Gender and alcohol moderate caregiver reported child behavior after prenatal cocaine

OBJECTIVE: The concurrence of prenatal alcohol exposure with other drug exposure, low socioeconomic status and environmental risk factors may obscure associations, if any, between prenatal cocaine exposure and child outcomes. This study evaluates the effects of prenatal cocaine exposure on child behavior in analyses stratified by gender and prenatal alcohol exposure status. METHODS: Maternal alcohol, cigarette, and illicit drug use were prospectively assessed by interview during pregnancy and postnatally. Maternal and neonatal urine were tested for drug exposure as clinically indicated. Caregiver report of child behavior was assessed with the Achenbach Child Behavior Checklist (CBCL). Dichotomous cocaine exposure was characterized as no (negative history and biologic markers), and any (positive history and/or biologic markers during pregnancy and/or positive urine screen at delivery from either mother or infant). RESULTS: Prenatal cocaine exposure was associated with adverse effects on offspring behavior that were moderated by the gender of the offspring as well as prenatal alcohol exposure. For girls without prenatal alcohol exposure, 6.5% of the unique variance in behavior was related to prenatal cocaine exposure. For these girls, the odds of scoring in the abnormal range for Aggression was 17 times control levels (95% confidence limits 1.4 to 203). These findings, though significant, have wide confidence intervals and need to be replicated in larger cohorts and on longitudinal follow-up.     

Continued effects of prenatal cocaine use: Preschool development

The relationship between prenatal cocaine use and preschooler's physical and cognitive development and behavioral characteristics was examined, controlling for other influences on child development. On average, children were 38.5 months old, women were 29.4 years old, had 12.3 years of education, and 47% were African American. During the first trimester, 18% of the women were frequent cocaine users (≥ 1 line/day). First trimester cocaine exposure predicted decreased head circumference at 3 years and lower scores on the short-term memory subscale of the Stanford–Binet Intelligence Scale (SBIS) [74]. There was no significant relationship between prenatal cocaine use and the other SBIS scales. First trimester cocaine use also predicted more total, internalizing, and externalizing behavior problems on the Child Behavior Checklist [3] and higher scores on the fussy/difficult scale of the Infant Characteristics Questionnaire [6]. Children who were exposed to cocaine throughout pregnancy had more behavior problems and were more fussy compared to children of women who never used cocaine prenatally. A repeated measures analysis showed that children of first trimester cocaine users became more fussy over time. These detrimental effects on growth and behavior are consistent with other reports in the literature and with the hypothesis that prenatal cocaine exposure affects development through changes in neurotransmitter systems.     

Prenatal cocaine exposure, gender, and adolescent stress response: A prospective longitudinal study

Prenatal cocaine exposure is associated with alterations in arousal regulation in response to stress in young children. However, relations between cocaine exposure and stress response in adolescence have not been examined. We examined salivary cortisol, self-reported emotion, heart rate, and blood pressure (BP) responses to the Trier Social Stress Test (TSST) in 49 prenatally cocaine and other drug exposed (PCE) and 33 non-cocaine-exposed (NCE) adolescents. PCE adolescents had higher cortisol levels before and after stress exposure than NCE adolescents. PCE girls showed an elevated anxiety response to stress (compared to NCE girls) and PCE boys showed a dampened diastolic BP response (compared to NCE boys). Girls showed higher anger response and lower pre-stress systolic BP than boys. Group differences were found controlling for potential confounding variables and were not moderated by caregiver–child relationship quality (although relationship quality predicted HPA axis and anxiety response). The findings suggest that prenatal drug exposure is associated with altered stress response in adolescence and that gender moderates this association.     

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.     

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 substance exposure: effects on attention and impulsivity of 6-year-olds

Attention and impulsivity of prenatally substance-exposed 6 year olds were assessed as part of a longitudinal study. Most of the women were light to moderate users of alcohol and marijuana who decreased their use after the first trimester of pregnancy. Tobacco was used by a majority of women and did not change during pregnancy. The women, recruited from a prenatal clinic, were of lower socio-economic status, and over half were African American. Attention and impulsivity were assessed using a Continuous Performance Task. Second and third trimester tobacco exposure and first trimester cocaine use predicted increased omission errors. Second trimester marijuana use predicted more commission errors and fewer omission errors. There were no significant effects of prenatal alcohol exposure. Lower Stanford-Binet Intelligence Scale composite scores, male gender, and an adult male in the household also predicted more errors of commission. Lower SBIS composite scores, younger child age, maternal work/ school status, and higher maternal hostility scores predicted more omission errors. These findings indicate that prenatal substance use has an effect on attentional processes.     

