Virginia Delaney-Black

Teacher-Assessed Behavior of Children Prenatally Exposed to Cocaine

Objective. Prenatal cocaine exposure has been associated with alterations in neonatal behavior and more recently a dose–response relationship has been identified. However, few data are available to address the long-term behavioral effects of prenatal exposures in humans. The specific aim of this report is to evaluate the school-age behavior of children prenatally exposed to cocaine. Methods. All black non–human immunodeficiency virus–positive participants in a larger pregnancy outcomes study who delivered singleton live born infants between September 1, 1989 and August 31, 1991 were eligible for study participation. Staff members of the larger study extensively screened study participants during pregnancy for cocaine, alcohol, cigarettes, and other illicit drugs. Prenatal drug exposure was defined by maternal history elicited by structured interviews with maternal and infant drug testing as clinically indicated. Cocaine exposure was considered positive if either history or laboratory results were positive. Six years later, 665 families were contacted; 94% agreed to participate. The child, primary caretaker (parent), and, when available, the biologic mothers were tested in our research facilities. Permission was elicited to obtain blinded teacher assessments of child behavior with the Achenbach Teachers Report Form (TRF). Drug use since the childs birth was assessed by trained researchers using a structured interview. Results. Complete laboratory and teacher data were available for 499 parent–child dyads, with a final sample size for all analyses of 471 (201 cocaine-exposed) after the elimination of mentally retarded subjects. A comparison of relative Externalizing (Aggressive, Delinquent) to Internalizing (Anxious/Depressed, Withdrawn, Somatic Complaints) behaviors of the offspring was computed for the TRF by taking the difference between the 2 subscales to create an Externalizing–Internalizing Difference (T. M. Achenbach, personal communication, 1998). Univariate comparisons revealed that boys were significantly more likely to score in the clinically significant range on total TRF, Externalizing–Internalizing, and Aggressive Behaviors than were girls. Children prenatally exposed to cocaine had higher Externalizing–Internalizing Differences compared with controls but did not have significantly higher scores on any of the other TRF variables. Additionally, boys prenatally exposed to cocaine were twice as likely as controls to have clinically significant scores for externalizing (25% vs 13%) and delinquent behavior (22% vs 11%). Gender, prenatal exposures (cocaine and alcohol), and postnatal risk factors (custody changes, current drug use in the home, childs report of violence exposure) were all related to problem behaviors. Even after controlling for gender, other prenatal substance exposures, and home environment variables, cocaine-exposed children had higher Externalizing–Internalizing Difference scores. Prenatal exposure to alcohol was associated with higher total score, increased attention problems, and more delinquent behaviors. Prenatal exposure to cigarettes was not significantly related to the total TRF score or any of the TRF subscales. Postnatal factors associated with problem behaviors included both changes in custody status and current drug use in the home. Change in custody status of the cocaine-exposed children, but not of the controls, was related to higher total scores on the TRF and more externalizing and aggressive behaviors. Current drug use in the home was associated with higher scores on the externalizing and aggressive subscales. Conclusions. Results of this study suggest gender-specific behavioral effects related to prenatal cocaine exposure. Prenatal alcohol exposure also had a significant impact on the TRF. Postnatal exposures, including current drug use in the home and the childs report of violence exposure, had an independent effect on teacher-assessed child behavioral problems. Furthermore, among the children prenatally exposed to cocaine, change in the childs custody status was a significant predictor of TRF scores. It remains possible that other unmeasured postnatal characteristics of the cocaine-using household may play important roles in teacher-assessed child behavior.

Prenatal cocaine: Quantity of exposure and gender moderation

ABSTRACT. Animal but few human studies have demonstrated gender-influenced differences in outcome related to prenatal cocaine exposure. Pregnant participants in a prospective pregnancy study were interviewed for drug use. Exposure was considered positive if history or laboratory tests were positive. An ordinal measure of exposure was also constructed. Six years later, the child and primary caretaker were tested to assess drug use in the home since birth and teacher-assessed child behavior. Data were complete for 473 children (204 cocaine exposed). Twenty-four of the exposed children (12%) were considered to have persistent pregnancy exposure based on positive urine screen at delivery. Boys with any prenatal cocaine exposure scored significantly higher (more problem behaviors) than nonexposed boys on the hyperactivity item. In contrast, no similar cocaine effect was observed for girls. When cocaine exposure was expressed as the three-level ordinal variable, boys, but not girls, with persistent exposure had more behavior problems (0.5 to 1.0 SD higher). Even after control for important covariates, boys with persistent exposure had more problems in central processing, motor skills, handling abstract concepts, and passivity to the environment. The magnitude of the relations reported in this research were moderate to large. In summary, both gender and the level of exposure had a significant behavioral effect on school-age behavior. In these analyses, the behavior of boys, but not girls, prenatally exposed to cocaine was significantly and negatively affected, and these findings remained after control for covariates, including prenatal alcohol or other illicit drug exposures and postnatal drug use in the home.

