Five-Year Neurodevelopmental Outcome of Neonatal Dehydration

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Five-Year Neurodevelopmental Outcome of Neonatal Dehydration

GABRIEL J. ESCOBAR, MD, PETRA LILJESTRAND, PHD, ESTHER S. HUDES, PHD, DONNA M. FERRIERO, MD, YVONNE W. WU, MD, MPH,RITA J. JEREMY, PHD, AND THOMAS B. NEWMAN, MD, MPH

bjective To determine the long-term outcome of neonatal dehydration.

tudy design We identified 182 newborns who were rehospitalized with dehydration (weight loss >12% of birth weightnd/or serum sodium >150 mEq/L) and 419 randomly selected controls from a cohort of 106,627 term and near-term infantsith birth weight >2000 g born between 1995 and 1998 in northern California Kaiser Permanente hospitals. Outcomes dataere obtained from electronic records, interviews, questionnaire responses, and neurodevelopmental evaluations performed

n a masked fashion.

esults Follow-up data to age at least 2 years were available for 173 of 182 children with a history of dehydration (95%) and72 of 419 controls (89%) and included formal evaluation at a mean age (�standard deviation) of 5.1 � 0.12 years for 106hildren (58%) and 168 children (40%), respectively. None of the cases developed shock, gangrene, or respiratory failure.either crude nor adjusted scores on cognitive tests differed significantly betweenroups. There was no significant difference between groups in the proportion of childrenith abnormal neurologic examinations or neurologic diagnoses. Frequencies of paren-

al concerns and reported behavior problems also were not significantly different in thegroups.

onclusions Neonatal dehydration in this managed care setting was not associatedith adverse neurodevelopmental outcomes in infants born at or near term.J Pediatr 2007;151:127-33)

ong-term outcomes of neonatal dehydration, which in developed nations usuallyresults from problems with establishing breast-feeding, are not known. Recentstudies have reported rehospitalization for neonatal dehydration in 0.25 to 5.9 of

000 live births.1-6 Estimates of the risk of the long-term consequences of neonatalehydration are based on either catastrophic cases7 or the outcomes of hypernatremia afteriarrheal dehydration. Infants with diarrheal dehydration have high rates (8% to 16%) of

ong-term neurologic damage.8-11 In developed nations, neonatal dehydration is likely toevelop more slowly than diarrheal dehydration, because it is most often due to insuffi-ient fluid intake and/or abnormally high levels of sodium in breast milk.12-15 For thiseason, long-term sequelae of neonatal dehydration in developed nations may be lessrequent or less severe than previous case series suggest.

In this report, we focus on nondiarrheal neonatal dehydration. We studied a cohortrom the northern California Kaiser Permanente Medical Care Program (KPMCP), aature managed care organization with integrated information systems.6,16-20 Given the

athophysiology of dehydration, which does not appear to affect any one particular partf the brain, we did not expect to find discrete neurologic deficits among our cohort;ather, we expected to find nonspecific neurodevelopmental problems affecting multipleomains (ie, decreases in performance across multiple areas measured).

BCL Child Behavior ChecklistI Confidence interval

CD International Classification of DiseasesIFee Juvenile and Infant Feeding StudyPMCP Kaiser Permanente Medical Care Program

PEDS Parent Evaluation of Developmental StatusVMI-4 Beery-Buktenica Developmental Test of

Visual-Motor Integration, fourth editionWPPSI-R Wechsler Preschool and Primary Scale of

Intelligence, revised

See editorial, p 110

From the Division of Research, PerinatalResearch Unit, Kaiser Permanente MedicalCare Program, Oakland, CA (G.E., P.L.,T.N.); Department of Inpatient Pediatrics,Kaiser Permanente Medical Center, WalnutCreek, CA (G.E.); and Departments of Ep-idemiology and Biostatistics (P.L., E.H.,T.N.), Neurology (D.F., Y.W.), and Pediat-rics (D.F., Y.W., R.J., T.N.), University ofCalifornia San Francisco, San Francisco, CA.

Supported by National Institute of Neuro-logical Diseases and Stroke grant RO1NS39683 and National Institutes of HealthPediatric Clinical Research Center grantM01 RR01271. Through the peer reviewprocess and occasional consultations withthe project officer, the funding agenciesprovided some guidance in the design andconduct of the study but did not participatein collection, management, analysis, or in-terpretation of data or in preparation, re-view, or approval of the manuscript.

