detected more specific intervention effects than

the PDI, and pointed towards effects on especially postural control. The subscales of the

AIMS can be useful to elucidate specific effects of an intervention on the motor system and

moreover, the subscales provide more detailed possible motor disturbances. Researchers

and interventionists may gain better insight into the gross motor development by using

the AIMS than the PDI of the BSID-II.

Motor impairment and associated deficits

Preterm birth is associated with motor impairments persisting throughout childhood.14

To elucidate the relation between motor impairment and other developmental deficits,

we compared a group of very preterm-born (<30 weeks’ gestation and/or birth weights

<1000 grams) and a group of term-born (>37 weeks’ gestation and birth weights >2500

grams) children at 5 years CA (Chapter 4).

Our study confirmed the high frequency of neurodevelopmental impairments

in very preterm-born children compared to their term-born peers at 5 years CA.

However, we found that very preterm-born children with motor impairments had other

developmental deficits more often as well, compared to very preterm-born children

without motor impairments. Especially complex minor neurological dysfunctions (MND)

and impairments in cognition, processing speed and visuomotor coordination occurred

more often. Motor impairments in term-born children was not associated with the other

developmental deficits.

Further, we found that 4 developmental deficits, complex MND, low IQ, slow

processing speed and hyperactivity/ inattention, mediated the relation between preterm

birth and motor outcome. Complex MND, which can be considered as a distinct form of

perinatally acquired brain dysfunction, is associated with damage to the cortico-striato-

thalamo-cortical and cerebello-thalamo-cortical pathways.15 Especially these brain

circuitries are vulnerable in very preterm-born children and are mutually involved in

both cognition and motor performance.16,17

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112 | Chapter 7

Intervention effects of the IBAIP at 5.5 years and over time

The IBAIP led, 5 years after the last intervention session, to improvements on performance

IQ, ball skills, and visual-motor integration in VLBW infants at 5.5 years CA (Chapter 5).

The IBAIP did not improve behavior at this time-point.

Thus, cross-sectional data-analyses revealed significant intervention effects of the

IBAIP on cognitive development at 6 months and 5.5 years corrected CA, and on motor

development at 6, 12 and 24 months and 5.5 years CA. However, this approach is insensitive

to individual developmental changes over time, and mean outcomes of the study groups

may therefore not be representative for the patterns of individual outcomes.18,19 To our

knowledge, no longitudinal data-analysis of outcomes of early intervention studies, has

been reported. Therefore, we additionally evaluated the intervention effects of the

IBAIP longitudinally from 6 months up to and including 5.5 years CA (Chapter 6).

We found that the IBAIP leads to long-term improvements on motor development

in VLBW infants. However, a longitudinal intervention effect on cognitive development

was not found.

We found that VLBW children with BPD benefitted longitudinally the most from the

intervention, both on the cognitive and motor domains. Low maternal education did not

influence intervention effects over time; but in children with multiple risks (low maternal

education and abnormal cranial ultrasound or BPD) a longitudinal intervention effect on

cognitive development was found.

The IBAIP may protect or can help to reorganize the vulnerable brain structures in VLBW

infants because the improvements on performance IQ, ball skills, and visual-motor

integration, found at 5.5 years CA, all involve visual-spatial abilities and motor responses,

and functionally overlap to a large extend. The most common brain injuries in VLBW

infants, as described in Chapter 4, are related to complex MND, problems in processing

speed and, visual-spatial and motor impairments.16,20,21

VLBW children with BPD benefitted the most from the IBAIP. BPD is associated with

damage of white matter and striato-thalamic structures, because of periods of hypoxia

and hypercarbia.22-24 Also, BPD has long-term adverse effects on cognitive and academic

achievements above and beyond the effects of VLBW.25 At 5.5 years CA, 59.5% of the

VLBW children with BPD in our cohort had complex MND versus 14.9% of the VLBW

infants without BPD. In the total intervention group 34.8% had complex MND versus

58.6% of the intervention children with BDP. This indicates that the children with BPD

had more damage in the above mentioned circuitries and that the IBAIP is especially

effective in improving development of VLBW infants with BPD.



7

It is assumed that qualitative good interactions between parent and child, accomplished

in early childhood, will continue in time and positively affect infants development.

Strengthening the parental sensitive-responsiveness and supporting the child’s self-

regulation in an early and sensitive period of brain development, possibly have

resulted in the sustained improvement at 5.5 years CA and earlier time-points.26-30 We

hypothesized the following underlying mechanisms: (1) improving early self-regulation

may affect the motor system because the self-regulatory strategies offered, enhances

midline orientation which strengthens the child’s control over posture and movements;

(2) the strength-based and scaffolding neurobehavioral support of the interventionist

and parent to the child. Strength-based support means building on the strengths of

both the child and parents. It is a positive approach to the child and parents, seeking

for possibilities instead of problems in behavior. Scaffolding support implies the process

in which parents continuously adjusts their interactions to the infant’s changing needs

for support over time.28 The strength-based support may improve the parents’ self-

confidence and, parents’ scaffolding efforts enhances the infants’ information processing

and abilities to explore.

The IBAIP versus comparable programs

Three intervention programs are comparable with the IBAIP because they also focus on

parent-infant interactions and infant development: the Norwegian modified Mother-

Infant Transaction Program (mMITP),31,32 the British Avon Premature Infant Project

(APIP),33,34 and the Australian Victorian Infant Brain Study-Plus (VIBeS-Plus).35,36 They all

found improvement in aspects of cognitive development. Only the IBAIP has led as well

to cognitive as to motor improvements, although the duration of intervention was short

compared to the other early intervention programs. The timing of the intervention, the

specific sensitive-responsive parent-infant approach of the IBAIP, and supporting the

child’s self-regulation to improve development, may be crucial in that respect.

In addition to the duration of the intervention, other differences which may

contribute to different outcomes between the early intervention studies were: (1)

composition of the patient groups; (2) composition of the control groups; (3) profession

of the interventionists, and (4) the length of follow-up.

In recent literature, the importance of supporting the parent in their mediation

role, is more and more emphasized.10 The extra psychological support in the mMITP

and VIBeS-Plus may have contributed to less parental stress and depression and less

behavioral problems of the infant. Although no effect on maternal psychological distress

was found in the first 2 years after the IBAIP was given,37 increased maternal sensitivity

in interaction with their VLBW infant was found.38 At 5.5 years CA, we found no positive

intervention effects on behavior.

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114 | Chapter 7

On both the mMITP as the IBAIP, a delayed intervention effect on cognitive

improvement was found. It remains speculative whether this delayed effect results from

methodological differences, insufficient sensitivity of measurements to reveal subtle

differences in cognition at earlier age or is related to the maturation process of the

involved brain areas. Aspects of mental function mature at different times in a child’s life

and synapse formation of higher cognitive capacities begin to mature by age 3 years.27

In chapter 4, we found that motor outcome in VLBW infants is strongly related with

cognitive outcome. Others demonstrated that several cognitive tasks (working memory,

processing speed, visual processing) are interrelated with motor tasks (coordination, fine

manual skills) in children without developmental delays.39,40 This indicates a common

neuro-anatomical background of processes in complex cognitive and motor actions.

Methodological considerations


Correcting for prematurity or not

In literature there is no consensus about until what age, the age should be corrected

for prematurity. According to the BSID manuals, correction for prematurity should be

applied as long as 24 months postnatal age.12,41 The American Academy of Pediatrics

recommends that test scores should be corrected for prematurity up to 3 years of age

because it is assumed that at later ages VLBW infants catch up to their chronological

same-age peers.42 But Wilson-Ching et al.43 found substantial lower scores in cognitive

developmental tests in the pre-school and school-age years in preterm infants and they

suggested that for research purposes, correcting beyond age 3 is necessary because it

removes an important bias against those born preterm. There can be a great risk of

misinterpreting change over time if corrected age is employed in early assessments but

chronological age is used beyond age 3. We decided to assess the VLBW infants at their

corrected age In the studies presented in this thesis. In the study described in chapter 4,

we found substantial differences in all developmental domains between very preterm-

born children, using the corrected age, and term-born children at the disadvantage of

the very preterm-born group. If we had used the chronological age, these difference

would have been even bigger, indicating that at age 5 preterm-born children did not

catch up to their chronological same-age peers.

Normative data

We used the normative Canadian data of the AIMS because no Dutch norms are available

(Chapter 3). Psychometric properties of a developmental test might be influenced by

culture-specific elements. Previous studies have shown that, unlike infants in North



7

America, infants in Europe are predominantly placed in prone position to sleep, which

has led to later attainment of early motor milestones, such as rolling over and sitting

up.44,45

In 2006 a norm scale for preterm infants was introduced because the gross motor

developmental profile of preterm infants may reflect a variant of typical gross motor

development, specific for this population.46 The consequence of using the preterm

norm scale is that infants with mildly abnormal motor development will be classified as

normal whereas, especially in the very preterm group, a high incidence of mild, often co-

occurring, neurodevelopmental problems have been found at 5 years of age.3 Moreover,

preterm AIMS scores were not investigated in relation to 5 years’ motor outcome.

Therefore, we chose to use the general population scores of the AIMS to compare with.

Questionnaires

No significant intervention effect was found on behavior at 5.5 years of CA (Chapter

5). In both groups, 10.8% of the parents reported behavior difficulties in their children.

This is low compared to other studies in very preterm-born children.3 We only used

the parents’ form and not the teachers’ form of the SDQ, and this may have led to an

incomplete representation of this domain. The psychometric properties of the SDQ are

strong, but the reliability of the teacher form seems stronger compared to that of the

parent form.47 This may be explained by the different nature of the relationship with

the child and different contexts, where different behaviors are shown. According to a

recent study, investigating the validity of multi-informant reports of the SDQ in preterm

infants, multi-informant reports are the best for detecting attention deficit hyperactivity

disorder, and emotional or conduct disorders.48 Unfortunately, we did not apply these

reports in our follow-up at age 5.5 years.


