Emerging
Developmental
Sequelae
in the
‘Normal’
Extremely
Low Birth Weight
Infant
Marc
F. Collin,
MDf;
Carey
L. Halsey,
MSEd*;
and Craig
L. Anderson,
MD*
From the *Depa,.ment of Pediatrics, Loyo/a University Medical Center, Maywood, Illinois and epartment of Pediatrics, MetroHealth Medical Center, Cleveland, Ohio
ABSTRACT. Thirty-six extremely low birth weight
(<1000 g birth weight) children received neurodevelop-mental testing in infancy (mean age = 19.1 months), and
again in early childhood (mean age = 46.5 months).
Children were categorized into a high-risk group (n = 20) if bronchopulmonary dysplasia and/or Grades III or IV
intracranial hemorrhage were present or a low-risk group (n = 16) if neither were present. Using standardized
testing and neuromotor examination, 24 (67%) of 36 children showed normal infant development. Only 11 (31%) of 36 children (P < .005) had normal development upon reassessment in early childhood. A decline in de-velopmental status occurred in both groups. This inch-cates that for the extremely low birth weight population, normal infant development is poorly predictive of contin-ued normal development. With or without major compli-cations, extremely low birth weight places children at substantial risk for ongoing and emerging developmental problems with age. Pediatrics 1991;S8:115-120; extremely
low birth weight, development, follow-up.
ABBREVIATIONS. ELBW, extremely low birth weight; ICH,
intracranial hemorrhage; BPD, bronchopulmonary dysplasia;
GCI, General Cognitive Index; SGA, small for gestational age; MDI, Mental Development Index.
Advances in perinatal and neonatal care have
enabled dramatic improvement in the survival of
infants born weighing less than 1000 g. In 1952,
the survival rate for extremely low birth weight (ELBW) infants was 4%,’ whereas recent reports place neonatal survival in this group at 50% to 60% or more.25 Because of this dramatic improvement in survival rates, the emphasis in recent years has
begun to shift from concerns of mortality toward a better understanding of the scope and nature of
morbidity.
Most follow-up studies of the ELBW population
have followed children only into infancy.68 More
recently, others have extended follow-up into
pre-school, with few reporting school-age data.9’2 The latter suggest that among children without major handicap, a significant portion (40% to 64%) re-quire special education or additional services in
school. It would be optimal to identify those chil-then at risk for disability as early in life as possible. In that way one could potentially intervene and ameliorate, if not eliminate, the child’s impairment.
Our data will show that within the ELBW
pop-ulation the utilization of traditionally accepted high-risk neonatal factors (severe intracranial hem-orrhage ETCH] and/or bronchopulmonary dysplasia [BPD] )will not preferentially identify those chil-then destined to have abnormal neurodevelopmen-tal outcomes. Additionally, normal developmental
status in infancy does not portend continued
nor-mal status.
MATERIALS
AND
METHODS
Population
Received for publication Apr 20, 1990; accepted Aug 20, 1990. Presented at the Society for Pediatric Research, Washington, DC, May 1, 1989.
Reprint requests to (C.L.A.) Division of Neonatology, Loyola
University Perinatal Center, 2160 S First Aye, Maywood, IL
60153.
PEDIATRICS (ISSN 0031 4005). Copyright © 1991 by the American Academy of Pediatrics.
The neonatal intensive care unit at Loyola
Uni-versity Medical Center is a 50-bed unit with ap-proximately 650 annual admissions; 80% are born
at the perinatal center. Newborns are also
trans-ferred from 13 community hospitals.
In 1984-1986, 11% ofneonatal intensive care unit
nearly one half of these weighed less than 750 g. For those years our neonatal survival rate within
this ELBW population was 58%.
Seventy-eight ELBW infants admitted during a
26 month period (January 1984 through February 1986) survived infancy and were eligible for
outpa-tient developmental assessment. All children with developmental delay were offered early interven-tion resources. Seventy infants (90%) received at
least one developmental assessment. This report
focuses on a group of children from this cohort. The data include only children evaluated during both the infancy period (12-25 mo) and the
pre-school period (35-56 mo). Thirty-six children met
this criterion, excluding one child with multiple
congenital anomalies.
Chart review for each infant noted gestational age, birth weight, appropriateness of weight for
gestation, gender, race, place of birth, and duration
of mechanical ventilation and oxygen supplemen-tation. The Hollingshead scale was used to assess
socioeconomic status.
