Growth and pubertal milestones during adolescence in offspring prenatally exposed to cigarettes and marihuana.

Weight, height, head circumference, and pubertal milestones were examined in one hundred fifty-two 13- to 16-year-old adolescents for whom prenatal exposure to marihuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle-class sample participating in an ongoing, longitudinal study and whose growth has been monitored since birth. The weight of the 13- to 16-year-old children of heavy cigarette smokers, after statistical adjustment, did not differ from control subjects but they had a significantly higher Ponderal Index (PI). These observations continued those noted when these subjects were 9 to 12 years of age. Among the male offspring of cigarette smokers, pubertal milestones occurred at an earlier age than among male adolescents born to nonsmokers. Active smoking by the offspring did not moderate these findings. Maternal marihuana use was not associated with any growth measurement or the timing of pubertal milestones.     

Alcohol,tobacco and marijuana use among pregnant teenagers: 6-year follow-up of offspring growth effects

This prospective study evaluated the relations between maternal alcohol, tobacco and marijuana use during pregnancy and children's growth at 6 years. In this cohort of pregnant teenagers and their offspring, mothers were recruited from an urban prenatal clinic between 1990 and 1995, and observed from their fourth prenatal month. At the delivery assessment, there were 413 live-born singletons. At the 6-year visit, 345 children and mothers were evaluated. Prenatal alcohol and marijuana exposure were significantly associated with growth deficits, after controlling statistically for other prenatal substance use, current maternal substance use, current environmental tobacco exposure (ETS) and sociodemographic and growth-related covariates. There was a significant negative association between the second and third trimester alcohol exposure and offspring height. Third trimester alcohol exposure predicted reduced skinfold thickness. Exposure to any prenatal marijuana in the second trimester was significantly associated with shorter stature. First trimester tobacco exposure was associated with increased skinfold thickness among the 6-year-olds. The effects of prenatal alcohol exposure on growth at birth persisted in older children despite a low level of exposure during gestation. Effects of prenatal marijuana exposure on reduced height were not anticipated and occurred only when use was categorized as any/none. These data are consistent with an emerging body of evidence indicating that, by contrast to the growth deficits associated with smoking during pregnancy, which are evident at birth, the shorter stature associated with prenatal alcohol exposure continues to be evident during childhood.     

The effects of prenatal tobacco and marijuana use on offspring growth from birth through 3 years of age

This is a prospective study of prenatal substance use. Women were interviewed during their fourth and seventh months of pregnancy, at delivery, and at 8, 18, and 36 months postpartum. At birth, there were 763 liveborn, singleton offspring in the sample. At each phase, the offspring were examined and measured for growth. Data are presented on the relationship between tobacco and marijuana use and the size of the offspring at birth, 8, 18, and 36 months of age. At birth, there was a significant inverse relationship between tobacco use and weight, length, and head circumference. At 8 months of age, only length continued to be associated with prenatal tobacco exposure. By 18 months of age, there was no relationship between prenatal tobacco exposure and size of the offspring. Prenatal marijuana exposure was only associated with decreased length at birth. Neither tobacco nor marijuana use predicted gestational age or morphological abnormalities.     

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.     

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.     

Cocaine exposure and developmental outcome from birth to 6 months

The theoretical framework for many of the early studies of prenatal cocaine exposure has been rooted in the basic concepts of teratology/developmental toxicology. Few have published longitudinal analyses of the complex interplay between the relative effects of prenatal cocaine exposure and perinatal and environmental factors on development. The purpose of this paper was to use structural equation modeling to describe the direct and indirect effects of prenatal drug exposure on developmental outcome from birth to age 6 months. Key variables considered for study include prenatal drug exposure, perinatal medical characteristics, maternal/caregiver/family characteristics, the home environment, and neurobehavioral outcomes. We prospectively enrolled 154 predominantly crack-using women. A priori exclusion criteria included: <18 years old, major illnesses diagnosed prior to pregnancy, chronic use of legal drugs, and any use of illicit drugs other than cocaine and marijuana. From the pool of noncocaine users, 154 subjects were matched to users on pregnancy risk, parity, race, and socioeconomic status. At the end of each trimester, experienced staff conducted private interviews prompting memory of amount and timing of past drug use. Urine specimens were collected at two unanticipated times; positive screens were confirmed by gas chromatography/mass spectroscopy. Measures analyzed include medical (birth) and developmental (birth, 1 month, 6 months) assessments, all performed by blinded evaluators, as well as caregiver characteristics and environmental factors (birth, 1 month). A series of four theoretical models was tested, one for each time point (birth, 1 month, 6 months) and a longitudinal model spanning birth to 6 months. Key findings include direct effects of prenatal cocaine exposure on development at birth in the birth model and on development at birth and 6 months in the longitudinal model. In addition, indirect effects of prenatal cocaine exposure were identified on development at birth, 1 month, and 6 months, mediated through the prenatal use of alcohol and tobacco and the birth head circumference. Implications of these and other findings, including the advantages and limitations of structural equation modeling, are discussed.     

