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Background: The degree to which prenatal alcohol exposure (PAE) may influence alcohol and drug use in adulthood is difficult to determine. That is because PAE is highly correlated with environmental factors, including low socioeconomic status and exposure to parental drinking, and with behavioral problems, such as, attention‐deficit/hyperactivity disorder (ADHD), which are correlated with alcohol use and abuse. Methods: Participants were 121 young adults from our Detroit Longitudinal Cohort study. Mothers were recruited during pregnancy and interviewed about their alcohol consumption using a timeline follow‐back procedure. At 19 years, their offspring were interviewed regarding current and past use of alcohol, cigarettes, and other illicit drugs. Results: PAE was associated with greater alcohol, cannabis, and cigarette use. PAE, assessed using overall alcohol intake during pregnancy and alcohol dose per occasion, was associated with larger quantities of alcohol per occasion and greater alcohol tolerance in early adulthood. These effects persisted after control for demographic background, sex, age and education of participant, home environment, other prenatal drug exposure, and postnatal alcohol and drug use by the primary caregiver. Whereas ADHD predicted average alcohol consumed/month during young adulthood, PAE predicted alcohol dose/drinking occasion, and the effect on dose/occasion was not mediated by ADHD. Conclusions: The effects of PAE on alcohol and cannabis use in young adulthood are not attributable to being reared in an environment that is socioeconomically disadvantaged or in one in which there is extensive maternal drinking. Furthermore, PAE was related to enhanced alcohol tolerance in young adults, a risk factor for alcohol use disorder later in life. Although ADHD was associated with greater alcohol consumption in early adulthood, it did not mediate the effect of PAE on offspring's alcohol use. [ABSTRACT FROM AUTHOR]

In this paper, we respond to the criticisms and concerns raised by D.V. Cicchetti, A.S. Kaufman, & S.S. Sparrow (this issue) in their review of the PCB literature, with particular attention to our own research in Michigan. We agree that multiple comparisons and functional significance are issues that would benefit from more discussion. However, because the effects associated with exposure to environmental contaminants are generally subtle, the risk of Type II error would be unacceptably high if researchers were to adopt the authors' recommendation to use a Bonferroni correction. We describe the hierarchical approach we have used to deal with the issue of multiple comparisons, which emphasizes the need to base interpretation on consistent patterns in the data and on replicated findings. The issue of confounding is one that has received considerable attention in the PCB studies and, given that one can never measure every possible confounder, the range of control variables that have been evaluated is impressive. We disagree with the authors' assertion that only standardized test scores are sufficiently reliable for use in these studies; behavioral teratogens often involve subtle effects, which can be identified most effectively by innovative, narrow-band tests that have not yet been normed. Moreover, longitudinal statistical analysis is not necessarily the method of choice for the issues being addressed in this literature. One important new development that Cicchetti et al. fail to note is the emergence of evidence from both the Michigan and Dutch cohorts indicating that breast-fed children are markedly less vulnerable. It is not yet clear to what degree this protective effect is attributable to nutrients in breast milk or to more optimal intellectual stimulation by nursing mothers, or both. However, the discovery of effect modifiers that can explain individual differences in vulnerability marks an important advance in our growing understanding of the teratogenic effects of exposure to environmental contaminants on child development. (Contains 4 tables and 1 figure.)

In four year olds who had been exposed to polychlorinated biphenyls (PCBs) before birth, prenatal exposure was associated with less efficient visual discrimination processing and more errors in short memory scanning. Postnatal exposure was unrelated to cognitive performance. (GLR)

Background: Rodent studies have consistently shown that prenatal alcohol exposure (PAE) impairs performance on the Morris water maze (MWM), a test of spatial navigation. A previous study comparing boys with fetal alcohol syndrome (FAS) to controls found poorer performance on the virtual water maze (VWM), a human analogue of the MWM. We examined PAE effects on virtual navigation in both sexes using the VWM in a moderately exposed Detroit cohort (N = 104; mean = 19.4 year) and a heavily exposed Cape Town, South African cohort (N = 62; mean = 10.4 year). Methods: The task requires the participant to learn the location of a hidden platform in a virtual pool of water. The set of acquisition trials requires the participant to learn the location of the hidden platform and to return to that location repeatedly. The single‐probe trial requires the participant to return to that location without knowing that the platform has been removed. Results: No effects of FASD diagnostic group or PAE were detected on virtual navigation in the Detroit moderately exposed cohort. By contrast, in the more heavily exposed Cape Town cohort, the FAS/partial FAS (PFAS) group took longer to locate the hidden platform during acquisition than nonsyndromal heavily exposed (HE) and control groups, an effect that persisted even after controlling for IQ. Among boys, both the FAS/PFAS and HE groups performed more poorly than controls during acquisition, and both boys and girls born to women who binge drank performed more poorly than those born to abstainers/light drinkers. Both amount and frequency of PAE were related to poorer performance during the probe trial at 10 years of age. Conclusions: These data demonstrate deficits in spatial navigation among heavily exposed syndromal boys and girls and in nonsyndromal exposed boys. [ABSTRACT FROM AUTHOR]

