WHAT IS NEXT FOR PRETERM INFANTS?

Melissa R. Johnson, Ph.D. WakeMed

November 2008

DEVELOPMENTAL CHALLENGES

Medical Social Environmental

MEDICAL ISSUES

Respiratory issues» Respiratory Distress Syndrome (RDS)

» Chronic Lung Disease (CDL)

» Bronchopulmonary Dysplasia (BPD)

» Pneumothorax

NEUROLOGIC ISSUES

Intraventricular hemorrhage (IVH)» Grades I-IV (some don’t use)» Outcome NOT certain

Periventricular leukomalacia (PVL) Very worrisome but NOT certain- symmetry

matters Hypoxic-ischemic encephalopathy (HIE) Cerebral palsy (CP) / Chronic encephalophy

VISUAL ISSUES

Retinopathy of prematurity (ROP)» Cause still debated

» Therapies still improving

» Close follow-up often critical

Other medical issues

Necrotizing enterocolitis (NEC) Other infections Other causes of prolonged illness, poor

nutrition

PSYCHOSOCIAL CHALLENGES

Poverty and other chronic stressors Substance abuse Maltreatment history in family of origin Domestic violence Parental mental illness

Attachment difficulties Other family and community stresses

– Child care– Siblings– Language– Transportation– Education

ENVIRONMENTAL CHALLENGES

NICU environment» Sound, light, handling, positioning, parental

access Loss of expected environment for brain

development

DEVELOPMENTAL TRENDS IN OUTCOME

Literature keeps growing Babies are surviving smaller, younger Doctors have more tools to help

» High frequency ventilators, better CPAP

» Artificial surfactants

» Better nutrition strategies

A look at the research

Complicated, but still helpful Rapidly evolving Variability- numbers, SES, percent

followed, location, size at birth, age at follow-up, source of FU info, control group, etc etc etc

Below: a few of best studies from 90’s and some from 2000-2008

20 MO. OUTCOME OF ELBW

114 premies from 500-750 g Born 1990-1992; compared to 82-88 Survival from 600-700 grams

increased from 23% to 43% 20% MDI <70, 10% CP

– Hack et al, JAMA vol. 276, 1996

PATTERNS OF COGNITIVE DEVELOPMENT

Looked for patterns - under 1500 g N=203 to age 6

37% stayed in average range 42% declined from average to below

average- mostly after age 2 Only 8% improved

– Koller et al, Pediatrics vol 99, 1997

ELBW OUTCOME AT 8 YEARS

156 survivors 501-1000 compared to matched controls in Ontario, CN

Used multiattribute health status classification

14% had no functional limitation; 58% had reduced function in one or more areas; 28 % had three areas affected. Controls: 50%, 48%, 2%

Areas most likely to be affected: cognition, sensation

– Saigal et al, J. Peds, vol 125, 1994

ELBW BEHAVIORAL OUTCOME AT 8 YEARS

81 survivors 800 g or less; matched controls

Lower global IQ’s, fm skills Trouble with persistence, easily

discouraged, needed much adult support and approval

“Subtle organizing problems”» Grunau (quoted in Aug 1995 Peds News)

MATERNAL COMPLIANCE AND OUTCOME

152 infants under 1000 g; 110 compliant, 42 noncompliant w/ EI fu

MDI scores: compliant = 75.59 noncompliant = 68.24

PDI scores: compliant = 82.97 noncompliant = 74.54

– Bonnet et al, Pediatrics supplement, 1998

ELBW OUTCOME AT 18 MO.

1151 babies 401-1000 g. Only 1/3 under 900 g had MDI >85 60% 901-1000 g > 85 Neuro exams, walking, etc better Best predictors: IVH, BPD, family ed

– Vohr et al, SPR abstract, 1998

OUTCOME FOR SWEDISH ELBW CHILDREN

633 babies followed prospectively survival over 23 wks- 59% 362 assessed at 36 mo 25 had CP, 16 blind 86 % functionally nl- range from 69 %

for 23-24 wks to 91 % for >27 wks– Finnstrom et al, Acta Paediatrica 1998

SCHOOL-AGE OUTCOME

68 <750 g; 65 between 750-1499 g Neonatal risk index predicted outcome

better than social risk index (surprise) but proximal social risk more sig.

Of hi NRI kids, only 15 % had IQ >85 Of lo NRI kids, 33 % had IQ > 85 38/26 % had behavior problems

– Taylor et al, Devel. & Behav Peds, 1998

UNDER 801 G- AGE 5 OUTCOME

Compared survivors from ‘83-’85 vs ‘86-’89 (% survival the same- more under 600 g)

No sig. difference between cohorts 21% had severe disabilities Sig. factors: ICH and SES

– Kilbride & Daily, J. Perinatology, 1998

OUTCOME FOR 12 YO VLBW CHILDREN

138 children under 1250 g and 93 under 1500 g born from ‘80-83 (UK)

Compared to matched controls, 8 pts lower IQ- mainly due to Performance .

12% of VLBW and 7% of controls below 70. Gaps widened from age 6 to 12.

