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Copyright 1997 by The Johns Hopkins University School of Hygiene and Public Health
All rights reserved
Relation between Very Low Birth Weight and Developmental Delay among
Preschool Children Without Disabilities
Diana E. Schendel, 1 Joseph W. Stockbauer,2 Howard J. Hoffman,3 Allen A. Herman,4 Cynthia J. Berg,5 and
Wayne F. Schramm 2
Received for publication July 8,1996, and accepted for publication June 26, 1997.
Abbreviations: AGA, appropriate-for-gestational age; DELAY,
developmental delay; Denver II, Denver Developmental Screening
Test II; MLBW, moderately low birth weight; MMIHS, Missouri Maternal and Infant Health Survey; NBW, normal birth weight; SGA,
small-for-gestational age; VLBW, very low birth weight.
1
Developmental Disabilities Branch, Division of Birth Defects
and Developmental Disabilities, National Center For Environmental
Health, Centers for Disease Control and Prevention, Atlanta, GA.
2
Bureau of Health Data Analysis, State Center for Health Statistics, Missouri Department of Health.
3
Epidemiology, Statistics and Data Systems Branch, Office of
the Director, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD.
4
Epidemiology Branch, Division of Epidemiology, Statistics and
Prevention Research, National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD.
5
Pregnancy and Infant Health Branch, Division of Reproductive
Health, National Center for Chronic Disease Prevention and Health
Promotion, Centers for Disease Control and Prevention, Atlanta,
GA.
Reprint requests to Dr. Diana E. Schendel, Developmental Disabilities Branch, Division of Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford
Highway, N.E., Mailstop F15, Chamblee, GA 30341-3724.
740
The authors examined the relation between very low birth weight (VLBW: <1,500 g) and possible developmental delay (DELAY) in the absence of frank developmental disability among young children. The prevalence of DELAY in a population-based cohort (Missouri resident births born from December 1989 through
March 1991) of singleton VLBW children (n = 367) was compared with the prevalence of DELAY among both
moderately low birth weight (MLBW: 1,500-2,499 g; n = 553) and normal birth weight (NBW: >2,500 g; n =
555) singleton control children. DELAY was defined by nine measures of performance on the Denver
Developmental Screening Test II at a median adjusted age of 15 months (range: 9-34 months). Subjects were
asymptomatic for disabling conditions at developmental follow-up. Apparently well VLBW children were
consistently at greater risk for both moderate and severe measures of DELAY and for DELAY across four
functional areas than were either the MLBW (adjusted odds ratios: 1.4-2.7) or NBW children (adjusted odds
ratios: 2.1-6.3). The greatest prevalence of DELAY tended to be among appropriate-for-gestational age VLBW
children who were also the most premature. This study supports developmental follow-up of nondisabled
VLBW children because of the significantly elevated risk for DELAY among apparently normal infants. Am J
Epidemiol 1997; 146:740-9.
obtaining consent and completing a maternal questionnaire prior to discharge; mothers of infants who were
born elsewhere and identified from the birth certificate
files completed the questionnaire by mail.
Both MLBW and NBW control infants were drawn
from singleton livebirths in the MMIHS study population in approximately a 1:1 case-to-control ratio.
Among infants who were not born in one of the five
urban hospitals, controls were randomly selected from
the birth certificate files on the basis of frequency
matching with cases by maternal race (black, nonblack), age (<20 years, 20-24 years, ^25 years), and
residence (residence in St. Louis City, St. Louis
County, Kansas City, or Jackson County vs. residence
elsewhere in Missouri). For the urban hospital sample,
once a case infant was identified from delivery room
logs, a control was identified by choosing the next
infant recorded in the log with the appropriate birth
weight and whose mother fit in the same race-age
stratum as the case infant's mother.
The sample population for this analysis was derived
from all singleton case and control children enrolled in
the MMIHS who completed the Denver II [i.e., survivors who, at the time of developmental follow-up, had
no frank physical or other limitations, specifically,
cerebral palsy or other orthopedic problem (n = 11),
chronic health condition (n = 4), nonresponsive (n =
3), homeless (n = 2), Down's syndrome (n = 1), blind
{n = 1), unspecified brain injury (n 1), and who
were not lost to follow-up as a result of adoption,
refusal to participate, or no reply]. All participants
were tested between the adjusted age (i.e., chronological age adjusted for prematurity if a child was aged
<2 years and was born > 2 weeks prematurely) of 9
and 34 months; about 50 percent of the children in
each birth weight group had been tested by the adjusted age of 15 months.
The Denver II was administered primarily by local
county health department staff in a child's home (preferred) or other location (e.g., the Women, Infants, and
Children program office). All staff who administered
the test were trained by nurses from the Missouri
Department of Health who had undergone a training
program established by developers of the Denver II.
