Lead (Pb) exposure is associated with adverse neurological development. Most notably, it has been observed through externalizing behavior symptoms, as observed among Inuit children from northern ...Québec. Evidence for a persistent neurological impact of early Pb exposure later in life is however scarce. Pb exposure may initiate a developmental cascade that increases the risk of long-term behavior problems.
Testing for direct associations between childhood Pb concentrations and adolescent externalizing symptoms and substance use, as well as indirect associations through childhood behavior assessments.
The study sample is a longitudinal cohort of Inuit children (n = 212) followed since birth. Blood Pb concentrations were measured during childhood (median age = 11.4 years) and adolescence (median age = 18.5 years). Externalizing/inattentive behavior were teacher-assessed through the Teacher Report Form and the Disruptive Behavior Disorders Rating Scale for children. At the adolescence follow-up, behavior problems were self-reported by filling Achenbach's Youth Self-Report, the Barkley Adult ADHD-IV Rating Scale, and the Diagnostics Interview Schedule for Children. Adolescent substance use was also self-assessed through the DEP-ADO. Direct and indirect associations of child Pb concentrations with adolescent outcomes were tested through mediation models.
Child blood Pb concentrations were not directly associated with any adolescent outcomes. On the contrary, childhood Pb exposure was indirectly associated, through childhood externalizing behavior assessments, with adolescent externalizing behaviors, binge drinking, and cannabis use. These indirect associations held after controlling for adolescents’ concurrent Pb blood concentrations.
Our results highlight the indirect but lasting effects of child Pb exposure on adolescent behavior problems, and the importance of childhood externalizing behavior in this relationship. Adverse early-life environment put children on a riskier developmental trajectory, increasing their likelihood of lifelong psychological, social and health problems.
•Child Pb associated with adolescent externalizing behavior and substance use.•These associations mediated by child externalizing behaviors.•Early-life impairments may put children on a riskier developmental trajectory.
To examine the relation of prenatal polychlorinated biphenyl (PCB) exposure to child performance on neuropsychological tests of attention and information processing.
In this prospective, longitudinal ...study, assessment of prenatal PCB exposure was based on umbilical cord serum and maternal serum and milk concentrations. The children were tested in their homes at age 11 years. Multiple regression was used to examine the relation of this exposure to performance on 15 neuropsychological tests after controlling for a broad range of potential confounding variables.
Adverse effects were seen primarily in children who had not been breast fed. Among these children, prenatal PCB exposure was associated with greater impulsivity, poorer concentration, and poorer verbal, pictorial, and auditory working memory. There was no evidence of visual-spatial deficit or increased hyperactivity.
These findings are consistent with earlier reports of greater vulnerability to prenatal PCB exposure in children who were not breast fed. It is not clear whether the protection offered by breast-feeding is caused by nutrients in breast milk or better quality of intellectual stimulation often provided by breast-feeding mothers.
Background
The ability to identify and interpret facial emotions plays a critical role in effective social functioning, which may be impaired in individuals with fetal alcohol spectrum disorders ...(FASD). We previously reported deficits in children with fetal alcohol syndrome (FAS) and partial FAS (PFAS) on the “Reading the Mind in the Eyes” (RME) test, which assesses the interpretation of facial emotion. This follow‐up study in adolescents was designed to determine whether this impairment persists or represents a developmental delay; to classify the RME stimuli by valence (positive, negative, or neutral) and determine whether RME deficits differ by affective valence; and to explore how components of executive function mediate these associations.
Methods
The RME stimuli were rated and grouped according to valence. Sixty‐two participants who had been administered the RME in late childhood (mean ± SD = 11.0 ± 0.4 years) were re‐administered this test during adolescence (17.2 ± 0.6 years). Overall and valence‐specific RME accuracy was examined in relation to prenatal alcohol exposure (PAE) and FASD diagnosis.
Results
Children with FAS (n = 8) and PFAS (n = 15) performed more poorly on the RME than non‐syndromal heavily exposed (HE; n = 19) and control individuals (n = 20). By adolescence, the PFAS group performed similarly to HE and controls, whereas the FAS group continued to perform more poorly. No deficits were seen for positively valenced items in any of the groups. For negative and neutral items, in late childhood individuals with FAS and PFAS performed more poorly than HE and controls, but by adolescence only the FAS group continued to perform more poorly. Test–retest reliability was moderate across the two ages. At both timepoints, the effects in the FAS group were partially mediated by Verbal Fluency but not by other aspects of executive function.
Conclusions
Individuals with full FAS have greater difficulty interpreting facial emotions than those with non‐syndromal HE and healthy controls in both childhood and adolescence. By contrast, RME deficits in individuals with PFAS in childhood represent developmental delay.