Presented in part at the Pediatric AcademicSocieties Meeting, San Francisco, California,May 2, 2004 and at the American Academyof Pediatrics Annual Meeting, San Francisco,October 9, 2004.

Submitted for publication Oct 10, 2006;last revision received Feb 8, 2007; acceptedMar 2, 2007.

Reprint requests: Dr Gabriel J. Escobar, Di-vision of Research, Perinatal Research Unit,Kaiser Permanente Medical Care Program,2000 Broadway, 2nd floor, Oakland, CA94612. E-mail: [email protected].

0022-3476/$ - see front matter

Copyright © 2007 Mosby Inc. All rightsreserved.

PC Motor Performance Checklist
10.1016/j.jpeds.2007.03.009
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METHODSThis report covers 2 of the 3 cohorts in the Jaundice and

nfant Feeding (JIFee) study, a follow-up study of infantsith neonatal jaundice or dehydration and randomly selected

ontrols. We identified subjects born in 1995 to 1996 inrevious nested case-control studies.6,19,21 Study participantsere drawn from KPMCP live births between 1995 and 1998

n � 106,627) with birth weight of at least 2000 g andestational age of at least 36 weeks (1995-96 birth cohort) or4 weeks (1997-98 birth cohort). Eligible subjects had toeet the dehydration definition given below (cases) or were

andomly selected from the 1995-96 and 1997-98 birth co-orts (controls) (Figure). We excluded subjects who had diedn � 1), whose primary care provider declined contact (n �), or who were diagnosed with a genetic or congenitalisorder likely to affect neurodevelopment (n � 20). Out-omes in the hyperbilirubinemia cohort have been reportedreviously.22 The study was approved by the institutionaleview boards for the Protection of Human Subjects of thePMCP, the University of California San Francisco, and thetate of California. Parents or guardians provided written

nformed consent for examinations.

efinition of DehydrationMacaulay’s studies8,9 defined hypernatremia as serum

odium level �150 mEq/L, while Maisels’ work supports the

igure. Selection, enrollment, and follow-up of the study subjects. See the

otion that losing �12% of birth weight is excessive.23 To be p

28 Escobar et al

ncluded as a case in our study, infants had to meet theollowing criteria: (1) rehospitalization within 15 days ofischarge from the birth hospitalization, (2) diagnosis ofehydration by the treating physician, and (3) weight loss12% of birth weight or serum sodium level �150 mEq/L.o identify possible cases, we scanned the KPMCP hospital-

zation database for the following International Classificationf Diseases (ICD)24 diagnosis codes: 276.0 (hyperosmolalitynd/or hypernatremia), 276.5 (volume depletion), 276.9electrolyte and fluid disorders not elsewhere classified), 775.5other transient electrolyte disturbance), 778.4 (disturbancesf temperature regulation, which includes dehydration fever),79.3 (feeding problems), 783.2 (abnormal weight loss),83.3 (feeding difficulties/mismanagement), 784.4 (lack oformal physiologic development), 785.50 (shock, unspeci-ed), and 785.59 (shock, other).

redictor VariablesWe obtained perinatal data on eligible subjects from

others’ and infants’ medical records6,21 and additional datan potential confounding variables from caregivers, includingssessment of parental depression using the Center for Epi-emiologic Studies Depression Scale,25 a 20-item self-admin-stered questionnaire designed for screening for depression inhe general population; higher scores indicate increased pres-nce of symptoms. We used birth certificate data to categorize

or a complete description of dehydration criteria.

arent race and education (linked for 96%) and 2000 US

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ensus data on median household income in census tractslinked for 95%) when these variables were missing fromuestionnaires.

OUTCOME VARIABLES

verviewNeurodevelopmental evaluations were performed at a

ean age of 5.1 years by examiners masked to study group.arents who declined formal evaluations were provided auestionnaire-only study option. We also searched KPMCPlectronic records for the following ICD neurologic diagnosisodes: 320 to 360 (nervous system disorders); 378 to 378.9strabismus); 389.1 and 389.2 (hearing loss); 773.4 and 774.7kernicterus); 780.5 (sleep disturbance); 781, 781.2, 781.3,nd 781.9, (movement, gait, coordination, or posture prob-ems); 794 to 794.19 (abnormal brain imaging); and 796.1abnormal reflexes).

