Published online September 24, 2007
PEDIATRICS Vol. 120 No. 4 October 2007, pp. e1017-e1027 (doi:10.1542/peds.2006-3482)
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ARTICLE

Effects of Prenatal Cocaine Exposure on Growth: A Longitudinal Analysis

Gale A. Richardson, PhDa, Lidush Goldschmidt, PhDb and Cynthia Larkby, PhDa

a Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
b University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. There has been a limited amount of research on the long-term effects of prenatal cocaine exposure on growth of the infant, and there has been no use of longitudinal growth models. We investigated the effects of prenatal cocaine exposure on offspring growth from 1 through 10 years of age by using a repeated-measures growth-curve model.

METHODS. Women were enrolled from a prenatal clinic and interviewed at the end of each trimester of pregnancy about their cocaine, crack, alcohol, marijuana, tobacco, and other drug use. Fifty percent of the women were white, and 50% were black. Follow-up assessments occurred at 1, 3, 7, and 10 years of age.

RESULTS. Cross-sectional analyses showed that children exposed to cocaine during the first trimester (n = 99) were smaller on all growth parameters at 7 and 10 years, but not at 1 or 3 years, than the children who were not exposed to cocaine during the first trimester (n = 125). The longitudinal analyses indicated that the growth curves for the 2 groups diverged over time: children who were prenatally exposed to cocaine grew at a slower rate than children who were not exposed. These analyses controlled for other factors associated with child growth.

CONCLUSIONS. To our knowledge, this is the first study of the long-term effects of prenatal cocaine exposure to conduct longitudinal growth-curve analyses using 4 time points in childhood. Children who were exposed to cocaine during the first trimester grew at a slower rate than those who were not exposed. These findings indicate that prenatal cocaine exposure has a lasting effect on child development.

Key Words: prenatal cocaine exposure • growth • longitudinal analyses • growth-curve model

Abbreviations: AIC—Akaike information criteria

Rates of cocaine use during pregnancy have varied from 2.6% in a partially rural sample from Florida1 to 8% in a prenatal clinic in Pittsburgh2 to 18% in an inner-city sample from Boston.3 Despite these rates of cocaine use during pregnancy, little is known about the long-term effects of cocaine exposure on the offspring. In particular, it is unclear whether any early growth deficits will persist into childhood. Much of the research has focused on the neonatal and infancy period, with some studies reporting that prenatal cocaine exposure has a detrimental effect on growth,3–8 and some reporting that it has no detrimental effect.9–13 Some investigators have begun to explore the effects of prenatal cocaine exposure on growth into the preschool- and school-age periods. Hurt et al14 found reduced weight and head circumference at 2 and 2 1/2 years in cocaine-exposed infants, although these analyses did not control for alcohol, marijuana, and tobacco use, and Chasnoff et al15 found that head circumference was reduced at 4 and 6 years in children exposed prenatally to multiple drugs. Minnes et al16 found relationships between a cocaine metabolite in infant meconium and height-for-age and weight-for-height z scores at 6 years, with control for correlates of prenatal cocaine exposure, and Covington et al17 reported that prenatal cocaine exposure was associated with reduced height at 7 years in offspring of women over 30 years of age, after controlling for prenatal alcohol and tobacco use.

By contrast, other studies have not found significant effects on the growth of cocaine-exposed preschool and school-age offspring.14,18 Chasnoff et al15 found no effect of prenatal drug exposure on height or weight at 4, 5, or 6 years, and there was no difference in the rate of growth over the 3 years on any growth parameter. There was no effect of prenatal cocaine exposure on weight, height, or head circumference at 6 years,16 on weight at 7 years,17,19 or on height and head circumference at 7 years.19 Thus, the literature on the long-term effects of prenatal cocaine exposure on growth is limited, has yielded conflicting results, and has not assessed growth past 7 years of age. In addition, the rate of growth was investigated only by Chasnoff et al,15 who compared polydrug-exposed children with nonexposed children.