All infants underwent real-time ultrasonography of the brain within the first 7 days of life (mean =
5 days). Hemorrhage status was graded 0 through
Iv
using the method of Papile et al.’3 Grades IIIand IV were considered severe ICH. Diagnostic criteria for BPD included mechanical ventilation during the first week of life, a need for supplemental oxygen beyond 28 days of life, and characteristic radiographic changes.
Assessment
Procedures
Evaluations of all children occurred at least once between 12 and 25 months. Each received stand-ardized testing using the Gesell Developmental
Schedules (if between 12 and 15 months) or the
Bayley Scales of Infant Developmental-Mental Scale (if between 15 and 25 months) administered
by a child development specialist. Additionally,
each child received a neuromotor examination by a neonatologist and a pediatric physical therapist. The following criteria defined normal development: (1) a score of >84 on the standard psychometric
test of infant development, which represents scores within one standard deviation from the mean score
of 100 on either test; and (2) no disturbance of tone or movement as assessed independently and agreed on by the neonatologist and pediatric physical ther-apist.
Reexamination occurred during the preschool
period, between 36 and 56 months of age. The
McCarthy Scales of Children’s Abilities were ad-ministered by a child development specialist. The McCarthy scales include five subscales (Verbal,
Perceptual/Performance, Quantitative, Memory,
and Motor). The General Cognitive Index (GCI)
score is a summation of the Verbal, Perceptual/ Performance, and Quantitative scales. The
follow-ing criteria defined normal development: (1) a score
of >84 on the GCI and a standard score of >40 on
the Motor subscale (This represents scores within
one standard deviation of the mean score.) and (2)
no cerebral palsy. Children not meeting the criteria for “normal” were classified as abnormal. Although
inexact, normal development is more easily defined than deviations from normal.
Data Analysis
We compared developmental classifications for
each child between the two age periods. “High-risk”
children suffered from BPD and/or severe ICH;
“low-risk” children had neither of these complica-tions. Certain factors, such as delivery room
resus-citation, the need for mechanical ventilation, and treatment for apnea of prematurity, are nearly
uni-versal components for children born weighing less than 1000 g and were, therefore, not considered separately. The x2 method of analysis was used to
compare differences.
RESULTS
Table 1 compares the high-risk and low-risk groups regarding birth weight, gestational age,
gen-TABLE 1. Study Groups
Characteristic Low Risk (n=16)
High Risk (n=20)
Mean birth weight, g 829 817 (Range) (520-970) (600-970) Mean gestational age, 28.6 26.6
wk
(Range) (25-36) (23-30)
Male 5 6
Female 11 14
Race
White 13 16
Black 2 1
Hispanic 1 1
Other 0 2
Inborn 15 17
Intracranial hemorrhage
Grade III . . . 5
Grade IV ‘. . 2
Bronchopulmonary dys- .. . 16
plasia (02 >28 d) Ventilator days
Mean 33.6 59.2
Median 40.5 62.0
(Range) (1-75) (34-100)
Oxygen days
Mean 7.1 66.4
Median 4.0 59.0
der, race, and place of birth. Analysis of SGA (small .05). Of note, while 5 of 6 SGA children were normal for gestational age) status showed all such infants during infancy, none were normal at their preschool to be in the low-risk group; therefore, these children assessment.
were both included and excluded from analysis. Fifteen of 36 study infants were referred for early
Using the Hollingshead Scale of Socioeconomic intervention services during the first year because Status, 92% of the families had a classification of of developmental delay. Twelve infants actually
1-3, indicating at least high school education and received services (physical, occupational, and/or gainful employment. Sixty-nine percent scored speech therapy). Intensity and duration varied.
1-2, generally suggesting college education and This group of 12 included 7 children abnormal at semiprofessional/professional occupations. There both age points, 4 children who changed classifica-was no significant difference between the high-risk tions from normal to abnormal, and 1 child who and low-risk groups. was normal at both assessments.
Overall, 24 (67%) of 36 children were normal Most abnormal infants (83%) remained abnor-when seen in infancy (range = 12-25 months; mean mal, including children with cerebral palsy, global = 19.1 months). Only 11 infants (31%) subse- retardation, and one autistic child. Two children
quently demonstrated normal development when previously classified as abnormal later tested in the reassessed during preschool (range = 36-56 normal range. Both children were in the high-risk
months; mean = 46.5 months) (P < .005). Compar- group because of
BPD;
they had normal motor isons within the high-risk group showed 11 (55%) examination results but low mental developmentof 20 were normal in infancy, while only 6 (30%) of scores that subsequently normalized.
