Directory UMM :Data Elmu:jurnal:B:Biological Psichatry:Vol47.Issue11.2000:
Psychiatric Sequelae of Low Birth Weight at
11 Years of Age
Naomi Breslau and Howard D. Chilcoat
Background: We examined the relationship between low
birth weight (LBW) and psychiatric problems at age 11
years.
Methods: Random samples of 6-year-old LBW and normal birth weight (NBW) children from two socioeconomically disparate communities were identified, traced, and
assessed. We targeted the 1983–1985 cohort of newborns
who reached age 6 in 1990 –1992, the scheduled period of
fieldwork. Of the 1,095 in the target sample, 823 (75%)
were assessed. Five years later, the sample was reassessed. Behavior problems were evaluated by standardized behavior problems scales rated by mothers and
teachers. A multiple regression application that combines
data from multiple informants was used. Prospective data
were used to estimate the incidence of severe attention
problems during the follow-up period.
Results: Information from mothers and teachers revealed
that LBW was associated with an excess of attention
problems at age 11 in the urban but not in the suburban
children. In the urban setting, LBW children had a higher
incidence of clinically significant attention problems than
NBW children. Although LBW children scored higher than
NBW children on externalizing problems, the effect was
accounted for in large part by maternal smoking in
pregnancy.
Conclusions: The LBW-attention problems association
observed in the urban community suggests an interaction
between biologic vulnerability associated with premature
birth and environmental risk associated with social disadvantage. Further research and replication are called for.
Biol Psychiatry 2000;47:1005–1011 © 2000 Society of
Biological Psychiatry
Key Words: Low birth weight, attention problems, urban
versus suburban
From the Departments of Psychiatry and Biostatistics & Research Epidemiology,
Henry Ford Health System, Detroit, Michigan (NB, HDC), the Department of
Psychiatry, Case Western Reserve University School of Medicine, Cleveland,
Ohio (NB), and the Department of Psychiatry, University of Michigan School
of Medicine, Ann Arbor (NB).
Address reprint requests to Naomi Breslau, Ph.D., Henry Ford Health System,
Department of Psychiatry, 1 Ford Place, 3A, Detroit MI 48202-3450.
Received August 23, 1999; revised November 30, 1999; accepted December 3,
1999.
© 2000 Society of Biological Psychiatry
Introduction
L
ow birth weight (LBW) serves as a marker for
defining high-risk newborns, as it is correlated with
prenatal risk factors, intrapartum complications, and neonatal disease, and is comprised primarily of premature
births. The commonly used definition of 2500 g for LBW
provides striking contrasts in mortality and morbidity,
although a relationship with some outcomes can be observed up to 3500 to 4000 g (Kleinman 1992). The
improved survival of LBW infants has provided a compelling rationale for continued research into later development of LBW children.
With few exceptions, recent studies on the long-term
neuropsychiatric sequelae of LBW have focused on the
extreme low end of the birth weight distribution, that is,
very low birth weight (#1500 g) or extremely low birth
weight (#1000 or even #750 g). Very low birth weight
(VLBW) is associated with high rates of peri- or intraventricular hemorrhage, severe respiratory distress syndrome,
and other neonatal diseases with severe neurologic and
cognitive consequences. Follow-up studies of VLBW
children at school age have documented increased rates of
behavioral and cognitive problems, even in the absence of
neurologic abnormalities identified in infancy or early
childhood. A distinct pattern of behavior problems has
been suggested, with high levels of activity and inattention
(Buka et al 1992; Hack et al 1992; McCormick et al 1990).
An increased risk for attention-deficit/hyperactivity disorder (ADHD) was reported in VLBW children (Botting et
al 1997; Szatmari et al 1990). The few studies that
included a wider range of the LBW distribution suggest
that the increased prevalence of psychiatric problems is
not confined to the VLBW range but applies also to LBW
children with birth weight greater than 1500 g (McCormick et al 1996, 1992).
We previously reported on the psychiatric sequelae of
LBW (#2500 g) at 6 years of age, based on data on LBW
and normal birth weight (NBW) children randomly selected from an urban, largely disadvantaged community,
and a suburban middle class community (Breslau et al
1996a). Based on mothers’ reports elicited by structured
diagnostic interviews, a higher prevalence of DSM-III-R
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1006
N. Breslau and H.D. Chilcoat
BIOL PSYCHIATRY
2000;47:1005–1011
ADHD was observed in LBW versus NBW children,
primarily in the urban setting. Data from teachers on a
standardized behavior problem checklist revealed an excess in attention problems in LBW versus NBW children,
and the magnitude of the excess was greater in urban than
suburban children. Mothers’ ratings on a parallel behavior
checklist yielded consistent findings with those from
teachers’ ratings.
This report focuses on the psychiatric sequelae of LBW
at 11 years of age, using both mothers’ and teachers’
ratings of attention, externalizing, and internalizing problems. The statistical method used in this study combines
data from both informants for estimating the effects of
LBW on behavior problems. The approach evaluates the
extent to which the estimated effect of LBW on behavior
problems varies between the two types of informants and
across settings. We test whether the previously observed
LBW effects on attention problems and their differential
magnitude in the urban versus suburban setting are in
evidence at 11 years of age, and whether LBW children
have a higher incidence of clinically significant inattention
during the 5-year follow-up interval. We also test the
effects of LBW on externalizing and internalizing problems, areas on which the evidence at 6 years of age was
less clear.
Methods and Materials
Sample and Data
Random samples of 6-year-old LBW and NBW children from
two socioeconomically disparate populations were identified,
traced, and assessed. The 1983–1985 cohort of newborns who
reached 6 years of age in 1990 –1992, the scheduled period of
fieldwork, were targeted. Two major hospitals in southeast
Michigan were selected, one in the city of Detroit (urban) and the
other in a nearby middle-class suburb (suburban). In each
hospital, for each year from 1983 through 1985, random samples
of LBW and normal birth weight newborns were drawn. Children
with severe neurologic impairment, chiefly cerebral palsy, severe
mental retardation, or blindness, were excluded. Of the 1095 in
the target sample, 823 (75%) participated in the assessment at 6
years of age. Children were assessed as they passed their sixth
birthday, with those born in 1983 assessed in 1990 and those
born in 1984 and 1985 assessed in 1991 and 1992, respectively.
(Detailed information on the sample and the population has been
published [Breslau et al 1994, 1996a].)
Five years later, in 1995–1997, the sample was reassessed,
with children in each birth year cohort evaluated as they passed
their eleventh birthday. Of the total sample of 823 who were
assessed at 6 years of age, 32 (3.9%) moved out of state. Of the
target sample of 791 remaining in the Detroit area, 717 (90.6%)
were reassessed (Breslau et al 2000). At both assessments,
written informed consent was obtained from the mothers.
Behavior problems in the children were evaluated by the Child
Behavior Checklist (CBCL) rated by mothers, and the Teacher
Report Form (TRF) rated by teachers (Achenbach 1991a,
1991b). All assessments were conducted blindly with respect to
the LBW status of the children. Assessments at age 11 were
conducted blindly with respect to the results of the previous
assessment. In this report, we focus on the attention problems
subscale and on the internalizing and externalizing composite
scales. The attention problems subscale has 20 items, among
them the cardinal symptoms of ADHD (e.g., fails to finish things
he/she starts; can’t concentrate, pay attention for long; can’t sit
still; fidgets; daydreams or gets lost in his/her thoughts; difficulty
following directions; impulsive or acts without thinking; messy
work; inattentive, easily distracted; fails to carry out assigned
tasks). The internalizing scale is the sum of three subscales:
withdrawn, somatic complaints, and anxious/depressed. The
externalizing scale is the sum of two subscales: delinquent and
aggressive. T scores based on age and sex distributions of
normative samples were used. Scores on these scales can also be
used to identify children with clinically significant psychopathology by applying empirically based cutoffs to define cases. We
used cutoffs of 60 for the internalizing and externalizing composite scales and a cutoff of 67 for the attention problems
subscale (Achenbach 1991a, 1991b).