Outcome definition
741
742
Schendel et al.
Information on risk factors for DELAY were obtained from the maternal questionnaire and the child's
birth certificate. These factors included sex of the
child and maternal age, race, residence, education
level, and marital and Medicaid status at birth of the
child, and smoking and alcohol use. Although maternal race, age, and residence were used as matching
variables in selecting control children, it was decided
to include these variables as covariates in this analysis,
because, in terms of these risk factors, the distribution
of the Denver II sample population differed slightly
from that of the original set of case and control infants.
Smoking and alcohol use were measured by two vari-
and gross motor skills). One of the two domainspecific measures was whether a child failed one or
more tasks in each domain for which 75-90 percent of
children of the same adjusted age would pass (denoted
as receiving one or more caution scores in a given
domain); the other measure was whether a child failed
one or more tasks in each domain for which at least 90
percent of children of the same adjusted age would
pass (denoted as receiving one or more delay scores in
a given domain). The ninth outcome, denoted as overall test performance, was based on the total number of
caution and/or delay scores received across all domains and was categorized as follows: 1) questionablereceived two or more caution scores and/or a
maximum of one delay score, 2) abnormalreceived
two or more delay scores, 3) normalreceived a maximum of one caution score, and 4) untestablerefused
to perform one or more tasks.
The nine outcomes reflect two basic levels of
DELAY: 1) a moderate degree of DELAY that was
generally represented by a questionable overall test
performance, plus the four domain-specific outcomes
for children who received one or more caution scores
in a given domain, and 2) a severe degree of DELAY
that was represented by an abnormal overall test performance, plus the four domain-specific outcomes for
children who received one or more delay scores in a
given domain.
743
TABLE 1. Derivation of the MMIHS Denver II sample* of births to Missouri residents from December 1,
1989 through March 31,1991
VLBWf
Potential MMIHS subjects*
Enrolled MMIHS subjects
Survivors at time of follow-up among
enrolled subjects
Survivors with Denver II follow-up
Loss to follow-up for Denver II among
survivors due to
No reply/refusal
Adoption
Physical/other limitation
MLBWt
NBWt
No.
No.
No.
1,013
780
77H
1,061
800
75H
1,040
798
77H
530
367
68#
69**
787
553
98#
70**
793
555
99#
70**
147
3
13
220
5
9
234
3
1
* MMIHS Denver II sample, children enrolled in the Missouri Maternal and Infant Health Survey who
completed the Denver Developmental Screening Test II.
t VLBW, very low birth weight (<1,500 g); MLBW, moderately low birth weight (1,500-2,499 g); NBW, normal
birth weight (>2,500 g).
$ Singleton births originally identified as case or control infants.
Subjects whose mothers returned maternal survey questionnaire.
H Percent of potential subjects.
# Percent of enrolled subjects.
** Percent of all survivors at follow-up.
744
Schendel et al.
TABLE 2. Distribution of risk factors for developmental delay for children in the MMIHS Denver II
samplef of births to Missouri residents from December 1,1989 through March 31 ,1991
Risk
factor
NBWt
(n=555)
MLBWt
(n = 553)
No.
No.
No.
180
187
49.1
50.9
253
300
45.8
54.2
290
265
52.2
47.8
86
245
36
23.4
66.8
9.8
119
394
40
21.5
71.3
7.2
131
385
39
23.6
69.4
7.0
105
257
29.0
71.0
158
388
28.9
71.1
148
403
26.9
73.1
130
226
36.5
63.5
205
343
37.4
62.6
221
325
40.5
59.5
181
185
49.5
50.5
269
284
48.6
51.4
310
241
56.3
43.7
132
220
37.5
62.5
267
277
49.1
50.9
236
309
43.3
56.7
131
39
197
35.7
10.6
53.7
175
42
336
31.6
7.6
60.8
207
35
313
37.3
6.3
56.4
137
219
38.5
61.5
241
300
44.6
55.4
185
366
33.6
66.4
93
260
26.4
73.6
150
395
27.5
72.5
149
398
27.2
72.8
Sex
Male
Female
Maternal age (years)
<20
20-34
235
Maternal education
<High school
>High school
Maternal race
Black
Nonblack
Married at birth*
Yes
No
Medicaid client**
Yes
No
Maternal residence
Urban
Suburban
Rural
Smoke any trimester
Yes
No
Alcohol any trimester
Yes
No
VLBW*
(n = 367)
745
TABLE 3. Measures of fetal growth and maturity for children in the MMIHS Denver II sample* of births
to Missouri residents from December 1,1989 through March 31,1991
Fetal
VLBWt
MLBWt
NBWt
Mean
SDt
Mean
SD
Mean
SD
1,088
(268)
2,184
(267)
3,414
(485)
28.4
(" = 553)
(2.8)
39.4
measure
(n = 367)
(3.0)
35.6
(n = 365)
Growth status at birth
(n = 555)
(n = 546)
No.
