Although both fetal and long-term growth restriction are well documented in fetal alcohol spectrum disorders, effects on pattern of growth trajectory have not been characterized. Furthermore, the ...degree to which growth trajectories are related to fetal alcohol-related neurocognitive deficits is unknown.
Ninety-three heavy drinking pregnant women and 64 controls were recruited at initiation of prenatal care in Cape Town, South Africa. Small for gestational age (SGA) was defined as birth weight <10th percentile. Length/height, weight, and head circumference were measured at 6.5 and 12 months and 5, 9, and 13 years. Four growth trajectories were identified: SGA with long-term postnatal growth restriction (length/height-for-age <10th percentile through 13 years); SGA with catch-up growth; no SGA or postnatal growth restriction; and late-onset postnatal stunting. IQ was assessed at 5 and 10 years, and learning, memory, and executive function at 10 years.
Children born SGA with postnatal growth restriction were most heavily exposed. Exposure was intermediate for those born SGA with catch-up growth and lowest for those without prenatal or postnatal growth restriction. Effects on neurocognition were strongest in children with both prenatal and long-term growth restriction, more moderate in those with fetal growth restriction and postnatal catch-up, and weakest in those without growth restriction.
These findings validate the use of growth restriction in the diagnosis of fetal alcohol spectrum disorders and identify growth trajectory as a biomarker of which heavily exposed children are at greatest risk for cognitive developmental deficits.
Alcohol consumption during pregnancy can result in a range of adverse postnatal outcomes among exposed children. However, identifying at-risk children is challenging given the difficulty to confirm ...prenatal alcohol exposure and the lack of early diagnostic tools. Placental surveys present an important opportunity to uncover early biomarkers to identify those at risk. Here, we report the first transcriptome-wide evaluation to comprehensively evaluate human placental pathways altered by fetal alcohol exposure. In a prospective longitudinal birth cohort in Cape Town, South Africa, we performed bulk tissue RNAseq in placenta samples from 32 women reporting heavy drinking during pregnancy and 30 abstainers/light drinkers. Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed to assess associations between fetal alcohol exposure and placental gene expression patterns at a network-wide and single gene level, respectively. The results revealed altered expression in genes related to erythropoiesis and angiogenesis, which are implicated in established postnatal phenotypes related to alcohol exposure, including disruptions in iron homeostasis, growth, and neurodevelopment. The reported findings provide insights into the molecular pathways affected by prenatal alcohol exposure and highlight the potential of placental biomarkers for detecting and understanding the effects of alcohol on fetal development.
Background: The beneficial effects of prenatal and early postnatal intakes of omega-3 (n−3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, ...few studies have examined the extent to which these benefits continue to be evident in childhood.
Objective: The aim of this study was to examine the relation of n−3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community.
Design: In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test–Children’s Version.
Results: Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n−3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA–related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory.
Conclusion: To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n−3 PUFA intake in utero on memory function in school-age children.
Background
We recently demonstrated the acceptability and feasibility of a randomized, double‐blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we ...report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function.
Methods
Sixty‐nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid‐pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape‐flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months.
Results
Infants born to choline‐treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline‐treated infants showed considerable catch‐up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory.
Conclusions
This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol‐exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory.
Choline supplementation has been shown to mitigate adverse effects of prenatal alcohol exposure on neurobehavior in animals, including eyeblink conditioning (EBC). In a randomized, double‐blind trial, human infants born to choline‐supplemented mothers showed greater increases in conditioned responses, compared with those whose mothers received placebo. Within the choline arm, degree of maternal adherence strongly predicted EBC performance. Choline‐treated infants also showed considerable catch‐up growth in weight and head circumference and better visual recognition memory compared to the placebo group.
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.
Heavy alcohol use in adults with prenatal alcohol exposure (PAE) has been attributed to PAE‐related behavioral problems and the child‐rearing environment. In our follow‐up of 121 young adults born to mothers who drank prenatally, PAE was associated with higher levels of alcohol consumed per occasion at age 19 years and by greater alcohol tolerance after control for confounders. Of note, attention‐deficit/hyperactivity disorder (ADHD) also predicted greater alcohol use but did not mediate the relation of PAE and young adult alcohol use.
We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction ...and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort 87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls, with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD).
Exposure to environmental contaminants is an important public health concern for the Inuit population of northern Québec, who have been exposed to mercury (Hg), polychlorinated biphenyls (PCBs) and ...lead (Pb). During the last 25 years, the Nunavik Child Development Study (NCDS) birth cohort has reported adverse associations between these exposures and brain function outcomes. In the current study, we aimed to determine whether contaminant exposure is associated with alterations of the corpus callosum (CC), which plays an important role in various cognitive, motor and sensory function processes. Magnetic resonance imaging (MRI) was administered to 89 NCDS participants (mean age ± SD = 18.4 ± 1.2). Diffusion-weighted imaging was assessed to characterize the microstructure of the CC white matter in 7 structurally and functionally distinct regions of interest (ROIs) using a tractography-based segmentation approach. The following metrics were computed: fiber tract density, fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Multiple linear regression models adjusted for sex, age, current alcohol/drug use and fish nutrients (omega-3 fatty acids and selenium) were conducted to assess the association between diffusion-weighted imaging metrics and Hg, PCB 153 and Pb concentrations obtained at birth in the cord blood and postnatally (mean values from blood samples at 11 and 18 years of age). Exposures were not associated with fiber tract density. Nor were significant associations found with cord and postnatal blood Pb concentrations for FA. However, pre- and postnatal Hg and PCB concentrations were significantly associated with higher FA of several regions of the CC, namely anterior midbody, posterior midbody, isthmus, and splenium, with the most pronounced effects observed in the splenium. FA results were mainly associated with lower RD. This study shows that exposure to Hg and PCB 153 alters the posterior microstructure of the CC, providing neuroimaging evidence of how developmental exposure to environmental chemicals can impair brain function and behavior in late adolescence.
