Gestational Cocaine Exposure and Intrauterine

Growth: Maternal Lifestyle Study

Henrietta S. Bada, MD, MPH, Abhik Das, PhD, Charles R. Bauer, MD, Seetha Shankaran, MD,
Barry Lester, PhD, Linda L. Wright, MD, Joel Verter, PhD, Vincent L. Smeriglio, PhD,
Loretta P. Finnegan, MD, and Penelope L. Maza, PhD
OBJECTIVE: To estimate the effects of cocaine exposure on
intrauterine growth and to investigate at what point in
gestation growth deviation would be manifested.
METHODS: This is a secondary analysis of data from a
multicenter project, the Maternal Lifestyle Study, designed
to determine infant outcomes of in utero cocaine or opiates
exposure. Four centers of the National Institute of Child
Health and Human Development Neonatal Research Net-
work enrolled 11,811 maternalinfant dyads. A total of
1072 infants were cocaine exposed, 7565 were cocaine neg-
ative by maternal history and meconium results, and 3174
were excluded from analysis because of unconrmed neg-
ative exposure. Outcome measures included birth weight,
length, and head circumference.
RESULTS: Percentile estimates for birth weight, length, and
head circumference revealed growth deceleration in co-
caine-exposed infants evident after 32 weeks gestation.
There was signicant interaction between cocaine and ges-
tational age. After controlling for confounders, at 40 weeks
gestation, cocaine exposure was estimated to be associated
with a decrease of 151 g, 0.71 cm, and 0.43 cm in birth
weight, length, and head circumference, respectively.
Smoking had a negative impact on all growth measure-
ments, with some indication of a doseeffect relationship.
Heavy alcohol use was associated with decrease in weight
and length only. Opiates had signicant effect only on birth
weight.
CONCLUSION: In utero cocaine exposure is associated with
growth deceleration involving all measurements, becom-
ing more pronounced with advancing gestation. (Obstet
Gynecol 2002;100:91624. 2002 by The American Col-
lege of Obstetricians and Gynecologists.)
From the 1999 and 2000 National Household Survey on
Drug Abuse, the annual rates of current use of illicit
drugs, tobacco, and alcohol were 7.5%, 30.3%, and
47.2%, respectively,
1
among women 1544 years old.
Of those women who were pregnant in the same age
group, 3.3%, 19%, and 12.4%, respectively, used illicit
drugs, tobacco, and alcohol, indicating that a large num-
ber of women continued their substance use during
pregnancy. In the United States in 2000, there were
4,063,000 births to women aged 1544 years.
2
Using
estimates of substance use during pregnancy, the ap-
proximate numbers of births in 2000 complicated by
maternal use of illicit drugs, tobacco, and alcohol were
134,079, 774,814, and 503,812, respectively. Thus, from
the public health perspective, the impact of substance use
during pregnancy extends far beyond maternal health to
that of a large number of the unborn population.
Intrauterine growth restriction has been reported in
infants born to drug-abusing mothers. Described mani-
festations of growth restriction in gestational cocaine
exposure included lower birth weight, smaller head cir-
cumference, and decrease in birth length,
35
and in some
studies, only one or two of these parameters were affect-
ed.
68
Reverse pattern of asymmetric growth restric-
tion,
9,10
wherein head circumference is decreased rela-
tive to birth weight, has also been described.
Furthermore, it is not clear at what point in gestation or
fetal life does growth deviation or deceleration become
evident. Effects of drug exposure on growth are also
difcult to assess because of confounding effects of other
factors, such as alcohol, tobacco, marijuana, and mater-
nal medical and obstetric complications.
4,5,11
The objec-
tive of this study was to characterize intrauterine growth
From The University of Kentucky, Lexington, Kentucky; Research Triangle
Institute, Research Triangle Park, North Carolina; University of Miami, Miami,
Florida; Wayne State University, Detroit, Michigan; Brown University, Provi-
dence, Rhode Island; National Institute of Child Health and Human Development,
Bethesda, Maryland; George Washington University, Washington, DC; National
Institute on Drug Abuse, Bethesda, Maryland; Center for Substance Abuse
Treatment, Rockville, Maryland; and Administration for Children, Youth and
Families, Washington, DC.
