Growth from birth onwards of children prenatally exposed to drugs: a literature review

Reductions in birth weight and length have been independently attributed to prenatal exposure to alcohol, cigarettes and cocaine. While pregnant women often use multiple substances, studies have not consistently controlled for exposure to other agents or other important differences in maternal lifestyle associated with the use of these substances. Despite these difficulties, the preponderance of evidence suggests that prenatal alcohol and cocaine independently reduce birth measurements. This review synthesizes the scientific literature focusing on prenatal exposures and the relationship to child growth. First examined are studies that investigated the link between prenatal exposures and birth weight and length, followed by the effects of these substances on childhood growth. Studies vary in the number of subjects, cohort characteristics, measurement of exposure and control for potential confounders. Differences in sample characteristics and size, as well as degree of statistical control for potential confounders and the examination of moderating characteristics, have led to differing conclusions regarding the long-term effect of prenatal substance exposure on growth. Large-scale, well-designed studies are needed to clearly examine the unique contribution of both varying prenatal exposures and the magnitude and timing of these exposures on childhood growth deficits.     

Prenatal cocaine exposure and childhood obesity at nine years

Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04-9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, CI .59-1.93) or both (OR 1.21, CI 0.66-2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity.     

Gender and alcohol moderate prenatal cocaine effects on teacher-report of child behavior

Prenatal cocaine exposure has been associated with behavior problems at school age. However, the correspondence between use of cocaine and alcohol during pregnancy is often high, making appropriate allocation of variance and control for other exposures and their interactions difficult. Additionally, gender-specific effects are not typically reported. The purpose of the current study was to determine the degree to which gender-specific effects of prenatal cocaine exposure on teacher-reported child externalizing behavior problems were evident when evaluated in relation to prenatal alcohol exposure. Subjects were singleton infants of mothers who were prospectively evaluated during pregnancy. At age seven, 499 children (214 exposed prenatally to cocaine) were evaluated in our laboratory and teacher reports were solicited. Analyses stratified by gender and prenatal alcohol exposure status, and controlled for significant pre- and postnatal confounders, revealed that among boys with prenatal alcohol exposure, those with persistent cocaine exposure throughout pregnancy had significantly higher levels of Delinquent Behavior compared to boys with no cocaine exposure. Boys with any prenatal cocaine exposure were twice as likely as unexposed boys to have clinically significant Externalizing Behavior scores. However, no association was found between prenatal cocaine exposure and scores on Externalizing Behavior and specific syndromes for boys with no prenatal alcohol exposure. Among girls with no prenatal alcohol exposure, those with persistent cocaine exposure had significantly higher levels of Externalizing Behaviors and Aggressive Behaviors compared to girls with no prenatal cocaine exposure after control for confounding, and were almost five times as likely to have clinically significant Externalizing Behavior scores. However, for girls with prenatal alcohol exposure, no association between prenatal cocaine exposure and scores on Externalizing Behavior and specific syndromes was found after control for confounding. The current findings support gender- and alcohol-moderated effects of prenatal cocaine exposure on school-age teacher-reported child behavior problems. These findings are similar to what we have reported for independent parent-reported behavioral evaluation.     

Pre-natal exposures to cocaine and alcohol and physical growth patterns to age 8 years

Two hundred and two primarily African American/Caribbean children (classified by maternal report and infant meconium as 38 heavier, 74 lighter and 89 not cocaine-exposed) were measured repeatedly from birth to age 8 years to assess whether there is an independent effect of pre-natal cocaine exposure on physical growth patterns. Children with fetal alcohol syndrome identifiable at birth were excluded. At birth, cocaine and alcohol exposures were significantly and independently associated with lower weight, length and head circumference in cross-sectional multiple regression analyses. The relationship over time of pre-natal exposures to weight, height, and head circumference was then examined by multiple linear regression using mixed linear models including covariates: child's gestational age, gender, ethnicity, age at assessment, current caregiver, birth mother's use of alcohol, marijuana and tobacco during the pregnancy and pre-pregnancy weight (for child's weight) and height (for child's height and head circumference). The cocaine effects did not persist beyond infancy in piecewise linear mixed models, but a significant and independent negative effect of pre-natal alcohol exposure persisted for weight, height, and head circumference. Catch-up growth in cocaine-exposed infants occurred primarily by 6 months of age for all growth parameters, with some small fluctuations in growth rates in the preschool age range but no detectable differences between heavier versus unexposed nor lighter versus unexposed thereafter.     