Maternal and neonatal effects of moderate cocaine use during pregnancy

Thirty-four women who reported using cocaine during pregnancy were compared to 600 women who reported no cocaine use during pregnancy and none for the year prior to pregnancy. Subjects were participants in a prospective, longitudinal study of prenatal substance use. The sample consisted of young, predominantly single, low-income women attending a public prenatal clinic. Women were interviewed at the end of their first, second and third trimesters regarding cocaine, alcohol, marijuana, tobacco and other drug use. The majority of the cocaine users were light to moderate users who decreased their use during pregnancy. The cocaine group was more likely to be white and to use alcohol, marijuana, tobacco and other illicit drugs more heavily than the comparison group. The cocaine users had more previous fetal losses but did not differ on other obstetrical complications. Infant growth, morphology and behavior were not affected.     

Personality traits as predictors of early alcohol inebriation among young adolescents: Mediating effects by mental health and gender-specific patterns

The aim of this study was to predict alcohol inebriation and mental health (internalizing and externalizing problems plus well-being), and potential gender-specific patterns among young adolescents, by a biopsychosocial model of personality traits. Self-reported data from 853 adolescents (479 girls) in Sweden, aged 13–15 years, from the Longitudinal Research on Development In Adolescence (LoRDIA) program were used. Predictions from personality to inebriation and mediating effects of mental health were estimated by means of logistic regression and generalized structural equation modelling. Separated gender analyses were performed throughout the study to reveal potential gender-specific patterns. Externalizing problems, Novelty Seeking and Cooperativeness had independent effects on alcohol inebriation for both genders as well as Harm Avoidance among girls and Internalizing problems among boys. Novelty Seeking and Self-Directedness had indirect effects through externalizing problems and Harm Avoidance and Self-Directedness had indirect effects through internalizing problems for boys. Self-directedness showed an indirect effect through externalizing problems for girls. The combination of an immature character (low Self-directedness and Cooperativeness) with an extreme temperament profile (high Novelty Seeking and low Harm Avoidance) was a predictor of inebriation across gender, both directly and indirectly through mental health. This study contributes with valuable information about gender-specific considerations when developing and conducting preventative interventions targeting psychological risk and resilience factors for early alcohol inebriation among young adolescents.     

Maternal cocaine use and infant behavior

We hypothesized that prenatal cocaine exposure results in less optimal infant behavior and more impaired maternal-infant interaction in healthy term infants. Infants were evaluated with the Neonatal Behavioral Assessment Scale (NBAS) at days 1-3 and 11-30 of age, and mother-infant pairs with the Nursing Child Assessment of Feeding Scale (NCAFS) at 7-16 weeks of age. Drug use was determined from confidential interviews, urine assays and medical records. Cocaine-exposed infants (N = 51) were no different than unexposed comparison infants (N = 60) on the first NBAS exam. On the second NBAS exam, 20 cocaine-exposed infants had slightly lower motor cluster scores compared with those of 32 unexposed infants (p = 0.01), but this difference was reduced after control for several confounding variables. The NCAFS detected no differences between groups in maternal or infant behavior. Infants in this population showed no clinically meaningful effects of cocaine exposure on behavior or maternal-infant interaction.     

Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status.