We studied the associations of motor impairment with other developmental deficits in a

cohort of 81 very preterm-born and 84 term-born children at 5 years of CA (Chapter 4).

Term-born children were recruited from the school or social network of the very preterm-

born group or via mainstream schools in the neighbourhood of our hospital. Excluded

were children of the term-born group with a planned or current referral for learning or

behavioral problems. This strategy enabled us the comparison with normal developing

children but not with term-born children with learning or behavioral problems.

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116 | Chapter 7

Intervention effects of IBAIP at 5.5 years and over time

Statistical issues

The strengths of the early intervention study is that all group comparisons were

done within the design of a randomized controlled trial. However, despite random

assignment, more infants in the intervention group received respiratory therapy (i.e.

surfactant treatment, continuous positive airway pressure and oxygen therapy ≥28 days).

In addition, occurrence of septic periods and need for indomethacin was higher in the

intervention group. This inequality remained at all follow-up time-points and formed a

disadvantageous issue in this trial. The between group differences have been statistically

adjusted, as these perinatal characteristics are known to influence neurodevelopment

(Chapter 5, 6). Only after these corrections, positive intervention effects were found.

A limitation inherent to follow-up studies is attrition bias. The response rate at 5.5

years CA was 80% in the intervention group and in the control group 74%. This was

reasonable, taken into account that the cohort was drawn from a multicultural, urban

population, in which education was low in 38% of the parents. Nevertheless, we had

sufficient power (82%) to detect possible differences between the intervention and

the control group. The assessed children did not differ from the non-participants with

respect to sociodemographic and perinatal factors, except that mothers of participants

were more often born in the Netherlands than those of the non-participants. Therefore,

we assumed that the results of the assessed cohort could be generalized to the total

cohort of VLBW infants.

Longitudinal data analysis and test characteristics

There are no comprehensive cognitive or motor developmental tests that can be applied

from infancy to childhood and therefore, different instruments for both cognitive and

motor development were used in the longitudinal data analysis (Chapter 6). In our study,

only total IQ effects on cognitive development could be analyzed over time, because the

mental scale of the BSID-II-NL does not have a verbal and performance separation, as in

the WPSSI. That is unfortunate because intervention effects at age 5.5 were found for

performance and not total IQ. The mental and motor scale of the third version of the

BSID41 has now 5 subscales; fine and gross motor, language (receptive and expressive)

and cognitive development. Further research is warranted to investigate the correlation

between cognitive outcomes on the BSID-III and the items of the WPPSI and also on

motor outcomes of the BSID-III and the MABC-2 items in VLBW children.



7

Clinical Implications


As self-regulatory competence of a child plays a key role in cognitive, motor and

behavioral development, a neurobehavioral analyses should be considered to be used

complementary to currently used other infant assessments. Not only to denominate

intervention goals, but also in neonatal follow-op assessment protocols in the first

year. The IBA is a reliable and valid tool (Chapter 2) that gives a better insight into

the infant’s developmental goals or underlying problem areas and may contribute to

the professional’s understanding and evaluation of the self-regulatory competence and

abilities to participate in interactions.

The AIMS should be added to the neonatal follow-up protocol to assess motor

development in VLBW infants from term age to 18 months of age. In Chapter 4 we found

that this instrument is superior in finding motor impairments than the more often used

PDI of the BSID-II-NL. Furthermore, the instrument has the advantage of incorporating

other motor developmental elements like the gravitational position of the infant, weight

bearing and postural alignment. These are necessary elements to observe in VLBW infants

because they are known to experience difficulties in these qualitative aspects of motor

development, because of reduced active flexion power and discrepancies between the

active and passive muscle tone.49,50


Long-term follow-up of VLBW children after discharge from hospital throughout their

school career should be implemented, in order to identify those children in need for

support. Neonatal follow-up differs by hospital. In general the duration of neonatal

follow-up is 2 years. However, the follow-up of very preterm-born children at age 5

revealed a high frequency of co-occurring mild developmental impairments in different

domains (Chapter 4). It is important to recognise that especially very preterm-born children

with motor impairment are also highly likely to have more often complex MND and low

IQ, slow processing speed and visuomotor coordination problems than very preterm-

born children without motor impairment. At age 5, the task complexity increases and

information processing becomes more important. Therefore, mild impairments become

more noticeable and a burden at school-age. The combination of problems decreases

the potential to compensate and puts these children at risk for later learning disabilities

and social problems.1 Therefore, other deficits should be taken into account, when very

preterm-born children are referred for motor impairment.

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118 | Chapter 7

Intervention effects of IBAIP at 5.5 years and over time

Due to improved and technologically more advanced care on the neonatal intensive

care unit (NICU) and the lowering of the limit of active intervention to 24 weeks

gestational age in the Netherlands, more preterm-born children do survive. However,

they are longer exposed to risk factors, that may have an adverse effect on brain- and

neurodevelopment. Therefore, the focus on healthy survival of preterm-born children

remains very important, and should include optimal neurodevelopmental care and

support for these children and their parents. Combining NICU-based interventions, such

as done in the Caffeine for Apnea of Prematurity (CAP) trial51,52 to reduce biological

risks, and to support the parent-infant relationship and infant development as done in

the IBAIP, will reinforce the positive neurodevelopmental outcomes because biological

factors account for only a portion of the variance associated with VLBW infant’s long-

term outcomes.53

An increase in the duration of the IBAIP will possible lead to more cognitive gains if the

intervention have an extension in the most sensitive period of cognitive development.

No improvements, based on individual developmental outcomes over time, on cognition,

except for the subgroup of VLBW infants with BPD, were found (Chapter 6). Possibly,

because the intervention was given in the relative short period of 6 months after

discharge from hospital.

More attention should be given to the well-being of the mother and/or father,

especially in social risk families, because this may strengthen the resources and capabilities

of the parents to achieve a sensitive and responsive parent-child relationship. To obtain

more positive effects of the IBAIP on behavior and in children with low educated mothers,

adding the support of a psychologist to the intervention is recommended.

The results of the studies on the effects of the IBAIP have led to the implementation

of an early intervention program for VLBW infants in the Netherlands. The period of

intervention has been extended to 12 months CA after discharge from hospital and more

attention will be given to the mental well-being of the mother.

Conclusion and suggestions for future research

The IBAIP effectively supports the neurodevelopment of VLBW infants until 5.5 years of

CA. VLBW infants with BPD benefitted most from the early intervention. The results of

the studies on the effects of the IBAIP have led to the development and implementation

of an early intervention program in the Netherlands. The outcomes of this so-called ToP

program (Transmurale Ontwikkelingsondersteuning voor Prematuur geboren kinderen

en hun ouders, translated: transmural developmental support for preterm infants and



7

their parents), needs to be evaluated in future research in order to determine if the ToP

intervention elements, like the duration of the program until 12 months and psycho-

education, further improve effective developmental care and support for VLBW children

and their parents.

Strengthening the parental sensitive-responsiveness and the child’s self-regulation

in an early and sensitive period of brain development, underlies the effects of

neurodevelopmental improvement by the IBAIP. Future research is warranted to

determine if parental sensitive-responsiveness and self-regulatory competence in

other infant populations, with biological and environmental factors contributing to

the risk of disabilities, are also the key elements to support and improve long-term

neurodevelopmental outcomes.

The clinimetric properties reliability, sensitivity and responsiveness of the Infant

Behavioral Assessment (IBA) are satisfactory to good to evaluate and support

neurobehavioral organization (i.e. self-regulation) in VLBW infants. However, research

use of the IBA requires a careful creation of the sample interaction for each specific

infant group and/or age. Therefore, additional validation of the IBA in different infant

populations and at different ages is warranted.

Although the scores indicate an acceptable consistency with which different observers

can create the same analyses of infant behavior, some refinement of the IBA definitions

may be needed. Differences in scoring may occur when the infant displays the behavior

for a very short moment, or as part of another movement. Adding a time component

to the definitions of some of the motor items of the IBA may further enhance inter-

observer agreement.

Since the abilities in which VLBW infants’ experience difficulties as trunk control and

trunk rotation, are underrepresented in both the second and third version of the BSID,

future research is needed in order to develop a set of neurodevelopmental assessment

instruments that are able to assess long-term neurodevelopment in VLBW infants. A first

step is to investigate the correlation between the AIMS and the motor scores of the third

edition of the BSID, as well as between AIMS scores and motor outcomes of the MABC-2

at school age.

How cultural differences might affect the administration of the AIMS, needs to be

investigated by establishing Dutch norm values of the AIMS.

The clinical implication of differences between corrected and uncorrected

developmental outcomes in children with different low gestational ages at different

time-points in childhood needs further study, in order to obtain agreement until when

correcting for prematurity.

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120 | Chapter 7

References

1. De Kleine MJK, den Ouden AL, Kollée LAA et al. Development and evaluation of a follow up assessment of preterm infants at 5 years of age. Arch Dis Child 2003;88:870–875.


3. Potharst ES, Van Wassenaer AG, Houtzager BA, Van Hus JWP, Last BF, Kok JH. High incidence of multi- domain disabilities in very preterm children at five years of age. J Pediatr 2011;159:79-85.


5. Hedlund R. (1998). The Infant Behavioral Assessment and Intervention Program.© Available from: http://www.ibaip.org. Accessed Jan 12, 2012.



8. Verkerk G, Jeukens-Visser M, Koldewijn K et al. The infant behavioral assessment and intervention program in very low birth weight infants improves independency in mobility in daily activities at preschool age. J Pediatr 2011;159:933-938.

9. Hedlund R, Tatarka M. (1986,1988). The Infant Behavioral Assessment.© Available from: http://www.ibaip.org. Accessed Jan 12, 2012.

10. Shonkoff JP. Leveraging the biology of adversity to address the roots of disparities in health and development. PNAS 2012;109:17302-17307.