Prenatal cocaine exposure and small-for-gestational-age status: effects on growth at 6 years of age

Objective

To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.

Study design

Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.

Results

At birth cocaine-exposed infants (n = 364) had significantly lower growth parameters compared to non-exposed children (n = 771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).

Conclusions

Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.     

Four-year language outcomes of children exposed to cocaine in utero

A large cohort of children exposed to cocaine in utero (n=189) were followed prospectively from birth to 4 years of age and compared to nonexposed children (n=185) on the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P), a measure of receptive and expressive language abilities. Children exposed to cocaine in utero performed more poorly on the expressive and total language measures than nonexposed children after controlling for confounding variables, including prenatal exposure to alcohol, marijuana, and tobacco, as well as medical and sociodemographic variables. Children exposed to cocaine had more mild receptive language delays than nonexposed children and were less likely to have higher expressive abilities. Also, maternal factors such as language ability, performance IQ, race, and education correlated with child language abilities. Prenatal cigarette and marijuana exposure were related to deficits in specific language skills. Children placed in adoptive or foster care who were cocaine exposed demonstrated superior language skills compared to children exposed to cocaine who remained in biological relative or mother's care. These findings support a cocaine-specific effect on language skills in early childhood that may be modified with an enriched environment.     

Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed children

Dysmorphologic and anthropometric assessments were performed on 154 6-year-old children prenatally exposed to cocaine (PCE) and 131 high-risk controls (NCE) of similar race and social class. Adjusted mean height z scores demonstrated a dose-response with metahydroxybenzoylecgonine above a threshold of 100 ng/g of meconium and greater cocaine exposure predicted lower weight for height z score. Higher average alcohol exposure throughout pregnancy and 3rd trimester predicted lower head circumference and weight z scores, respectively. Severity of marijuana use also predicted lower height for age but greater weight for height. There was not an increased rate of minor anomalies among the PCE cohort, nor was a consistent phenotype identified. After controlling for covariates, higher average prenatal cigarette exposure predicted higher incidence of cranial facial abnormalities. First trimester alcohol exposure predicted greater rates of ear abnormalities and third trimester marijuana exposure predicted greater rates of chest and head shape abnormalities. These finding indicate that prenatal cocaine exposure has a negative effect on specific growth outcomes including standardized height and weight for height, but not a systematic pattern of structural abnormalities.     

Prenatal cocaine exposure: Effects on the development of school-age children

The offspring of 28 women who reported light to moderate cocaine use during pregnancy were compared with those of 523 women who reported no cocaine use during pregnancy and none for the year prior to pregnancy. Subjects were participants in two prospective, longitudinal studies of prenatal substance use. Women were interviewed during their fourth and seventh months of pregnancy, at delivery, and at 8, 18, 36, and 72 months postpartum regarding cocaine, alcohol, marijuana, tobacco, and other drug use. At 6 years, children underwent physical examination, and their cognitive development, academic achievement, and behavior were assessed. The women in the cocaine group were more likely to be Caucasian and to use more alcohol, marijuana, tobacco, and other illicit drugs than those in the comparison group. When demographic and substance use differences between the groups were controlled, there were no significant effects of prenatal cocaine exposure on the growth, intellectual ability, academic achievement, or teacher-rated classroom behavior of the 6-year-old offspring. Children prenatally exposed to cocaine did show deficits in their ability to sustain attention on a computerized vigilance task.     