eurodevelopmental EvaluationsLicensed child psychologists administered the Wechsler

reschool and Primary Scale of Intelligence-RevisedWPPSI-R)26 and the Beery-Buktenica Developmental Testf Visual-Motor Integration-fourth edition (VMI-4).27 Childeurologists and a child neurology clinical nurse specialist (2xaminations) conducted standard neurologic examinationsnd entered an overall impression on a 5-point scale: 1,normal;” 2, “normal/questionable;” 3, “abnormal with mini-al functional disability;” 4, “abnormal with moderate func-

ional disability;” and 5, “abnormal with severe functionalisability.” To maximize sensitivity, neurologists were in-tructed to select “normal/questionable” for anything slightlyuspicious on examination. Research assistants assessed motorkills using the Motor Performance Checklist (MPC), a val-dated 12-item screening instrument that includes items suchs throwing a ball and putting beans in a bottle; each item iscored as either pass (0) or fail (1).28

arent QuestionnairesParents completed the Parent Evaluation of Develop-

ental Status (PEDS)29 and the Child Behavior ChecklistCBCL)30 questionnaires as part of either the formal evalu-tion or the questionnaire-only arm of the study (Figure). TheEDS is a 10-item instrument that asks whether parents haveny concerns about areas of their child’s development; answersre “no,” “yes,” and “a little.” The CBCL is a checklist of 120roblem behaviors grouped into syndrome scales. Its “Inter-alizing” score summarizes “Withdrawn,” “Somatic Com-laints,” and “Anxious/Depressed” syndrome scales, and itsExternalizing score” summarizes “Delinquent” and “Aggres-ive Behavior” syndrome scales.

tatistical AnalysisWe assessed bivariate associations using �2, Fisher’s

xact, rank-sum, or t tests; only 2-tailed P values are reported. n

ive-Year Neurodevelopmental Outcome of Neonatal Dehydration

o test for interactions between study group and study par-icipation, we included interaction terms in linear or logisticegression models.

For multivariate analyses of outcomes, we used back-ard stepwise multiple regression with P to remove .10, with

he main predictor variable (dehydration case status) forcednto all models. Additional candidate predictor variables, se-ected based on biological plausibility or previous studies,ncluded maternal and paternal race and education level,ousehold income, maternal age, maternal smoking, gesta-ional age, sex, small for gestational age (below the 10thercentile), 5-minute Apgar score, initial exclusive breast-eeding, parental depression, and examiner. We imputedissing values for income for multivariate analyses in 7 sub-

ects. In addition to summary scores on each of the mainnstruments, we looked for differences in each of the subtestsf the WPPSI-R and in each item of the MPC, PEDS, andBCL.

To address the possibility that neurologic examinationesults might be biased due to preferential participation ofontrols whose parents were concerned about their child’sevelopment, we repeated analyses of neurologic examina-ions, stratifying on whether the parents had concerns aboutotor problems on the PEDS.

We hypothesized that 1 subgroup of infants might be atncreased risk for adverse outcome: those who had eithererum sodium level �160 mEq/dL or weight loss �15%. Weompared the outcomes of this group with the outcomes ofhe controls in separate analyses. All statistical analyses wereerformed using Stata 8 (StataCorp, College Station, TX).

RESULTS

ligibility and EnrollmentA full examination, completed parental questionnaire,

r record of an outpatient visit at age 2 years or older wasvailable for 95% of the dehydration group and 89% of theontrol group (Figure; P � .06). Among those not formallyvaluated, the age at time of the last follow-up visit (mean �tandard deviation) was 4.8 � 2.6 years. Subjects in theehydration group were more likely than controls to consento formal evaluations (58% vs 40%; P � .001).

We first compared demographic and clinical character-stics of the subjects with and without formal evaluationsithin each group. In the dehydration group, formally eval-ated subjects had higher birth weights than those who wereot formally evaluated (3511 vs 3337 g; P � .015) and a lowerverage weight loss (12.8% vs 14.0% of birth weight; P �05). There were no differences between dehydrated infantsho were and were not formally evaluated with respect to sex,estational age, mother’s age, percent with serum sodiumeasured, mean serum sodium level, dehydration diagnoses,

xclusive breast-feeding at the time of discharge from theirth hospitalization, number of prenatal visits, maternal ed-cation, and poverty indicators. Among controls, there were
o significant differences among formally evaluated and non-
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valuated infants with respect to any of the predictor variables,xcept for a statistically significant but clinically trivial (1 day)ifference in gestational age.