•Corpus callosum diffusion MRI in relation to Hg, PCBs and Pb was assessed in Inuit adolescents.•Hg and PCB exposures were associated with fractional anisotropy and radial diffusivity metrics.•The most pronounced effects were observed in the posterior parts of the corpus callosum.
Prenatal alcohol exposure (PAE) causes growth restriction that worsens in the first year of life. However, the roles of postnatal nutrition in fetal alcohol growth restriction and the impact of ...postnatal alcohol exposure via breastmilk on growth remain unknown. We aimed to compare infant feeding practices during the first 6.5 months of life between heavy drinkers and abstainers/light drinkers, to examine whether these practices play confounding roles in fetal alcohol growth restriction, and to determine the impact of postnatal alcohol exposure via breastmilk on growth. Eighty-seven heavy-drinking pregnant women and 71 abstainers/light drinkers (controls) were recruited prenatally from antenatal clinics in Cape Town, South Africa. Demographic background and alcohol, cigarette, marijuana, and methamphetamine use during pregnancy were assessed pre- and postnatally. Infant feeding practices were assessed at 6.5 months postpartum using the USDA Infant Feeding Questionnaire. Infant weight, length, and head circumference were measured at 2 weeks, 6.5 and 12 months, and 5 years. Neither prenatal nor postnatal alcohol consumption was related to the duration of breastfeeding, exclusive breastfeeding, exclusive formula, or mixed feeding. Complementary feeding practices were remarkably similar between exposure groups. PAE was related to all postnatal anthropometry measures at all age points, independent of infant feeding practices. Postnatal alcohol exposure via breastmilk was unrelated to any anthropometry outcome after control for PAE. In conclusion, fetal alcohol-related postnatal growth restriction was not attributable to differences in postnatal infant feeding practices or postnatal alcohol exposure and is thus likely a direct teratogenic effect of PAE.
Prenatal alcohol exposure (PAE) is associated with postnatal iron deficiency (ID), which has been shown to exacerbate deficits in growth, cognition, and behavior seen in fetal alcohol spectrum ...disorders. However, the mechanisms underlying PAE-related ID remain unknown.
We aimed to examine biochemical measures of iron homeostasis in the mother, placenta, neonate, and 6.5-month-old infant.
In a prenatally recruited, prospective longitudinal birth cohort in South Africa, 206 gravidas (126 heavy drinkers and 80 controls) were interviewed regarding alcohol, cigarette, and drug use and diet at 3 prenatal visits. Hemoglobin, ferritin, and soluble transferrin receptor (sTfR) were assayed twice during pregnancy and urinary hepcidin:creatinine was assayed once. Infant ferritin and hemoglobin were measured at 2 weeks and 6.5 months and sTfR was measured at 6.5 months. Histopathological examinations were conducted on 125 placentas and iron transport assays (iron regulatory protein-2, transferrin receptor-1, divalent metal transporter-1, ferroportin-1, and iron concentrations) were conducted on 63.
In multivariable regression models, prenatal drinking frequency (days/week) was related to higher maternal hepcidin and to sequestration of iron into storage at the expense of erythropoiesis in mothers and neonates, as evidenced by a lower hemoglobin (g/dL)-to-log(ferritin) (ug/L) ratio mothers: raw regression coefficient (β) = −0.21 (95% CI: −0.35 to −0.07); neonates: β = −0.15 (95% CI: −0.24 to −0.06). Drinking frequency was also related to decreased placental ferroportin-1:transferrin receptor-1 (β = −0.57 for logged values; 95% CI: −1.03 to −0.10), indicating iron-restricted placental iron transport. At 6.5 months, drinking frequency was associated with lower hemoglobin (β = −0.18; 95% CI: −0.33 to −0.02), and increased prevalences of ID (β = 0.09; 95% CI: 0.02–0.17) and ID anemia (IDA) (β = 0.13; 95% CI: 0.04–0.23). In causal inference analyses, the PAE-related increase in IDA was partially mediated by decreased neonatal hemoglobin:log(ferritin), and the decrease in neonatal hemoglobin:log(ferritin) was partially mediated by decreased maternal hemoglobin:log(ferritin).
In this study, greater PAE was associated with an unfavorable profile of maternal-fetal iron homeostasis, which may play mechanistic roles in PAE-related ID later in infancy.
Polychlorinated biphenyls — synthetic hydrocarbon compounds once used as insulating materials in electrical transformers and capacitors — are among the most ubiquitous and persistent environmental ...contaminants.
1
,
2
Although these lipophilic compounds have been banned in the United States and most Western nations since the 1970s, their residues persist and can be detected in the tissues of most residents of industrialized countries.
3
Consumption of fatty sports fish from contaminated waters is a major source of human exposure.
Two prospective studies — one in Michigan,
4
the other in North Carolina
5
— have linked in utero exposure to polychlorinated biphenyls to adverse effects . . .
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