The effects of prenatal cocaine exposure and gender on inhibitory control and attention

Children exposed prenatally to cocaine show deficits in emotion regulation and inhibitory control. While controlling for the measures of medical complication in the perinatal period, environmental risk, and prenatal polydrug exposure (alcohol, tobacco, and marijuana), we examined the effects of prenatal cocaine exposure and gender on attention and inhibitory control in 203 children at ages 6, 9, and 11. Cocaine exposure affected the performance of males, but not females. Heavily exposed males showed deficits in the attention and the inhibition tasks. In addition, a significantly greater proportion of heavily exposed males (21%) than unexposed males (7%) or heavily exposed females (7%) failed to complete the task (p < 0.01). Even without those poorest performing subjects, the overall accuracy for heavily exposed males (81%) was significantly reduced (p < 0.05) compared to lightly exposed males (87%) and unexposed males (89%). The findings highlight the importance of considering gender specificity in cocaine exposure effects. Processes by which cocaine effects may be specific to males are discussed.     

Prenatal cocaine and alcohol exposures affect rat behavior in a stress test (the Porsolt swim test).

Prenatal cocaine and alcohol exposures have been associated with a variety of adverse effects ranging from subtle neurobehavioral abnormalities to major malformations. In this study, we used the Porsolt swim test to assess the effects of prenatal cocaine and alcohol exposures on stress-related behavior. Pregnant Long-Evans rats were injected daily with 80 mg/kg cocaine HCl (SC) or 6.2-6.5 g/kg ethyl alcohol (PO) from gestation days 7-20 with half the dose given in the morning and the other half in the afternoon. Pair-fed and ad lib control groups were also used. One male offspring from each litter was evaluated in the Porsolt swim test at the age of 120 days. The alcohol and cocaine groups were less immobile (i.e., struggled more to escape) than the controls. These results suggest that prenatal exposure to either alcohol or cocaine can adversely affect behavior in stressful or fearful situations.     

Severity of prenatal cocaine exposure and child language functioning through age seven years: a longitudinal latent growth curve analysis

The current study estimates the longitudinal effects of severity of prenatal cocaine exposure on language functioning in an urban sample of full-term African-American children (200 cocaine-exposed, 176 noncocaine-exposed) through age 7 years. The Miami Prenatal Cocaine Study sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and toxicology assays of maternal and infant urine and infant meconium. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals--Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal latent growth curve analyses were used to examine two components of language functioning, a more stable aptitude for language performance and a time-varying trajectory of language development, across the three time points and their relationship to varying levels of prenatal cocaine exposure. Severity of prenatal cocaine exposure was characterized using a latent construct combining maternal self-report of cocaine use during pregnancy by trimesters and maternal and infant bioassays, allowing all available information to be taken into account. The association between severity of exposure and language functioning was examined within a model including factors for fetal growth, gestational age, and IQ as intercorrelated response variables and child's age, gender, and prenatal alcohol, tobacco, and marijuana exposure as covariates. Results indicated that greater severity of prenatal cocaine exposure was associated with greater deficits within the more stable aptitude for language performance (D = -0.071, 95% CI = -0.133, -0.009; p = 0.026). There was no relationship between severity of prenatal cocaine exposure and the time-varying trajectory of language development. The observed cocaine-associated deficit was independent of multiple alternative suspected sources of variation in language performance, including other potential responses to prenatal cocaine exposure, such as child's intellectual functioning, and other birth and postnatal influences, including language stimulation in the home environment.     

Longitudinal influence of prenatal cocaine exposure on child language functioning

The present study estimates the longitudinal effects of in utero cocaine exposure on language functioning at 3, 5 and 7 years of age in an urban sample of 443 full-term children (236 cocaine-exposed and 207 noncocaine-exposed) participating in the Miami Prenatal Cocaine Study. The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and urine and meconium toxicology assays. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal Generalized Linear Model and Generalized Estimating Equations (GLM/GEE) analyses revealed an association between prenatal cocaine exposure and deficits in total language functioning after statistically controlling for child sex, visit age, prenatal exposure to alcohol, marijuana and tobacco and over 20 additional medical and sociodemographic covariates drawn from potentially confounding influences assessed at birth and follow-up visits (D=-0.17; 95% CI=-0.32, -0.03; P=.019). The link from prenatal cocaine exposure to later language deficits does not appear to be mediated by cocaine-associated deficits in birth weight, length or head circumference. Overall, the evidence tends to support an inference of a stable cocaine-specific effect on indicators of language functioning during early childhood through age 7 years.     