Additional factors that might influence growth must also be considered. For example, prenatal alcohol exposure was found to be associated with long-term growth deficits in some studies,17,20–23 but not in others.24,25 In addition, growth is influenced by characteristics such as gender, race, and age,26,27 parental size,28 demographic and environmental variables,29,30 and maternal nutrition31 and smoking.32,33 These characteristics must be considered when investigating the relationship between prenatal cocaine exposure and growth.

We previously reported that cocaine use during early pregnancy predicted decreased gestational age, birth weight, length, and head circumference.8 The purpose of this report was to investigate the effects of prenatal cocaine exposure on offspring growth during the follow-up periods from 1 through 10 years of age. Strengths of this study include the following: the sample was enrolled prenatally; approximately equal numbers of black and white women were enrolled; good follow-up rates were obtained; detailed information was collected about all types of drug use; covariates associated with prenatal cocaine exposure were controlled statistically; and a repeated-measures growth-curve model was used to model growth longitudinally.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Design
This study was part of a program of research on the effects of prenatal substance exposure on the long-term growth and development of the offspring, which we refer to as the Maternal Health Practices and Child Development Project. This study was designed specifically to evaluate the effects of prenatal cocaine exposure. Women 18 years or older who attended the prenatal clinic at Magee-Womens Hospital in Pittsburgh, Pennsylvania, from March 1988 through December 1992 were eligible to participate. Written consent was obtained according to the guidelines established by the University of Pittsburgh Institutional Review Board and by the Magee-Womens Hospital Research Review and Human Experimentation Committee. A certificate of confidentiality, obtained from the Department of Health and Human Services, assured participants that their responses could not be subpoenaed.

Women were initially approached for interview during their fourth or fifth prenatal month. Women were not enrolled in this cohort if they came in for their first prenatal visit after the fifth month. No information was obtained from the medical charts about a woman's drug use before she was asked to participate in the study. The women were asked about their use of cocaine, crack, alcohol, marijuana, tobacco, and other drug use for the year before pregnancy and for the first trimester. Information was also obtained regarding sociodemographic and lifestyle characteristics, social support, and psychiatric symptomatology. These measures are referred to as the core assessment. All women who reported using any cocaine or crack during the first trimester were enrolled. The next woman interviewed who reported no cocaine or crack use during pregnancy or the year before pregnancy was also enrolled. Ninety percent of those women eligible to be interviewed consented to participate in the study. Medical chart reviews of a random sample of women who refused to participate indicated that only 5% had a history of drug use during the current pregnancy.

Of the women initially interviewed, 320 (18%) met the inclusion criteria and were enrolled in the study. Women selected for the study were interviewed at 7 months about their substance use during the second trimester and they completed the core assessment. The women were interviewed again 24 to 48 hours postpartum, when they were asked about third trimester substance use and the core assessment was repeated. All newborns received comprehensive physical examinations, generally within 24 to 48 hours of delivery, by the study nurse clinicians who were unaware of prenatal exposure status. The children were assessed again at 1, 3, 7, and 10 years of age. The core assessment was administered at all phases, including questions about current substance use.

Of the 320 women selected for the study, 17 became ineligible for participation because of abortion/miscarriage/infant death (n = 5), home delivery (n = 1), or moving out of the area (n = 11). Of the remaining 303 eligible women, 1 was lost to follow-up and 2 refused additional participation. Thus, delivery assessments were completed on 300 mothers. Four pairs of twins and 1 child with Trisomy 21 were excluded from additional follow-up, resulting in a birth cohort of 295 mothers and infants.

At 1, 3, 7, and 10 years postpartum, we achieved completion rates of 89%, 89%, 83%, and 78% of the birth cohort, respectively. These completion rates are good for a longitudinal study, especially one of lower socioeconomic status women, some of whom are using drugs. Of the 295 mother–infant pairs in the birth cohort, 228 pairs were seen at the 10-year phase. Five women refused the 10-year phase only, 10 refused any additional contact, 26 were lost to follow-up, 17 moved too far away to come in for the assessment, 4 children were in foster care and could not be located, and 5 children had died. Subjects who participated in the 10-year phase (n = 228) did not differ in prenatal exposure status or sociodemographic characteristics from those who did not participate at 10 years (n = 67). In addition, 4 children were excluded from the analysis because they had disorders that might affect growth (Alagille syndrome, Tourette syndrome, sickle cell disease), resulting in a sample size of 224. There was no relation between exposure status and child death or disability. There were an additional 5, 4, and 26 children who were excluded from the height, weight, and head circumference analyses, respectively (see "Statistical Methods" for additional details).