11. Shonkoff JP, Boyce WT, McEwan BS. Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. JAMA 2009;301:2252–2259.


13. Van der Meulen BF, Ruiter SAJ, Lutje Spelberg HC et al. The Bayley Scales of Infant Development – Second edition, Dutch Manual (BSID-II- NL). Lisse: Swets Test Publisher; 2002.


15. Hadders-Algra M. Two distinct forms of minor neurological dysfunction: perspectives emerging from a review of data of the Groningen Perinatal Project. Dev med Child Neurol 2002;44:561-567.

16. Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol 2009;8:110-124.

17. Diamond A. Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex. Child Dev 2000;71:44-56.

18. Karmiloff-Smith A. Neuroimaging of developing brain: Taking “developing” seriously. Hum Brain Mapp 2010;31:934-941.



7

19. Sadeghi N, Prastwaw M, Fletcher PT, Wolff J, Gilmore JH, Gertig G. Regional characterization of longitudinal DT-MRI to study white matter maturation of the early developing brain. Neuroimaging 2012;68:236-247.

20. Clark CAC, Woodward LJ. Neonatal cerebral abnormalities and later verbal and visuospatial working memory abilities of children born very preterm. Dev neuropsychology 2010;35:622-642.

21. Spittle AJ, Cheong H, Doyle LW et al. Neonatal white matter abnormalities predicts childhood motor impairment in very preterm born children. Dev Med Child Neurol 2011;55:1000-1006.

22. Perlman JM, Volpe JJ. Movement disorder of premature infants with severe bronchopulmonary dysplasia; a new syndrome. Pediatrics 1989;84:215-218.

23. Subramian S, El-Mhandes A, Dhanireddy R, Koch MA. Association of bronchopulmonary dysplasia and hypercarbia in ventilated infants with birth weights of 500-1499 gram. Matern Child Health J 2011;1:17-26.

24. Gagliardi L, Bellu R, Zanini R et al. Bronchopulmonary dysplasia and white matter damage in the preterm infant; a complex relationship. Peadiatr Perinat Epidemiol 2009;23:582-590.

25. Short EJ, Klein NK, Lewis BA et al. Cognitive and academic consequences of Bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. Pediatrics 2003:112:359-366.


27. National Scientific Council on the Developing Child at Harvard University (2007).The timing and quality of early experiences combine in shape brain architecture. Working paper #5. Retrieved April 2014, from http://www.developingchild.net.

28. Spittle AJ, Orton J, Doyle LW, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev 2007:CD005495.

29. Erickson SJ, Duvall SW, fuller J, Schrader R, Maclean P, Lowe JR. Differential associations between maternal scaffolding and toddler emotion regulation in toddlers born preterm and full term. Early Hum Dev 2013;89:699-704

30. Lowe JR, Erickson SJ, Maclean P, Schrader R, fuller J. Association of maternal scaffolding to maternal education and cognition in toddlers born preterm and full term. Acta Peadiatr 2013;102:72-77.

31. Kaaresen PI, Ronning JA, Tunby J, Nordhov SM, Ulvund SE, Dahl BD. A randomized controlled trial of an early intervention program in low birth weight children: Outcome at 2 years. Early Hum Dev 2008;84:201-209.

32. Nordhov SM, Ronning JA, Dahl LB, Ulvund SE, Tunby J, Kaaresen PI. Early intervention improves cognitive outcomes for preterm infants: randomized controlled trial. Pediatrics 2010;126:1088-1094.

33. Robinson M, Israel C, Parker D et al. Randomized trial of parental support for families with very preterm children. Arch Dis Child 1998;79:4-11.

34. Johnson S, Ring W, Anderson P et al. Randomized trial of parental support for families with very preterm children: outcome at 5 years. Arch Dis Child 2005;90:909-15.

35. Spittle AJ, Anderson PJ, Lee KJ et al. Preventive care at home for very preterm infants improves infant and caregiver outcomes at 2 years. Pediatrics 2010;126:171-178.

36. Spencer-Smith MM, Spittle AJ, Doyle LW et al. Long-term benefits of home-based preventive care for preterm infants: a randomized trial. Pediatrics 2012;130:1094-1101.

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122 | Chapter 7

37. Meijssen D,Wolf MJ, Koldewijn K et al. Maternal psychological distress in the first two years after very preterm birth and early intervention. Early Child Dev Care 2011;181:1-11.

38. Meijssen D,Wolf MJ, Koldewijn K et al. The effect of the Infant Behavioral Assessment and Intervention Program on mother-infant interaction after very preterm birth. J Child Psychol Psychiatry 2010;51:1287-95.

39. Roebers CM, Kauer M. Motor and cognitive control in a normative sample of 7-year-olds. Dev Sci 2009;12:175-181.

40. Davis E, Pitchford NJ, Limback E. The interrelation between cognitive and motor development in typically developing children ages 4-11 yeas in underpinned by visual processing and fine manual control. J Psych 2011;102:569-584.

41. Bayley N. Bayley Scales of Infant and Toddler Development. 3rd ed. San Antonio, Texas: Harcourt Assessments Inc;2006.

42. Marlow N. Neurocognitive outcome after very preterm birth. Arch Dis Child Fetal Neonatal Ed 2004;89:224-228.

43. Wilson-Ching M, Pascoe L, Doyle LW, Anderson PJ. Effects of correcting for prematurity on cognitive test scores in childhood. J Paed and Child Health 2014;50:182-188.

44. Bryant GM. Davis KJ, Newcombe RG. The Denver Developmental Screening Test; achievement of test items in the first year of life by Denver and Cardiff infants. Dev Med Child Neurol 1974;16:475-484.

45. Fung KP, Lau SP. Denver Developmental Screening Test: cultural variables. J Pediatr 1985;106:343.

46. Van Haastert IC, De Vries LS, Helders PJM et al. Early Gross motor development of preterm infants according to the Alberta Infant Motor Scale. J Pediatr 2006;149:617-622.

47. Stone LL, Otten R, Engels RCME, Vermulst AA, Janssens JMAM. Psychometric properties of the parent and teacher versions of the Strengths and difficulties questionnaire for 4 to 12 year olds: a review. Clin Child Fam Psychol Rev 2010;13:254-274.

48. Johnson S, Hollis C, Marlow N, Simms V, Wolke D. Screening for childhood mental health disorders using the Strengths and Difficulties Questionnaire: the validity of multi-informant reports. Dev Med Child Neurol 2014;56:453-459.

49. Dewey D, Creighton DE, Heath JA et al. Assessment of Developmental Coordination Disorder in children born with extremely low birth weights. Dev Neuropsy 2011;36:42-46.

50. De Groot L, Van De Hoek AM, Hopkins B, Touwen BC. Development of relationship between active and passive muscle power in preterms after term age. Neuropediatrics 1992;23:298-305.

51. Smith B, Anderson PJ, Doyle LW. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA 2012;307:275-282.

52. Doyle LW, Schmidt B, Anderson PJ et al. Reduction in developmental coordination disorder with neonatal caffeine therapy. J Pediatr 2014, doi:10.1016/jpeds.2014.04.016.

53. National Scientific Council on the Developing Child at Harvard University (2007). Excessive stress disrupts the architecture of the developing brain. Working paper #3. Retrieved April 2014, from http://www.developingchild.net.

Summary / Samenvatting

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124 | Summary / Samenvatting


Summary / Samenvatting | 125

S

English summary

The general aim of this thesis was to expand the knowledge on an early intervention

program for very preterm-born children, to provide optimal neurodevelopmental care

and support for these vulnerable children and their parents. In this thesis the effects of the

Infant Behavioral Assessment and Intervention Program (IBAIP) on neurodevelopmental

outcome of very preterm-born and very low birth weight (VLBW) children (<32 weeks

and/or <1500 gram), who were enrolled in a randomized clinical trial over a period from

6 months up to and including 5.5 years, are presented. In addition, the relation between

motor impairments and other developmental deficits in another cohort of 5 year-old

very preterm-born and term-born children was investigated. As the outcome of research

depends on the quality of the assessment instruments used in a study, the clinimetric

properties of three instruments were evaluated.

Chapter 1 introduces the background, the aims and the outline of this thesis. The chapter

provides information on factors influencing neurodevelopment in VLBW infants, the

measurement of neurodevelopmental outcomes and the focus of the early intervention

program, the IBAIP.

There are many biological and environmental factors contributing to the risk of

disabilities in preterm-born infants. Although the incidence of severe handicaps, such

as cerebral palsy, is decreasing, VLBW infants still remain at great risk for a broad range

of mild, often co-occurring, neurodevelopmental deficits. At age 5, 45% of the children

have mild neurological problems, 39% have cognitive deficits, 30% have motor deficits

and 27% have behavioral problems. These deficits often persists throughout childhood

and have a negative influence into adulthood because they crucially affect the child’s

exploration of the world and involvement in academic and social activities.

The Infant Behavioral Assessment and Intervention Program (IBAIP) is a post-discharge,

preventive neurobehavioral intervention program. The program aims to support the

infants’ self-regulatory competence as well as the multiple developmental functions via

responsive parent-infant interactions, focusing on environmental, behavioral, and early

developmental factors. The accompanying assessment tool of the IBAIP intervention is

the Infant Behavioral Assessment (IBA). It is an observational tool that systematically

observes and interprets the developing infants’ neurobehavioral organization, in order

to investigate the infant’s competence to approach information, to self-regulate and the

infant’s expressions of stress during interactions. Thus, the IBAIP supports the infant’s

growth, the infant’s motivation to explore, and the possibility to learn from information.

Between 2004 and 2007, a multicenter randomized controlled trial (RCT) was

conducted to compare the effects of the IBAIP to standard follow-up care, with respect

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to cognitive and motor development, infants’ behavioral regulation, well-being of the

parents, and parent-infant interaction. Results of this study included improved cognitive,

motor, behavioral development and mother-infant interaction at 6 months CA and

improved motor development at 24 months CA, in favor of the parents and infants who

received the IBAIP intervention. Moreover, at 24 months CA, also improved cognitive

development was found in high risk subgroups who received the IBAIP. A follow-up

study at the preschool age of 44 months found improved independency in mobility in

daily activities. Between 2009 and 2011, the parents of all children participating in the

original RCT, were invited to the participate in a second follow-up study to evaluate the

effects of the IBAIP at the age of 5.5 years CA.