Table I shows the clinical and demographic character-stics of cases and controls with and without formal evalua-ions. There was no evidence of bias due to refusal of formalvaluation. For example, although cases with formal evalua-ions were slightly more likely to have been exclusively breast-ed at the time of discharge from the birth hospitalizationhan were cases without an evaluation (92% vs 88%), a similarifference (64% vs 58%) was evident among controls, andeither this nor any of the other interaction terms was sig-ificant; that is, there was no evidence of differential partic-

pation of cases and controls by any of the predictor variables.

linical Characteristics of the Formallyvaluated Subjects

Cases and controls with formal evaluations were similarith respect to gestational age, sex, maternal race, maternal

ducation, father’s education, and income. Cases were moreikely to have mothers over age 25 (87% vs 74%; P � .02) and

able I. Demographic characteristics of subjects and

Characteristic

No formal evaluation

Cases(dehydrated)*

(n � 76)Controls(n � 251)

estational age �38 weeks (%) 15% 10%umber (%) with sodium �160

mEq/L or weight loss �15%22 (28.9%) N/A

aternal age �25 years (%) 82% 72%xclusive breast-feeding at initial

discharge88% 58%

reast-fed for at least 6 months† 56% 50%other’s race/ethnicity‡White 34% 42%Black 5% 12%Asian 34% 24%Hispanic 12% 19%ther/missing 15% 4%other any college§ 83% 61%

ather any college§ 78% 59%edian household income for

census tract of residence ($)70,417 57,349

edian age at last recordedoutpatient visit

5.6 5.5

ollow-up (visits, exams, orquestionnaires) to age �2years

88% 81%

/A, not available.Cases were infants rehospitalized with dehydration with serum sodium �150 mEq/LFrom questionnaire; available for only 68 controls and 18 cases for those without formFrom mother’s self-report at the time of admission for delivery. P values in this row aFrom birth certificate for subjects who did not complete questionnaires.Rank-sum test.

ere more likely to have been exclusively breast-fed at the t

30 Escobar et al

ime of discharge (Table I). No infant had an ICD code forhock (785.50 or 785.59). Chart review confirmed that nonfant experienced shock, gangrene, or respiratory failure.

All but 15 of the 106 formally evaluated cases haderum sodium measured; 20 (19%) had a level �150 mEq/L,4 (60%) had a level of 150 to 159 mEq/L, and 7 had a levelf 160 to 167 mEq/L. Only 1 of these 106 cases did not haveweight obtained at time of hospitalization; 34 (32%) hadeight loss �12%, 49 (46%) had weight loss of 12% to 14.9%,

nd 22 (21%) had weight loss of 15% to 32%. A total of 49 ofhe cases, or 27 (25.5%) of those with full exams, had moreevere dehydration, with serum sodium level �160 mEq/L oreight loss �15%.

utcomesThere were no significant differences between the cases

nd controls on the WPPSI-R or VMI-4 (Table II). Table IIIompares key dichotomous outcomes and indicates that chil-ren in the dehydration group were not more likely to haveeurologic examination scores of 2 (“questionable”) or worse20.8% vs 28.6%; P � .3), and that they were about as likely

ir parents by evaluation status

Formal evaluation P for interactionof dehydration

by formalevaluation

status

Cases(dehydrated)*

(n � 106)Controls(n � 168) P

7 17% 14% .52 .69A 27 (25.5%) N/A N/A N/A

9 87% 74% �.02 .5801 92% 64% �.001 .66

8 52% 45% .26 .9201 .494 54% 46% .20 .081 3% 11% �.02 .469 17% 16% .84 .346 21% 23% .72 .391 6% 4% .57 .1101 90% 86% .35 .141 77% 74% .51 .1101¶ 66,471 62,073 .48¶ .09

1 6.5 6.0 .08 .67

6 100% 100% N/A N/A

r weight loss �12% of birth weight. See the text for details.luations.verall �2; those in the next 5 rows are for the comparison of each race with all others.