Statistical Analysis
A regression analytic strategy, applying generalized estimating
equations (GEE; Diggle et al 1994; Liang and Zeger 1986; Zeger
and Liang 1986), was used to estimate the effects of LBW on the
three areas of children’s problems, namely, attention problems,
internalizing, and externalizing, measured by mothers on the
CBCL and by teachers on the TRF. The statistical approach
allows the use of information from multiple informants (i.e.,
parent and teacher). Estimates of interactions between type of
informant and risk factors determine whether data from multiple
informants can be combined to yield a single more precise
estimate of the effect of a risk factor (e.g., LBW). Also, the
approach permits assessments of interactions between one risk
factor and another (i.e., LBW and urban setting). The method
was proposed by Fitzmaurice et al (1995) for combining data on
children’s psychopathology gathered from multiple informants
and was demonstrated in previous reports from this study. In this
analysis, two data records are used for each child, representing
mother and teacher scores on the CBCL and TRF, respectively.
The basic model used to estimate the effects of LBW is displayed
in the equation below. The equation does not display other terms
that were included in the analysis (i.e., variables adjusted in the
analysis and interactions of secondary interest).
Y 5 a 1 b1 (LBW) 1 b2 (informant) 1 b3 (setting) 1 b4
(LBW 3 informant) 1 b5 (LBW 3 setting), where child’s
outcome (Y) is measured by the t score from the CBCL or TRF;
LBW 5 1 if LBW and 0 if normal birth weight; informant 5 1
if teacher and 0 if mother; setting 5 1 if urban and 0 if suburban.
The interaction coefficient of LBW and informant, b4, tests
whether the estimated effect of LBW varies by type of informant.
Psychiatric Sequelae of Low Birth Weight
BIOL PSYCHIATRY
2000;47:1005–1011
1007
Table 1. Sample Characteristics at First Assessment
Urban
% black
Mother’s education
% ,High school
% High school
% Part college
% College
Maternal age: mean (SD)
% single mothers
% maternal smoking at baseline
% maternal smoking in pregnancy
Age at assessment (months)
Birth weight
% #1,500
% 1,501–2,000
% 2,001–2,500
Apgar score
% 1 min #5
% 5 min #5
% SGA (,10th percentile)
In NICU
% 0 days
% #2 weeks
% .2 weeks
Suburban
LBW
(n 5 238)
NBW
(n 5 176)
LBW
(n 5 235)
NBW
(n 5 174)
80.2
73.9
11.5
3.0
29.8
23.5
37.0
9.7
31.8 (6.4)
37.8
53.5
43.8
79.7 (4.2)
21.6
26.1
38.6
13.6
31.7 (5.5)
32.9
41.7
22.0
79.8 (4.9)
7.2
30.2
39.2
23.4
34.3 (5.0)
14.0
36.0
35.2
80.8 (4.8)
7.5
30.5
33.9
28.2
34.7 (4.8)
8.6
20.1
16.7
80.9 (4.4)
14.7
21.4
63.9
17.4
17.9
64.7
15.6
2.1
24.4
5.8
0.6
21.7
2.6
20.5
4.1
0.0
58.4
13.4
28.2
93.8
6.2
54.5
5.5
40.0
98.9
0.6
0.5
LBW, low birth weight (#2,500 g); NBW, normal birth weight ($2,500 g); SGA, small for gestational age; NICU, neonatal
intensive care unit.
The coefficient for LBW, b1, in this model, which includes an
interaction between LBW and setting, estimates the effect of
LBW in the suburban setting. The corresponding estimate in
urban children is equal to b1 plus b5, the coefficient for the
interaction of LBW and setting (which estimates the difference
between the effect of LBW in the urban and the suburban
settings).
GEE provides regression coefficients and their standard errors,
taking the correlation between parents’ and teachers’ ratings into
account. The potential bias due to the fact that the information on
each child comes from two informants is reduced and estimates
are more efficient (Diggle et al 1994; Liang and Zeger 1986;
Zeger and Liang 1986).
The analysis included child’s sex, maternal education, and
maternal history of smoking as covariates. These were introduced in two successive models, with maternal history of
smoking added in the second model to assess its role in the
LBW– behavior problems association. Maternal smoking in
pregnancy is an established risk factor for LBW (Kleinman et al
1988; Kramer 1987). In this study, the rate of smoking in
pregnancy in mothers of LBW children was 39.4%, a substantially higher rate than the rate in mothers of NBW children,
19.3%. Further, maternal smoking has been reported to be
associated with conduct problems in childhood and criminal
behavior in adult males (Brennan et al 1999; Fergusson et al
1998; Ra¨sa¨nen et al 1999; Wakschlag et al 1997; Weitzman et al
1992). Information on maternal smoking was elicited from
mothers at the first assessment when the children were 6 years of
age in two separate sections of the interview. The first is a series
of questions on pregnancy and perinatal history, which included
a question on whether or not the mother smoked daily for at least
2 months during pregnancy. The second is the National Institute
of Mental Health Diagnostic Interview Schedule—Revised, substance use disorders section (Robins et al 1989), which provided
information on smoking status up to the time of the interview.
These data were used to classify mothers into three categories:
smoked during pregnancy, smoked at time of initial assessment
when the child was 6 years of age but not during pregnancy, and
neither. (Only a handful of mothers who smoked during the index
pregnancy did not smoke at the time of the initial assessment.)
Results
Description of Sample
The urban and suburban subsets differed markedly in
racial composition, maternal education, and maternal marital status (Table 1); however, differences between the
LBW and NBW subsets within settings were small. The
urban subset was predominantly black and had a higher
proportion of single mothers and mothers with less than
high school education, compared to the suburban subset. A
comparison of the initial sample of 823 with the follow-up
sample of 717 revealed only minor differences.
1008
N. Breslau and H.D. Chilcoat
BIOL PSYCHIATRY
2000;47:1005–1011
Table 2. Mothers’ and Teachers’ Mean (SD) Ratings at Age
11 of Three Behavior Problems by Low Birth Weight vs.
Normal Birth Weight
Mother
Urban
LBW (n 5 217)
NBW (n 5 164)
Suburban
LBW (n 5 194)
NBW (n 5 142)
Total (n 5 717)
Teacher
Urban
LBW (n 5 186)
NBW (n 5 151)
Suburban
LBW (n 5 180)
NBW (n 5 135)
Total (n 5 652)
Attention
Internalizing
Externalizing
58.8 (9.9)
55.8 (7.3)
52.7 (10.9)
51.5 (10.2)
52.2 (11.4)
50.4 (10.8)
55.1 (7.5)
53.8 (6.7)
56.1 (8.3)
50.4 (10.7)
48.6 (9.7)
51.0 (10.6)
48.4 (10.1)
46.3 (10.3)
49.6 (10.9)
56.9 (8.2)
54.7 (7.0)
50.3 (9.9)
48.8(9.8)
53.9 (10.8)
52.5 (11.0)
53.7 (5.9)
54.0 (6.8)
54.9 (7.2)
49.0 (9.5)
48.7 (9.8)
49.3 (9.7)
48.5 (8.9)
48.3 (7.6)
50.9 (10.0)
Data given as mean (SD). LBW, low birth weight (#2,500 g); NBW, normal
birth weight (.2,500 g).
Mothers’ and Teachers’ Ratings of Behavior
Problems: Descriptive Data
Table 2 presents the data on which the multivariate
analysis was based. According to mothers’ ratings, LBW
children scored higher (i.e., manifesting more problems)
than NBW children in all three behavioral domains.
According to teachers’ ratings, LBW children scored
slightly higher than NBW children on attention and
externalizing problems. Urban children received higher
scores than suburban children on all three behavioral
domains, according to both mothers and teachers.