The studies described in Chapter 2 and 3 concern the measurement instruments to

evaluate development in VLBW infants.

Because the IBA is primarily intended to be used in a qualitative manner, in

conjunction with the IBAIP, the clinimetric properties of the IBA needed to be further

investigated in their ability as research tool. Chapter 2 describes the reliability, sensitivity

and responsiveness of the IBA. Videotaped assessments of 176 VLBW infants participating

in the RCT on the effect of the IBAIP, served to evaluate the IBA observation. Inter-

rater reliability was based on 40 videos scored by two independent observers. The inter-

observer agreement was moderate (in approach) to good (in self-regulation and stress)

and observers achieved an item-by-item agreement of 93% for the total assessment.

Sensitivity was evaluated in 169 infants at 35-38 weeks postmenstrual age by

comparing the IBA results between VLBW infant with or without biological high risk

factors (gestational age ≤28 weeks or bronchopulmonary dysplasia (BPD). The sensitivity

of the IBA was demonstrated by significant differences found between the 2 groups

differing in risk for adverse outcomes. All outcomes pointed in the expected direction,

indicating less approach and/or more stress behaviors in infants at high risk.

IBA responsiveness was investigated by calculating the effect size (ES) over the

period over the period between 0 to 6 months CA by calculating the effect size (ES) in

the total group and a subgroup of infants with oxygen-dependency ≥28 days. Larger

differences between ESs in the randomized groups reflect the responsiveness of the IBA.

Intervention infants with oxygen-dependency ≥28 days showed the largest change. The

clinimetric properties reliability, sensitivity and responsiveness of the IBA are satisfactory

to good to evaluate and support neurobehavioural organization in VLBW infants.

Complementary use of the IBA to neurological and developmental measures provides a

more comprehensive picture of the infants development.



S

In the light of the need for sensitive assessment tools that measure change in

neurodevelopment in VLBW children, our aim of the study in chapter 3 was to compare

the Alberta Infant Motor Scale (AIMS) with the Psychomotor scale (PDI) of the Dutch

second edition of the Bayley Scales of Infant Development (BSID-II-NL) in their ability

to evaluate intervention effects in VLBW infants. At 12 months CA, 116 of 176 VLBW

infants participating in the RCT were assessed with both the AIMS and the PDI. Abnormal

motor development was found in 27.7% of all participating VLBW infants based on the

AIMS versus 2.6% based on the PDI of the BSID-II-NL. Corrected for baseline differences,

significant intervention effects were found for AIMS and PDI scores. The highest effect

size was for the AIMS total score and subscale sit. A significant reduction of abnormal

motor development in the intervention group was only found with the AIMS. It was

concluded that the responsiveness of the AIMS to detect intervention effects in VLBW

infants was better than the PDI at 12 months CA. Therefore, caution is recommended

in monitoring VLBW infants only with the PDI, and the additional use of the AIMS is

advised when evaluating intervention effects on motor development at 12 months CA.

Chapter 4 concerns motor impairments and links with other developmental deficits in

very preterm-born infants in comparison with term-born infants. The aim of the study

was to elucidate the relation between motor impairment and other developmental

deficits in a cohort of 81 very preterm-born children, born <30 weeks’ gestation and/or

birth weights <1000 gram, and 84 term-born children at 5 years of (corrected) age.

The used measurement instruments were the second edition of the Movement

Assessment Battery for Children (MABC-2), Touwen’s neurological examination,

the third Dutch version of the Wechsler Preschool and Primary Scale of Intelligence

(WPPSI-III-NL), processing speed and visuomotor coordination tasks of the Amsterdam

Neuropsychological Tasks (ANT) and the Strengths and Difficulties Questionnaire

(SDQ). Two visits in which the assessments took place were scheduled in the hospital.

A mediation model was tested to analyse the extent to which the other developmental

deficits mediate the association between preterm birth and motor impairment.

Motor impairments occurred in 32% of the very preterm-born children compared

with 11% of their term-born peers. Very preterm-born children with motor impairments

had a substantial higher rate of other abnormal test outcomes than very preterm-born

children without motor impairments. Of the children with motor impairments, 58% had

complex minor neurological dysfunctions, 54% had low IQ, 69% had slow processing

speed, 58% had visuomotor coordination problems and 27%, 50% and 46% had conduct,

emotional and hyperactivity problems respectively. Neurological dysfunction and low

IQ were associated with motor impairments. Slow processing speed and attention

problems were additional variables associated with impaired manual dexterity. These

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four developmental deficits mediated the relation between preterm birth and motor

impairments. Therefore, these deficits should be taken into account when very preterm-

born children are referred for motor impairments.

Chapter 5 describes the effects of the IBAIP in VLBW infants on cognitive, neuromotor,

and behavioral development at 5.5 years CA.

Cognitive and motor development and visual-motor integration were assessed with

the WPPSI-III-NL, the MABC-2, and the Developmental Test of Visual Motor Integration

(VMI). Neurological conditions were assessed with the neurological examination

according to Touwen and behavior with the SDQ.

Of the 176 children participating in the RCT, 136 children (69 in the intervention and

67 in the control group) were available for follow-up (response rate 77.3%).

After adjustment for perinatal and sociodemographic differences, low performance

IQ occurred significantly less often in the intervention than in the control group. Motor

impairment, abnormal visual-motor integration and abnormal neurological examination

were not significantly different between the groups. After adjustment, intervention

effects were found on block design and vocabulary subtests of the WPSSI, on the MABC-

2 component aiming and catching and on the VMI, all in favour of the intervention

children. There were no differences between the intervention and control groups with

respect to behavioral outcomes (SDQ).

These results show that, 5 years after the intervention, the IBAIP has a sustained

effect on cognitive and motor development and leads to improvements on performance

IQ, ball skills and visual-motor integration in VLBW children.

Cross-sectional data-analyses revealed positive intervention effects on cognitive

development at 6 months and 5.5 years corrected CA, and on motor development at 6,

12 and 24 months and 5.5 years CA. But a cross sectional approach lacks insight in the

individual developmental changes over time and, to our knowledge, no longitudinal

data-analysis of outcomes of early intervention studies, has been reported. Therefore,

the study in Chapter 6 aimed to investigate the longitudinal effects of the IBAIP in VLBW

infants on cognitive and motor development from 6 months up to and including 5.5

years CA.

Longitudinal data were analyzed in the total group of 176 VLBW infants and in three

subgroups with biological or environmental or a combination of biological-environmental

risk factors. At 6, 12, and 24 months CA, cognitive and motor development were assessed

with the BSID-II-NL. At 5.5 years CA the WPPSI-III-NL and the MABC-2 were used.

A positive longitudinal intervention effect on motor development was found, but

not on cognitive development. In the subgroup “VLBW children with bronchopulmonary



S

dysplasia (BPD)” longitudinal intervention effects were found for both cognitive

(effect=0.7SD) and motor (effect=0.9SD;) outcome in favour of the intervention children.

Maternal education hardly influenced intervention effects over time, but in children

with combined biological and social risks an intervention effect of 0.8SD was found on

cognitive development.

It was concluded that the IBAIP leads to long-term improvements on motor

development in VLBW infants. Particularly VLBW children with BPD benefit from the

intervention, both on the cognitive and motor domains.

Chapter 7 comprises the general discussion. In this chapter the main findings,

methodological considerations, clinical implications and future research perspectives are

reflected upon.

In our search to provide optimal neurodevelopmental care and support for very

preterm-born infants and their parents, we conclude that the IBAIP has effectively

supported the neurodevelopment of VLBW infants with a sustained effect at 5.5 years

CA, and also a longitudinal intervention effect from 6 months up to and including 5.5

years CA. VLBW infants with BPD benefitted most from the early intervention. However,

no positive intervention effects were found on behavior and on cognitive development

over time for the total VLBW group.

The following clinical implications are formulated.

(1) As self-regulatory competence of a child plays a key role in cognitive, motor and

behavioral development, the IBA should be considered complementary to other usual

infant assessment tools. (2) The AIMS should be added to the neonatal follow-up

protocol to assess motor development in VLBW infants. (3) At age 5, the task complexity

increases and information processing becomes more important. Therefore, neurological

dysfunction, low IQ, slow processing speed and attention problems should be taken into

account, when very preterm-born children are referred for motor impairments. (4) An

increase in the duration of the IBAIP will possibly lead to more cognitive gains if the

intervention takes place in the most sensitive period of cognitive development. (5) To

obtain more positive intervention effects of the IBAIP on behavior and in children with

low educated mothers, adding the support of a psychologist to the intervention should

be considered.

Several suggestions for future research are suggested.

(1) Additional validation of the IBA in different infant populations and at different ages

is warranted. (2) The need in order to develop a set of neurodevelopmental assessment

instruments that are able to assess long-term neurodevelopment in VLBW infants.

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(3) The results of the studies on the effects of the IBAIP have led to the implementation

of an early intervention program. The outcomes of this so- called ToP program needs

to be evaluated in order to determine if the extension of the program and additive

psycho-education to the interventionists, improves optimal developmental care and

support for VLBW children and their parents. (4) It is necessary to determine if parental

sensitive-responsiveness and self-regulatory competence in other infant populations,

with biological and environmental factors contributing to the risk of disabilities, are also

the key elements to support and improve long-term neurodevelopmental outcomes.