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inimal disability”) or worse (7.6% vs 7.1%; P � .8). Strat-fying on motor concerns on the PEDS did not alter theesults. On the MPC, neither the mean total score nor the

able II. Results of testing with the WPPSI-R and th

Test Cases Con

PPSI-R†Verbal IQ

Number of subjects 104 16Mean score 102.7 10

Performance IQNumber of subjects 104 16Mean score 106.8 10

Full-scale IQNumber of subjects 104 16Mean score 105.3 10

MI-4‡Visual-motor integration


Visual perceptionNumber of subjects 102 16Mean score 106.7 10

Motor coordinationNumber of subjects 102 16Mean score 101.8 10

Multiple linear regression. Models varied; most included paternal race and education.Scores on the WPPSI-R are distributed with a mean of 100 and standard deviation oScores on the VMI-4 are distributed with a mean of 100 and standard deviation of 1

able III. Outcomes according to neurologic examin

Outcome Dehydrated gr

eurologic examinationNormal 84/106 (79.3%Normal or questionable 14/106 (13.2%Abnormal with minimal disability 6/106 (5.7%Abnormal with moderate disability 1/106 (0.9%Abnormal with severe disability 1/106 (0.9%Normal or questionable, or worse 22/106 (20.8%Abnormal with minimal disability, or worse 8/106 (7.6%otor performance checklist (MPC)†Score �5 31/106 (29.3%

EDS questionnaireAt least 1 “yes” answer‡ 27/126 (21.4%

BCL preclinical or clinical total score§Internalizing behavior 17/123 (13.8%Externalizing behavior 13/123 (10.6%utpatient follow-up to age �2 years 164/182 (90.1%ne or more neurologic diagnoses 8/182 (4.4%

Odds ratios and P values were calculated with the use of multiple logistic-regression aHigher scores indicate worse function; a score of 4 or more was considered abnormalA response of “yes” indicates a parent concern regarding the child’s development.The internalizing score summarizes the syndrome scales for “withdrawn,” “somatic comdelinquent behavior” and “aggressive behavior.” A T score is classified as preclinical if it0 (approximately 2 standard deviations above the mean).

roportion of children with scores of 4 or worse or 5 or worse i


iffered significantly between the groups. Only 1 of the 12ndividual items differed between the 2 groups; children in theehydration group were more likely to fail the “copy shapes”

ery-Buktenica VMI-4

Adjusted difference (95% CI)* P

0.2 (�3.3 to 3.7) 0.9

�0.8 (�4.1 to 2.6) 0.7

�0.7 (�4.0 to 2.6) 0.7

�0.8 (�4.0 to 2.5) 0.7

�1.0 (�5.4 to 3.4) 0.7

�0.9 (�4.9 to 3.0) 0.6

he range in this study was 46 to 149.range in this study was 45 to 150.

n, the MPC, PEDS questionnaire, and CBCL*

Control group Adjusted odds ratio (95% CI) P

120/168 (71.4%) N/A36/168 (21.4%) N/A10/168 (6.0%) N/A2/168 (1.2%) N/A0/168 (0%) N/A

48/168 (28.6%) 0.73 (0.39 to 1.36) .312/168 (7.1%) 1.13 (0.43 to 2.94) .8

58/167 (34.7%) 0.83 (0.48 to 1.45) .5

56/239 (23.4%) 0.86 (0.50 to 1.48) .6

24/226 (10.6%) 1.45 (0.74 to 2.87) .324/226 (10.6%) 1.06 (0.51 to 2.19) .9

349/419 (83.3%) 1.84 (1.04 to 3.25) .0418/419 (4.3%) 1.02 (0.44 to 2.40) .96

s. The covariates included in each model are available from the investigators.ghtly older children (mean age, 5.5 years).

,” and “anxious/depressed.” The externalizing score summarizes the syndrome scales forast 60 (approximately 1 standard deviation above the mean), and clinical if it is at least

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Results of the CBCL and PEDS were available for alightly larger group of children (n � 126 in the dehydrationroup and n � 239 in the control group). On the CBCL,here were no significant differences in total “Internalizing” orotal “Externalizing” behavior scores or in any of the 8 com-osite scales. Of the 120 specific characteristics and behaviorsddressed in the CBCL, 3 were statistically significantly moreommonly reported for children in the dehydration groupP from rank sum test): “disability” (15% vs 7%; P � .019),allergy” (42% vs 23%; P � .001), and “shyness” (63% vs 52%;

� .05).Parents of children in both groups reported an average

f 1.5 concerns on the PEDS, and the proportions with 1 orore concerns were also similar (21% vs 23%; P � .6). Thereere no differences in the proportions answering “yes” or “a

ittle” on any item except for 1. Parents of children withehydration were more likely to report a concern about theirhild’s speech (26% vs 18%; P � .017). To further evaluateossible speech pathology, we looked for indications of speechroblems noted by the psychologist or the neurologist; ratesid not differ significantly between the groups (11% in theehydration group vs 16% in the control group, P � .40).