Supported by National Institutes of Health (NIH) National Institute of Child
Health and Human Development through cooperative agreements:
U10HD27856 (to HSB), U01HD36790 (to AD), U10HD21397 (to CRB),
U10HD21385 (to SS), U10HD27904 (to BL), and U01HD19897 (to JV);
and interagency agreement with the National Institute on Drug Abuse (NIDA),
Administration for Children, Youth and Families (ACYF), and Center for
Substance Abuse Treatment (CAST).
916 VOL. 100, NO. 5, PART 1, NOVEMBER 2002 0029-7844/02/$22.00
2002 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc. PII S0029-7844(02)02199-3
associated with in utero exposure to cocaine, in a large
population recruited and being evaluated prospectively
as part of a multicenter collaborative effort, the Maternal
Lifestyle Study.
12,13
A large study population has the
potential for investigating not only effects of cocaine
exposure on growth but also of other factors. We hy-
pothesized that deviation in growth associated with
in utero cocaine exposure would be evident at each week
of gestation throughout pregnancy, independent of the
effects of other factors, including maternal use of other
substances, such as opiates, alcohol, tobacco, and or
marijuana.
MATERIALS AND METHODS
The Maternal Lifestyle Study is conducted in four cen-
ters of the National Institute of Child Health and Human
Development Neonatal Research Network. These cen-
ters include Brown University, Providence, RI; Univer-
sity of Miami, Miami, FL; The University of Tennessee,
Memphis, TN; and Wayne State University, Detroit,
MI. The Research Triangle Institute, Research Triangle
Park, NC, serves as a data coordinating center, a role
assumed in the early phase of the study by the Biostatis-
tics Coordinating Center of George Washington Uni-
versity, Washington, DC. Detailed description of meth-
ods and subjects enrollment has been reported.
12,13
The
study had approval from the Institutional Review Board
of each participating institution.
Motherinfant dyads from singleton gestations were
recruited from May 1993 to May 1995, if infants birth
weight was at least 500 g and gestational age was less
than 43 weeks by best obstetric estimate. Mothers were
approached in the hospital after delivery, informed con-
sent obtained, and then they were interviewed briey for
history of smoking, alcohol consumption, and drug use
during pregnancy and in the last year. At interview,
tobacco use during pregnancy was categorized into no
smoking, some smoking (less than half a pack per day),
or heavy smoking (at least half a pack per day), and
alcohol consumption into no alcohol, some alcohol (less
than one drink per month), moderate alcohol (13 drinks
per month), or heavy alcohol drinking (at least one drink
per week). A separate question asked whether more than
ve drinks were consumed on any given day (binge).
Mothers were also asked about their date of rst prenatal
care visit, number of visits, and prepregnancy weight.
Meconium was collected and the presence of metabo-
lites determined by gas chromatography/mass spectros-
copy.
13
Trained and certied research staff masked to
exposure status performed physical examination and
obtained growth measurements on the infants. Maternal
and infant medical records were abstracted for informa-
tion on treatment, procedures, diagnoses, maternal age,
weight at delivery admission, hospitalization during
pregnancy, and reproductive history. We dichotomized
prenatal care into inadequate or intermediate and ade-
quate care, based on the Kessner Index.
14
Reproductive
history was dened as abnormal if parity was 5 or if a
mother had 2 previous premature births or abortions.
We dened cocaine exposure as maternal self-report
of cocaine use during pregnancy or meconium analysis
yielded cocaine metabolites. Cocaine-negative infants
were those born to mothers who denied cocaine use,
with conrmation by a negative meconium analysis.
Opiate exposure was similarly determined. All statistical
analyses were done using SAS statistical software (SAS
Institute Inc., Cary, NC). Exploratory statistical analyses
compared demographic and other characteristics be-
tween cocaine-exposed and cocaine-negative infants us-
ing t test (continuous variables) or
2
test (categorical
factors). A nonparametric method (KolmogorovSmir-
nov) was used to compare equality of distributions be-