Effects of prenatal cocaine exposure on infant reactivity and regulation

The purpose of this study was to examine the role of prenatal cocaine exposure and associated risk factors on infant reactivity and regulation at 7 months of infant age. Participants consisted of 167 mother-infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure, who completed the arm restraint procedure at the 7-month assessment (87 cocaine exposed, 80 non-cocaine exposed). We hypothesized that cocaine exposed infants would display higher arousal or reactivity and lower regulation during a procedure designed to arouse anger/frustration. Results indicated that cocaine exposed infants were more reactive to increases in the level of stress from trial 1 to trial 2 but exhibited no change in the number of regulatory strategies as stress increased, unlike the control group infants. Infant birth weight moderated the association between cocaine exposure and infant regulation. Among cocaine exposed infants, those with lower birth weight displayed higher reactivity compared to those with higher birth weight. Contrary to expectations, there were no indirect effects between cocaine exposure and infant reactivity/regulation via environmental risk, parenting, or birth weight. Results are supportive of a teratological model of prenatal cocaine exposure for infant reactivity/regulation in infancy.     

Effects of prenatal alcohol exposure at school age. I. Physical and cognitive development

Alcohol is a potent teratogen associated with dysmorphology, growth retardation, and neurological damage in children with the full fetal alcohol syndrome (FAS); alcohol is also associated with growth retardation and behavioral alterations in neonates prenatally exposed to various dosages. Questions remain about the long-term consequences of prenatal alcohol exposure. This study reports on the follow-up of a subsample of 68 children, the majority of whom were low income and black (mean age: 5 years, 10 months) who were first evaluated as neonates. Physical and cognitive outcomes of 25 children of women who drank throughout pregnancy [absolute alcohol (AA)/week: mean = 11.80 oz), even after receiving an educational intervention to stop drinking, were compared with outcomes of children in two contrast groups: a) women (n = 22) who stopped drinking (AA/week: mean = 11.46 oz) in the second trimester after an educational intervention but resumed postpartum; and b) women who did not drink during pregnancy and who drank little postnatally (n = 21). Children were compared for alcohol-related birth defects (ARBDs), growth (height, weight, and head circumference), and cognitive, academic, and adaptive measures. Neonatal and current physical measures were correlated to determine predictability of neonatal status. When the effects of age and gender were controlled, children in the continued-to-drink group showed significantly more ARBDs and had smaller head circumferences than those in the other two groups. When current drinking reported by caretakers was controlled, the children who were exposed throughout pregnancy also showed significant and consistent deficits in several areas of intellectual functioning including sequential processing (short-term memory and encoding) and overall mental processing. Alcohol-exposed children displayed significant deficits in preacademic skills when compared with children of nondrinkers, with both alcohol groups deficient in premath and reading skills. There were no differences in adaptive behavior at follow-up. These data suggest that alcohol exposure throughout pregnancy is correlated with persistent physical differences as well as identifiable deficits in sequential memory processes and specific academic skills. However, even when alcohol use is limited to the first part of pregnancy, significant deficits in academic skills and growth parameters are measurable.     

Cognitive and social development in preschool children born to women using substances

Prenatal substance exposure is associated with physical birth defects and increased risk of regulatory and neuropsychological difficulties of children born to mothers using substances while pregnant. Myriad factors, such as maternal psychopathology, stress, and poor living circumstances, may influence childhood development in addition to the teratological effect of prenatal substance exposure. This study explores the long-term developmental consequences in children from birth to age 7 born to women using substances and are in treatment. A series of t tests were performed to explore group effects on the cognitive and social dimensions of Griffiths Mental Development Scales compared with Swedish norms. The results showed significant effects on eye and hand coordination in children aged birth to 7 years and on hearing and speech, practical reasoning, and the general quotient in children aged 3 to 7 years. Children who were exposed primarily to alcohol in utero scored significantly lower on the personal and social skills subscale, eye and hand coordination subscale, and the general quotient than children exposed primarily to substances other than alcohol. These effects did not appear to be mediated by the mothers' social background or treatment history. The results suggest that children who are exposed to substances, in particular alcohol, in utero are vulnerable overall, but especially in eye and hand coordination and personal and social skills.     