We previously reported poorer performance in children with fetal alcohol syndrome (FAS) and partial FAS (PFAS) on the “Reading the Mind in the Eyes” assessment of the ability to interpret facial emotion. In this follow‐up of 62 adolescents, those with PFAS performed similarly to controls, but those with FAS continued to perform more poorly. The groups also differed depending on affective valence of the facial expressions. Performance by the FAS group was partially mediated by verbal fluency but not by other aspects of executive function.
Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are ...thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children.
We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n=290) were evaluated at birth and at 8–14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood.
Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood.
Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children.
•Polychlorinated biphenyls and lead are thought to affect fetal and child growth.•We examined their relations with the fetal and postnatal growth of Inuit children.•Exposure to PCBs during childhood is negatively related to growth and weight.•Prenatal Pb exposure is associated with reduced growth during childhood.
Background
This paper reports findings from the first longitudinal study on the evolution of the physical phenotypes of fetal alcohol syndrome (FAS) and partial FAS (PFAS) from early childhood ...through adolescence.
Methods
The sample consisted of 155 children (78 males and 77 females) born to women recruited at an antenatal clinic serving a Cape Coloured (mixed ancestry) population in Cape Town, South Africa. Two expert FASD dysmorphologists, blind regarding prenatal alcohol exposure, independently evaluated each child’s growth and dysmorphology at 4 clinics conducted over an 11‐year period. Case conferences were held to reach consensus regarding which children had FAS or PFAS growth and physical features using the Revised Institute of Medicine (2005) guidelines.
Results
The prevalence of the physical phenotype was stable across the 4 ages for about half of the children with FAS and about one‐third of those with PFAS but more variable for the others. Test–retest reliability was substantial for the FAS phenotype, but poorer for PFAS. Two distinct patterns were seen: a “strong phenotype” that was consistently identified and a less consistent one in which dysmorphic features and/or anthropometric deficits fluctuated or diminished with age. The physical phenotype was most apparent during early childhood and least apparent during puberty, due to differences in timing of the growth spurt and the evolving adult face. Short palpebral features and small head circumference diminished with age, flat philtrum fluctuated, while thin vermilion and weight and height restriction were stable.
Conclusions
Key facial features that characterize FASD in early childhood diminish or evolve in some individuals, making diagnostic examinations that rely on these characteristics most sensitive during early childhood and school age. Moreover, puberty poses classification problems due to variability in timing of the growth spurt. Given that several features and small head circumference diminished with age, many individuals would be misdiagnosed if only examined at a later age.
Expert FASD dysmorphologists examined 155 children born to heavy drinking and control women at four clinics conducted over an 11‐year period. The FAS physical phenotype was most apparent during childhood and least during puberty. Short palpebral features and small head circumference diminished with age, flat philtrum fluctuated, while thin vermilion and weight and height restriction were stable. Given that several features and small head circumference diminished, many individuals would be misdiagnosed if only examined at a later age.
The present study aims at measuring the association between household food insecurity and psychological distress in adolescents in Inuit communities, concurrently and overtime from childhood to ...adolescence.
The study used measures of internalising behaviours (anxiety, withdrawn attitude, somatic complaints and depression) as indicators of psychological distress during adolescence, a concurrent measure of household food insecurity in adolescence and an assessment of longitudinal patterns of household food insecurity from childhood to adolescence. We collected descriptive information at birth, childhood and adolescence on potential confounders.
Inuit communities of Nunavik in northern Quebec, Canada.
The study consisted of 212 participants from the Nunavik Child Development Study, who have been assessed at birth, childhood (mean age = 11 years, range = 9-13 years) and adolescence (mean age = 18 years, range = 16-21 years).
Concurrent severe household food insecurity in adolescence was associated with higher measures of psychological distress: depression (βstd = 0·26, P < 0·01) and withdrawn attitude (βstd = 0·20, P = 0·04). Persistent household food insecurity (both at childhood and adolescence) was associated with higher levels of adolescent depression (βstd = 0·18, P = 0·02) and anxiety (βstd = 0·17, P = 0·03).
Adolescents from Nunavik living with higher food insecurity and those having experienced food insecurity in both childhood and adolescence were more likely to report symptoms of psychological distress. Considering the high level of distress experienced by young Inuit, existing initiatives to reduce food insecurity in Nunavik communities should be targeted to include children and adolescents.
Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders worldwide. The placenta is the crucial interface between mother and ...fetus. Prenatal alcohol exposure (PAE) has been shown to alter placental structure and expression of genes in bulk placental tissue samples, but prior studies have not examined effects on placental cell-type composition or taken cell-type into consideration in transcriptome analyses.