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.     

Prenatal and preschool age lead exposure: relationship with size

This report examines possible adverse effects on size and growth associated with subclinical prenatal and preschool age lead exposure in an urban cohort followed prospectively from birth through early childhood. Measurements of weight, stature (length), and head circumference were obtained at birth and during five subsequent in-home assessments. Prenatal lead exposure was assessed by cord (n = 185) and maternal (n = 162) blood lead levels at delivery. Preschool blood lead samples were obtained at ages six months (n = 151), two years (n = 165), three years (n = 165), and four years, ten months (n = 164). Multivariate longitudinal analyses incorporating adjustment for covariates revealed no statistically significant adverse effects of prenatal lead exposure on either neonatal size or on subsequent growth through age four years, ten months. Similarly, no statistically significant adverse effects were found between the preschool lead indices derived from blood collected at or after age two years and ensuing size measurements. We also found no evidence for an interaction between pre- and postnatal lead exposure. A marginal inverse association was exhibited between blood lead at six months and subsequent measures of head circumference. Limitations in the implications of this result in the context of many nonsignificant tests were discussed.     

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.     

Pre- and postnatal lead effect on head circumference: a case for critical periods

We examined the association of maternal prenatal [range of median blood lead level 7.5-9.0 microg/dl (0.36-0.43 micromol/l) during pregnancy] and child postnatal blood lead level [range of median blood lead level from birth to 48 months 7.0-10.0 microg/dl (0.34-0.48 micromol/l)] with head circumference in from 119 to 199 children from the Mexico City Prospective Lead Study. We used repeated multiple regression modeling with a standard set of control variables, entering blood lead level last. Using Bonferroni-corrected probability values to control for inflation of Type I error due to multiple testing at each age, we found significant negative associations (p<0.05, two-tailed) between 6-month head circumference and 36-week maternal blood lead level, and 36-month head circumference and 12-month blood lead level. Over the 25-75% interquartile range of measured blood lead, head circumference decreased around 0.4 cm. Over the 1-35 microg/dl (0.05-1.68 micromol/l) range of maternal blood lead at 36 weeks, the estimated reduction in 6-month head circumference was 1.9 cm (95% CI = 0.9-3.0 cm). These results suggest that children are more vulnerable to certain effects of lead exposure at specific age ranges, and that the effect of lead on head circumference only becomes evident for brief periods in the first 4 years of life. We discuss various artifacts as well as possible mechanisms by which lead might have produced the observed pattern of results. We suggest that higher lead exposure prevalent several decades ago might have subtly influenced published normative human growth data.     

Marijuana impairs growth in mid-gestation fetuses

Marijuana (Cannabis sativa) is the most commonly used illicit drug by pregnant women, but information is limited about the effects of prenatal cannabis exposure on fetal development. The present study evaluated the influence of early maternal marijuana use on fetal growth. Women electing voluntary saline-induced abortions were recruited at a mid-gestational stage of pregnancy (weeks 17-22), and detailed drug use and medical histories were obtained. Toxicological assays (maternal urine and fetal meconium) were used in conjunction with the maternal report to assign groups. Subjects with documented cocaine and opiate use were excluded. Main developmental outcome variables were fetal weight, foot length, body length, and head circumference; ponderal index was also examined. Analyses were adjusted for maternal alcohol and cigarette use. Marijuana (n=44)- and nonmarijuana (n=95)-exposed fetuses had similar rates of growth with increased age. However, there was a 0.08-cm (95% CI -0.15 to -0.01) and 14.53-g (95% CI -28.21 to 0.86) significant reduction of foot length and body weight, respectively, for marijuana-exposed fetuses. Moreover, fetal foot length development was negatively correlated with the amount and frequency of marijuana use reported by the mothers. These findings provide evidence of a negative impact of prenatal marijuana exposure on the mid-gestational fetal growth even when adjusting for maternal use of other substances well known to impair fetal development.     