Results from GEE Analysis of the Combined Data
from Mothers and Teachers
Table 3 presents results from GEE models that estimate
the effects of LBW on behavior problems as continuous
measures, adjusted for setting (urban vs. suburban), child’s
Table 3. Regression Estimates and Standard Errors (in
Parentheses) of Behavior Problems at Age 11 from
Generalized Estimating Equation Analysis of Mothers’ and
Teachers’ Data
LBW (vs. NBW)
Teacher (vs. mother)
Urban (vs. suburban)
Male (vs. female)
Mom , college (vs.
college)
LBW 3 urban
Attention
Externalizing
Internalizing
.46 (.63)
21.19a (.33)
1.21 (.68)
1.49a (.47)
2.06a (.54)
1.26a (.63)
1.33a (.45)
3.93a (.64)
1.57a (.63)
3.99a (.77)
1.14 (.59)
21.70a (.50)
1.68a (.61)
.53 (.59)
.60 (.74)
—
—
2.14a (.93)
LBW, low birth weight (#2,500 g); NBW, normal birth weight ($2,500 g).
a
Coefficient exceeds twice its standard error (p , .05).
sex, informant (teacher vs. mother), and maternal education (,college vs. college). Regression coefficients and
standard errors are presented. These coefficients represent
differences in the mean standardized ratings of behavior
problems associated with each of the independent variables, adjusted for all the other variables in the model. A
positive value that exceeds twice its standard error indicates a statistically significant (,.05) excess in behavior
problems associated with a given category, relative to the
reference category. Interactions between informant and
LBW or other risk factors were not significant, even when
a liberal a was used (p , .15). The absence of a significant
two-way interaction between informant and LBW and a
three-way interaction of these two variables with setting
indicates that the effects of LBW on behavior problems
did not vary by type of informant.
A significant interaction between LBW and urban
setting was observed for attention problems (p 5 .02;
Table 3). Specifically, the results show a small and
nonsignificant LBW effect in suburban children (estimated by the coefficient of LBW, i.e., .46), whereas the LBW
effect in urban children was large and statistically significant (estimated by the sum of the coefficients of LBW
and LBW 3 urban, (i.e., .46 1 2.14; Table 3).
No interactions were detected between LBW and setting
for externalizing or internalizing problems. For externalizing problems, a significant difference was observed
between LBW and NBW across settings, with LBW
children scoring higher than NBW children. In contrast,
for internalizing problems, the difference between birth
weight groups was not significant.
No significant interactions were found between LBW
and sex with respect to any of the three behavioral
domains; however, there was a trend for a greater LBW
effect on attention problems in males in the urban setting
and on externalizing problems in males across both settings. In each case, the excess in problems associated with
LBW was twice as large in males than in females.
We examined the potentially confounding effects of
maternal smoking on the observed association between
LBW and behavior problems. The results, which appear in
Table 4, show that maternal smoking during pregnancy or
during the child’s early years did not account for the
observed effect of LBW on attention problems in the
urban setting. In contrast, a comparison of the results in
Table 4 to those in Table 3 shows that maternal smoking
accounts in part for the effect of LBW on externalizing
problems: The introduction of maternal smoking into the
model reduced the coefficient of externalizing problems
associated with LBW from 1.26 to .77, which was no
longer statistically significant. No interactions were detected between maternal smoking and sex or LBW.
Apart from the observed relationship between LBW and
Psychiatric Sequelae of Low Birth Weight
BIOL PSYCHIATRY
2000;47:1005–1011
Table 4. Regression Estimates and Standard Errors (in
Parentheses) of Behavior Problems from Generalized
Estimating Equations Analysis Controlling for Maternal
Smoking
Attention
LBW (vs. NBW)
Teacher (vs. mother)
Urban (vs. suburban)
Male (vs. female)
Less than college
(vs. college)
Smoked in pregnancy
Smoked/not in pregnancyb
LBW 3 Urban
Externalizing Internalizing
.28 (.63)
21.18 (.33)a
1.07 (.69)
1.48 (.47)a
1.82 (.56)a
.77 (.65)
1.34 (.45)a
3.60 (.66)a
1.56 (.63)a
3.28 (.80)a
1.05 (.60)
21.70 (.50)a
1.53 (.63)a
.51 (.60)
.35 (.77)
.90 (.60)
.43 (.77)
2.16 (.93)a
2.55 (.78)a
1.43 (1.05)
—
.68 (.71)
1.27 (1.04)
—
LBW, low birth weight (#2,500 g); NBW, normal birth weight (.2,500 g).
a
Coefficient exceeds twice its standard error (p , .05).
b
Smoked at first assessment when child was 6 years of age but did not report
smoking during pregnancy.
behavior problems, several other findings are of interest.
Urban children scored higher than suburban children on
externalizing and internalizing problems. Child’s sex and
maternal education were related to attention and externalizing problems: On both problem areas boys scored higher
than girls, and children whose mothers had less than
college education scored higher than children of college
educated mothers. Neither sex nor maternal education was
related to internalizing problems. An excess of externalizing problems was observed in children whose mothers
smoked during pregnancy but not in children whose
mothers smoked at the time of the initial interview but not
during pregnancy. The GEE results also revealed differences between informants on all three behavior problem
areas: Compared to mothers, teachers gave higher ratings
on externalizing problems but lower ratings on attention
and internalizing problems.
Additional Analysis: Incidence of Clinically
Significant Attention Problems in Urban Children
at Age 11
Applying cutoffs that define a clinically significant level
of attention problems, we examined the extent to which
LBW urban children showed a higher incidence of a
severe level of attention problems during the 5-year
Table 5. Incidence of Severe Attention Problems in Low Birth
Weight (LBW) vs. Normal Birth Weight (NBW) Urban
Children from 6 to 11 Years of Age
Teachers
LBW (n 5 153)
NBW (n 5 138)
%
11.1
5.8
a
Mothers
%
LBW (n 5 185)
NBW (n 5 156)
17.3b
8.3
Suburban children were excluded from this analysis.
x (1) 5 2.61, p 5 .10.
b 2
x (1) 5 5.93, p 5 .015.
a 2
1009
follow-up interval (Table 5 ). In each of the two analyses,
one based on the CBCL and the other on the TRF, children
who scored above the cutoff point at age 6 were excluded
from the sample as not at risk for incidence of a clinically
significant level of attention problems at age 11. According to mothers’ ratings, there was more than a two-fold
higher incidence of severe attention problems in LBW
versus NBW urban children. Similar results were observed
in teachers’ data (Table 5). A parallel analysis in the
suburban subset detected no differences in the incidence of
clinically significant attention problems between LBW
and NBW children according to either mothers or teachers
(p . .45).
Discussion
Information from mothers and teachers on children’s
behavior problems at age 11 revealed that the effect of
LBW on attention problems differed between the urban
and suburban settings. Specifically, LBW signaled an
excess in children’s attention problems in the urban
disadvantaged community, but not in the suburban middle
class community. This finding was not accounted for by
history of maternal smoking during pregnancy or during
the child’s early years. Furthermore, there was evidence to
suggest that in the urban setting the incidence of clinically
significant attention problems was more than twice as high
in LBW than NBW children. With respect to externalizing
problems, evidence of LBW effects was detected in both
urban and suburban children, but the effect was accounted
for in large part by history of maternal smoking in
pregnancy. No LBW effect was observed with respect to
internalizing problems.
With respect to the role of maternal smoking in child
behavior problems, we found that prenatal exposure to
smoking signaled an increase in externalizing problems
regardless of LBW status, replicating previous reports on
the effects of maternal smoking during pregnancy on
aggression and disruptive behavior in children and criminality in adult males. No association was found between
maternal smoking in pregnancy and children’s attention or
internalizing problems.
In this study, we examined the relationship of LBW
with children’s behavior problems as dimensional variables, measured by standardized ratings by mothers and
teachers. Although behavior problem scales do not yield
psychiatric diagnoses, the utility of dimensional measures,
in terms of clinical correlates and prognosis, has been
emphasized (Jensen and Watanabe 1999).
Another limitation is the reliance on mothers’ reports of
smoking during pregnancy elicited when the children were
6 years of age. Of particular concern is the possibility of
under-reporting; however, a bias of this type would have
1010
BIOL PSYCHIATRY
2000;47:1005–1011
resulted in an under-estimation of the confounding effect
of smoking in pregnancy on the LBW– externalizing
problems association, increasing the likelihood that the
“true” association is smaller than that estimated in this
model.
Important strengths of our approach deserve mention.
Data come from mothers and teachers, allowing a check
on potential bias in mothers’ reports of behavior problems
associated with LBW status (Chilcoat and Breslau 1997).