Cognitive and Social Development in Preschool Children Born to Women Using Substances

Prenatal substance exposure is associated with physical birth defects and increased risk of regulatory and neuropsychological difficulties of children born to mothers using substances while pregnant. Myriad factors, such as maternal psychopathology, stress, and poor living circumstances, may influence childhood development in addition to the teratological effect of prenatal substance exposure. This study explores the long-term developmental consequences in children from birth to age 7 born to women using substances and are in treatment. A series of t tests were performed to explore group effects on the cognitive and social dimensions of Griffiths Mental Development Scales compared with Swedish norms. The results showed significant effects on eye and hand coordination in children aged birth to 7 years and on hearing and speech, practical reasoning, and the general quotient in children aged 3 to 7 years. Children who were exposed primarily to alcohol in utero scored significantly lower on the personal and social skills subscale, eye and hand coordination subscale, and the general quotient than children exposed primarily to substances other than alcohol. These effects did not appear to be mediated by the mothers’ social background or treatment history. The results suggest that children who are exposed to substances, in particular alcohol, in utero are vulnerable overall, but especially in eye and hand coordination and personal and social skills.     

Prenatal drug exposure and selective attention in preschoolers

Deficits in sustained attention and impulsivity have previously been demonstrated in preschoolers prenatally exposed to cocaine. We assessed an additional component of attention, selective attention, in a large, poly-substance cocaine-exposed cohort of 4 year olds and their at-risk comparison group. Employing postpartum maternal report and biological assay, we assigned children to overlapping exposed and complementary control groups for maternal use of cocaine, alcohol, marijuana, and cigarettes. Maternal pregnancy use of cocaine and use of cigarettes were both associated with increased commission errors, indicative of inferior selective attention. Severity of maternal use of marijuana during pregnancy was positively correlated with omission errors, suggesting impaired sustained attention. Substance exposure effects were independent of maternal postpartum psychological distress, birth mother cognitive functioning, current caregiver functioning, other substance exposures and child concurrent verbal IQ.     

Effects of cocaine/polydrug exposure and maternal psychological distress on infant birth outcomes

To assess teratogenic effects of cocaine exposure and maternal psychological distress on birth outcomes, we conducted a longitudinal prospective study of 415 infants (218 cocaine-exposed--CE, 197 nonexposed--NE). Drug exposure was determined through a combination of maternal self-report, urine, and meconium screens. Maternal psychological distress postpartum was evaluated through a standardized, normative, self-report assessment. An extensive set of confounding variables was controlled, including severity of exposure to alcohol, tobacco, marijuana and other drugs, maternal age, race, parity, number of prenatal care visits, educational, marital, and socioeconomic status, and verbal and nonverbal intelligence. CE infants were smaller on all birth parameters and more likely to be preterm, small for gestational age, and microcephalic than NE infants. Forty-one percent of cocaine users had clinically significant psychological symptoms, compared to 20% of a high-risk comparison group of noncocaine users. Consistent with a teratologic model, cocaine exposure independently predicted offspring birthweight, length, and head circumference. Maternal psychological distress self-reported postnatally also independently predicted head circumference. Tobacco, alcohol, and marijuana exposures were also significant independent predictors of some fetal growth parameters. In addition, maternal distress symptoms, which may be reflective of maternal mental health disorders or responses to stress, added significantly to the risk for poorer fetal growth.     

Newborn evaluations of toxicity and withdrawal related to prenatal cocaine exposure.