S

Nederlandse samenvatting

Dit proefschrift heeft als doel de kennis over een preventief vroeginterventie programma

verder uit te breiden om hierdoor de ontwikkelingsgerichte zorg aan zeer vroeg

geboren kinderen en hun ouders te kunnen optimaliseren. Het proefschrift beschrijft

het effect van het Infant Behavioral Assessment and Intervention Program (IBAIP) op

de ontwikkeling van zeer vroeg geboren kinderen (zwangerschapsduur <32 weken

en/of een geboortegewicht <1500 gram) die participeerden in een gerandomiseerd

klinisch onderzoek over een periode van 6 maanden tot en met 5,5 jaar gecorrigeerde

leeftijd. Ook wordt bij een cohort van zeer vroeg geboren en op tijd geboren kinderen

op 5 jarige leeftijd, de relatie onderzocht tussen motorische beperkingen en andere

ontwikkelingsproblemen. Aangezien de resultaten van een onderzoek afhangen van de

kwaliteit van de meetinstrumenten die tijdens het onderzoek worden gebruikt, zijn ook

de klinimetrische eigenschappen van drie meetinstrumenten onderzocht.

In hoofdstuk 1 wordt de algemene achtergrond informatie, het doel en de opzet van

dit proefschrift beschreven. Er wordt ingegaan op de factoren die van invloed zijn op de

ontwikkeling van zeer vroeg geboren kinderen, het meten van ontwikkelingsuitkomsten

en de principes van het vroeginterventie programma wat is gebruikt voor deze studie.

Er zijn bij zeer vroeg geboren kinderen diverse biologische en omgevingsfactoren

die een verhoogd risico geven op ontwikkelingsproblemen. Ernstige handicaps ten

gevolge van vroeggeboorte, zoals cerebrale parese, zijn afgenomen. Maar duidelijk is

geworden dat vooral combinaties van milde problemen vaak voorkomen, waardoor

kinderen moeilijk om kunnen gaan met meer complexe opdrachten of situaties. Op 5

jarige leeftijd heeft 45% van de zeer vroeg geboren kinderen neurologische problemen,

39% heeft milde cognitieve beperkingen, 30% heeft een motorische achterstand en

27% ondervindt gedragsproblemen. Deze beperkingen hebben een negatieve invloed

op latere schoolprestaties en sociale activiteiten en kunnen participatie in het dagelijkse

leven beperken.

Het Infant Behavioral Assessment and Intervention Programma (IBAIP) is een

preventief vroeginterventie programma. Het doel van het IBAIP is zowel de zelfregulatie

van het kind te verbeteren als de geïntegreerde ontwikkeling van het kind, door

middel van ondersteuning van responsieve en positieve ouderkind-interacties. IBAIP-

opgeleide kinderfysiotherapeuten kijken naar de organisatie van gedragsuitingen en

de zelfregulerende competenties van het kind binnen de context van de omgeving en

ondersteunen ouders bij het inzicht krijgen in waar hun kind aan toe is, waar het hulp

bij nodig heeft en hoe dit kan worden geven. Dit wordt beoordeeld aan de hand van

de individuele gedragsuitingen van het kind die vastgesteld worden met behulp van

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het Infant Behavioral Assessment (IBA). Dit observatie instrument geeft inzicht in het

zelfregulerend vermogen van het kind, het vermogen om toenadering te zoeken en de

mate van stress van het kind.

Het IBAIP stimuleert de ontwikkeling van het kind, de motivatie om te exploreren en

de mogelijkheid om te leren van informatie.

Tussen 2004 en 2007 werd een multicenter gerandomiseerde gecontroleerde studie

(RCT) uitgevoerd met als doel het IBAIP te vergelijken met standaard follow-up zorg op

het gebied van cognitieve en motorische ontwikkeling, gedragsregulatie van het kind,

welzijn van de ouders en de ouder-kindinteractie. Op 6 maanden werd bij de kinderen

die het IBAIP hadden gekregen een verbetering van de motorische en cognitieve

ontwikkeling en het gedrag gevonden en een verbetering van de ouder-kindinteractie.

Op 24 maanden werd, in het voordeel van de interventie kinderen, een verbetering in de

motoriek vastgesteld en een verbetering in cognitie bij kinderen met een hoog risico op

ontwikkelingsproblemen. Op de leeftijd van 44 maanden werd er een verbetering van

de dagelijkse vaardigheden, zoals lopen en fietsen gevonden.

Tussen 2009-2011 werden alle kinderen en hun ouders die hadden geparticipeerd in

de originele RCT uitgenodigd voor een tweede follow-up studie om het effect van het

IBAIP op de gecorrigeerde leeftijd van 5,5 jaar te onderzoeken.

De studies beschreven in hoofdstuk 2 en 3 hebben betrekking op de meetinstrumenten

die worden gebruikt om de mate van ontwikkeling bij zeer vroeg geboren kinderen te

bepalen.

Aangezien de IBA in eerste instantie alleen als kwaliteitsinstrument in samenwerking

met het IBAIP is ontwikkeld, was het noodzakelijk om de klinimetrische eigenschappen

van de IBA voor onderzoek verder te onderzoeken. Hoofdstuk 2 beschrijft de

betrouwbaarheid, sensitiviteit en responsiviteit van de IBA. De inter-beoordelaars

betrouwbaarheid is gebaseerd op 40 video’s die werden gescoord door 2 onafhankelijke

beoordelaars. De inter-beoordelaars betrouwbaarheid was matig (voor toenadering) tot

goed (voor zelfregulatie en stress) en op de totale test bereikte de beoordelaars voor

93% van de items overeenstemming.

De sensitiviteit van de IBA is beoordeeld door te onderzoeken of de IBA kan

discrimineren tussen de gedragsuitingen van 169 kinderen met of zonder hoog risico

factoren (zwangerschapsduur ≤28 weken en/of bronchopulmonaire dysplasie (BPD)). Er

werden duidelijk verschillen gevonden tussen de groepen in de te verwachte richting,

namelijk minder toenadering en/of meer stress gedragingen bij de kinderen met een

hoog risico.

De responsiviteit is onderzocht gedurende een periode van 6 maanden door de

effect grootte van de interventie in de totale groep en in een subgroep van kinderen



S

met zuurstof ondersteuning ≥28 dagen te onderzoeken. Grote verschillen in de effect

grootte tussen de groepen gaf de responsiviteit van de IBA weer. Interventie kinderen

met zuurstof ondersteuning ≥28 dagen lieten de grootste verandering in de tijd zien.

Deze studie toonde aan dat de IBA een betrouwbaar, sensitief en responsief instrument

is om de gedragsorganisatie van zeer vroeg geboren kinderen te beoordelen. De IBA

heeft een toegevoegde waarde, naast de al bestaande neurologische en functionele

ontwikkelingstesten, aangezien het een breder beeld van de ontwikkeling van het kind

verschaft.

Er is behoefte aan sensitieve instrumenten die veranderingen in de ontwikkeling van

zeer vroeg geboren kinderen kunnen meten. In hoofdstuk 3 wordt de Alberta Infant

Motor Scale (AIMS) vergeleken met de psychomotorische schaal (PDI) van de tweede

Nederlandse editie van de Bayley Scales of Infant Development (BSID-II-NL), om na te

gaan welke onderzoeksinstrument het meest geschikt is om de motorische effecten van

het IBAIP te beoordelen.

Op de gecorrigeerde leeftijd van 12 maanden zijn 116 van de 176 zeer vroeg geboren

kinderen onderzocht met zowel de AIMS als de PDI. Met de AIMS werd er in 27,7% van

de kinderen een abnormale motorische ontwikkeling geconstateerd, met de PDI maar

in 2,6%. Gecorrigeerd voor baseline verschillen, werden zowel met de AIMS als de PDI

positieve interventie effecten gevonden. Het grootste interventie effect werd op de totale

score en de deelscore “zit” van de AIMS gevonden. Een vermindering van de abnormale

motorische ontwikkeling werd alleen door de AIMS gevonden. Geconcludeerd werd dat

de responsiviteit van de AIMS om interventie effecten bij zeer vroeg geboren kinderen

op 12 maanden te vinden beter was dan die van de PDI.

Hoofdstuk 4 betreft de relatie tussen motorische beperkingen en andere

ontwikkelingsproblemen bij zeer vroeg geboren kinderen in vergelijking met op

tijd geboren kinderen, onderzocht op de leeftijd van 5 jaar. Het cohort bestond

uit 81 zeer vroeg geboren kinderen met een zwangerschapsduur <30 weken en/

of een geboortegewicht <1000 gram en 84 op tijd geboren kinderen. De gebruikte

meetinstrumenten waren de tweede editie van de Movement Assessment Battery for

Children (MABC-2), het neurologisch onderzoek van Touwen, de derde Nederlandse

versie van de Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL), de

verwerkingssnelheid en visueel-motorische coördinatie taken van de Amsterdamse

Neuropsychologische Testbatterij (ANT) en de SDQ (Strengths and Difficulties

Questionnaire), een gedragsvragenlijst. De kinderen kwamen twee maal naar het

ziekenhuis voor de onderzoeken. Er werd een mediation model gemaakt om de invloed

van de andere ontwikkelingsproblemen op het verband tussen vroeggeboorte en

motorische problemen te analyseren.

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Van de zeer vroeg geboren kinderen had 32% motorische problemen en van de

op tijd geboren kinderen ondervond 11% motorische problemen. Zeer vroeg geboren

kinderen met motorische problemen bleken naast de motorische beperkingen vaker

meerdere andere ontwikkelingsproblemen te hebben dan zeer vroeg geboren kinderen

zonder motorische problemen. Van de kinderen met motorische problemen had 58%

neurologische dysfuncties, 54% een laag IQ, 69% een langzame verwerkingssnelheid,

58% visueel-motorische coördinatie problemen en 27%, 50% en 46% had problemen

in respectievelijk gedrag, emotie en aandacht. Er werd een verband gevonden tussen

neurologische dysfuncties en laag IQ met motorische problemen. Daarnaast waren een

langzame verwerkingssnelheid en aandachtsproblemen geassocieerd met een beperkte

fijne motoriek. Geadviseerd werd met deze ontwikkelingsproblemen rekening te houden

als zeer vroeg geboren kinderen voor motorische beperkingen worden doorverwezen

voor onderzoek of therapie.