Prenatal marijuana use and neonatal outcome

In a longitudinal study of marijuana and other substance use during pregnancy, women were interviewed at each trimester of pregnancy. Growth parameters, morphological abnormalities and gestational age were assessed for the 519 liveborn singletons. There were few significant effects of marijuana use during pregnancy on birth weight, head or chest circumference, gestational age, or growth retardation after adjustment for covariates using a regression model for analysis. There was a small but significant negative effect of marijuana use during the first two months of pregnancy on birth length and a positive effect of marijuana use during the third trimester on birth weight.     

Early exposure to lead and juvenile delinquency

Cross-sectional studies have reported an association between lead (Pb) levels in bone and delinquent behavior in later childhood and adolescence. This is the first prospective longitudinal study of Pb and child development to address this question with comprehensive assessments of toxicant exposure and other developmental cofactors. A prospective longitudinal birth cohort of 195 urban, inner-city adolescents recruited between 1979 and 1985 was examined. Relationships between prenatal and postnatal exposure to Pb (serial blood Pb determinations) and antisocial and delinquent behaviors (self- and parental reports) were examined. Prenatal exposure to Pb was significantly associated with a covariate-adjusted increase in the frequency of parent-reported delinquent and antisocial behaviors, while prenatal and postnatal exposure to Pb was significantly associated with a covariate-adjusted increase in frequency of self-reported delinquent and antisocial behaviors, including marijuana use. Use of marijuana itself by Cincinnati Lead Study (CLS) teens was strongly associated with all measures of delinquent and antisocial behavior. This prospective longitudinal study confirmed earlier clinical observations and recent retrospective studies that have linked Pb exposure with antisocial behavior in children and adolescents. Both prenatal and postnatal exposure to Pb were associated with reported antisocial acts and may play a measurable role in the epigenesis of behavioral problems independent of the other social and biomedical cofactors assessed in this study.     

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.     

Visuospatial memory deficits emerging during nicotine withdrawal in adolescents with prenatal exposure to active maternal smoking.

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents. We examined visuospatial and verbal memory in 35 adolescent tobacco smokers with prenatal exposure to active maternal smoking and 26 adolescent tobacco smokers with no prenatal exposure to maternal smoking who were similar in age, educational attainment, general intelligence, and baseline plasma cotinine. Subjects were studied during ad libitum smoking and after 24 h of abstinence from smoking. A subset of subjects from each group also underwent functional magnetic resonance imaging while performing a visuospatial encoding and recognition task. Adolescent tobacco smokers with prenatal exposure experienced greater nicotine withdrawal-related deficits in immediate and delayed visuospatial memory relative to adolescent smokers with no prenatal exposure. Among adolescent smokers with prenatal exposure, nicotine withdrawal was associated with increased activation of left parahippocampal gyrus during early recognition testing of visuospatial stimuli and increased activation of bilateral hippocampus during delayed recognition testing of visuospatial stimuli. These findings extend prior preclinical work and suggest that, in human adolescent tobacco smokers, prenatal exposure to active maternal smoking is associated with alterations in medial temporal lobe function and concomitant deficits in visuospatial memory.     

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.     

Visuoperceptual functioning differs in 9- to 12-year olds prenatally exposed to cigarettes and marihuana

Visuoperceptual performance was examined in 146 9- to 12-year old children for whom prenatal exposure to marihuana and cigarettes had been ascertained. The subjects, participants in an ongoing longitudinal study, were from a low-risk, predominantly middle class sample. The tasks ranged in complexity from those that required basic visuoperceptual skills to those that required considerable integration and cognitive manipulation of such skills. Trend analysis revealed a dose dependent negative association between prenatal cigarette exposure and an overall score reflecting basic visuoperceptual functioning. This association remained after consideration of potential prenatal confounds, pre- and postnatal secondhand smoke exposure, and the nonperceptual demands of the tasks. This poorer performance in the basic visuoperceptual domain underlay a poorer performance in more complex visuoperceptual tasks among the offspring of cigarette smokers. In contrast, prenatal marihuana exposure was not associated with basic visuoperceptual functioning but was negatively associated with performance in visual problem solving situations. The interpretation of the marihuana findings is discussed in relation to a "top-down" integrative ability associated with executive function, the extant prefrontal literature, and earlier observations of this sample.     