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.

Expressive Language Development of Children Exposed to Cocaine Prenatally: Literature Review and Report of a Prospective Cohort Study.

It was hypothesized that prenatal exposure to cocaine and other substances would be related to delayed expressive language development. Speech and language data were available for 458 6-year olds (204 were exposed to cocaine). No significant univariate or multivariate differences by cocaine exposure group were observed. Classification and regression tree modeling was then used to identify language variable composites predictive of cocaine exposure status. Meaningful cut points for two language measures were identified and validated. Children with a type token ratio of less than 0.42 and with fewer than 97 word types were classified into a low language group. Low language children (n = 57) were more likely to be cocaine exposed (63.1%), with cocaine-exposed children 2.4 times more likely to be in the low language group compared with control children after adjustment for covariates. Prenatal cigarette, but not alcohol exposure, was also significantly related to expressive language delays.

Just Say “I Don't”: Lack of Concordance Between Teen Report and Biological Measures of Drug Use

BACKGROUND: Prevalence estimates of illicit drug use by teens are typically generated from confidential or anonymous self-report. While data comparing teen self-report with biological measures are limited, adult studies identify varying degrees of under-reporting. METHODS: Hair analyses for cocaine, opiates and marijuana were compared to confidential teen self- and parent-reported teen drug use in a longitudinal cohort of >400 high-risk urban teens and parents. RESULTS: Both teens and parents substantially underreported recent teen cocaine and opiate use. However, compared with parents, teens were more likely to deny biomarker-verified cocaine use. Teen specimens (hair) were 52 times more likely to identify cocaine use compared with self-report. Parent hair analyses for cocaine and opiate use were 6.5 times and 5.5 times, respectively, more likely to indicate drug use than were parental self-report. The lack of concordance between self-report and bioassay occurred despite participants knowledge that a “certificate of confidentiality” protected both teen and adult participants, and that the biological specimens would be tested for drugs. CONCLUSIONS: These findings confirm prior reports of adult under-reporting of their own drug use while extending our understanding of teens self-admitted drug use. The lack of concordance between teen self- or parent-reported teen drug use and biomarkers confirm our concerns that both teen- and parent-reported teen drug use is limited, at least for youth in high-risk urban settings. Methods of ascertainment other than self- or parent-report must be considered when health care providers, researchers and public health agencies attempt to estimate teen drug-use prevalence.

A 14-year retrospective maternal report of alcohol consumption in pregnancy predicts pregnancy and teen outcomes

Detecting patterns of maternal drinking that place fetuses at risk for fetal alcohol spectrum disorders (FASDs) is critical to diagnosis, treatment, and prevention but is challenging because information on antenatal drinking collected during pregnancy is often insufficient or lacking. Although retrospective assessments have been considered less favored by many researchers due to presumed poor reliability, this perception may be inaccurate because of reduced maternal denial and/or distortion. The present study hypothesized that fetal alcohol exposure, as assessed retrospectively during child adolescence, would be related significantly to prior measures of maternal drinking and would predict alcohol-related behavioral problems in teens better than antenatal measures of maternal alcohol consumption. Drinking was assessed during pregnancy, and retrospectively about the same pregnancy, at a 14-year follow-up in 288 African-American women using well-validated semistructured interviews. Regression analysis examined the predictive validity of both drinking assessments on pregnancy outcomes and on teacher-reported teen behavior outcomes. Retrospective maternal self-reported drinking assessed 14 years postpartum was significantly higher than antenatal reports of consumption. Retrospective report identified 10.8 times more women as risk drinkers (≥ one drink per day) than the antenatal report. Antenatal and retrospective reports were moderately correlated and both were correlated with the Michigan Alcoholism Screening Test. Self-reported alcohol consumption during pregnancy based on retrospective report identified significantly more teens exposed prenatally to at-risk alcohol levels than antenatal, in-pregnancy reports. Retrospective report predicted more teen behavior problems (e.g., attention problems and externalizing behaviors) than the antenatal report. Antenatal report predicted younger gestational age at birth and retrospective report predicted smaller birth size; neither predicted teen IQ. These results suggest that if only antenatal, in-pregnancy maternal report is used, then a substantial proportion of children exposed prenatally to risk levels of alcohol might be misclassified. The validity of retrospective assessment of prior drinking during pregnancy as a more effective indicator of prenatal exposure was established by predicting more behavioral problems in teens than antenatal report. Retrospective report can provide valid information about drinking during a prior pregnancy and may facilitate diagnosis and subsequent interventions by educators, social service personnel, and health-care providers, thereby reducing the life-long impact of FASDs.