Hoofdstuk 5 beschrijft de effecten van de IBAIP op de cognitieve en motorische

ontwikkeling en het gedrag op de gecorrigeerde leeftijd van 5,5 jaar. De cognitieve

en motorische ontwikkeling en de visueel-motorische integratie werden onderzocht

met de WPPSI-III-NL, the MABC-2 en de Developmental Test of Visual Motor Integration

(VMI). Neurologische condities werden getest met het neurologisch onderzoek volgens

Touwen, en het gedrag met de SDQ.

Van de 176 zeer vroeg geboren kinderen die participeerde in het RCT, waren 136

kinderen (69 in the interventie en 67 in de controle groep) beschikbaar voor de follow-

up op 5.5 jaar (response rate 77,3%).

Na correctie voor de perinatale en sociaal-demografische baseline verschillen, waren

er in de interventie groep minder kinderen met een laag performaal IQ dan in de

controle groep. Het aantal kinderen met motorische beperkingen, visueel-motorische

integratie problemen of neurologische dysfunctie verschilde niet tussen de groepen.

Positieve interventie effecten van het IBAIP werden na correctie voor baseline verschillen,

gevonden op de items blokpatronen en woordenschat van de WPSSI-III-NL, op de MABC-

2 component balvaardigheid en op de VMI. Er werd geen interventie effect gevonden

op gedrag (SDQ).

De resultaten laten zien dat er 5 jaar na het geven van de interventie, een blijvend

effect is van het IBAIP op de cognitieve en motorische ontwikkeling, in de zin van

een verbetering van het performaal IQ, de balvaardigheid en de visueel-motorische

coördinatie bij zeer vroeg geboren kinderen.

Door middel van cross-sectionele data analyses werden positieve interventie effecten

van het IBAIP op de cognitieve ontwikkeling gevonden op de gecorrigeerde leeftijd van



S

6 maanden en 5,5 jaar en op de motorische ontwikkeling op de gecorrigeerde leeftijd

van 6, 12 and 24 maanden en 5,5 jaar. Deze benadering geeft echter geen inzicht in de

individuele ontwikkelingsveranderingen over de tijd en zover wij weten, zijn er geen

longitudinale data analyses van vroeg interventie studies uitgevoerd. Het doel van de

studie in hoofdstuk 6 was dan ook het onderzoeken van de longitudinale effecten van

het IBAIP op de cognitieve en motorische ontwikkeling over de periode van 6 maanden

tot en met 5,5 jaar.

Longitudinale data werden geanalyseerd in de totale groep van 176 zeer vroeg

geboren kinderen en in 3 subgroepen van kinderen met een biologische risicofactor of

omgevingsrisico of een combinatie van deze risicofactoren. De cognitieve en motorische

ontwikkeling werd op de gecorrigeerde leeftijd van 6, 12 en 24 maanden onderzocht

met de BSID-II-NL en op de gecorrigeerde leeftijd van 5,5 jaar met de WPPSI-III-NL en

MABC-2.

Er werd een positief longitudinaal interventie effect op de motorische ontwikkeling

gevonden maar niet op de cognitieve ontwikkeling. In de subgroep van zeer vroeg geboren

kinderen met BPD werd een interventie effect op zowel de cognitieve (effect=0.7SD) als

motorische (effect=0.9SD) ontwikkeling over de tijd gevonden. Het opleidingsniveau van

de moeder beïnvloedde nauwelijks de interventie effecten over de tijd maar bij kinderen

met de combinatie van biologische en omgevingsrisico’s werd een positief effect op de

cognitieve ontwikkeling (effect=0.8SD) gevonden. We concludeerden dat het IBAIP de

motorische ontwikkeling van zeer vroeg geboren kinderen over de tijd verbeterd en dat

in het bijzonder zeer vroeg geboren kinderen met BPD van de interventie profiteren

zowel op het cognitieve als motorische domein van de ontwikkeling.

In hoofdstuk 7 worden de belangrijkste bevindingen van de studies in dit proefschrift

bediscussieerd. De gebruikte methode wordt besproken en de implicaties voor de

klinische praktijk en perspectieven voor de toekomst worden geformuleerd.

In onze zoektocht naar kennis over optimale ontwikkelingsgerichte zorg en

ondersteuning aan zeer vroeg geboren kinderen en hun ouders, bleek dat het IBAIP

effectief de ontwikkeling van deze kwetsbare kinderen verbetert op de leeftijd van 5,5

jaar en over de tijd. We hebben echter geen positieve interventie effecten op het gedrag

aangetoond en er is geen significante verbetering van de cognitieve ontwikkeling over

de tijd.

De volgende klinische implicaties werden geformuleerd.

(1) Aangezien de zelfregulatie van een kind een sleutelrol speelt in de cognitieve en

motorische ontwikkeling en het gedrag, wordt aanbevolen om de IBA te gebruiken naast

de bestaande neurologisch en functionele ontwikkelingsinstrumenten. (2) De AIMS is

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zeer waardevol om de motorische ontwikkeling van zeer vroeg geboren kinderen van

0 tot 18 maanden te evalueren en zou aan het neonatale follow-up protocol moeten

worden toegevoegd. (3) Op 5 jarige leeftijd neemt de complexiteit van taken toe en

gaat de verwerkingssnelheid een belangrijkere rol spelen. Het is daarom belangrijk als

een zeer vroeg geboren kind met motorische problemen wordt doorverwezen voor

onderzoek of therapie, aandacht te besteden aan mogelijke neurologische dysfuncties,

een laag IQ, een lage verwerkingssnelheid of aandachtsproblemen. (4) Een uitbreiding

van de duur van het IBAIP zal mogelijk tot een verdere verbetering van de cognitieve

ontwikkeling leiden als die uitbreiding plaats vindt in de sensitieve periode voor de

cognitieve ontwikkeling van het brein. (5) Uitbreiding van het interventie programma

met een psycholoog kan zinvol zijn voor het verminderen van de gedragsproblemen en

ook om kinderen met laag opgeleide moeders beter te kunnen begeleiden.

De volgende suggesties voor toekomstig onderzoek zijn geformuleerd.

(1) Validatie van de IBA in andere populaties en met andere leeftijden is gewenst. (2)

Vervolg onderzoek is nodig om een set van ontwikkelingsinstrumenten te ontwikkelen

die longitudinaal zowel de cognitieve als motorische ontwikkeling en het gedrag van

zeer vroeg geboren kinderen kunnen evalueren. (3) De resultaten van de studies naar de

effecten van het IBAIP hebben geleid tot het implementeren van een vroeg interventie

programma in Nederland. Evaluatie van de uitkomsten van het zo genoemde ToP

programma moet aangeven of een uitbreiding van de duur van de interventie en het

toevoegen van psycho-educatie aan IBAIP getrainde kinderfysiotherapeuten leidt tot

een verdere verbetering van de ontwikkelingsgerichte zorg en ondersteuning van zeer

vroeg geboren kinderen en hun ouders. (4) Verder onderzoek is gewenst om te bepalen

of ook in andere populaties van kinderen met biologische en/of omgevingsfactoren die

een verhoogde risico geven op ontwikkelingsproblemen, de sensitieve-responsiviteit

van ouders en de mate van zelfregulatie van kinderen, sleutel elementen zijn om de

ontwikkeling te verbeteren en ondersteunen.

List of contributing authors

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138 | List of contributing authors


List of contributing authors | 139

L

List of contributing authors

Christiaan J.A. Geldof, MSc Rebecca Holman, PhD

Department of Clinical Neuropsychology Clinical Research Unit

VU University University of Amsterdam

Amsterdam, the Netherlands. Amsterdam, the Netherlands

Martine Jeukens-Visser, PhD Joke H. Kok, MD, PhD

Department of Rehabilitation Department of Neonatology

Academic Medical Center Emma Children’s Hospital

Amsterdam, The Netherlands Academic Medical Center

Amsterdam, The Netherlands

Karen Koldewijn, PhD Frans Nollet, MD, PhD

Department of Rehabilitation Department of Rehabilitation

Academic Medical Center Academic Medical Center

Amsterdam, The Netherlands Amsterdam, The Netherlands

Eva S. Potharst, PhD Loekie Van Sonderen, MD

Psychosocial Department Department of Neonatology

Emma’s Children’s Hospital Emma’s Children’s Hospital

Academic Medical Center Academic Medical Center

Amsterdam, The Netherlands Amsterdam, The Netherlands

Aleid G. Van Wassenaer-Leemhuis, MD, PhD Marie-Jeanne Wolf, PhD

Department of Neonatology Department of Rehabilitation

Emma’s Children’s Hospital Academic Medical Center

Academic Medical Center Amsterdam, The Netherlands

Amsterdam, The Netherlands

Dankwoord

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142 | Dankwoord


Dankwoord | 143

D

Dankwoord

Mijn promotie-traject is een bijzondere reis geworden. Het begon met het uitstippelen

van de route, het halen van de juiste reispapieren en een sprong in het diepe. Eenmaal

onderweg waren er vele nieuwe ervaringen en leermomenten, bijzondere ontmoetingen,

hoogte- en dieptepunten, wachtijden en kwesties van volhouden en kilometers maken.

Om vervolgens te kunnen genieten van nieuwe in(uit)zichten en overwachte richtingen.

Aangekomen op mijn eindbestemming wil ik iedereen bedanken die mij kortere of

langere tijd op deze reis hebben vergezeld. Zonder jullie had ik dit proefschrift niet

kunnen schrijven oftwel deze reis kunnen voltooien.

“De ontdekkingsreizigsters”

Dr. M-J. Wolf en Dr. K. Koldewijn, Lieve Marie-Jeanne en Karen, jullie pionierswerk en

enthousiame ten aanzien van ontwikkelingsgerichte zorg voor prematuur geboren

kinderen en het starten van een effect onderzoek, hebben mij geïnspireerd om op een

andere manier naar ontwikkeling en interventie te gaan kijken. Ik wil jullie heel hartelijk

danken voor de bereidheid om jullie kennis en kunde te delen, alle deskundige adviezen

en warme, positieve support.