We leveraged an existent placenta single-cell RNA-seq dataset to perform cell-type deconvolution of bulk placental RNA-seq data from 35 heavy drinking pregnant women and 33 controls in a prospective birth cohort in Cape Town, South Africa. We used bivariate analyses and multivariable adjusted linear regression models to assess the relation of PAE on inferred placental cell-type proportions. We also examined differential expression of inflammatory response genes and PAE, using multivariable adjusted linear models.
Deconvolution analyses showed heterogeneous placenta cell-type composition in which stromal (27 %), endothelial (26 %) and cytotrophoblasts (18 %) were the predominant cell-types. PAE around conception was associated with a higher proportion of Hofbauer cells (B = 0.51, p = 0.035) in linear models adjusted for maternal age, infant sex, and gestational age. Among the 652 inflammatory genes examined, 35 were differential expressed in alcohol exposed placentas (FDR p < 0.05).
Our findings suggest that heavy alcohol exposure during pregnancy can influence the proportion of fetal placental villi macrophages (Hofbauer cells) and increased expression of inflammatory genes. Future studies are needed to further characterize these effects and to assess the potential functional roles of placental inflammation in FASD.
Background
Prenatal alcohol exposure (PAE) has been linked to poorer performance on the Morris water maze (MWM), a test of spatial navigation in rodents that is dependent on hippocampal functioning. ...We recently confirmed these findings in children with PAE on a human analog of the MWM, the virtual water maze (VWM). Previous studies have shown that the hippocampus is particularly sensitive to PAE. Our aim was to determine whether hippocampal volume mediates the relation between PAE and virtual navigation.
Methods
VWM and MRI hippocampal data were collected from 50 right‐handed 10‐year‐old children in a heavily exposed Cape Town, South African sample. PAE data had been collected from their mothers during pregnancy, and the children were examined by expert fetal alcohol spectrum disorder (FASD) dysmorphologists. In the VWM, the participant attempts to learn the location of a hidden platform in a virtual pool of water across a series of learning trials using only distal room cues. Hippocampal volumes were derived using FreeSurfer from MRI scans administered within 1 week of completing the VWM task.
Results
Both the fetal alcohol syndrome (FAS)/partial FAS and nonsyndromal heavy‐exposed (HE) groups had smaller hippocampal volumes than controls. PAE was associated with reduced right hippocampal volumes even after control for total intracranial volume (ICV). Hippocampal volume was also positively associated with VWM performance. The relation between PAE and VWM performance was partially mediated by right hippocampal volume but not by total ICV.
Conclusions
These data confirm previous reports linking PAE to poorer spatial navigation on the VWM and are the first to provide direct evidence that volume reductions in this region partially mediate the relation of FASD diagnosis to place learning, suggesting that PAE specifically impairs the ability to encode the spatial information necessary for successful location of the hidden platform on a navigation task.
Fetal alcohol spectrum disorders (FASD) are associated with impairments in spatial navigation and damage to the hippocampus. Individuals with lesions to the hippocampus exhibit impairments in spatial navigation. In a previous study, we showed that FASD was related poorer spatial navigation on the virtual water maze (VWM). This study found that FASD associated with reduced hippocampal volume even after controlling for reduced head size. Hippocampal volume partially mediated the effects of FASD on the virtual water maze.
Abstract Chronic exposure to methylmercury (MeHg), lead (Pb) and polychlorinated biphenyls (PCBs) has been associated with a range of attention deficits in children, but it is not known whether ...selective spatial attention is also altered. We modified the classic Posner paradigm, which assesses visuospatial attention, to also assess vigilance and impulsivity. This paradigm is based on the well-documented findings that a target will be detected more quickly if a visual cue indicates beforehand where it will appear, and more slowly if the cue indicates a false spatial location. In our task, visual distractors were introduced, in addition to the classic Posner trials, to assess impulsivity, and a central smiley face, whose eye-movement cued the location of the targets, to measure spatial attention. This task was administered to 27 school-age Inuit children (mean age = 11.2 years) from Nunavik (Arctic Quebec, Canada), in which pre- and postnatal exposures to environmental contaminants had been documented from birth. After controlling for the impact of confounding variables, multivariable regressions revealed that prenatal exposures to PCBs and Pb were significantly associated with greater inattention and impulsivity, respectively, while current exposure to Pb was significantly associated with longer reaction times. Although a significant correlation was observed between cord blood PCB concentration and decreased visuospatial performance, no significant association was found after adjustment for confounders. No effect was found for Hg exposures. These results suggest that our adapted Posner paradigm is sensitive in detecting a range of attention deficits in children exposed to environmental contaminants; implications for future studies are discussed.
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.
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