Effects on fetal growth and neonatal behavior of cocaine and alcohol use in pregnancy were investigated in infants born to women in a low-income, predominantly black population. Despite the increased use of cocaine by pregnant women and the accompanying public concern, behavioral studies of exposed neonates are limited in number and scope. In most studies, confounding factors (e.g., polydrug abuse, prematurity, infant health status) have not been controlled so the actual effects of cocaine and other drug exposure are not clear. Accordingly, this study investigated effects of prenatal drug exposure although controlling experimentally for other factors known to be associated with poor outcomes in infants: prematurity, other illicit drug use, associated diseases (e.g., sexually transmitted diseases [STDs]), and duration of drug use. In addition, other factors statistically controlled were: experimenter effects, timing of assessment, and effects of duration, amount, and frequency of cocaine, alcohol, marijuana, and nicotine exposure. One hundred and seven full-term infants were assessed at 2, 14, and 28 days using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) by testers blind to infant status. Growth factors (i.e., birthweight, length, head circumference) were also assessed.     

Interactive effects of prenatal alcohol and cocaine exposures on postnatal mortality, development and behavior in the Long-Evans rat

Polydrug abuse has increased substantially in recent years amongst obstetric patients. One of the most common drug combinations is alcohol and cocaine. To better understand the adverse consequences of this drug combination on pregnancy and the offspring, alcohol (2 g/kg, b.i.d.) and cocaine HCl (30 mg/kg, b.i.d.) were administered individually and in combination to separate groups of pregnant Long-Evans rats from gestation days 7-20. The pregnant dams were evaluated for maternal weight gain, food and water consumption, mortality, and gestational length. The offspring were evaluated for physical maturation, mortality, and behavior. The drug combination was found to have greater effects regarding decreased birth weight, increased postnatal mortality, and delayed physical maturation than either drug alone. Drug treatments also influenced activity monitor behavior in that prenatal cocaine exposure was associated with hypoactivity while the alcohol and the alcohol-plus-cocaine treatments were associated with hyperactivity in periweanling pups. Drug treatments had no significant effects on passive or active avoidance behaviors. These results suggest that combining alcohol and cocaine increases the risk to the offspring.     

Birth to age 7 growth of children prenatally exposed to drugs: a prospective cohort study

Prenatal exposure to cocaine, alcohol, and cigarettes has been linked to decreased birth weight and length. Unclear, however, is whether growth deficits persist into childhood. Women who were pregnant, African-American, not HIV-positive, and who delivered singleton infants were extensively screened throughout pregnancy for cocaine, alcohol, cigarette, and other illicit drug use. Of the approximately 1100 eligible subjects, 665 families were located at a 7-year postbirth follow-up and 540 participated. After appropriate control for potential confounders and prenatal exposures, prenatal exposure to cocaine, alcohol, and cigarettes each independently predicted birth weight and length. At age 7, prenatal cocaine exposure was significantly related to height deficits after accounting for other prenatal exposures and significant confounders. Children at age 7 exposed to cocaine in utero were up to 1 in. shorter and twice as likely to fall below the 10th percentile in height as the control children after accounting for other significant confounders including other prenatal exposures. Maternal age moderated the relation between prenatal exposures and child growth. Children born to women over 30 and exposed to cocaine were up to 2 in. shorter and four times more likely to have clinically significant height deficits at age 7. Children of older women and exposed to moderate-to-high levels of alcohol prenatally were up to 14 lb lighter and five times more likely to fall below the 10th percentile in weight. Similar growth restriction was not associated with prenatal exposures for children born to younger mothers. These outcomes add to the growing body of literature detailing long-term effects of prenatal drug exposure, suggesting differential effects for cocaine and alcohol, and indicating that maternal age may moderate these effects. Mechanisms for growth restriction and failure of catch-up under conditions of prenatal exposures are presented, suggesting further study of these developmental outcomes.     

Prenatal cocaine exposure: Effects on mother- and teacher-rated behavior problems and growth in school-age children

In this longitudinal study of prenatal cocaine exposure (PCE), school-age physical and cognitive development and behavioral characteristics were examined, while controlling for other factors that affect child development. At this follow-up phase, children were on average 7.2 years old, and their caregivers were 33.7 years old, had 12.5 years of education, and 48% were African American. During the first trimester, 20% of the women were frequent cocaine users (≥1 line/day). First trimester cocaine exposure predicted decreased weight and height at 7 years. There was no significant relationship between PCE and the cognitive and neuropsychological measures. Third trimester cocaine use predicted more total and externalizing behavior problems on the Child Behavior Checklist (Achenbach, 1991 [3]) and the Teacher Report Form (Achenbach, 1991 [4]), and increased activity, inattention, and impulsivity on the Routh Activity (Routh et al., 1974 [67]) and SNAP scales (Pelham and Bender, 1982 [55]). Children who were exposed to cocaine throughout pregnancy had more mother- and teacher-rated behavior problems compared to children of women who stopped using early in pregnancy or who never used cocaine prenatally. These detrimental effects of PCE on behavior are consistent with other reports in the literature and with the hypothesis that PCE affects development through changes in neurotransmitter systems. These school-age behaviors may be precursors of later adolescent behavior problems.     