Sample Characteristics
The women were selected from a prenatal clinic, and their characteristics reflect that sampling source. At the initial interview, the women were, on average, 25 years old (range: 18–41 years), with 12 years of education (range: 9–16 years) and a reported median family income of $496 per month (range: $0–$6000). Fifty percent of the women were white and 50% were black. At the initial interview, 43% worked and/or went to school, whereas by the third trimester, only 15% did either. Twenty-two percent were married at the time of delivery. According to Kessner's Prenatal Care Index,34 48% had adequate prenatal care, 47% had an intermediate level of care, and 5% had inadequate prenatal care.

Fifty-three percent of the infants were male. The mean 1- and 5-minute Apgar scores were 7.8 (range: 1–9) and 8.8 (range: 4–10), respectively. The mean gestational age was 39.7 weeks (range: 26–43 weeks), and the mean birth weight was 3243 g (range: 930–5600 g). Six percent were premature (<37 weeks), 9% were low birth weight (<2500 g), and 11% were small for gestational age, according to the Brenner et al35 standards.

At the 10-year follow-up, 13% of the children were not in maternal custody, in which case the custodian was interviewed. The mean age of the caregivers who were interviewed was 37 years (range: 27–74 years), 40% were married, the median family income was $1625/month, and 66% worked and/or attended school.

Assessment of Child Growth
At each follow-up phase, the child assessment staff were trained to reliability and periodic reliability checks were conducted during data collection. In addition, they were blind to prenatal and current drug use. The child's height (in), weight (lb), and head circumference (mm) were measured during the assessment visit in the project offices.

Measurement of Maternal Cocaine and Other Substance Use
Maternal use of cocaine and crack, as well as tobacco, alcohol, marijuana, and other illicit drugs, was assessed during detailed confidential interviewing. Interviewers were selected for their ability to discuss drug use comfortably and to identify accurately all drugs used, either by name, street name, or appearance. We asked about prepregnancy and first-trimester use at the fourth month visit, second trimester use at the seventh month visit, and third trimester use after delivery. At each follow-up phase, women were asked about use over the previous year. For each substance, questions were first asked about usual quantity and frequency of use, followed by questions about maximum and minimum quantity and frequency. For additional details on the interviewing techniques and their reliability, see Richardson et al.8

For these analyses, first-trimester cocaine use was coded as a dichotomous variable (use/no use) to compare the growth curves of the exposed and unexposed children. Because no woman initiated use during the second or third trimester, the first-trimester use group represents both women who used first trimester and stopped, as well as women who used throughout pregnancy. Of the 99 women in the cocaine use group, 67% used first trimester only, 13% used first and second or third trimester, and 20% used all 3 trimesters. The children who were exposed during the first trimester only were not different from the children exposed during the first and second and/or third trimesters, so the 2 groups were combined to increase the statistical power of the analyses. The no cocaine use group consisted of women who never used cocaine during pregnancy. The repeated-measures growth-curve model was not applied to second and third trimester cocaine use because there were insufficient numbers of women who used during those trimesters. Cocaine use at each of the follow-up phases was also dichotomized as use/no use.

The alcohol and marijuana variables were calculated as average number of drinks and joints per day during the first trimester and at each follow-up phase, respectively, and tobacco as number of cigarettes per day during the first trimester and at each follow-up phase.

Current Environmental Variables
Maternal education, income, work status, marital status, and substance use were assessed at each follow-up phase, as was child custody status (maternal versus nonmaternal). Maternal depression was also assessed at each follow-up phase using the Center for Epidemiologic Studies Depression Scale.36 The quality of the home environment was measured by the PROCESS Scale37 at the 1-year follow-up, by the Home Screening Questionnaire38 at the 3-year phase, and by the Home Observation for Measurement of the Environment Short Form39 at the 7- and 10-year phases. At 7 and 10 years, we assessed child nutritional status. Mothers reported the number of times per day that the child ate foods from each of the 4 food groups (dairy, protein, fruits/vegetables, and grains). We then evaluated whether the total recommended daily allowance was met.40 The recommended daily allowance variable ranged from 0 (did not meet the recommended level for any of the 4 food groups) to 4 (met the recommended level for all 4 food groups).