The correspondence of the findings from teachers, who
can be expected to be blind to the LBW status of children
at 11 years of age, with those of mothers, with respect to
LBW effects on attention problems, is noteworthy. In
addition to the analysis of cross-sectional data at age 11,
we estimated the incidence of new cases of clinically
significant attention problems in LBW and NBW children.
We found that, in the urban settings, LBW children had a
higher incidence of clinically significant attention problems than NBW children. These findings from the prospective data are specific to the urban setting, where we
have also observed LBW effects on attention problems in
the cross-sectional data at age 11 and at age 6.
Interactions between biologic vulnerabilities associated
with LBW and environmental risk associated with social
disadvantage have been previously reported with respect
to some outcomes (Breslau 1995; Levy-Shiff et al 1994;
McCormick et al 1992; McGauhey et al 1991; Werner et
al 1971; Werner and Smith 1982). In previous reports from
this sample we found no evidence of such an interaction
with respect to the effects of LBW on IQ, neuropsychologic tests performance, learning disabilities, and neurologic soft signs (Breslau et al 1994, 1996a, 1996b, 2000;
Johnson and Breslau, in press). On these other outcomes,
adverse effects of LBW were observed in the urban
disadvantaged community and the suburban middle class
community. The possibility that LBW disadvantaged children are vulnerable to the effects of LBW on attention
problems at ages 6 and 11, and to the escalation of
attention problems over time calls for further research and
replication in other samples.
Supported by Grants No. MH-44586 from the National Institute of
Mental Health (NB) and No. DA R29 11952 from the National Institute
of Drug Abuse (HDC).
References
Achenbach TM (1991a): Child Behavior Checklist for Ages
4 –18. Burlington: University of Vermont, Center for Children, Youth, and Families.
Achenbach TM (1991b): Teacher’s Report Form. Burlington:
University of Vermont, Center for Children, Youth, and
Families.
N. Breslau and H.D. Chilcoat
Botting N, Powls A, Cooke RW, Marlow N (1997): Attention
deficit hyperactivity disorders and other psychiatric outcomes
in very low birth weight children at 12 years. J Child Psychol
Psychiatry 38:931–941.
Brennan PA, Grekin ER, Mednick SA (1999): Maternal smoking
during pregnancy and adult male criminal outcomes. Arch
Gen Psychiatry 56:215–219.
Breslau N (1995): Psychiatric sequelae of low birth weight.
Epidemiol Rev 17:96 –106.
Breslau N, Brown GG, DelDotto JE, Kumar S, Ezhuthachan S,
Andreski P, et al (1996a): Psychiatric sequelae of low birth
weight at six years of age. J Abnorm Child Psychol 24:385–
400.
Breslau N, Chilcoat H, DelDotto J, Andreski P, Brown G
(1996b): Low birth weight and neurocognitive status at six
years of age. Biol Psychiatry 40:389 –397.
Breslau N, Chilcoat HD, Johnson EO, Andreski P, Lucia VC
(2000): Neurologic soft signs and low birthweight: Their
association and neuropsychiatric implications. Biol Psychiatry 47:71–79.
Breslau N, DelDotto JE, Brown GG, Kumar S , Ezhuthachan S,
Hufnagle KG (1994): A gradient relationship between low
birth weight and IQ at 6 years of age. Arch Pediatr Adolesc
Med 148:377–383.
Buka SL, Lipsitt LP, Tsuang MT (1992): Emotional and behavioral development of low-birthweight infants. In: Friedman
SL, Sigman MD, editors. The Psychological Development of
Low-Birthweight Children:Annual Advances in Applied Developmental Psychology. Norwood, NJ: Ablex, 187–214.
Chilcoat HD, Breslau N (1997): Does psychiatric history bias
mothers’ reports? An illustration of a new analytic approach.
J Am Acad Child Adolesc Psychiatry 36:971–979.
Diggle PJ, Liang K-Y, Zeger SL (1994): Analysis of Longitudinal Data. New York: Oxford University Press.
Fergusson DM, Woodward LJ, Horwood LJ (1998): Maternal
smoking during pregnancy and psychiatric adjustment in late
adolescence. Arch Gen Psychiatry 55:721–727.
Fitzmaurice GM, Laird NN, Zahner GEP, Daskalakis C (1995):
Bivariate logistic regression analysis of childhood psychopathology ratings using multiple informants. Am J Epidemiol
142:1194 –1203.
Hack M, Breslau N, Aram D, Weissman B, Klein N, BorawskiClark E (1992): The effect of very low birth weight and social
risk on neurocognitive abilities at school age. J Dev Behav
Pediatr 13:412– 420.
Jensen PS, Watanabe HK (1999): Sherlock Holmes and child
psychopathology assessment approaches: The case of the
false-positive. J Am Acad Child Adolesc Psychiatry 38:138 –
146.
Johnson EO, Breslau N (in press): Increased risk of learning
disabilities in low birth weight boys at age 11 years. Biol
Psychiatry.
Kleinman JC (1992): The epidemiology of low birth weight. In:
Friedman SL, Sigman MD, editors. The Psychological Development of Low-Birthweight Children: Annual Advances in
Applied Developmental Psychology. Norwood, NJ: Ablex,
25–35.
Kleinman JC, Pierre MB, Madan JH, Land GH, Schram WF
(1988): The effects of maternal smoking on fetal and infant
mortality. Am J Epidemiol 127:274 –282.
Psychiatric Sequelae of Low Birth Weight
Kramer MS (1987): Determinants of low birth weight: Methodological assessment and meta-analysis. Bull World Health
Organ 65:663–737.
Levy-Shiff R, Einat G, Mogilner MB, Lerman M, Krikler R
(1994): Biological and environmental correlates of developmental outcome of prematurely born infants in early adolescence. J Pediatr Psychol 19:63–78.
Liang K-Y, Zeger SL (1986): Longitudinal data analysis using
generalized linear models. Biometrika 73:13–22.
McCormick MC, Brooks-Gunn J, Workman-Daniels K, Turner J,
Peckham GJ (1992): The health and development status of
very low-birth-weight children at school age. JAMA 267:
2204 –2208.
McCormick MC, Gortmaker SL, Sobol AM (1990): Very low
birth weight children: Behavior problems and school difficulty in a national sample. J Pediatr 117:686 – 693.
McCormick MC, Workman-Daniels K, Brooks-Gunn J (1996):
The behavioral and emotional well-being of school-age children with different birth weights. Pediatrics 97:18 –25.
McGauhey PJ, Starfield BH, Alexander C, Ensminger ME
(1991): Social environment and vulnerability of low birthweight children: A social-epidemiological perspective. Pediatrics 88:943–953.
Ra¨sa¨nen P, Hakko H, Isohanni M, Hodgins S, Ja¨rvelin M-R,
BIOL PSYCHIATRY
2000;47:1005–1011
1011
Tiihonen J (1999): Maternal smoking during pregnancy and
risk of criminal behavior among adult male offspring in the
Northern Finland 1966 birth cohort. Am J Psychiatry 156:
857– 862.
Robins L, Helzer J, Cottler L, Golding E (1989): The NIMH
Diagnostic Interview Schedule, Version III, Revised. St.
Louis: Washington University.
Szatmari P, Saigal S, Rosenbaum P, Campbell D, King S (1990):
Psychiatric disorders at five years among children with
birthweights less than 1000g: A regional perspective. Dev
Med Child Neurol 32:954 –962.
Wakschlag LS, Lahey BB, Loeber R, Green SM, Gordon RA,
Leventhal BL (1997): Maternal smoking during pregnancy
and the risk of conduct disorder in boys. Arch Gen Psychiatry
54:670 – 676.
Weitzman M, Gortmaker S, Sobol A (1992): Maternal smoking
and behavior problems of children. Pediatrics 90:342–349.
Werner EE, Bierman JM, French FE (1971): The Children of
Kauai. Honolulu: University of Hawai Press.
Werner EE, Smith RS (1982): Vulnerable but Invincible: A
Longitudinal Study of Resilient Children and Youth. New
York: McGraw-Hill.