“De reisbegeleiding”

Prof. J.H. Kok en Prof. F. Nollet (promotoren) en Dr. A.G. Van Wasenaer-Leemhuis en

Dr. M. Jeukens-Visser (co-promotoren). Het hebben van 4 begeleiders uit 2 verschilende

windrichtingen (neonatologie en revalidatie) heeft geleid tot een kleurrijk landschap

aan wetenschappelijke interpretaties en scherpe, analytische, kritische vragen, met als

resultaat het steeds beter formuleren van de bevindingen. Joke, hartelijk dank voor je

zeer prettige manier van begeleiden, deskundige feedback en bereidheidheid mij te

ondersteunen op alle fronten van het promotie-traject. Frans, dank dat je voor paramedici

op de afdeling Revaldiatie de mogelijkheid hebt gecreërd om zich wetenschappelijk

verder te ontwikkelen en je scherpe, analytische blik en heldere commentaar bij het

schrijven van de manuscripten. Aleid, ik zie mezelf nog de eerste keer op je kamer zitten

met mijn verwachtingen en twijfels om deze reis te beginnen. Door je vertrouwen in mij

en je bereidheid om mijn co-promotor te worden, heb je een zeer grote bijdrage aan

mijn promotie geleverd. Mijn dank hiervoor is groot. Ik heb enorm veel van je geleerd.

Martine, ook jou ben ik veel dank verschuldigd voor alles wat je mij geleerd hebt, van het

voorbereiden van presentaties tot je onmisbare ondersteuning bij steeds ingewikkeldere

statistische analyses. Ondanks de toenemende drukte in je werk ten aanzien van het

vervolg traject van het prematuren onderzoek kon ik altijd bij je aankloppen. Ik zal onze

overleg momenten met een cappucino missen.

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144 | Dankwoord

“De overige expeditie leden”

Dr. L. Van Sonderen, Dr. E. Potharst en C. Geldof. Loekie, heel hartelijk dank voor de

zeer prettige samenwerking bij het data verzamelen, je bijdrage aan de artikelen en

je steun bij mijn eerste (poster)presentaties. Eva, jij ging mij voor in onze promotie-

avonturen. Hartelijk dank voor de gezellige lunches en fijne samenwerking tijdens het

PINO onderzoek. Christiaan, samen zijn we de rugzak van het STIPP-FOCUS project gaan

dragen. Hartelijk dank voor de fijne en leerzame samenwerking, de overlegmomenten

en het chaufferen tijdens onze dagtochten door het land. Veel succes met het afronden

van je eigen promotie-traject.

De leden van de beoordelingscommissie, bestaande uit Prof. J.G. Becher, Prof. M.A.

Grootenhuis, Prof. M.J. Jongmans, Prof. A.H.L.C. van Kaam, Prof. M.W.G. Nijhuis-van

der Sanden en Prof. J. Oosterlaan wil ik bedanken voor hun bereidwilligheid zitting

te nemen in de promotiecommissie en de tijd en aandacht die zij aan mijn proefschrift

hebben besteed.

“De bijzondere ontmoetingen”

Ik wil alle ouders en kinderen die participeerde in het onderzoek heel hartelijk danken

voor hun bereidwilligheid om 5 jaar na de interventie, weer naar het AMC te komen,

hun inzet ten behoefe van het onderzoek, openhartige verhalen en het enthousiame bij

het meedoen met alle “spelletjes”.

“De mede-reisgenoten”

Huub, Eric, Fieke, Alice, Irene en Saskia, bedankt voor de gezellige thee en koffiemomen-

ten in de onderzoekskamer, jullie hulp bij tal van kleine onderzoekshindernissen en

het kunnen stoom afblazen of delen in de successen. Ik wens jullie veel succes met

het voltooien van jullie eigen reis. Beste Gijs, jij hebt je reis een jaar eerder voltooid.

Aangezien we dezelfde groep onderzochten, had ons reisschema veel overeenkomsten

en konden we onze specifieke vragen samen bespreken. Dank hiervoor.

“De thuisblijvers”

Mijn collega’s in het kinderteam van de afdeling Revalidatie die het logistiek mogelijk

hebben gemaakt om mijn reis te voltooien. Lieve Wypke en Rob, mijn dank is groot voor

julle loyaliteit, het overnemen van vele klinische taken en jullie steun gedurende mijn

reis. Ook wil ik alle andere collega’s van het kinderteam en van de afdeling revalidatie

hartelijk danken voor jullie belangstelling in mijn onderzoek. Mariëlle, dank voor je

ondersteuning en het steeds weer zoeken naar mogelijkheden om deze reis tot een

goed einde te brengen.


Dankwoord | 145

D

“Het reisverslag”

En dan hebben we de foto’s nog. Annoek, heel hartelijk dank voor je tijd, creativiteit en

hulp bij het bewerken van de foto’s en de lay-out van de cover.

“Mijn trouwe metgezellen”

Familie en vrienden hebben geweten dat ik met een promotie-onderzoek bezig

was. Dank voor jullie opbeurende woorden, pep-talks, afleiding, belangstelling en

vanzelfsprekende steun de afgelopen jaren.

Lieve mam, heel veel dank voor de onvoorwaardelijke liefde, steun, stimulatie en

brede ontwikkeling die jij en pap mij hebben gegeven. Wat zou pap trots zijn geweest!!

Lieve Jacqueline en Ingrid, vriendinnen en fysiotherapeutische reisgenoten van het

eerste uur. Ik vind het geweldig dat jullie mijn para-nimfen willen zijn en veel dank voor

jullie onvoorwaardelijke steun. plezier en vriendschap de afgelopen (bijna) 30 jaar. Lieve

Meijer, mijn reismaatje voor het leven. Dank voor je liefde, steun, vertrouwen, humor en

relativering. Dat we nog maar vele mooie reizen mogen maken!

Appendix

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148 | Appendix


Appendix | 149

A

Appendix 1

List of Abbreviations

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152 | List of Abbreviations


List of Abbreviations | 153

L

List of abbreviations

ADHD Attention Deficit Hyperactivity Disorder

AIMS Alberta Infant Motor Scale

ANT Amsterdam Neuropsychological Test battery

APIP Avon Premature Infant Project

BPD Bronchopulmonary Dysplasia

BW Birth Weights

BSID-II/III-NL Bayley Scales of Infant Development, Dutch second/third edition

CA Corrected Age

CAP trial Caffeine in Apnea of Prematurity trial

CNS Central Nervous System

CP Cerebral Palsy

CPAP Continuous Positive Airway Pressure

CI Confidence Interval

ES Effect Size

GA Gestational Age

IBA© Infant Behavioral Assessment

IBAIP© Infant Behavioral Assessment and Intervention Program

IQ Intelligence Quotient

IVH Intraventricular Heamorrhage

LME Low Maternal Education

MABC-2 Movement Assessment Battery for Children, second version

mMITP modified version of the Mother-Infant Transaction Program

MND Minor Neurological Dysfunction

MR Multiple Risks

NICU Neonatal Intensive Care Unit

NIDCAP© Newborn Individualizes Developmental Care and Assessment Program

OR Odds Ratio

PDI Psychomotor Developmental Index (BSID-II)

PMA Post Menstrual Age

RCT Randomized Controlled Trial

ROP Retinopathy of Prematurity

SD Standard Deviation

SDQ Strength and Difficulties questionnaire

SE Standard Error

SES Social Economic Status

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154 | List of Abbreviations

ToP program Transmurale ontwikkelingsondersteuning voor Prematuur geboren

kinderen en hun ouders

VLBW Very Low Birth Weight

VMI Developmental test of Visual Motor Integration

VibeS-Plus Victorian Infant Brain Studies Plus

WPPSI-III-NL Wechsler Preschool and Primary Scale of Intelligence, Dutch third

version

Portfolio / Publications

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156 | Portfolio / Publications


Portfolio / Publications | 157

P

Portfolio / Publications

PhD student: Janeline W.P. van Hus

PhD period: December 2009 - December 2014

PhD supervisors: Prof. dr. J.H. Kok

Prof. dr. F. Nollet

PHD-TRAINING Year WorkloadHours/ECTS

GENERAL/ SPECIFIC COURSESInfant Behavioral Assessment and Intervention,Washington Research Institute and AMC

20022003 284 / 10

PubMed, AMC 2006 3 / 0.1Neurologisch Onderzoek van kinderen volgens Touwen,UMC Groningen

20072008 18 / 0.3

Reference Manager 2008 3 / 0.1The AMC World of Science, Graduate School for Medical Sciences, UVA Amsterdam 2009 20 / 0.7Clinical Epidemiology, Graduate School for Medical Sciences, UVA Amsterdam 2009 18 / 0.6Clinical Data Management, Graduate School for Medical Sciences, UVA Amsterdam 2009 22.5 / 0.7Practical Biostatistics, Graduate School for Medical Sciences, UVA Amsterdam 2010 40 / 1.1BSID-III-NL, Hogeschool van Utrecht 2012 7.5 / 0.3

SEMINARS, WORKSHOPS AND MASTER CLASSESMaster class: Sustained developmental effects of the IBAIP in VLBW infants at 5.5 years (oral), Amsterdam Kindersymposium, AMC en VU Amsterdam 2013 16 / 0.5

Lecture Neonatology: Van STIPP naar ToP. Van Interventie naar implementatie (oral), AMC Amsterdam 2014 16 / 0.5

Subtotal 448 / 14.9

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PRESENTATIONS

Research presentations, department of rehabilitation, AMC Neuromotor development in VLBW infants: a matter of attention of behavior (oral) 2009 14 / 0.5Motor impairment associated with developmental deficits in very preterm-born children at 5 years of age (oral) 2010 14 / 0.5First Results STIPP study follow-up 5.5 years (oral) 2011 14 / 0.5The IBAIP and the results in VLBW infants at 5.5 years (oral) 2012 14 / 0.5Motor impairment in very preterm born children: links with other developmental deficits at 5 years of age (oral) 2013 14 / 0.5Longitudinal developmental effects of the Infant Behavioral Assessment and Intervention Program in very low birth weight infants (oral) 2014 14 / 0.5