No.
All children
SGA*
AGA*
353
86
267
24.4
75.6
541
248
293
45.8
54.2
350
83
267
23.7
76.3
332
50
282
(1.5)
(n = 543)
15.1
84.9
No.
534
36
6.7
93.3
498
27
0
0.0
27
100.0
TABLE 4. Crude distribution of outcome measures indicating developmental delay for children in the
MMIHS Denver II samplet of births to Missouri residents from December 1,1989 through March 31,1991
Outcome
measure
MLBWJ
(n = 553)
VLBWt
(n = 367)
No.
No.
NBWt
(n = 555)
%
No.
Overall performance
Questionable*
Abnormal**
Normal
0 caution/delay***
1 caution only
Untestable
64
40
17.4
10.9
65
32
11.7
5.8
44
16
7.9
2.9
204
57
2
55.6
15.5
0.5
384
69
69.4
12.5
0.5
412
82
1
74.2
14.8
65
15
11.8
2.7
53
12
0.2
Domain-specific performance
Personal-social
>1 cautions*
1 delays**
Language
21 cautions*
1 delays****
Fine motor-adaptive
>1 cautions*****
21 delays*****
Gross motor
21 cautions***
>1 delays***
64
26
17.5
62
32
17.0
66
32
12.0
5.8
47
22
8.5
8.8
44
29
12.0
7.9
48
29
8.7
5.3
33
12
6.0
2.2
64
17.5
10.7
49
22
8.9
4.0
22
10
4.0
1.8
39
7.1
9.6
2.2
4.0
* VLBW vs. NBW, p <, 0.001 and VLBW vs. MLBW, p <, 0.05; ** VLBW vs. NBW, p <, 0.001 and VLBW vs.
MLBW, p <, 0.01; ** VLBW vs. NBW, p <, 0.001 and VLBW vs. MLBW, p <, 0.001; **** VLBW vs. NBW, p <; 0.01;
***** VLBW vs. NBW, p 5S 0.001.
t MMIHS Denver II sample, children enrolled in the Missouri Maternal and Infant Health Survey wtio completed
the Denver Developmental Screening Test II.
t VLBW, very low birth weight (<1,500 g); MLBW, moderately low birth weight (1,500-2,499 g); NBW, normal
birth weight (>2,500 g).
Testable children (VLBW, n = 365; MLBW, n = 550; NBW, n = 554).
Am J Epidemiol
* MMIHS Denver II sample, children enrolled in the Missouri Maternal and Infant Health Survey who completed
the Denver Developmental Screening Test II.
t VLBW, very low birth weight (<1,500 g); MLBW, moderately low birth weight (1,500-2,499 g); NBW, normal
birth weight (>2,500 g).
$ SD, standard deviation; SGA, small-for-gestational age (<10th percentile of birth weight for gestationai age,
by sex and race); AGA, appropriate-for-gestational age (10 percentile of birth weight for gestationai age, by sex
and race).
746
Schendel et al.
TABLE 5. Crude distribution by growth status at birth of outcome measures indicating developmental
delay for children in the MMIHS Denver II sample* of births to Missouri residents from December 1,1989
through March 31,1991, VLBW* and MLBW* children born prematurely only
Outcome
measure
AGA
MLBW
(n=50)
VLBW
(n = 267)
MLBW
(n = 282)
1,080
31.1
1,993
35.4
1,094
27.6
2,114
33.6
8.4
13.3
16.0
4.0
21.0
10.1
11.7
6.4
57.8
20.5
0.0
68.0
12.0
0.0
54.7
13.5
0.8
69.2
12.4
0.4
24.1
7.2
14.0
4.0
16.2
7.5
12.5
2.1
14.5
8.4
8.0
2.0
17.4
9.1
12.1
5.3
12.1
10.8
2.0
6.0
12.1
7.6
8.9
6.1
19.3
7.2
10.0
2.0
17.4
11.7
8.9
3.9
* AGA, VLBW vs. MLBW, p <, 0.01; **SGA, VLBW vs. MLBW, p < 0.05.
t MMIHS Denver II sample, children enrolled in the Missouri Maternal and Infant Health Survey who completed
the Denver Developmental Screening Test II.
% VLBW, very low birth weight (<1,500 g); MLBW, moderately low birth weight (1,500-2,499 g).
SGA, small-for-gestational age (<10th percentile of birth weight for gestationai age, by sex and race); AGA,
appropriate-for-gestational age (210th percentile of birth weight for gestationai age, by sex and race).