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.

Violence Exposure, IQ, Academic Performance,and Children’s Perception of Safety:Evidence of Protective Effects

Community violence exposure (CVE), a critical urban problem, is associated with negative academic outcomes. Children who report feeling safe, however, may perform better than those who do not. The purpose of this study was to examine the relations among CVE, feelings of safety, and cognitive outcomes among 6- and 7-year-olds born to women receiving prenatal care at an inner-city maternity hospital who participated in a prospective pregnancy study. In addition to obtaining measures of child CVE, IQ, reading, standardized school achievement, and grades, we also evaluated the primary caregiver in order to assess the home and family environment. Greater violence exposure and victimization were related to poorer child outcomes; however, feelings of safety were positively related to most of the cognitive measures, and positive caregiving was related to more optimal cognitive functioning. Increased feelings of safety may allow children to focus on critical school tasks to which they may otherwise be unable to attend.

Aerosolized PGE1: A selective pulmonary vasodilator in neonatal hypoxemic respiratory failure results of a Phase I/II open label clinical trial

Twenty term/near term neonates with hypoxemic respiratory failure and oxygenation index ≥20 were enrolled in a Phase I/II feasibility, safety and dose escalation study of inhaled PGE1 (IPGE1). Incremental doses of IPGE1, delivered by a jet nebulizer over a 2-h period, followed by weaning over 1 h, were given to 13 patients before receiving inhaled nitric oxide (INO) (Group I), and to seven patients, who failed to respond to INO (Group II). Response was defined as an increase in PaO2 of either ≥ 25 (full) or 10–25 (partial) torr. Exit criteria included an acute deterioration in oxygenation status, a persistent oxygenation index above 35 in Group I, or the availability of extracorporeal membrane oxygenation (ECMO) in Group II. The mean (SD) increase in PaO2 at the end of IPGE1 administration was 63 (62.3) in Group I (p = 0.024), and 40 (62.1) in Group II (p > 0.05). In Group I, 8 of 13 neonates had a full response, but 4 deteriorated following discontinuation of IPGE1. Of these four, two responded to INO and two were placed on ECMO. Five patients deteriorated before or during IPGE1, and none of them responded to INO. In Group II, three of seven patients had a full response to IPGE1. One patient with a partial response and all patients exiting before or during IPGE1 administration were placed on ECMO. The results of our study indicate that IPGE1 may be a safe, selective pulmonary vasodilator in neonatal hypoxemic respiratory failure.

History of In Utero Cocaine Exposure in Language-Delayed Children

To determine whether children with language delays are more likely to have been exposed to cocaine in utero than children with normal language development, a case-control study was undertaken. Based on routine office screening in our primary-care clinic over a 1-year period, we identified 29 consecutive children, aged 24 to 48 months, as language-delayed. They were compared with an approximate 2:1 match of children without language delay who had been seen in the clinic on the same days and who were of similar age. There was more reported cocaine use during pregnancy (six of 29, 21%) among the language-delayed children than among the controls (five of 71, 7%). This difference is statistically significant (P < 0.05, χ2 = 3.92; odds ratio = 3.4 ± 2.2). Discriminant analysis revealed that both cocaine and nicotine exposure were associated with delayed language development — with an unexpected negative, i.e., an antagonistic, protective, interactive effect (F[3,96] = 4.66, R2 = 12.7%, P<.005); neither gender nor caretaker contributed to language development in this sample. These results suggest that children with language delay detected in a clinical setting are more likely to have been exposed in utero to cocaine than children with normal language development. Prenatal cocaine exposure should be a risk factor in monitoring development in children.