20 performed in the normal range during the pre- A closer look at the 15 normal infants later school period (P < .05). The low-risk groups also considered abnormal reveals that 7 were high risk
showed a significant decline between time periods. while 8 were in the low-risk group. Socioeconomic Only (31%) of 16 were still normal in preschool, status did not differentiate these children from whereas 13 (81%) of 16 were normal in infancy (P those that remained in the normal classification. < .05). (Figure) Assessment information on individ- Their mean Mental Development Index (MDI) on ual children at both the infancy and preschool the Bayley Scales of Infant Development, admin-periods is listed in Table 2. istered in infancy, was 102 with a range of 88 to
Six children, all in the low-risk group, were SGA. 124. Motor examination results were normal. Pre-Four had been borderline SGA infants who were of school assessment revealed two broad groups: (1) 8
<31 weeks’ gestation, whereas only 2 were severely mildly impaired children who scored >1 SD below SGA and of>32 weeks’ gestation. Overall, 19 (63%) the mean on either the GCI (n = 3) or the Motor
of 30 average-for-gestational-age children were nor- subscale of the McCarthy Scales of Children’s Abil-mal in infancy compared with 11 (37%) of 30 pre- ities (n 5); (2) 7 significantly impaired children school (P < .005). Within the low-risk group, 8 who scored at least 1 SD below the mean on both
(80%) of 10 average-for-gestational-age children the
GCI
and the Motor subscale. Four of these 7were normal in infancy, whereas only 5 (50%) of 10 actually scored >2 SD below the mean in both
were still in the normal range in preschool (P < areas.
NORMAL DEVELOPMENTAL FINDINGS DISCUSSION
(ALL SUBJECTS)
I00 *p < 0.005
The literature cites a handicap rate in the ELBW
13 < 0.05 infant ranging between 22% and 72%.24,1419 The
80
24
1 1
1
definition of handicap varies; some refer only to major handicap, whereas others include all children not unequivocally normal. Also, most studies have been short-term, following their cohorts for 3 years
or less. Taken together, these studies suggest that
handicap rates have not dramatically changed,
con-20 trasting with plummeting mortality rates.
Unfor-tunately, this results in a larger number of children
0 with handicaps.
INFANCY PRESCHOOL Developmental follow-up studies tend to look at
-
TOTAL HIGH RISK E1 LOW P150K children at a single point in time, unintentionallyIN=361 IN=201 IN= 161
creating the impression that these “outcomes” are
Figure. Normal developmental findings (all subjects). static or final. Yet the concept of developmental
60
TABLE 2. Individual Assessment Information*
Study Subjects Cognitive
Bayley MDI/DQ Scores McCarthy GCI Motor Motor Exam Exams McCarthy Motor (Infancy) (Preschool) (Infancy) (Preschool)
76 94 92 82 85 <50 91 79 Autistic Untestable 89 110 107 102 61 106 93 <50 100 87 N N N N Poor balance N N CP/quadriplegia Poor coordination CP/quadriplegia N CP/diplegia N N N N N N N Poor balance 42 40 39 48 29 26 53 <22 Untestable Untestable 42
41 (Mild diplegia) 60 34 33 36 48 <22 52 39 High risk 1 88 2 123 3 107 4 91 5 73 6 90 7 100 8 Untestable 9 64 10 Untestable 11 107 12 100 13 128 14 117 15 Untestable 16 100 17 81 18 104 19 63 20 85 Low risk
21 98 76 N 33
22 109 130 N 67
23 102 90 N 35
24 104 92 N 49
25 100 103 N 37
26 124 <50 N <22
27 124 83 N 40
28 88 81 N 23
29 89 <50 N <22
30 85 87 N 42
31 108 72 N 24
32 105 89 N 49
33 115 116 N 45
34 75 <50 N <22
35 78 <50 N <22
36 68 <50 Poor balance <22
* Abbreviations: MDI, Mental Development Index; DQ, developmental quotient; Gd,
General Cognitive Index; CP, cerebral palsy; N, normal.
evolution is important. The dynamic nature of child development results in both qualitative and quan-titative changes. In ELBW children, we believe this maturation process uncovers diminished cortical
and motor functioning.