Statistical Methods
A repeated-measures growth-curve model was used to test whether the growth rate of children exposed prenatally to cocaine was different from that of children who were not exposed. In repeated-measures models, the successive errors are not independent of each other and the structure of their underlying variance-covariance matrix needs to be identified. Therefore, 2 competing models were considered: a random-coefficients model and a fixed effects model with an unstructured error variance-covariance matrix. The random-coefficients model is considered a 2-stage model. In the first stage, a growth curve as a function of age or time is fitted to each individual to take into account individual growth rates. It is assumed that these individual growth parameters have a common distribution. In the second stage, the growth parameters are expressed as a linear function of baseline covariates. In a fixed effects model, a single curve is fitted to the population mean and the variance-covariance matrix takes into account the within-individual correlations. This model is particularly suitable when the variances increase over time. Both models can handle unbalanced data,41 and therefore, they are appropriate for this cohort where not all children were measured at exactly the same age.* To compare the 2 models, the statistic Akaike information criteria (AIC) was used.42 AIC takes into account both the estimated likelihood and the number of parameters that need to be estimated. In this report, the estimated parameters from the fixed effects model are presented because it obtained a slightly better AIC than the random-coefficients model, although the results between the 2 models were similar.

The plots of height, weight, and head circumference over time were curvilinear. Therefore, in addition to including the age of the subjects at each phase, a quadratic term of age (age2) was included in the model. In addition to the intercept, the effects of the chosen variables on the initial slope and on the curvature of the growth curve were tested by including in the model the interaction between the variable and age and the interaction between the variable and the quadratic term, respectively.

As can be seen in Table 1, the range of child weight becomes wider with age. To obtain stable coefficients and reduce variation, the square root of weight was used in the repeated-measures analyses.


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  		TABLE 1 Mean Unadjusted Growth Parameters and Age at Assessment According to Cocaine Exposure

 
In repeated-measures analyses, discarding information about subjects who were not measured at all time points is considered inefficient. Missing values were estimated using regression imputation for cases that met the following criteria: (1) the subject participated in the 10-year phase; (2) only 1 measurement out of the 4 phases was missing; and (3) the data were missing at random without any specific pattern. The advantages of this method are: because of the high correlation between growth parameters measured at different time points, the missing values are imputed with great certainty; the imputation does not depend on the selected model; and the completed data can be analyzed by standard methods. However, because this method does not take into account imputation uncertainty, the final models were fit to the incomplete data using maximum likelihood estimation43,44 and the results were consistent with the models using the imputed data. For height, weight, and head circumference, 5, 4, and 26 children, respectively, had more than 1 measurement missing and were excluded from the analysis. Across all growth outcomes at all phases, data were imputed for 5% of the total measurements. Children with missing values were not different from those without missing values on any of the growth outcomes or on prenatal cocaine exposure.

For each outcome, the residuals of the final model versus the predicted values were plotted. If the fitted model is adequate, this plot should resemble a cloud around 0 without any specific pattern. In addition, although the diagnostics of the model assumptions are not well developed, the asymptotic test statistics are not robust to severe departures from normality. The histogram of the residuals for each outcome variable resembled a bell-shaped density and their q-q plot was almost linear. That is, the histogram and normal probability plot of the residuals did not indicate a major departure from normality.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Characteristics Associated With First-Trimester Cocaine Use
In the sample of 224 subjects, 44% (n = 99) of women used cocaine during the first trimester and 56% (n = 125) did not use during the first trimester. Table 2 shows that first-trimester users of cocaine were older, less likely to be white, less likely to be married, and had lower family incomes than women who were nonusers during the first trimester. Thirty-six percent of the first-trimester users had adequate prenatal care compared with 58% of the nonusers. Women who used cocaine/crack during the first trimester were significantly more likely to smoke tobacco, drink alcohol, and use marijuana and other illicit drugs during the first trimester than were the first-trimester nonusers. The first-trimester cocaine users also used alcohol and marijuana more heavily during the first trimester than did the first-trimester nonusers.