H Testable children (VLBW: SGA, n = 83; AGA, n = 265. MLBW: SGA, n = 50; AGA, n = 281).
of function, with the greatest risk for DELAY associated with the gross motor domain. This is consistent
with previous reports of poor motor functioning or
"motor clumsiness" in VLBW children without major
neurodevelopmental impairment (6, 9, 12), but may
indicate a greater risk for delay in acquiring gross
motor skills than fine motor skills among very young,
preschool-aged VLBW children.
This analysis drew upon a case-control study of
liveborn infants that included an entire 16-month cohort of VLBW infants born in Missouri. Despite the
relatively large follow-up sample size, one limitation
of the study may be that the Denver II sample may not
have been representative of the larger population from
which it was drawn. For selection bias to have an
impact on the study results, however, the bias would
have had to have been related to both birth weight and
developmental status (22). Mothers of VLBW children
who suspected or were aware of delayed development
in their children may have been particularly motivated
to participate in the follow-up study, thereby artificially increasing the prevalence of delay in the VLBW
Am J Epidemiol
SGA
VLBW
(n = 83)
747
TABLE 6. Adjusted odds ratios (95% confidence intervals) for outcome measures indicating
developmental delay for children in the MMIHS Denver II sample* of births to Missouri residents from
December 1,1989 through March 31,1991
VLBWf (n = 320) vs.
Outcome
measure
Overall performance
Questionable
Abnormal
NBWt
(n = 524)
OR*
95% CI*
OR
1.66
2.02
1.09-2.51
1.18-3.45
2.74
4.81
1.74-4.31
2.51-9.23
1.64
2.74
1.09-2.48
1.36-5.53
2.12
3.21
1.38-3.24
1.54-6.68
1.41
1.79
0.93-2.12
1.04-3.09
2.16
2.97
1.39-3.37
1.61-5.47
1.42
1.60
0.88-2.28
0.90-2.84
2.10
4.88
1.26-3.50
2.34-10.20
2.16
1.39-3.34
1.38-4.68
4.95
6.26
2.89-8.47
2.87-13.65
2.54
95% Cl
* MMIHS Denver II sample, children enrolled in the Missouri Maternal and Infant Health Survey who completed
the Denver Developmental Screening Test II.
t VLBW, very low birth weight (<1,500 g); MLBW, moderately low birth weight (1,500-2,499 g); NBW, normal
birth weight (>2,500 g).
t OR, odds ratio; Cl, confidence interval.
In calculating the adjusted odds ratio, residence was dropped from the multivariable regression model.
group relative to the other birth weight groups. Because all children to be tested with the Denver II had
to appear well and have no known physical limitations, however, it seems unlikely that selection bias
with respect to developmental status, alone or in combination with birth weight status, could have been
large.
Alternatively, bias in the follow-up sample could
have occurred with respect to other risk factors for
DELAY. However, estimates of the differences in the
distribution of risk factors for DELAY between the
larger pools of potential subjects or enrolled survivors
and the final Denver II sample suggest that the demographic and socioeconomic characteristics of children
in the samples were comparable, although children in
the Denver II sample tended to be less disadvantaged
socioeconomically. The results of this analysis possibly reflect a population that, overall, is at no greater
risk and perhaps is at a somewhat lower risk of
DELAY than is the larger population from which it
was drawn.
There was little apparent confounding by the nine
risk factors for DELAY that were included in the
multivariable analysis. In part, this was due to the
striking homogeneous distribution of risk factors
across the birth weight groups. In terms of the effects
of smoking and alcohol use, the variables we used
Am J Epidemiol
distinguished users from nonusers, but could not adjust for the effects of differences in the pattern of use
on the risk for DELAY. Finally, because the Denver II
sample was quite young as a whole (median adjusted
age, 15 months), the influence of socioeconomic factors on development may not have been as strong as
has been observed in older preschool- and school-aged
children (10, 23).
Prior to administering the Denver II, the tester must
determine the adjusted age of the child, a determination that is based on the child's gestational age. Thus,
by virtue of being aware of a child's prematurity, a
tester is not completely unaware of the child's birth
weight status. This knowledge could bias a tester's
judgment of the child's performance. It is possible that
the MMIHS testers (local county health department
staff trained by nurses from the Missouri Department
of Health) could have had a negative bias toward the
performance of children born prematurely, thereby
artificially increasing the prevalence of delay in the
VLBW group relative to the other birth weight groups.
On the other hand, the fact that all children, including
those born prematurely, were presumably well and
without any overt physical impairment could have had
the opposite effect.
In results of a study by Glascoe et al. (24) to assess
the accuracy of the Denver n, the screening test was
Domain-specific performance
Personal-social
1 cautions
1 delays
Language
>1 cautions
>1 delays
Fine motor-adaptive
>1 cautions
>1 delays
Gross motor
1 cautions
>1 delays
MLBWt
(n = 512)
748
Schendel et al.
ACKNOWLEDGMENTS
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