Background Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic-pituitary-gonadal axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development. Methods The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/ml), self-reported Tanner stages for pubertal development, and age at menarche (females). Results Prenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure, but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group × testosterone interaction term and potential confounders. Conclusions This study is the first to show a relation between prenatal alcohol exposure and increased testosterone during adolescence and evidence of decreased testosterone responsiveness in tissues related to pubertal development in humans. Further studies examining androgen receptor expression and other hormonal and cellular factors affecting pubertal development may reveal important mechanisms underlying these teratogenic effects of alcohol exposure. [ABSTRACT FROM AUTHOR]

Background Fetal alcohol-related growth restriction persists through infancy, but its impact later in life is less clear. Animal studies have demonstrated important roles for maternal nutrition in fetal alcohol spectrum disorders, but the impact of prenatal maternal body composition has not been studied in humans. This study examined the effects of prenatal alcohol exposure on longitudinal growth from birth through young adulthood and the degree to which maternal weight and body mass index ( BMI) moderate these effects. Methods Nearly 480 mothers were recruited at their first prenatal clinic visit to overrepresent moderate-to-heavy use of alcohol during pregnancy, including a 5% random sample of low-level drinkers and abstainers. They were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach. Their children were examined for weight, length/height, and head circumference at birth, 6.5 and 13 months, and 7.5, 14, and 19 years. Results In multiple regression models with repeated measures (adjusted for confounders), prenatal alcohol exposure was associated with longitudinal reductions in weight, height, and weight-for-length/ BMI that were largely determined at birth. At low-to-moderate levels of exposure, these effects were more severe in infancy than in later childhood. By contrast, effects persisted among children whose mothers drank at least monthly and among those born to women with alcohol abuse and/or dependence who had consumed ≥ 4 drinks/occasion. In addition, effects on weight, height, and head circumference were markedly stronger among children born to mothers with lower prepregnancy weight. Conclusions These findings confirm prior studies demonstrating alcohol-related reductions in weight, height, weight-for-height/ BMI, and head circumference that persist through young adulthood. Stronger effects were seen among children born to mothers with smaller prepregnancy weight, which may have been because of attainment of higher blood alcohol concentrations in smaller mothers for a given amount of alcohol intake or to increased vulnerability in infants born to women with poorer nutrition. [ABSTRACT FROM AUTHOR]

Background Many children with heavy exposure to alcohol in utero display characteristic alterations in brain size and structure. However, the long-term effects of low-to-moderate alcohol exposure on these outcomes are unknown. Methods Using voxel-based morphometry and region-of-interest analyses, we examined the influence of lower doses of alcohol on gray and white matter composition in a prospectively recruited, homogeneous, well-characterized cohort of alcohol-exposed ( n = 11, age 19.5 ± 0.3 years) and control ( n = 9, age 19.6 ± 0.5 years) young adults. A large proportion of the exposed individuals were born to mothers whose alcohol consumption during pregnancy was in the low-to-moderate range. Results There were no differences in total brain volume or total gray or white matter volume between the exposed and control groups. However, gray matter volume was reduced in alcohol-exposed individuals in several areas previously reported to be affected by high levels of exposure, including the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus. Notably, this gray matter loss was dose dependent, with higher exposure producing more substantial losses. Conclusions These results indicate that even at low doses, alcohol exposure during pregnancy impacts brain development and that these effects persist into young adulthood. [ABSTRACT FROM AUTHOR]

Benchmark dose (BMD) analysis is used to determine levels of exposure to environmental contaminants associated with increased public health risk. In this study we used a benchmark approach to evaluate the risks associated with prenatal exposure to polychlorinated biphenyls (PCBs). We evaluated for intellectual impairment a cohort of children whose prenatal PCB exposure had been assessed from biologic specimens. We calculated BMDs and lower-bound confidence limits (BMDLs) for four end points using four sets of risk criteria. BMDLs were estimated using three different statistical methodologies. The BMDs and BMDLs were remarkably consistent across the four end points for each set of risk criteria, but differed substantially for the different risk criteria. The proportion of the sample considered at risk ranged from 9.8% for the least protective criteria to 74.1% for the most protective. Two methodologies, likelihood ratio and bootstrapping, generated generally similar BMDLs. BMD analysis provides a straightforward, reliable method for evaluating levels of exposure associated with increased public health risk. In the analyses performed in this study, the number of individuals considered at risk depended more on the risk criterion selected than on the outcome assessed. Key words: benchmark dose analysis, dose—response, environmental contaminants, in utero exposure, organochlorine contaminants, polychlorinated biphenyls, risk analysis. Environ Health Perspect 110:393–398 (2002). [Online 8 March 2002] [ABSTRACT FROM AUTHOR]