tween cocaine-exposed and cocaine-negative groups.
Percentile estimates for each growth parameter, (birth
weight, length, and head circumference) at each gesta-
tional age determined by best obstetric estimate were
also graphically compared. These explorations indicated
that cocaine-associated deviation in growth measure-
ments started to become evident after 32 weeks gesta-
tion. Thus, subsequent analyses were carried out after
stratifying the data into gestational ages 32 weeks and
32 weeks.
Multivariate regression models were used to obtain
adjusted effects of cocaine exposure that controlled for
potential confounders. Likely confounders (clinical site,
opiate use, smoking, alcohol, and marijuana use) were
always adjusted for, regardless of statistical signicance.
In addition, other variables or potential confounders
were adjusted for only if they were statistically signi-
cant. These possible confounders included race, gender,
gestational age, interaction terms (cocaine gestational
age, opiate gestational age, cocaine alcohol, co-
caine opiate), and maternal factors: age, Medicaid
insurance, prenatal care, weight gain during pregnancy,
preeclampsia, hematologic disorders, abnormal repro-
ductive history, oligo-polyhydramnios, sexually trans-
mitted diseases, acquired immune deciency, thyroid
dysfunction, any hepatitis, diabetes (insulin dependent),
seizure disorder, chronic hypertension, and any hospital-
ization during pregnancy. A backward selection algo-
rithm was used to eliminate those possible confounders
that were not statistically signicant. For each categorical
factor with more than two levels that was signicant,
pair-wise comparison was carried out to determine the
917 VOL. 100, NO. 5, PART 1, NOVEMBER 2002 Bada et al Cocaine and Birth Measurements
precise nature of the differences between levels of that
factor.
RESULTS
A total of 19,079 motherinfant dyads were screened for
study recruitment. Of these, 16,988 dyads were eligible
for enrollment, and 11,811 (70%) mothers gave consent.
One thousand seventy-two (1072) infants were cocaine
exposed, whereas 7565 were conrmed cocaine nega-
tive. The remaining 3174 infants were born to mothers
who denied cocaine use, but history was unconrmed
because insufcient or no meconium was collected. This
group was excluded from the analysis. Table 1 shows
that maternal and infant characteristics of this group
were similar to the cocaine-negative group. It also shows
that mothers and infants in the cocaine-positive group
were signicantly different from the cocaine-negative
group. Tobacco, alcohol, marijuana, and opiate use were
present in both groups, though the respective prevalence
was much higher in the cocaine-positive group.
Figure 1A compares birth weight distribution between
cocaine-exposed and cocaine-negative groups. The co-
caine-exposed infants had signicantly lower birth
weight, mean ( standard deviation) of 2562 (732) g
compared to 3064 (778) g in the cocaine-negative group
(P .001). Figures 1B, 1C, and 1D, respectively, com-
pare the percentile estimates of birth weight, length, and
head circumference for each gestational age between
cocaine-exposed and cocaine-negative groups. These
plots suggest that deviation in each growth parameter
begins to be evident in cocaine-exposed infants after 32
weeks gestation, becoming progressively more pro-
nounced later in gestation.
Table 2 presents the adjusted effects of cocaine expo-
sure and other factors from multivariate regression anal-
yses for each gestational age stratum. Also shown are
estimates (95% condence interval [CI]) for likely con-
founders as well as possible confounders that were re-
tained in the model because signicant at P .05. At
gestational ages 32 weeks, after controlling for con-
Table 1. Comparison of Maternal and Infant Characteristics in Cocaine-Exposed, Cocaine-Negative, and Unconrmed
Cocaine-Negative Groups
Unconrmed
cocaine
exposure
(n 3174)
Cocaine negative
(n 7565)
Cocaine exposed*
(n 1072)
Maternal characteristics
Age (y) 26.5 (5.8) 26.1 (5.8) 30.2 (4.9)
Black 47 48 79
Married 41 40 13
Medicaid 62 61 86
Education 12 y 73 69 85
Prenatal care
Inadequate 14 12 47
Intermediate 17 17 22
Adequate 69 71 31
Sexually transmitted
diseases
14 14 28
Marijuana use 4 5 40
Smoking 20 20 83
Alcohol 29 31 72
Opiates 0.5 1 9
Infant characteristics
Male 50 52 51