Results of outpatient visits at �2 years of age werevailable for 173 of 182 cases (95%) and 372 of 419 controls89%). Eight (4.4%) of the children in the dehydration groupad any neurological diagnoses (eg, gait abnormality), com-ared with 18 (4.3%) of controls (risk difference � 0.1%; 95%onfidence interval [CI] � �3.5 to �3.7; P � .96).

We separately compared outcomes among the 27 chil-ren whose dehydration had been more severe (serum sodium

evel �160 mEq/L and/or weight loss �15%) with those ofontrols. The outcome pattern for the entire cohort held forhis subset, with a slight trend toward better scores for caseshat did not persist in multivariate models. The baby with theighest serum sodium in our cohort (167 mEq/L), whoxperienced 23% weight loss, had some of the highest IQcores in the sample (eg, verbal IQ � 121; visual VMI � 130)Table IV; available at www.jpeds.com).

DISCUSSIONIn this study with prospective neurodevelopmental as-

essment of children who experienced neonatal dehydration,e found little evidence of adverse effects. Although our

esults cannot be generalized to catastrophic dehydration,hey do provide reassurance that the more common possibledverse effects of dehydration, such as mild cognitive, behav-oral, or motor impairment, are unlikely to occur in the typef dehydration usually seen by primary care physicians.

Because dehydrated newborns tend to be hypernatre-ic,1,31 the pathophysiology relevant to neonatal dehydration

elates to hypernatremic states and to problems resulting fromhe intravenous fluid correction of such states.7,12,13,31-34 Ifehydration persists long enough, the adverse effects are sim-

lar to those mediated by acidosis and hypovolemic shock.34

owever, we found no significant differences between cases S

32 Escobar et al

nd controls. We did not find such differences even whenestricting the comparisons to the group of newborns with thereatest degree of dehydration.

Important limitations of our study must be noted. First,t is possible that favorable parent–infant interactions mighte masking deficits due to the adverse effects of dehydration.econd, none of our study subjects had shock, respiratoryailure, infarcts, or gangrene during their dehydration episode.hus, our findings apply to cases of neonatal dehydration that

s detected before these catastrophic events and cannot beeneralized to cases of severe dehydration that have end-rgan damage. Third, we had a higher participation ratemong dehydrated subjects than among controls. This is noturprising, because the research questions for the study werenherently less interesting for parents of the control children.f participants in the control group were at higher risk of badutcome than the control group as a whole, this could intro-uce a bias that would make the outcome among participatingontrols appear worse than it would have been with a moreepresentative sample, and thus make the outcomes in theehydration group look better in comparison. Based on datarom perinatal medical records and birth certificates, we haveittle evidence that this occurred. It is also reassuring that

eans on standardized tests in the dehydration group wereniformly and solidly average compared with national norms.ourth, 5 years is still a young age. If noncatastrophic dehy-ration has subtle effects on higher cortical function, whichould be manifested in difficulties with more complex tasks,

ssessment at 5 years might be too early to detect such effects.Findings from our study may not be generalizable to

ifferent populations in developed nations. Our sample camerom an insured population with a fairly high education levels well as a high rate of breast-feeding. These families hadeady access to a number of support services (ie, follow-uplinics and phone advice banks staffed by registered nurses)nd no barriers to prompt rehospitalization.

In conclusion, our findings support current Americancademy of Pediatrics recommendations for the follow-up ofewborns, which specify the need to assess newborn hydra-ion.35 They also suggest that parents of infants who experi-nced rehospitalization for dehydration in the newborn periodan be reassured that the episode is unlikely to have hadignificant adverse neurologic effects.

e thank Dr Joseph V. Selby for reviewing the manuscript; Peteorin, Ayawnna Smith, and Sandy Hammonds for research

ssistance; Michael Kohn for database development; Blong Xiongor programming; M. Jeffrey Maisels for consultation throughouthe project; and Kimberley Harris for formatting the manuscript.

e especially appreciate contributions from the other members ofhe JIFee study team, including Pilar Bernal, Russell Reiff, Jean

ayward, Amer Khan, Philip Sankar, Richard Friederich,teven Miller, Jonathan Strober, Karl Buddenhagen, Garyezowalli, Lynn Calonico, Pamela Braswell, and Giovanna
pinella (project officer for the study).