In general, certain neonatal diagnoses such as BPD have been associated with a higher incidence of adverse neurodevelopmental outcomes.2022 As with the ELBW literature, the criterion for devel-opmental delay varies widely, with some
research-ers using a Bayley Scale MDI <85 or >1 SD below the mean,23 others using >2 SD below the mean of
<68,24 and others even using a Bayley MDI <60 as their cutoff for abnormal development.20 The du-ration of follow-up is also most important as many authors report on outcomes at only 2 years of age
or less.20’23’24 Finally, the case definition of BPD,
itself, differs among authors.20’21’24 Considering the
many variables, comparisons among studies become difficult. However, the consensus in the literature
is that children with BPD have a higher rate (35% to 91%) of abnormal or delayed development than birth weight comparison groups without BPD. An exception is the report of Markestad and Fitzhard-inge,23 who found a 25% incidence of developmental delays; severe impairment occurred in only 10%
(MDI <70).
Deficiencies similar to those noted in the ELBW and BPD literature exist in ICH outcome reports.
groups.#{176}2’#{176}#{176}Papile and coworkers’ first report27 sug-gested that the risk for major handicap increased with the severity of ICH. TeKolste et al29 reported similar data.
Our data suggest that extremely low birth weight,
by itself, is the major risk factor for abnormal later
development. The rate of normal development as
determined at 4 years of age was the same irrespec-tive of whether the child additionally suffered from BPD and/or severe ICH. Thus, the designation of
high risk or low risk in children of extremely low birth weight is an artificial one. Two other studies, reporting outcomes to 2 years of age, had similar
findings. Bennett et al34 suggested that birth weight
alone is the best predictor of developmental out-come in a population of larger children with hyaline membrane disease. Markestad and Fitzhardinge23
concluded that early developmental outcome is
more closely associated with neonatal and perinatal
events than with the presence of BPD.
The downward drift seen between infancy and
preschool in our study children contrasts sharply
with the results of Kitchen et al,35’36 who reported
improvement in developmental status between age
periods. This discrepancy cannot be fully explained; yet methodology differed somewhat. While both
groups used the Bayley scales and a
neurodevelop-mental examination in infancy, the preschool
meas-ures differed. Kitchen’s group used the Wechsler Preschool and Primary Scales of Intelligence to measure cognitive status whereas we used the GCI of the McCarthy scales. We did not generally find cognitive scores to increase, as they did. This may be a function of comparing the Bayley to two dif-ferent tests known to measure similar abilities.37
The Kaufman and Kaufman review38 did note that
the Bayley scales were more continuous with the McCarthy scales than other preschool scales. Ad-ditionally, perhaps a clinical assessment of func-tional motor handicap used by Kitchen et al is not
comparable to a score on the Motor subscale of the McCarthy scales as we used. It is clear, however,
that substantial changes do occur in the
neurode-velopmental status of high-risk children over time. While Kitchen et al. documented changing neuro-developmental status in 37% and 62% of their two
cohorts, we demonstrated change in 47% between
infancy and preschool years.
Our findings suggest that normal infant devel-opment is poorly predictive of continued normal development in ELBW children. The current study confirms the presence of evolving developmental sequelae in the ELBW population. These results
serve to emphasize the need for extended
develop-mental follow-up.
ACKNOWLEDGMENTS
The March of Dimes Birth Defects Foundation
par-tially supported this work (grant 12-207).
We gratefully acknowledge the contributions of Paula Cox, MS, RPT, and Sheri Coddington, MSN, CPNP, to this study and Virginia Steege and Glenn Paveza for their assistance in manuscript preparation.
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OBFUSCATION WITH BIKINI BATHING SUITS
If war is too important to be left to military leaders, and medicine to
physicians, the interpretation of epidemiologic results cannot be relegated
exclusively to epidemiologists. The people who struggle to understand those
results can be helped by recalling the old adage that statistics are like a bikini
bathing suit: What is revealed is interesting; what is concealed is crucial.
Feinstein AR. Scientific standards in epidemiologic studies of the menace of daily life. Science.
1988;242:1257-1263.
1991;88;115
Pediatrics
Marc F. Collin, Carey L. Halsey and Craig L. Anderson
Infant
Emerging Developmental Sequelae in the `Normal' Extremely Low Birth Weight
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