The literature on prenatal cocaine exposure is unclear whether immediate postpartum effects on the infant are transient, related to either acute toxicity of cocaine, or to a withdrawal effect as cocaine is metabolized, or whether they might persist. This prospective, longitudinal study was designed to test the hypotheses that newborns urine-positive for cocaine metabolites, compared to those exposed but urine-negative, and to nonexposed controls would (1) have poorer neurobehavioral scores (toxicity effect) and (2) worsen or demonstrate less improvement over the first week (withdrawal effect). We approached over 2500 pregnant women designated to deliver at our referral hospital from public health clinics; 85% consented to participate in a longitudinal study. We excluded women <18 years old with major chronic illness and prenatal drug use except cocaine, marijuana, alcohol and tobacco. From positive urine toxicologies or admissions in private, thorough interviews, 154 were identified as prenatal cocaine users; 154 were selected from noncocaine users matched on socioeconomic status (SES), race, parity and location of prenatal care (that related to perinatal risk), for a total sample size of 308. Included in this article are the 155 surviving infants who were full-term, delivered vaginally and were well and available for testing over the first week postpartum. Infant urine specimens were collected, and neurobehavorial testing was performed by certified, blinded examiners using the Neonatal Behavioral Assessment Scale on days 1, 2-4 and 5-7 postpartum. In toxicity analyses, controlling for amount of prenatal drug exposures, only autonomic regulation demonstrated significant overall and cocaine drug group effects. Urine-positive newborns had the poorest scores (i.e., more startles, tremors). However, given that planned comparisons were not significant, these data provided little support for acute toxicity effects. In withdrawal analyses, only one significant change over time varied among exposure groups. Those infants exposed and positive for cocaine metabolites increased their scores on regulation of state on days 2-4 and decreased them on days 5-7 (when withdrawal might be evident). However, their scores on days 5-7 were not significantly lower than their initial scores, nor different from the days 5-7 scores of the exposed negatives or control infants, lending little support for withdrawal effects. Our data support those of other controlled studies in failing to demonstrate devastating early effects of prenatal cocaine exposure. They add to our understanding that effects observed do not appear to be related to acute toxicity nor to cocaine withdrawal. The uncertainty of persistent effects of cocaine exposure warrants long-term follow-up.     

The effects of prenatal cocaine exposure on problem behavior in children 4–10 years

BackgroundChildren prenatally exposed to cocaine may be at increased risk for behavioral problems due to disruptions of monaminergically regulated arousal systems and/or environmental conditions.ObjectiveTo assess behavioral outcomes of cocaine (CE) and non-cocaine-exposed (NCE) children, 4 through 10 years old, controlling for other prenatal drug exposures and environmental factors.MethodsLow socioeconomic status (SES), primarily African American children (n = 381 (193 (CE), 188 (NCE)) were recruited from birth. Generalized Estimating Equation (GEE) analyses were used to assess the predictive relationship of prenatal cocaine exposure to odds of caregiver reported clinically elevated behavioral problems at 4, 6, 9 and 10 years of age, controlling for confounders.ResultsPrenatal cocaine exposure was associated with increased rates of caregiver reported delinquency (OR = 1.93, CI: 1.09–3.42, p < 0.02). A significant prenatal cocaine exposure by sex interaction was found for delinquency indicating that only females were affected (OR = 3.57, CI: 1.67–7.60, p < 0.001). There was no effect of cocaine on increased odds of other CBCL subscales. Higher prenatal tobacco exposure was associated with increased odds of externalizing symptoms at 4, 9 and 10 years of age. For CE children, those in foster or adoptive care were rated as having more behavior problems than those in biologic mother or relative care. Greater caregiver psychological distress was associated with increased behavioral problems. There were no independent effects of elevated blood lead level on increased behavior problems after control for prenatal drug exposure and other environmental conditions.ConclusionPrenatal cocaine and tobacco exposure were associated with greater externalizing behavior after control for multiple prenatal drug exposures, other environmental and caregiving factors and lead exposure from 4 through 10 years of age. Greater caregiver psychological distress negatively affected caregiver ratings of all CBCL domains. Since cocaine and tobacco use during pregnancy and maternal psychological distress have the potential to be altered through prenatal educational, drug treatment and mental health interventions, they warrant attention in efforts to reduce rates of problem behaviors in children.