12- and 24-month neurobehavioural follow-up of children prenatally exposed to marihuana, cigarettes and alcohol

The motor, mental, and language development plus the home environment was examined in 217 twelve-month and 153 twenty-four-month-old children for whom prenatal exposure to marijuana, alcohol and cigarettes was previously ascertained. With this low-risk sample multiple regression analysis was used to assess the association between outcome measures and prenatal drug exposure while adjusting for potential confounding factors. Prenatal exposure to marijuana was uniquely positively associated with a series of items evaluating the child's attitudes and interests that reflect a cognitive factor. Moderate levels of alcohol were significantly associated with lower mental scores at 24 months of age. Prenatal maternal cigarette smoking was significantly associated with lower mental scores at 12 months of age and altered responses on auditory items at 12 and 24 months. However, at 24 months, the strong relationship of postnatal environmental factors with cognitive outcomes and with prenatal maternal smoking resulted in loss of significant, unique predictive power for maternal smoking. Based on the present work and supplemented by previously reported data pertaining to maternal attitudes during pregnancy and neonatal behaviour, a transactional interpretation is presented.     

Prenatal and postnatal cocaine exposure predict teen cocaine use

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use.     

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.     

Feto-placental morphological effects of prenatal exposure to drugs of abuse

The aim of the study was to find morphological changes in the feto-placental unit due to prenatal exposure to drugs of abuse. A blind histomorphometric study was performed using 225 placentas. Based on meconium testing, the fetuses were classified as exposed or unexposed to opiates, cocaine, cannabis or alcohol. To establish prenatal tobacco exposure, cotinine in cord blood was analyzed. At the microscopic level a non statistically significant reduction of placental vascularization was observed in cocaine, opiates and alcohol using mothers. In addition, alcohol-consuming mothers did not present with larger placental vessel diameter than controls. Prenatal use of cocaine and tobacco was associated with a decrease in newborn weight and length. Furthermore, tobacco use was associated with a higher rate of previous abortions. In conclusion, placentas from mothers using tobacco, cocaine, opiates or alcohol during pregnancy present vasculature changes that may explain the adverse perinatal outcomes in their newborns.     

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.     

Level of prenatal cocaine exposure and infant-caregiver attachment behavior

The objective of this longitudinal prospective cohort study was to determine whether level of prenatal cocaine exposure, or the interaction between level of prenatal cocaine exposure and contextual risk variables, was associated with a higher rate of infant-caregiver insecure attachment and disorganized attachment, or with alterations in infant crying or avoidant behavior, after controlling for prenatal exposure to alcohol, tobacco, and marijuana, the quality of the proximal caregiving environment, and other covariates. Subjects were 154 full-term 12-month-old infants (64 unexposed, 61 with lighter cocaine exposure, 29 with heavier cocaine exposure) and their primary caregivers from low-income, urban backgrounds. Exposure status was determined in the maternity ward by biologic assay (infant meconium and/or maternal or infant urine) and maternal self-report. At the 12-month follow-up visit, infants were videotaped with their primary caregiver in Ainsworth's Strange Situation. Reliable coders masked to exposure status scored videotapes for attachment variables, amount of crying, and level of avoidance. Contrary to popular perceptions, level of prenatal cocaine exposure was not significantly related to secure/insecure attachment status, disorganized attachment status, or rated level of felt security. Foster care status also was not associated with attachment status. However, heavier prenatal cocaine exposure, in interaction with maternal contextual variables (public assistance or multiparity) was associated with alterations in infant socio-affective behavior, including a higher level of behavioral disorganization, more avoidance of the caregiver, and less crying.