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  		TABLE 2 Sample Characteristics According to First-Trimester Cocaine Use

 
Women who used cocaine during pregnancy were also more likely to be single and to use alcohol, marijuana, and tobacco at the follow-up phases than were the women who did not use cocaine prenatally (data not shown). More of the prenatally exposed children were in nonmaternal custody at 1 year (6% vs 1%; P < .05) and at 10 years (21% vs 6%; P < .01) than the nonexposed children. There were no other differences between the groups on the other current environmental variables.

Infants of women who used cocaine first trimester were more likely to be premature and low birth weight, and they had decreased gestational age, birth weight, length, and head circumference compared with infants of women who did not use cocaine first trimester (Table 2). When regression analyses were conducted to control for other factors associated with prenatal cocaine exposure, first-trimester exposure remained a significant predictor of gestational age, but not of the growth parameters.8

Cross-sectional Analyses
Table 1 shows the unadjusted growth parameters by first-trimester cocaine exposure. In cross-sectional analyses, there was no difference between infants exposed to cocaine and those not exposed to cocaine in growth at 1 and 3 years. There were significant differences between the groups on all of the growth parameters at 7 and 10 years of age. For example, at 10 years, the children who were exposed to cocaine during the first trimester were ~1 inch shorter and 12 lb lighter than those children who were not exposed to cocaine during the first trimester.

Before conducting the longitudinal analyses, it was necessary to determine which covariates to enter into the longitudinal model. Cross-sectional analyses were conducted for each follow-up phase to make this determination. The following variables were considered for inclusion in the cross-sectional models: child age, gender, race, nutrition, home environment, and custody status; maternal height, education, work, income, marital status, depression; and cocaine, alcohol, marijuana, and tobacco use during the first trimester and at the current follow-up phase. Table 3 shows the results from the regression analyses that were conducted for each growth parameter at each age. Males were taller at 1 year and females were taller at 10 years. Black children were taller at 3, 7, and 10 years. Greater maternal height predicted greater child height at each phase. More first-trimester cigarette use and higher depression scores predicted decreased height at 1 year, and more maternal education predicted increased height at 10 years. For weight, male gender and maternal height predicted increased weight at 1 and 3 years, and higher depression scores predicted reduced weight at 1 year. For head circumference, male gender and maternal height predicted increased head circumference at 1, 3, and 7 years. Current work status, lower family income, and better home environment predicted larger head circumference at 1 year, and nonmaternal custody and current marijuana use predicted smaller head circumference at 3 years. Table 3 also shows that first-trimester cocaine use was a significant predictor of decreased height, weight, and head circumference at 7 and 10 years when other variables were entered into the model. For example, at 10 years, the children who were exposed to cocaine were about three quarters of an inch shorter and 10 lb lighter than the children who were not exposed, after adjusting for other significant predictors of growth.


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  		TABLE 3 Significant Cross-Sectional Predictors

 
Longitudinal Analyses
Based on the cross-sectional analyses, variables that were significant for 2 or more phases were included in the longitudinal analyses. Thus, the following variables were used for the longitudinal model: child gender, race, maternal height, and first-trimester cocaine and cigarette{dagger} use, as well as age and age2, as previously described.

The observed mean height, weight, and head circumference of the exposed and unexposed children over time are presented in Figs 1 through 3, respectively. These figures show that although there was no difference between the 2 groups at the earliest follow-up phases, the growth curves for weight and head circumference diverged as the children matured. The next step was to investigate whether these differences were statistically significant after controlling for the identified covariates.


Figure 1
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  		FIGURE 1 Height versus age according to first-trimester cocaine exposure.

 

Figure 2
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  		FIGURE 2 Weight versus age according to first-trimester cocaine exposure.

 

Figure 3
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  		FIGURE 3 Head circumference versus age according to first-trimester cocaine exposure.