Gestational age (wk)

2532 11 8 16
3336 14 14 27
3742 75 78 57
Birth weight (g)
5011500 8 5 10
15012500 16 16 34
2500 76 79 56
All data are percentages, except age, which is expressed as mean (standard deviation).
* P .001 compared with cocaine-negative group, all variables except infant gender.

Not signicant.
918 Bada et al Cocaine and Birth Measurements OBSTETRICS & GYNECOLOGY
founders, cocaine did not have a signicant effect on
growth. Growth measurements increased with increas-
ing gestational age, but there was no interaction with
cocaine exposure. Neither was there any interaction
between cocaine and alcohol. Opiates, smoking, alcohol,
or marijuana had no signicant effect on growth during
early gestation. Female infants were signicantly smaller
than male infants. Race had an effect only on head
circumference: White infants had larger head circumfer-
ence than black infants. Oligo-polyhydramnios and ab-
normal reproductive history were associated with a de-
crease in all growth parameters, whereas preeclampsia
was associated with lower birth weight and length but
had no effect on head size. Adequate prenatal care was
associated with lower birth weight, length, and head
circumference, when compared with inadequate and
intermediate care. At early gestation, signicantly more
mothers with preeclampsia (76% versus 54%), abnormal
uid volume (65% versus 51%), or previous hospitaliza-
tion during pregnancy (72% versus 66%) had adequate
prenatal care compared with those without these compli-
cations.
After 32 weeks gestation, cocaine exposure was asso-
ciated with signicant deviation in all growth measure-
ments, with substantially larger effects at higher gesta-
tional age. At 40 weeks gestation, adjusted effects of
cocaine exposure (95% CI) for birth weight, length, and
head circumference, respectively, were 151.28 g
(202.6, 100.0), 0.71 cm (1.03, 0.40), and
0.43 cm (0.62, 0.24). Opiates had signicant effect
on birth weight, and some effect on length (P .08) and
had no interaction with cocaine exposure. There was an
interaction between opiate and gestational age for length
(P .03), with signicant negative effect at earlier gesta-
Figure 1. A) Birth weight frequency distribution of cocaine-exposed (cocaine) infants compared to the cocaine-negative
(cocaine) group. BD) Percentile estimates (10th, 50th, and 90th) for birth weight, birth length, and head circumfer-
ence, respectively, for each gestational age comparing the cocaine and cocaine groups.
Bada. Cocaine and Birth Measurements. Obstet Gynecol 2002.
919 VOL. 100, NO. 5, PART 1, NOVEMBER 2002 Bada et al Cocaine and Birth Measurements
Table 2. Results of Multivariate Regression Analyses Showing the Adjusted Effects of Cocaine Exposure on Growth Measurements and Gestational Ages 32
Weeks and 32 Weeks
Variables
Birth weight (g) Birth length (cm) Head circumference (cm)
Coefcient (95% CI) P Coefcient (95% CI) P Coefcient (95% CI) P
Gestational age 32 wk
Cocaine 8.2 (80.4, 96.9) .855 0.25 (1.0, 0.5) .513 0.16 (0.31, 0.63) .502
Opiate 78.1 (230.7, 74.4) .315 0.48 (1.77, 0.8) .460 0.43 (1.23, 0.37) .293
Site 2* 72.0 (3.9, 140.1) .039 0.48 (0.1, 1.05) .104 0.25 (0.11, 0.61) .175
Site 3* 222.8 (147.2, 298.4) .001 1.06 (0.42, 1.70) .001 0.50 (0.09, 0.92) .018
Site 4* 44.4 (43.0, 131.7) .319 0.24 (0.99, 0.5) .520 0.15 (0.69, 0.38) .578
Gestational age (per wk) 145.2 (134.8, 155.6) .001 1.37 (1.28, 1.46) .001 0.87 (0.81, 0.92) .001
Female gender 69.0 (122.7, 15.4) .012 0.78 (1.23, 0.32) .001 0.46 (0.74, 0.17) .002
Race: white

0.54 (0.16, 0.92) .005

Race: other

0.04 (1.02, 0.94) .940

Smoking 0.50 pack per day

10.0 (103.7, 83.6) .834 0.63 (1.42, 0.16) .120 0.19 (0.69, 0.31) .455
Smoking 0.50 pack per day

54.7 (28.1, 137.5) .195 0.02 (0.72, 0.68) .954 0.02 (0.46, 0.42) .920
Alcohol, some

11.1 (63.8, 86.1) .771 0.10 (0.54, 0.73) .763 0.23 (0.16, 0.63) .251
Alcohol, moderate

53.0 (71.0, 177.0) .402 0.37 (0.70, 1.43) .498 0.34 (0.32, 1.01) .313
Alcohol, heavy