Abstract: Serum samples from 285 4-year-old Michigan children were evaluated for levels of 11 environmental contaminants. Polychlorinated biohenyls (PCBs) were found in half the samples tested; polybrominated biphenyls (PBBs) in 13-21 percent; dicholorodiphenyl trichloroethane (DDT), in more than 70 percent. Nursing (Mothers' milk) was the principal source of these exposures. Congener specific analysis documented the presence of at least one highly toxic PCB congener, 2,3',4,4',5-pentachlorobiphenyl. The data demonstrate the multigenerational impact of female exposure to persistent organic environmental contaminants. [ABSTRACT FROM AUTHOR]

Background: Previous studies using the California Verbal Learning Test-Children's Version (CVLT-C) to examine effects of heavy prenatal alcohol exposure on verbal learning and memory have reported impaired information acquisition (i.e., encoding), rather than retrieval, as the primary mechanism underlying learning and memory impairment. We administered the CVLT-C to 2 independent cohorts to determine whether (i) effects on encoding are also seen at moderate exposure levels, using both categorical (diagnostic/exposure group) and continuous exposure measures; (ii) these deficits are specific or secondary to alcohol-related impairment in IQ; (iii) effects on retrieval can be detected over and above effects on initial encoding; and (iv) effects on learning are attributable to less efficient learning strategy use., Methods: We administered the CVLT-C and Wechsler Intelligence Scale for Children to 151 Cape Town heavy and nonexposed children (M = 10.3 years), and 291 Detroit adolescents recruited to over-represent moderate-to-heavy prenatal alcohol exposure (M = 14.4 years)., Results: Effects on encoding in the heavily exposed Cape Town cohort and on retrieval in both cohorts were significant after adjustment for IQ. Although effects on retrieval were no longer significant in Cape Town after control for initial encoding, effects on recognition memory continued to be evident in Detroit. Children with full or partial fetal alcohol syndrome were less able to use the semantic cluster encoding strategy implicit in the CVLT-C., Conclusions: Effects on verbal learning were seen primarily in the more heavily exposed Cape Town cohort; effects on recall and recognition memory were also seen at moderate exposure levels in Detroit. These effects were not attributable to alcohol-related impairment in overall intellectual competence. The finding that effects on retention continued to be evident after statistical adjustment for initial encoding in Detroit suggests that a fetal alcohol-related deficit in retrieval is not secondary to a failure to encode the initial information. These data confirm that this impairment in initial learning is mediated, in part, by failure to use the semantic cluster learning strategy., (Copyright © 2015 by the Research Society on Alcoholism.)

Background: Previous research has demonstrated that heavy prenatal alcohol exposure affects the size and shape of the corpus callosum (CC) and compromises interhemispheric transfer of information. The aim of this study was to confirm the previous reports of poorer performance on a finger localization test (FLT) of interhemispheric transfer in a cohort of heavily exposed children and to extend these findings to a cohort of moderately exposed young adults., Methods: In Study 1, the FLT was administered to 40 heavily exposed and 23 nonexposed children from the Cape Coloured community of Cape Town, South Africa, who were evaluated for fetal alcohol syndrome (FAS) dysmorphology and growth. Anatomical images of the CC were obtained using structural MRI on a subset of these children. In Study 2, the FLT was administered to a cohort of 85 moderate-to-heavily exposed young adults participating in a 19-year follow-up assessment of the Detroit Prenatal Alcohol Exposure cohort, whose alcohol exposure had been ascertained prospectively during gestation., Results: In Study 1, children with FAS showed more transfer-related errors than controls after adjustment for confounding, and increased transfer-related errors were associated with volume reductions in the isthmus and splenium of the CC. In Study 2, transfer-related errors were associated with quantity of alcohol consumed per occasion during pregnancy. More errors were made if the mother reported binge drinking (> or =5 standard drinks) during pregnancy than if she drank regularly (M > or = 1 drink/day) without binge drinking., Conclusions: These findings confirm a previous report of impaired interhemispheric transfer of tactile information in children heavily exposed to alcohol in utero and extend these findings to show that these deficits are also seen in more moderately exposed individuals, particularly those exposed to binge-like pregnancy drinking.

Researchers in the Netherlands have reported that the associations of prenatal polychlorinated biphenyl (PCB) exposure with poorer cognitive performance in childhood are generally stronger and statistically significant only among non-breast-fed children. This paper reports a similar pattern of greater vulnerability among non-breast-fed children in the Michigan cohort of children whose mothers had eaten PCB-contaminated Lake Michigan fish. It is difficult to determine from prospective human longitudinal data whether the apparent decreased vulnerability among breast-fed children is due to nutrients in breast milk that might attenuate the adverse neurochemical effects of this exposure and/or the more optimal intellectual stimulation that was provided by the breast-feeding mothers in these cohorts. The latter interpretation was supported by analyses demonstrating that virtually all of the positive associations between breast-feeding and cognitive outcome can be accounted for statistically by measures of quality of parental intellectual input and that the adverse effects associated with prenatal PCB exposure were also markedly stronger in children raised by less verbally competent mothers, who presumably provided less optimal intellectual stimulation. Because there were no consistent patterns of differential vulnerability for either gender, these data did not support the hypothesis that prenatal PCB exposure may disrupt cognitive development due to the estrogenic or antiestrogenic properties of its congeners and metabolites.