Zeger SL, Liang K-Y (1986): Longitudinal data analysis for
discrete and continuous outcomes. Biometrics 42:121–130.
11 Years of Age
Naomi Breslau and Howard D. Chilcoat
Background: We examined the relationship between low
birth weight (LBW) and psychiatric problems at age 11
years.
Methods: Random samples of 6-year-old LBW and normal birth weight (NBW) children from two socioeconomically disparate communities were identified, traced, and
assessed. We targeted the 1983–1985 cohort of newborns
who reached age 6 in 1990 –1992, the scheduled period of
fieldwork. Of the 1,095 in the target sample, 823 (75%)
were assessed. Five years later, the sample was reassessed. Behavior problems were evaluated by standardized behavior problems scales rated by mothers and
teachers. A multiple regression application that combines
data from multiple informants was used. Prospective data
were used to estimate the incidence of severe attention
problems during the follow-up period.
Results: Information from mothers and teachers revealed
that LBW was associated with an excess of attention
problems at age 11 in the urban but not in the suburban
children. In the urban setting, LBW children had a higher
incidence of clinically significant attention problems than
NBW children. Although LBW children scored higher than
NBW children on externalizing problems, the effect was
accounted for in large part by maternal smoking in
pregnancy.
Conclusions: The LBW-attention problems association
observed in the urban community suggests an interaction
between biologic vulnerability associated with premature
birth and environmental risk associated with social disadvantage. Further research and replication are called for.
Biol Psychiatry 2000;47:1005–1011 © 2000 Society of
Biological Psychiatry
Key Words: Low birth weight, attention problems, urban
versus suburban
From the Departments of Psychiatry and Biostatistics & Research Epidemiology,
Henry Ford Health System, Detroit, Michigan (NB, HDC), the Department of
Psychiatry, Case Western Reserve University School of Medicine, Cleveland,
Ohio (NB), and the Department of Psychiatry, University of Michigan School
of Medicine, Ann Arbor (NB).
Address reprint requests to Naomi Breslau, Ph.D., Henry Ford Health System,
Department of Psychiatry, 1 Ford Place, 3A, Detroit MI 48202-3450.
Received August 23, 1999; revised November 30, 1999; accepted December 3,
1999.
© 2000 Society of Biological Psychiatry
Introduction
L
ow birth weight (LBW) serves as a marker for
defining high-risk newborns, as it is correlated with
prenatal risk factors, intrapartum complications, and neonatal disease, and is comprised primarily of premature
births. The commonly used definition of 2500 g for LBW
provides striking contrasts in mortality and morbidity,
although a relationship with some outcomes can be observed up to 3500 to 4000 g (Kleinman 1992). The
improved survival of LBW infants has provided a compelling rationale for continued research into later development of LBW children.
With few exceptions, recent studies on the long-term
neuropsychiatric sequelae of LBW have focused on the
extreme low end of the birth weight distribution, that is,
very low birth weight (#1500 g) or extremely low birth
weight (#1000 or even #750 g). Very low birth weight
(VLBW) is associated with high rates of peri- or intraventricular hemorrhage, severe respiratory distress syndrome,
and other neonatal diseases with severe neurologic and
cognitive consequences. Follow-up studies of VLBW
children at school age have documented increased rates of
behavioral and cognitive problems, even in the absence of
neurologic abnormalities identified in infancy or early
childhood. A distinct pattern of behavior problems has
been suggested, with high levels of activity and inattention
(Buka et al 1992; Hack et al 1992; McCormick et al 1990).
An increased risk for attention-deficit/hyperactivity disorder (ADHD) was reported in VLBW children (Botting et
al 1997; Szatmari et al 1990). The few studies that
included a wider range of the LBW distribution suggest
that the increased prevalence of psychiatric problems is
not confined to the VLBW range but applies also to LBW
children with birth weight greater than 1500 g (McCormick et al 1996, 1992).
We previously reported on the psychiatric sequelae of
LBW (#2500 g) at 6 years of age, based on data on LBW
and normal birth weight (NBW) children randomly selected from an urban, largely disadvantaged community,
and a suburban middle class community (Breslau et al
1996a). Based on mothers’ reports elicited by structured
diagnostic interviews, a higher prevalence of DSM-III-R
0006-3223/00/$20.00
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1006
N. Breslau and H.D. Chilcoat
BIOL PSYCHIATRY
2000;47:1005–1011
ADHD was observed in LBW versus NBW children,
primarily in the urban setting. Data from teachers on a
standardized behavior problem checklist revealed an excess in attention problems in LBW versus NBW children,
and the magnitude of the excess was greater in urban than
suburban children. Mothers’ ratings on a parallel behavior
checklist yielded consistent findings with those from
teachers’ ratings.
This report focuses on the psychiatric sequelae of LBW
at 11 years of age, using both mothers’ and teachers’
ratings of attention, externalizing, and internalizing problems. The statistical method used in this study combines
data from both informants for estimating the effects of
LBW on behavior problems. The approach evaluates the
extent to which the estimated effect of LBW on behavior
problems varies between the two types of informants and
across settings. We test whether the previously observed
LBW effects on attention problems and their differential
magnitude in the urban versus suburban setting are in
evidence at 11 years of age, and whether LBW children
have a higher incidence of clinically significant inattention
during the 5-year follow-up interval. We also test the
effects of LBW on externalizing and internalizing problems, areas on which the evidence at 6 years of age was
less clear.
Methods and Materials
Sample and Data
Random samples of 6-year-old LBW and NBW children from
two socioeconomically disparate populations were identified,
traced, and assessed. The 1983–1985 cohort of newborns who
reached 6 years of age in 1990 –1992, the scheduled period of
fieldwork, were targeted. Two major hospitals in southeast
Michigan were selected, one in the city of Detroit (urban) and the
other in a nearby middle-class suburb (suburban). In each
hospital, for each year from 1983 through 1985, random samples
of LBW and normal birth weight newborns were drawn. Children
with severe neurologic impairment, chiefly cerebral palsy, severe
mental retardation, or blindness, were excluded. Of the 1095 in
the target sample, 823 (75%) participated in the assessment at 6
years of age. Children were assessed as they passed their sixth
birthday, with those born in 1983 assessed in 1990 and those
born in 1984 and 1985 assessed in 1991 and 1992, respectively.
(Detailed information on the sample and the population has been
published [Breslau et al 1994, 1996a].)
Five years later, in 1995–1997, the sample was reassessed,
with children in each birth year cohort evaluated as they passed
their eleventh birthday. Of the total sample of 823 who were
assessed at 6 years of age, 32 (3.9%) moved out of state. Of the
target sample of 791 remaining in the Detroit area, 717 (90.6%)
were reassessed (Breslau et al 2000). At both assessments,
written informed consent was obtained from the mothers.
Behavior problems in the children were evaluated by the Child
Behavior Checklist (CBCL) rated by mothers, and the Teacher
Report Form (TRF) rated by teachers (Achenbach 1991a,
1991b). All assessments were conducted blindly with respect to
the LBW status of the children. Assessments at age 11 were
conducted blindly with respect to the results of the previous
assessment. In this report, we focus on the attention problems
subscale and on the internalizing and externalizing composite
scales. The attention problems subscale has 20 items, among
them the cardinal symptoms of ADHD (e.g., fails to finish things
he/she starts; can’t concentrate, pay attention for long; can’t sit
still; fidgets; daydreams or gets lost in his/her thoughts; difficulty
following directions; impulsive or acts without thinking; messy
work; inattentive, easily distracted; fails to carry out assigned
tasks). The internalizing scale is the sum of three subscales:
withdrawn, somatic complaints, and anxious/depressed. The
externalizing scale is the sum of two subscales: delinquent and
aggressive. T scores based on age and sex distributions of
normative samples were used. Scores on these scales can also be
used to identify children with clinically significant psychopathology by applying empirically based cutoffs to define cases. We
used cutoffs of 60 for the internalizing and externalizing composite scales and a cutoff of 67 for the attention problems
subscale (Achenbach 1991a, 1991b).