 
A repeated-measures quadratic growth curve was fitted to the growth outcomes of children measured at 4 time points. The estimated parameters and their significance levels are presented in Table 4. In this table, the estimated coefficient of each variable represents the effect of the variable on the initial status or the intercept of the growth curve, and the interaction between the variable and age represents the effect of the variable on the slope, or linear portion, of the growth curve.


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  		TABLE 4 Estimates of Repeated-Measures Coefficients Using a Fixed Model

 
For height, there was no significant effect of first-trimester cocaine on the intercept of the growth curve, and there was no significant difference between the initial slopes of the growth curves for the exposed and nonexposed groups. For weight, there was a significant cocaine x age interaction: The initial slope of the growth curve for children who were prenatally exposed to cocaine was estimated to be 0.41 (coefficient of age – coefficient of cocaine x age: 0.46–0.05) compared with a slope of 0.46 for the nonexposed children. There was also a significant cocaine x age interaction for head circumference: The initial slope of the growth curve for children who were prenatally exposed to cocaine was estimated to be 12.38 (12.77–0.39) compared with a slope of 12.77 for the nonexposed children. These results indicate that the growth curves for the 2 groups diverged: children who were prenatally exposed to cocaine grew at a slower rate than did the children who were not exposed to cocaine.

For each growth parameter, the coefficient of first-trimester cocaine exposure was not statistically different from 0, indicating that cocaine exposure had no effect on initial status. This is consistent with the cross-sectional regression analyses where cocaine exposure was not found to be related to the growth parameters at age 1 (the initial starting point for the growth-curve analyses).

The interactions between each variable and the quadratic growth component (age2) were also tested and none was found to be statistically significant. Thus, there was no effect of prenatal cocaine exposure on the acceleration of growth over time.

Gender and the gender x age interaction were significant for each growth parameter, indicating that although boys were initially bigger than girls, the gap between the 2 genders decreased over time.

The final model was repeated excluding severe outliers (>3 standardized residuals). There were 3 outliers each for height, weight, and head circumference. The cocaine x age interaction remained statistically significant when these cases were removed.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
This is a unique investigation of the long-term effects of prenatal cocaine exposure on offspring growth from 1 through 10 years of age. It is the first report to conduct longitudinal growth-curve analyses using 4 time points in childhood. The cross-sectional analyses showed that the offspring who were exposed to cocaine during the first trimester were not different in their growth at 1 and 3 years from the offspring who were not exposed. At 7 and 10 years, the exposed group was significantly smaller than the nonexposed group on all 3 growth parameters. The longitudinal growth-curve analyses showed that there was a significant cocaine x age interaction for weight and head circumference, indicating that the exposed group grew at a slower rate than the nonexposed group. That is, the growth curve for the exposed group diverged from that of the nonexposed group. These analyses controlled for other factors associated with child growth, such as maternal height, gender, and exposure to other drugs.

At birth, we found that infants who were exposed to cocaine during the first trimester had reduced gestational age compared with those who were not exposed, but were not different in height, weight, or head circumference, although there were effects of second trimester cocaine exposure on growth.8 There were no effects of first-trimester cocaine use on growth at 1 and 3 years. This lack of effect of prenatal cocaine exposure on infant growth is consistent with reports from other well-controlled studies.12,18 In addition, we found that the children exposed to cocaine prenatally grew at a slower rate than those who were not exposed, so that by 7 and 10 years of age, there was a significant effect of prenatal cocaine exposure on child size. Only 2 studies have followed children to 7 years of age, 1 of which reported effects on growth17 and 1 of which did not.19 This is the first report of the effects of prenatal cocaine exposure on growth at 10 years of age.

This pattern of an emergence of effects with increasing age is consistent with one of the tenets of the teratologic model, which states that some effects may only be manifested at later stages of development.45 These are referred to as latent or sleeper effects. There has been insufficient research on the long-term effects of prenatal cocaine exposure to determine if the latent effects that we found are consistent. However, they have been found in studies of teratogenic exposure to other drugs such as alcohol and marijuana.23,46,47 In our study, we found that these latent effects were due to cocaine exposure, and not to the effects of other drugs.