41.9 (63.2, 147.0) .434 0.34 (0.55, 1.23) .454 0.31 (0.25, 0.86) .281
Marijuana use 76.3 (9.3, 162.0) .081 0.34 (0.39, 1.07) .356 0.13 (0.59, 0.32) .559
Adequate prenatal care 59.3 (119.1, 0.43) .052 1.02 (1.52, 0.51) .001 0.31 (0.62, 0.01) .059
Oligo-polyhydramnios 112.6 (201.0, 24.1) .013 1.15 (1.91, 0.40) .003 0.82 (1.28, 0.35) .001
Preeclampsia 205.3 (283.8, 126.7) .001 1.51 (2.17, 0.85) .001
Abnormal reproductive history 113.6 (180.8, 46.3) .001 0.92 (1.49, 0.35) .002 0.49 (0.85, 0.14) .007
Hematologic disorder 153.4 (289.0, 17.9) .027 1.2 (2.3, 0.005) .051
R
2
.537 .585 .588
Gestational age 32 wk
Cocaine

151.28 (202.6, 100.0) .001 0.71 (1.03, 0.40) .001 0.43 (0.62, 0.24) .001
Opiate 72.9 (144.8, 1.09) .047 0.13 (0.47, 0.72)

.675 0.14 (0.41, 0.12) .297

Site 2* 25.9 (56.1, 4.2) .092 0.49 (0.67, 0.31) .001 0.32 (0.43, 0.21) .001
Site 3* 16.5 (16.2, 49.2) .322 0.39 (0.19, 0.59) .001 0.04 (0.16, 0.08) .468
Site 4* 26.6 (7.6, 60.9) .128 0.04 (0.25, 0.18) .730 0.08 (0.22, 0.06) .252
Gestational age (per wk) 136.5 (123.5, 149.6) .001 0.82 (0.61, 1.02) .001 0.38 (0.33, 0.43) .001
Cocaine gestational age 32.9 (46.9, 18.8) .001 0.10 (0.18, 0.01) .025 0.06 (0.11, 0.01) .031
Female gender 138.5 (158.6, 118.4) .001 0.79 (0.91, 0.66) .001 0.54 (0.62, 0.47) .001
Race: white

135.0 (107.6, 162.5)

#
.001 0.46 (0.29, 0.63) .001 0.31 (0.21, 0.42) .001
Race: other

51.2 (0.46, 102.0) .048 0.20 (0.13, 0.52) .232 0.25 (0.05, 0.44) .014
Smoking 0.50 pack per day

119.4 (157.1, 81.8) .001 0.51 (0.75, 0.28) .001 0.25 (0.39, 0.11) .001
Smoking 0.50 pack per day

172.1 (203.6, 141.0)** .001 0.78 (0.98, 0.58) .001 0.35 (0.47, 0.23) .001
Alcohol, some

9.0 (15.6, 33.3) .480 0.07 (0.09, 0.22) .392 0.004 (0.09, 0.10) .927
Alcohol, moderate

15.4 (30.0, 60.6) .505 0.03 (0.31, 0.25) .841 0.05 (0.11, 0.22) .537
Alcohol, heavy

66.0 (113.9, 18.0)

.007 0.36 (0.66, 0.07)