35% of VLBW needed remediation (12% of controls)

– Botting et al, Devel Med Child Neuro, 1998

TEEN SCHOOL OUTCOMES

150 500-1000 g survivors, controls Born 1977-1982 Neurosensory impairments in 28 % of

ELBW, 1% of controls Mean IQ = 89 Spec. Ed or retained: 58 % vs. 13 %

Saigal et al, Peds, 2000

OUTCOME FOR ELBW TODDLERS

1151 4001-1000 g survivors in NICH network, seen at 18-22 mo, b. 1993-1994 (78%) f/u

25 % had abnl neuro exam 37 % Bayley II MDI < 70 29 % Bayley II PDI , 70 9 % vision impairment 11 % hearing impairment

» Vohr et al, Pediatrics, 2000

MORE ELBW TODDLERS

Born 92-95, seen at 20 mo 24 % major abnormalities 42 % Bayley II MDI , 70 Neurosensory abnormalities and/or low

MDI = 48 %» Hack et al, Seminars in Neonat, 2000

SWEDISH LBW OUTCOME AT 10

61 of 65 10 y.o. survivors b. at under 29 wks compared to controls (b. 85-86)

Mean IQ of preterms = 90; controls = 106

38 % of preterms below grade level 32 % had behavior problems; 10 % of

controls

20 % had ADHD, 8 % of controls 30 % in SE, 1.6 % of controls

» Sternqvist, Ab Initio Intl, 2001-2002

www.childrenshospital.org/brazelton/abinitio/art2.html

VLBW OUTCOME AT 20

242 survivors from 1977-1979 , controls HS grads: 74 % of preterms, 83 % of

controls Men, but not women, less likely to

continue studies 10% had neurosensory impairments; 1 % of controls

Preterms had lower rates of ETOH, drugs, pregnancy, even without impaired group.» Hack et al, NEJM, 2002

15 YR F/U OF PRETERMS AFTER SURFACTANT

< 29 wks b. 1985-87 followed at 7 and 14 (126/132)

At 7, 31 % nonimpaired; 21 % severe impairment; 32 % in self-contained SE

19 % CGI < 70; 15 % CP

As teens, CP same; 29 % SE; 19 % had 1 severe disability; 41 % had no impairment.

Conclusion: even with surfactant, sig minority will have ongoing compromise

D’Angio, Pediatrics, Dec. 2002

Chance for improvement?!

Longitudinal data on PPVT-R on 296 children under 1250 g

Scores increased from 88 at 36 months to 99 at 96 months; similar for IQ verbal and FS scores

Mat ed and 2 parents helped NOT for children with worse IVH

» Ment et al., 2003

Academics at ages 11 and 17

Detroit area preterm children tested on Woodcock-Johnson

3-5 point deficits independent of family factors and urban/suburban

At 17, preterms 50% more likely to score below the mean in both reading and math ; cog deficits noted at age 6

Breslau, Paneth & Lucia, 2004

ELBW infants with NL HUS

Babies born ‘95-’99 under 1000 g with NORMAL head ultrasounds

Nearly 30% had either CP or MDI ↓ 70 Lung problems (pneumothorax, long

vent) and low SES were related» Laptook et al, 2005

Behavioral outcomes

Large French study compared preterm to term children at age 3

Preterms had much higher levels of behavior problems; Children in “high” total range- 20% of preterms, 9% of term.» Delobel-Ayoub et al, 2006

Emotional regulation and development

ER scale from Bayley II: attention, frustration tol, coop, activity, hypersensitivity

Income and ER influenced MDI Poorer ER associated with lower MDI

even controlling for income» Lowe, Woodward & Papile, 2005

Outcome for families

Study of impact of ELBW birth on families at school age

Impact greater in ELBW than controls High parent/SES risk, neurodevel

outcome, and functional impact of chronic conditions predicted greatest family impact» Drotar et al, 2006

NEC and development

Babies under 1000 g vs controls More babies with NEC had lowered PDI Entire preterm group had lower MDI

compared to controls» Salhab et al., 2004

Infections and development

Multicenter study of children under 1000 g

Infections predicted more CP, lower MDI and PDI scores, and more vision impairment» Stoll et al, 2004

How many domains?

Under 30 week sample of 157 children seen at age 5 (Dutch)

39% “normal” 17% single disability 44% multiple disabilities

» Van Baar et al., 2005

8 year f/u of under 1000 g

Born ‘92-’95, 219 children, controls Need for services: 65% vs 27% Functional limitations: 64% vs 20% CP 14% vs 0, IQ ↓ 85 38% vs 14% Sig impact on motor skills, academics,

adaptive, health» Hack et al, 2005

What about bigger premies?

Study of 32-33, 34-36, and term babies Followed K-5 Bigger premies had a range of

academic delays compared to term; more special ed, more teacher concerns» Chyi et al, 2008

Prematurity and later mental health

F/U to teens of non-handicapped preterms- increase in psych sx, esp anxiety and depression (Schothorst et al, 2007)

Lg group in adulthood- increased depression (Nokumura et al, 2007)

LBW predicted depression in NC teen girls, not boys (Costello et al, 2007)

BUT some GOOD news

Compared group of 501-1000 g with term births at ages 22-25 (Canada)

90% follow up Similar % grad HS (82-87%) 33-34% in post-secondary ed Except for disabled, similar % working or in

school, living on own, married, parents» Saigal et al, 2006

WHAT WE DON’T KNOW AND WHY

Why disability rates have stayed high How any individual baby will do, as

specifically as families need For certain, what interventions are most

effective, when and why

WHY SO HARD TO ANSWER?

Research varies as to age and size group, timing of follow-up, size of N, use of controls, % followed, instruments used, definitions

Research published now based on babies born several years ago

Interaction of medical, social and environmental variables

Inconsistency of early intervention Inconsistency of special ed eligibility,

definitions and services

CONCLUSION: THESE BABIES ARE SPECIAL. LET’S OFFER AS MUCH HELP AS POSSIBLE!