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9. Newman T, Escobar G, Gonzales V, Armstrong M, Gardner M, Folck B.requency of neonatal bilirubin testing and hyperbilirubinemia in a large health main-

enance organization. Pediatrics 1999;104(5 Pt 2):1198-203.0. Escobar GJ, Joffe SJ, Gardner MN, Armstrong MA, Folck BF, Carpenter DM.ehospitalization in the first two weeks after discharge from the neonatal intensive carenit. Pediatrics 1999;104(e2):1-9.1. Newman TB, Xiong BX, Gonzales VM, Escobar GJ. Prediction and prevention ofxtreme neonatal hyperbilirubinemia in a mature health maintenance organization. Archediatr Adolesc Med 2000;154:1140-7.2. Newman T, Liljestrand P, Jeremy R, Ferriero D, Wu Y, Hudes E, et al. Outcomesmong newborns with total serum bilirubin levels of 25 mg per deciliter or more. N EnglMed 2006;354:1889-900.3. Maisels MJ, Gifford K. Breast-feeding, weight loss, and jaundice. J Pediatr983;102:117-8.4. International Classification of Diseases, 9th Revision, Clinical Modification (4thd). Los Angeles, CA: Practice Management Information Corp; 1995.5. Radloff LS. The CES-D Scale: a self-report depression scale for research in theeneral population. Appl Psychol Measur 1977;1:385-401.6. Wechsler D. The Wechsler Preschool and Primary Scale of Intelligence-Revised.an Antonio, TX: The Psychological Corp, 1989.7. Beery K. The Beery-Buktenica Developmental Test of Visual-Motor Integration,ourth edition revised. Parsippany, NY: Modern Curriculum Press; 1997.8. Gwynne K, Blick B. Motor Performance Checklist for 5-year-olds: a tool fordentifying children at risk of developmental coordination disorder. J Paediatr Child

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1. Heldrich FJ, Shaw SS. Case report and review of literature: hypernatremia inreast-fed infants. Maryland Med J 1990;39:475-8.2. Comay SC, Karabus CD. Peripheral gangrene in hypernatraemic dehydration ofnfancy. Arch Dis Child 1975;50:616-9.3. Roddey OF Jr, Martin ES, Swetenburg RL. Critical weight loss and malnutritionn breast-fed infants. Am J Dis Child 1981;135:597-9.4. Finberg L, Kravath R, Hellerstein S. Hypernatremic dehydration. In: Water andlectrolytes in Pediatrics: Physiology, Pathology and Treatment: Finberg L, KravathE, Hellerstein S, editors. Philadelphia: Saunders; 1993. p. 124-34.5. American Academy of Pediatrics Committee on Fetus and Newborn. Hospital
tay for healthy term newborns. Pediatrics 1995;96(4 Pt 1):788-90.
133

Ti

W

V

T*†‡§ 5.

1

able IV. Results of testing with the WPPSI-R and thnfants with serum sodium >160 mEq/L and/or weigh

Test Cases* Co

PPSI-R‡Verbal IQ


Performance IQNumber of subjects 27 1Mean score 106.0 1

Full-scale IQNumber of subjects 27 1Mean score 106.9 1

MI-4§Visual-motor integration


Visual perceptionNumber of subjects 27 1Mean score 112.5 1

Motor coordinationNumber of subjects 27 1Mean score 102.8 1

he range in this study was 45 to 150.Cases are a subset of 27 with more severe dehydration.Multiple linear regression. Models varied; most included paternal race and education.Scores on the WPPSI-R are distributed with a mean of 100 and standard deviation oScores on the VMI-4 are distributed with a mean of 100 and standard deviation of 1

e Beery-Buktenica VMI-4 for a subset of dehydratedt loss >15%

ntrols Adjusted difference (95% CI)† P

62 1.9 (�3.5 to 7.4) .501.1

65 �1.7 (�7.3 to 3.9) .606.0

62 �0.2 (�5.5 to 5.1) .904.0

65 �1.9 (�7.1 to 3.4) .502.2

64 3.8 (�3.4 to 10.9) .305.9

65 �0.6 (�6.9 to 5.8) .900.4

f 15. The range in this study was 46 to 149.

33.e1 Escobar et al The Journal of Pediatrics • August 2007

Five-Year Neurodevelopmental Outcome of Neonatal Dehydration

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