Statistical Analysis
A regression analytic strategy, applying generalized estimating
equations (GEE; Diggle et al 1994; Liang and Zeger 1986; Zeger
and Liang 1986), was used to estimate the effects of LBW on the
three areas of children’s problems, namely, attention problems,
internalizing, and externalizing, measured by mothers on the
CBCL and by teachers on the TRF. The statistical approach
allows the use of information from multiple informants (i.e.,
parent and teacher). Estimates of interactions between type of
informant and risk factors determine whether data from multiple
informants can be combined to yield a single more precise
estimate of the effect of a risk factor (e.g., LBW). Also, the
approach permits assessments of interactions between one risk
factor and another (i.e., LBW and urban setting). The method
was proposed by Fitzmaurice et al (1995) for combining data on
children’s psychopathology gathered from multiple informants
and was demonstrated in previous reports from this study. In this
analysis, two data records are used for each child, representing
mother and teacher scores on the CBCL and TRF, respectively.
The basic model used to estimate the effects of LBW is displayed
in the equation below. The equation does not display other terms
that were included in the analysis (i.e., variables adjusted in the
analysis and interactions of secondary interest).
Y 5 a 1 b1 (LBW) 1 b2 (informant) 1 b3 (setting) 1 b4
(LBW 3 informant) 1 b5 (LBW 3 setting), where child’s
outcome (Y) is measured by the t score from the CBCL or TRF;
LBW 5 1 if LBW and 0 if normal birth weight; informant 5 1
if teacher and 0 if mother; setting 5 1 if urban and 0 if suburban.
The interaction coefficient of LBW and informant, b4, tests
whether the estimated effect of LBW varies by type of informant.
Psychiatric Sequelae of Low Birth Weight
BIOL PSYCHIATRY
2000;47:1005–1011
1007
Table 1. Sample Characteristics at First Assessment
Urban
% black
Mother’s education
% ,High school
% High school
% Part college
% College
Maternal age: mean (SD)
% single mothers
% maternal smoking at baseline
% maternal smoking in pregnancy
Age at assessment (months)
Birth weight
% #1,500
% 1,501–2,000
% 2,001–2,500
Apgar score
% 1 min #5
% 5 min #5
% SGA (,10th percentile)
In NICU
% 0 days
% #2 weeks
% .2 weeks
Suburban
LBW
(n 5 238)
NBW
(n 5 176)
LBW
(n 5 235)
NBW
(n 5 174)
80.2
73.9
11.5
3.0
29.8
23.5
37.0
9.7
31.8 (6.4)
37.8
53.5
43.8
79.7 (4.2)
21.6
26.1
38.6
13.6
31.7 (5.5)
32.9
41.7
22.0
79.8 (4.9)
7.2
30.2
39.2
23.4
34.3 (5.0)
14.0
36.0
35.2
80.8 (4.8)
7.5
30.5
33.9
28.2
34.7 (4.8)
8.6
20.1
16.7
80.9 (4.4)
14.7
21.4
63.9
17.4
17.9
64.7
15.6
2.1
24.4
5.8
0.6
21.7
2.6
20.5
4.1
0.0
58.4
13.4
28.2
93.8
6.2
54.5
5.5
40.0
98.9
0.6
0.5
LBW, low birth weight (#2,500 g); NBW, normal birth weight ($2,500 g); SGA, small for gestational age; NICU, neonatal
intensive care unit.
The coefficient for LBW, b1, in this model, which includes an
interaction between LBW and setting, estimates the effect of
LBW in the suburban setting. The corresponding estimate in
urban children is equal to b1 plus b5, the coefficient for the
interaction of LBW and setting (which estimates the difference
between the effect of LBW in the urban and the suburban
settings).
GEE provides regression coefficients and their standard errors,
taking the correlation between parents’ and teachers’ ratings into
account. The potential bias due to the fact that the information on
each child comes from two informants is reduced and estimates
are more efficient (Diggle et al 1994; Liang and Zeger 1986;
Zeger and Liang 1986).
The analysis included child’s sex, maternal education, and
maternal history of smoking as covariates. These were introduced in two successive models, with maternal history of
smoking added in the second model to assess its role in the
LBW– behavior problems association. Maternal smoking in
pregnancy is an established risk factor for LBW (Kleinman et al
1988; Kramer 1987). In this study, the rate of smoking in
pregnancy in mothers of LBW children was 39.4%, a substantially higher rate than the rate in mothers of NBW children,
19.3%. Further, maternal smoking has been reported to be
associated with conduct problems in childhood and criminal
behavior in adult males (Brennan et al 1999; Fergusson et al
1998; Ra¨sa¨nen et al 1999; Wakschlag et al 1997; Weitzman et al
1992). Information on maternal smoking was elicited from
mothers at the first assessment when the children were 6 years of
age in two separate sections of the interview. The first is a series
of questions on pregnancy and perinatal history, which included
a question on whether or not the mother smoked daily for at least
2 months during pregnancy. The second is the National Institute
of Mental Health Diagnostic Interview Schedule—Revised, substance use disorders section (Robins et al 1989), which provided
information on smoking status up to the time of the interview.
These data were used to classify mothers into three categories:
smoked during pregnancy, smoked at time of initial assessment
when the child was 6 years of age but not during pregnancy, and
neither. (Only a handful of mothers who smoked during the index
pregnancy did not smoke at the time of the initial assessment.)
Results
Description of Sample
The urban and suburban subsets differed markedly in
racial composition, maternal education, and maternal marital status (Table 1); however, differences between the
LBW and NBW subsets within settings were small. The
urban subset was predominantly black and had a higher
proportion of single mothers and mothers with less than
high school education, compared to the suburban subset. A
comparison of the initial sample of 823 with the follow-up
sample of 717 revealed only minor differences.
1008
N. Breslau and H.D. Chilcoat
BIOL PSYCHIATRY
2000;47:1005–1011
Table 2. Mothers’ and Teachers’ Mean (SD) Ratings at Age
11 of Three Behavior Problems by Low Birth Weight vs.
Normal Birth Weight
Mother
Urban
LBW (n 5 217)
NBW (n 5 164)
Suburban
LBW (n 5 194)
NBW (n 5 142)
Total (n 5 717)
Teacher
Urban
LBW (n 5 186)
NBW (n 5 151)
Suburban
LBW (n 5 180)
NBW (n 5 135)
Total (n 5 652)
Attention
Internalizing
Externalizing
58.8 (9.9)
55.8 (7.3)
52.7 (10.9)
51.5 (10.2)
52.2 (11.4)
50.4 (10.8)
55.1 (7.5)
53.8 (6.7)
56.1 (8.3)
50.4 (10.7)
48.6 (9.7)
51.0 (10.6)
48.4 (10.1)
46.3 (10.3)
49.6 (10.9)
56.9 (8.2)
54.7 (7.0)
50.3 (9.9)
48.8(9.8)
53.9 (10.8)
52.5 (11.0)
53.7 (5.9)
54.0 (6.8)
54.9 (7.2)
49.0 (9.5)
48.7 (9.8)
49.3 (9.7)
48.5 (8.9)
48.3 (7.6)
50.9 (10.0)
Data given as mean (SD). LBW, low birth weight (#2,500 g); NBW, normal
birth weight (.2,500 g).
Mothers’ and Teachers’ Ratings of Behavior
Problems: Descriptive Data
Table 2 presents the data on which the multivariate
analysis was based. According to mothers’ ratings, LBW
children scored higher (i.e., manifesting more problems)
than NBW children in all three behavioral domains.
According to teachers’ ratings, LBW children scored
slightly higher than NBW children on attention and
externalizing problems. Urban children received higher
scores than suburban children on all three behavioral
domains, according to both mothers and teachers.