.016 0.12 (0.30, 0.06) .186

Marijuana use 0.6 (39.4, 40.5) .972 0.01 (0.24, 0.25) .962 0.09 (0.05, 0.24) .208
Adequate prenatal care 30.5 (7.3, 53.7) .009 0.18 (0.04, 0.32) .012 0.10 (0.01, 0.18) .027
Oligo-polyhydramnios 169.3 (212.2, 126.4) .001 0.74 (1.0, 0.48) .001 0.36 (0.52, 0.20) .001
Preeclampsia 173.4 (220.5, 126.3) .001 0.61 (0.90, 0.32) .001 0.47 (0.65, 0.30) .001
9
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tion. Thus, estimate (95%CI) of opiate effect on length at
33 weeks was 1.1 cm (2.2, .00), P .05, whereas at
36 weeks it was 0.6 cm (1.2, 0.2), P .06. Smoking
had signicant effects on all measurements, with a trend
toward increasing negative effects with more cigarettes
smoked during pregnancy. Heavy alcohol use had a
signicant effect only on weight and length. There was
no interaction between cocaine and alcohol use, indicat-
ing independent and additive effects with both exposures
present. Binge drinking and maternal weight gain during
pregnancy were not signicant predictors of growth. As
in the lower gestational age stratum, medical factors had
a signicant negative impact on growth. Oligo-polyhy-
dramnios and preeclampsia had signicant negative ef-
fects on all measurements. A history of hospitalization
during pregnancy was associated with decrease in birth
weight. Infants of mothers with insulin-dependent diabe-
tes had higher birth weight and larger head circumfer-
ence. Later in gestation, adequate prenatal care was
associated with signicantly higher growth measure-
ments compared to inadequate/intermediate care.
DISCUSSION
In utero exposure to illicit drugs, including cocaine, is
reported to be associated with increased incidence of low
birth weight (weight 2500 g),
6,8,11
shortened gesta-
tion,
15,16
lower mean birth weight,
35
or weight less than
the tenth or the 20th percentile of a commonly refer-
enced intrauterine growth curve.
5,6,17
The large number
in our study provided us with a rich data set, enabling us
to characterize more comprehensively infant growth fol-
lowing gestational cocaine exposure, while controlling
for confounders known to negatively impact fetal
growth.
In term or near-term infants, cocaine exposure has
been reported to result in the shift of birth weight and
head circumference to the lower percentile.
5,17
A moder-
ating effect by gestational age on the impact of drug
exposure on weight and length but not head circumfer-
ence was reported by Brown et al,
18
who observed more
extreme growth decits at term gestation. With rapid
growth velocity in the fetus after 30 weeks gestation,
19
any negative impact of cocaine on growth would likely
result in restriction or deceleration that becomes more
evident at later weeks of gestation. In fact, as evidenced
by the statistically signicant interaction terms between
cocaine and gestational age, growth restriction became
more pronounced as gestation approached term.
We further observed that the negative impact of co-
caine on growth remained signicant after adjusting for
the effects of opiate, tobacco, alcohol, marijuana, and
other factors. Zuckerman et al
4
found that gestational
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921 VOL. 100, NO. 5, PART 1, NOVEMBER 2002 Bada et al Cocaine and Birth Measurements
cocaine exposure was associated with a decrease in
weight, length, and head circumference, and these mea-
surements negatively correlated with the number of
cigarettes smoked per day but not with the daily volume
of alcohol intake. Our ndings are consistent with their
results, but we also found a negative effect of heavy
alcohol use at later gestation. Jacobson et al
20
observed
larger decits in birth weight related to heavy drinking
compared with decits from heavy smoking and that
cocaine effects were attributable to shortened gestation.
In our sample, the negative impact of alcohol on growth
was of lesser magnitude than the effects of smoking or
cocaine, and the effect of cocaine was not attributable to
shortened gestation.
Decreased growth measurements in cocaine exposure
have been attributed to maternal and obstetric risk fac-
tors, sociodemographic factors, lack of prenatal care, and
undernutrition.
3,4,11,21
In our study, growth measure-
ments were signicantly decreased in blacks, girls, and
those with maternal medical or obstetric complications.
Our mothers on Medicaid had infants with smaller head
size; low socioeconomic status has been correlated with
small head size and poor neurological outcome.
22
Of
interest was our nding of brain sparing with preeclamp-
sia early in gestation, evolving into symmetrical growth
restriction at later gestation. In cocaine-exposed infants,
the incidence of low birth weight has been reported to
decrease with increased number of prenatal care visits.
21
MacGregor et al
15
found improved growth measure-
ments with comprehensive prenatal care. We also found
higher growth measurements with adequate prenatal
care in infants born after 32 weeks, but an inverse
relationship was noted between prenatal care and
growth during gestation 32 weeks. Health behavior
may have been a factor (ie, mothers sought early care
because of complications, necessitating more visits).
Richardson et al
23
found no effect of prenatal care on
birth weight following prenatal cocaine exposure; how-
ever, the true impact of prenatal care may not be evident,
because prenatal care utilization may not indicate con-
tent of services received.
24
Growth restriction associated with in utero cocaine