Research presentations, department of neonatology, AMCComparing motor outcome of two instruments in a neurobehavioral intervention program in VLBW infants at 1 year corrected age (oral) 2010 12 / 0.4

First Results STIPP study follow-up 5.5 years (oral) 2011 12 / 0.4Sustained developmental effects of the IBAIP in VLBW infants at 5.5 years (oral) 2012 14 / 0.5Motor impairment in very preterm born children: links with other developmental deficits at 5 years of age (oral) 2013 12 / 0.4

Plenary sessions study groupSTIPP-FOCUS 5.5 years: test-instruments (oral) 2009 16 / 0.6STIPP 12 months: Clinimetry IBA (oral) 2009 16 / 0.6STIPP-FOCUS 5.5 years: Framework and Protocol (oral) 2009 16 / 0.6STIPP-FOCUS 5.5 years: Protocol and State of affairs (oral) 2010 16 / 0.6

Subtotal 198 / 7.1



P

(Inter)national conferences

EKZ Scientific Symposium, Amsterdam. (Poster: A neurobehavioral intervention program in VLBW infants: comparing motor outcome at 1 year CA, using 2 instruments 2011 14 / 0.5

International WCPT Congress, World Physical Therapy 2011,Amsterdam. (Poster: Reliability, sensitivity and responsiveness of the IBA in very preterm infants) 2011 14 / 0.5

20th anniversary conference Dutch Neonatal Follow-up working group, (LNF). (Poster: Developmental effects of the IBAIP in VLBW infants at 5.5 years) 2012 14 / 0.5

4th Congress of the European Academy of Pediatric Societies (EAPS), Istanbul. (Poster: Sustained developmental effects of the IBAIP in VLBW infants at 5.5 years) 2012 14 / 0.5

Pediatric Academy Societies (PAS), annual congress, Washington DC. (Poster: Motor impairment and it’s association with Neurological, Cognitive, Neuropsychological and Behavioral disabilities in Very Preterm children at 5 years of age 2013 14 / 0.5

Amsterdam Kindersymposium, Academic pediatric departments VUmc and AMC, Amsterdam. (Poster: Sustained developmental effects of the IBAIP in VLBW infants at 5.5 years) 2013 14 / 0.5

5th symposium , Dutch Neonatal Follow-up working group, (LNF),Radboud University Nijmegen. (Oral: Longitudinal developmental effects of the IBAIP in VLBW infants) 2014 14 / 0.5

Pediatric Academy Societies (PAS), annual congress, Vancouver. (Poster: Motor impairment and it’s association with Neurological, Cognitive, Neuropsychological and Behavioral disabilities in Very Preterm children at 5 years of age 2014 14 / 0.5

5th Congress of the European Academy of Pediatric Societies (EAPS), Barcelona. (Oral: Longitudinal developmental effects of the IBAIP in very preterm-born infants) 2014 14 / 0.5

Subtotal 126 / 4.5

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Attended (Inter)national conferencesCongress Impact of Intervention: “Can we effect typical and atypical development of human brain? UMCG, Groningen 2010 18 / 0.63rd Symposium Dutch Neonatal Follow-up working group (LNF), AMC Amsterdam 2011 8 / 0.3Conference Ultra-early intervention. Karolinska University, NICAP Training Center, Stockholm 2012 8 / 0.3Congress Mastery of manual skills, Recent insights into typical and atypical development of manual ability, UMCG, Groningen 2012 8 / 0.3

TEACHINGPediatric rehabilitation for medical students, University of Beira (Mozambique) 2008 20 / 0.7IBA training assistant, AMC Amsterdam 2009 3 / 0.1 Clinical neurobehavioral care for nurses. Clinical department pediatric and pediatric surgery, AMC Amsterdam 2009 18 / 0.6IBA training assistant, AMC Amsterdam 2010 3 / 0.1Clinical neurobehavioral care for nurses. Clinical department pediatric and pediatric surgery, AMC Amsterdam 2010 18 / 0.6Clinical neurobehavioral care for nurses. Clinical department pediatric and pediatric surgery, AMC Amsterdam 2011 18 / 0.6Clinical neurobehavioral care for nurses. Clinical department pediatric, AMC Amsterdam 2012 18 / 0.6

PARAMETERS OF ESTEEM

Best poster presentation Amsterdam Kindersymposium, Academic pediatric departments VUmc and AMC, Amsterdam, Award: Publication in Nederlands Tijdschrift voor Kindergeneeskunde 2014

Subtotal 140 / 4.8

TOTAL 912 / 31.3



P

PUBLICATIONS

Van Hus JWP. De tiende hersenzenuw en de emotie van allergische astmatici. Fysiocoop

1988;14:9-11.

Koldewijn K, Van Hus JWP, Van Wassenaer AG, Jeukens-Visser M, Kok JH, Nollet F, Wolf

M-J. Reliability, sensitivity and responsiveness of the Infant Behavioral Assessment in very

preterm infants. Acta Peadiatr 2012;110:258-63

Potharst ES, Van Wassenaer A, Houtzager B, Van Hus JWP, Last BF, Kok JH. High

incidence of multi-domain disabilities in very preterm children at 5 years of age. J Pediatr

2011;159:79-85

Van Hus JWP, Jeukens-Visser M, Koldewijn K, Geldof CJA, Kok JH, Nollet F, Van Wassenaer-

Leemhuis AG. Sustained developmental effects of the Infant Behavioral Assessment

and Intervention Program in very low birth weight infants at 5.5 years corrected age. J

Pediatr 2013;163:1112-9.

Van Hus JWP, Jeukens-Visser M, Koldewijn K, Van Sonderen L, Kok JH, Nollet F,

Van Wassenaer-Leemhuis AG. Comparing two motor assessment tools to evaluate

neurobehavioural intervention effects in very low birth weight infants at 1 year. Phys

Ther 2013: 93:1475-83.

Van Hus JWP, Potharst ES, Jeukens-Visser M, Kok JH, Van Wassenaer-Leemhuis AG. Motor

impairment in very preterm born children: links with other developmental deficits at 5

years of age. Dev Med Child Neurol 2014;56;587-594

Van Hus JWP, Jeukens-Visser M, Van Wassenaer-Leemhuis AG, Koldewijn K, Meijssen DE,

Verkerk G, Van Baar AL, Nollet F, Kok JH, Wolf M-J. Het STIPP-onderzoek; Een RCT naar

het effect van een vroeginterventie bij zeer vroeg geboren kinderen op de ontwikkeling

van het kind, het welbevinden van de ouder en de ouder-kindinteractie. Tijdschr

Kindergeneeskd 2014;82:94-105.

VERDEDIGING

Hierbij bent u uitgenodigd voor de openbare verdediging

van het proefschrift van Janeline W. P. Van Hus


neurobehavioral intervention in very

preterm-born children

Op vrijdag 5 december 2014om 10.00 uur

in de Agnietenkapel van de Universiteit van AmsterdamOudezijds Voorburgwal 231

1012 EZ Amsterdam

Janeline Van HusVrolikstraat 337C

1092 TA [email protected]

06 20 34 42 22

PARANIMFENIngrid Hofsteede

[email protected] 15 61 84 37

Jacqueline [email protected]

06 40 14 08 47

RECEPTIETer plaatse na afloop van de verdediging



Janeline van Hus werd geboren op 23 januari 1963 te Amsterdam. Na het behalen van haar HAVOdiploma aan de Chr. Scholengemeenschap “Buitenveldert” te Amsterdam in 1981, volgde zij de opleiding Fysiotherapie bij Stichting Academie voor Paramedische Beroepen ‘Leffelaar’, waar zij in 1985 met lof afstudeerde. Janeline’s eerste publicatie ‘De tiende hersenzenuw en de emotie van allergisch astmatici’ vloeide voort uit haar eindexamen scriptie en grote interesse in de ontwikkeling van kinderen. Janeline startte haar loopbaan in het Pediatric Rehabilitation Hospital and Center for severely handicapped children ‘Alyn’ te Jeruzalem (Israël) en het Universitätsspital “Inselspital” te Bern (Zwitserland), waar zij haar eerste ervaringen als kinderfysiotherapeut opdeed. In 1989 trad Janeline in dienst bij het Revalidatiecentrum ‘Rijndam-Adriaanstichting’ te R’dam, waar zij zich met veel plezier 12 jaar lang alle ins en out van de kinder-revalidatie eigen maakte, vele opleidingen en cursussen volgden en in 1997 haar registratie kinderfysiotherapie behaalde. Naast haar werk zette zij zich in voor korte ontwikkelingsprojecten in Thailand en Mozambique op het gebied van onderwijs en kinderrevalidatie. In 2000 maakte Janeline de overstap naar de afdeling Revalidatie van het Academisch Medisch Centrum te A’dam waar zij zich bezig houdt met de klinische kinder-fysiotherapeutische zorg. Geïnspireerd door het neurologisch gedragsonderzoek bij het prematuur geboren kind, volgde Janeline in 2002-2003 de IBAIP opleiding en participeerde in een effect onderzoek. Dit resulteerde in 2009 tot het opzetten van een vervolgonderzoek, beschreven in dit proefschrift. Tijdens het onderzoekstraject schoolde Janeline zich in epidemiologie, statistiek en klinisch data management aan de AMC Graduate School forMedical Science. Janeline is getrouwd met haar grote liefde Meijer die ze tijdens het uitvoeren van haar 3 passies; reizen, bergwandelen en fotografie, in 2006 in Patagonië ontmoette.



Academisch proefschriftUniversiteit van Amsterdam

Cover statue Tom Otterness ‘Sprookjesbeelden aan Zee’ Scheveningen 2012Cover design Annoek Louwers Janeline van HusPhotography Janeline van HusLay out & print Gildeprint, Enschede

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