Results from GEE Analysis of the Combined Data
from Mothers and Teachers
Table 3 presents results from GEE models that estimate
the effects of LBW on behavior problems as continuous
measures, adjusted for setting (urban vs. suburban), child’s
Table 3. Regression Estimates and Standard Errors (in
Parentheses) of Behavior Problems at Age 11 from
Generalized Estimating Equation Analysis of Mothers’ and
Teachers’ Data
LBW (vs. NBW)
Teacher (vs. mother)
Urban (vs. suburban)
Male (vs. female)
Mom , college (vs.
college)
LBW 3 urban
Attention
Externalizing
Internalizing
.46 (.63)
21.19a (.33)
1.21 (.68)
1.49a (.47)
2.06a (.54)
1.26a (.63)
1.33a (.45)
3.93a (.64)
1.57a (.63)
3.99a (.77)
1.14 (.59)
21.70a (.50)
1.68a (.61)
.53 (.59)
.60 (.74)
—
—
2.14a (.93)
LBW, low birth weight (#2,500 g); NBW, normal birth weight ($2,500 g).
a
Coefficient exceeds twice its standard error (p , .05).
sex, informant (teacher vs. mother), and maternal education (,college vs. college). Regression coefficients and
standard errors are presented. These coefficients represent
differences in the mean standardized ratings of behavior
problems associated with each of the independent variables, adjusted for all the other variables in the model. A
positive value that exceeds twice its standard error indicates a statistically significant (,.05) excess in behavior
problems associated with a given category, relative to the
reference category. Interactions between informant and
LBW or other risk factors were not significant, even when
a liberal a was used (p , .15). The absence of a significant
two-way interaction between informant and LBW and a
three-way interaction of these two variables with setting
indicates that the effects of LBW on behavior problems
did not vary by type of informant.
A significant interaction between LBW and urban
setting was observed for attention problems (p 5 .02;
Table 3). Specifically, the results show a small and
nonsignificant LBW effect in suburban children (estimated by the coefficient of LBW, i.e., .46), whereas the LBW
effect in urban children was large and statistically significant (estimated by the sum of the coefficients of LBW
and LBW 3 urban, (i.e., .46 1 2.14; Table 3).
No interactions were detected between LBW and setting
for externalizing or internalizing problems. For externalizing problems, a significant difference was observed
between LBW and NBW across settings, with LBW
children scoring higher than NBW children. In contrast,
for internalizing problems, the difference between birth
weight groups was not significant.
No significant interactions were found between LBW
and sex with respect to any of the three behavioral
domains; however, there was a trend for a greater LBW
effect on attention problems in males in the urban setting
and on externalizing problems in males across both settings. In each case, the excess in problems associated with
LBW was twice as large in males than in females.
We examined the potentially confounding effects of
maternal smoking on the observed association between
LBW and behavior problems. The results, which appear in
Table 4, show that maternal smoking during pregnancy or
during the child’s early years did not account for the
observed effect of LBW on attention problems in the
urban setting. In contrast, a comparison of the results in
Table 4 to those in Table 3 shows that maternal smoking
accounts in part for the effect of LBW on externalizing
problems: The introduction of maternal smoking into the
model reduced the coefficient of externalizing problems
associated with LBW from 1.26 to .77, which was no
longer statistically significant. No interactions were detected between maternal smoking and sex or LBW.
Apart from the observed relationship between LBW and
Psychiatric Sequelae of Low Birth Weight
BIOL PSYCHIATRY
2000;47:1005–1011
Table 4. Regression Estimates and Standard Errors (in
Parentheses) of Behavior Problems from Generalized
Estimating Equations Analysis Controlling for Maternal
Smoking
Attention
LBW (vs. NBW)
Teacher (vs. mother)
Urban (vs. suburban)
Male (vs. female)
Less than college
(vs. college)
Smoked in pregnancy
Smoked/not in pregnancyb
LBW 3 Urban
Externalizing Internalizing
.28 (.63)
21.18 (.33)a
1.07 (.69)
1.48 (.47)a
1.82 (.56)a
.77 (.65)
1.34 (.45)a
3.60 (.66)a
1.56 (.63)a
3.28 (.80)a
1.05 (.60)
21.70 (.50)a
1.53 (.63)a
.51 (.60)
.35 (.77)
.90 (.60)
.43 (.77)
2.16 (.93)a
2.55 (.78)a
1.43 (1.05)
—
.68 (.71)
1.27 (1.04)
—
LBW, low birth weight (#2,500 g); NBW, normal birth weight (.2,500 g).
a
Coefficient exceeds twice its standard error (p , .05).
b
Smoked at first assessment when child was 6 years of age but did not report
smoking during pregnancy.
behavior problems, several other findings are of interest.
Urban children scored higher than suburban children on
externalizing and internalizing problems. Child’s sex and
maternal education were related to attention and externalizing problems: On both problem areas boys scored higher
than girls, and children whose mothers had less than
college education scored higher than children of college
educated mothers. Neither sex nor maternal education was
related to internalizing problems. An excess of externalizing problems was observed in children whose mothers
smoked during pregnancy but not in children whose
mothers smoked at the time of the initial interview but not
during pregnancy. The GEE results also revealed differences between informants on all three behavior problem
areas: Compared to mothers, teachers gave higher ratings
on externalizing problems but lower ratings on attention
and internalizing problems.
Additional Analysis: Incidence of Clinically
Significant Attention Problems in Urban Children
at Age 11
Applying cutoffs that define a clinically significant level
of attention problems, we examined the extent to which
LBW urban children showed a higher incidence of a
severe level of attention problems during the 5-year
Table 5. Incidence of Severe Attention Problems in Low Birth
Weight (LBW) vs. Normal Birth Weight (NBW) Urban
Children from 6 to 11 Years of Age
Teachers
LBW (n 5 153)
NBW (n 5 138)
%
11.1
5.8
a
Mothers
%
LBW (n 5 185)
NBW (n 5 156)
17.3b
8.3
Suburban children were excluded from this analysis.
x (1) 5 2.61, p 5 .10.
b 2
x (1) 5 5.93, p 5 .015.
a 2
1009
follow-up interval (Table 5 ). In each of the two analyses,
one based on the CBCL and the other on the TRF, children
who scored above the cutoff point at age 6 were excluded
from the sample as not at risk for incidence of a clinically
significant level of attention problems at age 11. According to mothers’ ratings, there was more than a two-fold
higher incidence of severe attention problems in LBW
versus NBW urban children. Similar results were observed
in teachers’ data (Table 5). A parallel analysis in the
suburban subset detected no differences in the incidence of
clinically significant attention problems between LBW
and NBW children according to either mothers or teachers
(p . .45).
Discussion
Information from mothers and teachers on children’s
behavior problems at age 11 revealed that the effect of
LBW on attention problems differed between the urban
and suburban settings. Specifically, LBW signaled an
excess in children’s attention problems in the urban
disadvantaged community, but not in the suburban middle
class community. This finding was not accounted for by
history of maternal smoking during pregnancy or during
the child’s early years. Furthermore, there was evidence to
suggest that in the urban setting the incidence of clinically
significant attention problems was more than twice as high
in LBW than NBW children. With respect to externalizing
problems, evidence of LBW effects was detected in both
urban and suburban children, but the effect was accounted
for in large part by history of maternal smoking in
pregnancy. No LBW effect was observed with respect to
internalizing problems.
With respect to the role of maternal smoking in child
behavior problems, we found that prenatal exposure to
smoking signaled an increase in externalizing problems
regardless of LBW status, replicating previous reports on
the effects of maternal smoking during pregnancy on
aggression and disruptive behavior in children and criminality in adult males. No association was found between
maternal smoking in pregnancy and children’s attention or
internalizing problems.
In this study, we examined the relationship of LBW
with children’s behavior problems as dimensional variables, measured by standardized ratings by mothers and
teachers. Although behavior problem scales do not yield
psychiatric diagnoses, the utility of dimensional measures,
in terms of clinical correlates and prognosis, has been
emphasized (Jensen and Watanabe 1999).
Another limitation is the reliance on mothers’ reports of
smoking during pregnancy elicited when the children were
6 years of age. Of particular concern is the possibility of
under-reporting; however, a bias of this type would have
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2000;47:1005–1011
resulted in an under-estimation of the confounding effect
of smoking in pregnancy on the LBW– externalizing
problems association, increasing the likelihood that the
“true” association is smaller than that estimated in this
model.
Important strengths of our approach deserve mention.
Data come from mothers and teachers, allowing a check
on potential bias in mothers’ reports of behavior problems
associated with LBW status (Chilcoat and Breslau 1997).