exposure may be explained by undernutrition.
25
We
found that maternal weight gain during pregnancy was
not signicantly related to growth measurements. Our
mothers may possibly have had poor recall of their
prepregnancy weight, and we were unable to detect the
true relationship between maternal weight gain and in-
trauterine growth. Moreover, factors such as endocrine
inuences have been suggested in the mechanism of
growth deceleration in cocaine exposure.
2630
In some reports,
9,10
the head size of drug-exposed
infants was noted to be disproportionately smaller than
expected for body weight and length,
30
a reverse pattern
of asymmetrical growth restriction.
9
However, many
studies
5,16,23,31,32
including ours found symmetrical
growth restriction following gestational cocaine expo-
sure. Doseeffect relationship has been reported be-
tween newborn head circumference and concentrations
of cocaine metabolite (benzoylecgonine) in maternal
33
or
neonatal hair.
34
We used gas chromatography/mass
spectroscopy for meconium testing, and qualitative and
quantitative differences in metabolites detected were ob-
served in different infants.
13
Thus, it would have been
problematic in our study to look for dose-effects based
on meconium results. Because drug metabolites in meco-
nium are likely to represent exposure in the later months
of pregnancy, our infants could have been exposed for
several months duration (ie, throughout gestation or
equivalent to heavy exposure). The mean decrease in
head size noted in our cocaine-exposed infants at 40
weeks gestation is comparable to Bateman and Chiribo-
gas
33
observation of 0.44 .17-cm decrease in head
circumference in babies exposed to high levels of co-
caine. Kuhn et al
35
found a doseresponse relationship
between cocaine concentrations in maternal hair and
birth weight but not head size. We could have investi-
gated dose of exposure at recruitment through a detailed
maternal interview of drug use by month or trimester of
pregnancy, but this was precluded by the large number
of subjects enrolled in the Maternal Lifestyle Study.
The exclusion of infants with unconrmed negative
exposure status from analysis may be a source of bias;
however, these infants were likely nonexposed, because,
in addition to a negative maternal self-report, infant and
maternal characteristics for this group were similar to the
cocaine-negative group. Furthermore, in this population,
the probability of cocaine conrmation by meconium
testing, given that a mother denied use, is only .024.
13
Our ndings, therefore, likely represent underestimates
of the true association between cocaine and growth
restriction.
Because of variability in population characteristics and
prevalence of cocaine use among clinical centers, we
controlled for clinical site in our analysis; however,
generalizability of our ndings is limited because our
study population was drawn from urban areas, with a
large proportion of low socioeconomic status. Despite
this limitation, our large sample, conrmation of expo-
sure by meconium analysis using a highly specic and
sensitive method, rigorous training and masking of re-
search personnel to exposure status, and controlling for
multiple confounders, lead us with a high degree of
condence to conclude that in utero cocaine exposure is
associated with fetal growth restriction involving all birth
measurements.
922 Bada et al Cocaine and Birth Measurements OBSTETRICS & GYNECOLOGY
Unless growth measurements are below the tenth
percentile of a reference growth curve,
3639
the impact of
drug use on fetal growth would not be as evident in the
newborn period. Exposed infants may have measure-
ments above the tenth percentile and anthropometrically
similar to nonexposed infants. Based on the United
States national reference for fetal growth,
39
10% of in-
fants are born with birth weight less than 2929 g. A151-g
mean downward shift in birth weight due to cocaine
exposure will result in a three-fold increase (to 32%) in
the prevalence of infants born with weight less than tenth
percentile. Compounding the effects of cocaine are the
independent negative impact of frequently co-occurring
factors, such as smoking, alcohol, opiates, abnormal
reproductive history, and lack of prenatal care.
The long-term impact of cocaine on growth deviation
will need to be determined in the context of exposure to
both prenatal and postnatal factors.
40
The follow-up
phase of our study has been designed to address some of
these concerns. Our ndings support the need to achieve
many objectives of Healthy People 2010. To address the
problemof lowbirth weight, early access to prenatal care
will likely detect medical and obstetric complications and
provide intervention toward smoking cessation and al-
cohol and drug treatment. From the public health per-
spective, a greater impact on decreasing rates of lowbirth
weight can be achieved by continued and expanded
primary prevention programs against tobacco, alcohol,
and drug use specically directed to children and youth.
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Address reprint requests to: Henrietta S. Bada, MD, MPH,
University of Kentucky Chandler Medical Center, Depart-
ment of Pediatrics, Room MS-473, 800 Rose Street, Lexington,
KY 40536; E-mail: hbada2@uky.edu.
Received February 28, 2002. Received in revised form May 13, 2002.
Accepted June 6, 2002.
924 Bada et al Cocaine and Birth Measurements OBSTETRICS & GYNECOLOGY