The effect of cocaine use on growth was associated with exposure during the first trimester of pregnancy. Each of the 3 growth parameters was affected, indicating symmetric growth retardation. This pattern of effects is consistent with literature indicating that symmetric growth retardation is caused by insults during the first part of pregnancy.48,49

There was a statistically significant difference between the children exposed to cocaine and those not exposed, for example, approximately a 10-lb difference in weight at 10 years of age after controlling for other factors associated with growth. However, both groups were still in the normal range for growth and therefore would not be identified during a routine pediatric visit as growing abnormally. Nevertheless, these findings demonstrate that prenatal cocaine exposure has a long-term effect on development. Whereas these growth effects are not, on average, clinically significant, they are important because they add to our knowledge about the consequences of prenatal cocaine exposure. In addition, it is important for clinicians to realize that these effects are not dramatic, but are an indication that a teratogen has had an impact. The existence of effects that emerge at later ages highlights the importance of conducting careful history-taking and examinations.

The validity of our findings is strengthened by their consistency with other reports in the literature. For example, we found that factors such as gender, race, and maternal height were associated with growth, as have Karlberg et al28 and Kuczmarski et al.26 We also found that prenatal tobacco exposure was a significant predictor of height at 1 year, but not of growth at any other age. This finding is consistent with the literature that shows that the effects of prenatal tobacco exposure on infant growth dissipate over time.50,51 There were no effects of prenatal marijuana exposure on childhood growth, a finding that is also consistent with the literature.21,32,52,53 In addition, we found that there were no effects of prenatal alcohol exposure on childhood growth. The literature has been inconsistent in this area, with some studies finding long-term effects on growth21 and others finding that the growth effects dissipate with time.25

The strengths of this study include the prospective design, large number of subjects, and statistical control for confounding factors. In addition, women enrolled in this project represent a healthy population from a prenatal clinic. All women received prenatal care by their fourth or fifth month of pregnancy. Also, all women were interviewed at the same time points and at frequent intervals to minimize recall bias. Furthermore, the interview techniques have been used in previous studies of substance use in pregnancy and have been shown to be reliable and valid.54–56

A potential limitation of this study is that biological measures were not used to document drug use. Although it is possible that some women who used drugs denied use on interview and were misclassified, this would reduce the differences between groups and would not affect the significant findings in this report. In addition, although urine screening can identify women who deny use, it fails to detect many cocaine users because of the short time period for detection, that is, ~3 days.57 As we reported, our interviews identified a significantly higher percentage of users than did urine screening.8 Detailed, confidential interviewing close to the time of use is an effective way to identify users and to characterize the quantity and pattern of use.2,58 Moreover, the rates of cocaine use reported and our findings are comparable to reports from other studies of prenatal cocaine exposure.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
This is the first study, to our knowledge, to report effects of prenatal cocaine exposure on child growth through 10 years of age. Longitudinal growth analyses showed that children who were exposed to cocaine during the first trimester of pregnancy grew at a slower rate than did those children who were not exposed to cocaine. These analyses controlled for other factors associated with growth, including exposure to other drugs. These findings indicate that prenatal cocaine exposure has a lasting effect on child development. We continue to follow this cohort into adolescence to determine if these growth deficits persist.


   ACKNOWLEDGMENTS
 
This research was supported by National Institute on Drug Abuse grants DA05460, DA06839, DA08916, and DA012401 (Dr Richardson, principal investigator).


   FOOTNOTES
 
Accepted Mar 16, 2007.

Address correspondence to Gale A. Richardson, PhD, Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213. E-mail: gar{at}pitt.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.

* Subjects' actual age at each phase, expressed as a continuous variable, was used to account for age differences at the time of assessment. Back

{dagger} First-trimester cigarette use was only significant for 1 phase but was included to be sure that all other prenatal drug use was controlled. Back


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Eyler F, Behnke M, Conlon M, Woods N, Frentzen B. Prenatal cocaine use: a comparison of neonates matched on maternal risk factors. Neurotoxicol Teratol. 1994;16 :81 –87[CrossRef][Web of Science][Medline]
  2. Richardson GA, Day NL, McGauhey PJ. The impact of prenatal marijuana and cocaine use on the infant and child. Clin Obstet Gynecol. 1993;36 :302 –318[CrossRef][Web of Science][Medline]
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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