Prenatal cocaine exposure and school-age intelligence

Assessments of the possible consequences of prenatal exposure to cocaine have been limited by lack of control for socio-demographic confounders and lack of follow-up into the school years. We evaluated intelligence at ages 6–9 years in 88 children from a cohort of 280 born between September 1, 1985 and August 31, 1986 and identified at birth as cocaine-exposed, and in a group of unexposed (n=96) births of comparable gender and birthweight. IQ scores did not differ between children with and without prenatal exposure to cocaine (mean 82.9 vs. 82.4, difference=0.5 points, 95% CI-3.1, 4.1); results were unchanged with adjustment for child height, head circumference and prior residence in a shelter or on the street, and for caregiver IQ and home environment (mean difference=2.2 points, 95% CI-1.5, 5.8).     

Verbal and nonverbal fluency in children with heavy prenatal alcohol exposure

OBJECTIVE: Executive function deficits, including verbal fluency, have been documented in children with histories of prenatal alcohol exposure. Whereas nonverbal fluency impairments have been reported in adults with such exposure, these abilities have not been tested in children. Deficits in both verbal and nonverbal fluency were predicted and assessed in children and adolescents with histories of heavy prenatal alcohol exposure. METHOD: There was a total of 28 (54% female) subjects; children with heavy prenatal alcohol exposure with (n = 10) and without (n = 8) fetal alcohol syndrome (FAS) were compared to nonexposed controls (n = 10) on the design and verbal fluency measures from the Delis-Kaplan Executive Function System. Both fluency measures consist of three conditions, including a new set-shifting task. All tests require the generation of multiple responses within both rule and time constraints. RESULTS: Data were analyzed using repeated measures analyses of variance and hierarchical regression analyses. Compared to controls, children with heavy prenatal alcohol exposure with and without FAS displayed deficits in both fluency domains, but did not differ from each other. In addition, prenatal alcohol exposure was a significant predictor of performance on the set-shifting design fluency task above and beyond performance on more traditional fluency tasks. IQ was not a significant predictor for the traditional or set-shifting fluency measures, whereas diagnostic group remained a significant predictor when IQ was included in the model. CONCLUSIONS: This study adds to the literature on the integrity of executive functions in children with heavy prenatal alcohol exposure, documenting fluency impairment in both verbal and nonverbal domains. It is important to note that these impairments were demonstrated in higher functioning alcohol-exposed children, both with and without FAS, and that diagnostic group explained such deficiencies above and beyond general intellectual ability.     

Estimated effects of in utero cocaine exposure on language development through early adolescence

The potential longitudinal effects of prenatal cocaine exposure (PCE) on language functioning were estimated from early childhood through early adolescence in a large, well-retained urban sample of 451 full-term children (242 cocaine-exposed, 209 non-cocaine-exposed) participating in the Miami Prenatal Cocaine Study (MPCS). The 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. Age-appropriate versions of the Clinical Evaluation of Language Fundamentals (CELF) were used to measure total, expressive, and receptive language at ages 3, 5, and 12 years. Longitudinal latent growth curve (LLGC) modeling of the data revealed an association between PCE (measured dichotomously as yes/no) and lower functioning in expressive and total language scores, after considering other sources of variation including child's age at testing, sex, prenatal exposure to alcohol, marijuana, and tobacco, and additional medical and social-demographic covariates. Analyses of level of PCE showed a gradient, i.e. dose-dependent, relationship between PCE level and expressive, receptive, and total language scores in the models controlling for age, child's sex, and other prenatal drug exposures. With additional covariate control these findings were most stable for the total language score. The evidence supports an inference about an enduring stable cocaine-specific effect on children's language abilities, with no effect on language growth over time in the longitudinal trajectory of language development.