The correspondence of the findings from teachers, who
can be expected to be blind to the LBW status of children
at 11 years of age, with those of mothers, with respect to
LBW effects on attention problems, is noteworthy. In
addition to the analysis of cross-sectional data at age 11,
we estimated the incidence of new cases of clinically
significant attention problems in LBW and NBW children.
We found that, in the urban settings, LBW children had a
higher incidence of clinically significant attention problems than NBW children. These findings from the prospective data are specific to the urban setting, where we
have also observed LBW effects on attention problems in
the cross-sectional data at age 11 and at age 6.
Interactions between biologic vulnerabilities associated
with LBW and environmental risk associated with social
disadvantage have been previously reported with respect
to some outcomes (Breslau 1995; Levy-Shiff et al 1994;
McCormick et al 1992; McGauhey et al 1991; Werner et
al 1971; Werner and Smith 1982). In previous reports from
this sample we found no evidence of such an interaction
with respect to the effects of LBW on IQ, neuropsychologic tests performance, learning disabilities, and neurologic soft signs (Breslau et al 1994, 1996a, 1996b, 2000;
Johnson and Breslau, in press). On these other outcomes,
adverse effects of LBW were observed in the urban
disadvantaged community and the suburban middle class
community. The possibility that LBW disadvantaged children are vulnerable to the effects of LBW on attention
problems at ages 6 and 11, and to the escalation of
attention problems over time calls for further research and
replication in other samples.
Supported by Grants No. MH-44586 from the National Institute of
Mental Health (NB) and No. DA R29 11952 from the National Institute
of Drug Abuse (HDC).
References
Achenbach TM (1991a): Child Behavior Checklist for Ages
4 –18. Burlington: University of Vermont, Center for Children, Youth, and Families.
Achenbach TM (1991b): Teacher’s Report Form. Burlington:
University of Vermont, Center for Children, Youth, and
Families.
N. Breslau and H.D. Chilcoat
Botting N, Powls A, Cooke RW, Marlow N (1997): Attention
deficit hyperactivity disorders and other psychiatric outcomes
in very low birth weight children at 12 years. J Child Psychol
Psychiatry 38:931–941.
Brennan PA, Grekin ER, Mednick SA (1999): Maternal smoking
during pregnancy and adult male criminal outcomes. Arch
Gen Psychiatry 56:215–219.
Breslau N (1995): Psychiatric sequelae of low birth weight.
Epidemiol Rev 17:96 –106.
Breslau N, Brown GG, DelDotto JE, Kumar S, Ezhuthachan S,
Andreski P, et al (1996a): Psychiatric sequelae of low birth
weight at six years of age. J Abnorm Child Psychol 24:385–
400.
Breslau N, Chilcoat H, DelDotto J, Andreski P, Brown G
(1996b): Low birth weight and neurocognitive status at six
years of age. Biol Psychiatry 40:389 –397.
Breslau N, Chilcoat HD, Johnson EO, Andreski P, Lucia VC
(2000): Neurologic soft signs and low birthweight: Their
association and neuropsychiatric implications. Biol Psychiatry 47:71–79.
Breslau N, DelDotto JE, Brown GG, Kumar S , Ezhuthachan S,
Hufnagle KG (1994): A gradient relationship between low
birth weight and IQ at 6 years of age. Arch Pediatr Adolesc
Med 148:377–383.
Buka SL, Lipsitt LP, Tsuang MT (1992): Emotional and behavioral development of low-birthweight infants. In: Friedman
SL, Sigman MD, editors. The Psychological Development of
Low-Birthweight Children:Annual Advances in Applied Developmental Psychology. Norwood, NJ: Ablex, 187–214.
Chilcoat HD, Breslau N (1997): Does psychiatric history bias
mothers’ reports? An illustration of a new analytic approach.
J Am Acad Child Adolesc Psychiatry 36:971–979.
Diggle PJ, Liang K-Y, Zeger SL (1994): Analysis of Longitudinal Data. New York: Oxford University Press.
Fergusson DM, Woodward LJ, Horwood LJ (1998): Maternal
smoking during pregnancy and psychiatric adjustment in late
adolescence. Arch Gen Psychiatry 55:721–727.
Fitzmaurice GM, Laird NN, Zahner GEP, Daskalakis C (1995):
Bivariate logistic regression analysis of childhood psychopathology ratings using multiple informants. Am J Epidemiol
142:1194 –1203.
Hack M, Breslau N, Aram D, Weissman B, Klein N, BorawskiClark E (1992): The effect of very low birth weight and social
risk on neurocognitive abilities at school age. J Dev Behav
Pediatr 13:412– 420.
Jensen PS, Watanabe HK (1999): Sherlock Holmes and child
psychopathology assessment approaches: The case of the
false-positive. J Am Acad Child Adolesc Psychiatry 38:138 –
146.
Johnson EO, Breslau N (in press): Increased risk of learning
disabilities in low birth weight boys at age 11 years. Biol
Psychiatry.
Kleinman JC (1992): The epidemiology of low birth weight. In:
Friedman SL, Sigman MD, editors. The Psychological Development of Low-Birthweight Children: Annual Advances in
Applied Developmental Psychology. Norwood, NJ: Ablex,
25–35.
Kleinman JC, Pierre MB, Madan JH, Land GH, Schram WF
(1988): The effects of maternal smoking on fetal and infant
mortality. Am J Epidemiol 127:274 –282.
Psychiatric Sequelae of Low Birth Weight
Kramer MS (1987): Determinants of low birth weight: Methodological assessment and meta-analysis. Bull World Health
Organ 65:663–737.
Levy-Shiff R, Einat G, Mogilner MB, Lerman M, Krikler R
(1994): Biological and environmental correlates of developmental outcome of prematurely born infants in early adolescence. J Pediatr Psychol 19:63–78.
Liang K-Y, Zeger SL (1986): Longitudinal data analysis using
generalized linear models. Biometrika 73:13–22.
McCormick MC, Brooks-Gunn J, Workman-Daniels K, Turner J,
Peckham GJ (1992): The health and development status of
very low-birth-weight children at school age. JAMA 267:
2204 –2208.
McCormick MC, Gortmaker SL, Sobol AM (1990): Very low
birth weight children: Behavior problems and school difficulty in a national sample. J Pediatr 117:686 – 693.
McCormick MC, Workman-Daniels K, Brooks-Gunn J (1996):
The behavioral and emotional well-being of school-age children with different birth weights. Pediatrics 97:18 –25.
McGauhey PJ, Starfield BH, Alexander C, Ensminger ME
(1991): Social environment and vulnerability of low birthweight children: A social-epidemiological perspective. Pediatrics 88:943–953.
Ra¨sa¨nen P, Hakko H, Isohanni M, Hodgins S, Ja¨rvelin M-R,
BIOL PSYCHIATRY
2000;47:1005–1011
1011
Tiihonen J (1999): Maternal smoking during pregnancy and
risk of criminal behavior among adult male offspring in the
Northern Finland 1966 birth cohort. Am J Psychiatry 156:
857– 862.
Robins L, Helzer J, Cottler L, Golding E (1989): The NIMH
Diagnostic Interview Schedule, Version III, Revised. St.
Louis: Washington University.
Szatmari P, Saigal S, Rosenbaum P, Campbell D, King S (1990):
Psychiatric disorders at five years among children with
birthweights less than 1000g: A regional perspective. Dev
Med Child Neurol 32:954 –962.
Wakschlag LS, Lahey BB, Loeber R, Green SM, Gordon RA,
Leventhal BL (1997): Maternal smoking during pregnancy
and the risk of conduct disorder in boys. Arch Gen Psychiatry
54:670 – 676.
Weitzman M, Gortmaker S, Sobol A (1992): Maternal smoking
and behavior problems of children. Pediatrics 90:342–349.
Werner EE, Bierman JM, French FE (1971): The Children of
Kauai. Honolulu: University of Hawai Press.
Werner EE, Smith RS (1982): Vulnerable but Invincible: A
Longitudinal Study of Resilient Children and Youth. New
York: McGraw-Hill.
Zeger SL, Liang K-Y (1986): Longitudinal data analysis for
discrete and continuous outcomes. Biometrics 42:121–130.