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Prenatal alcohol exposure (PAE) is associated with alterations in maternal and infant iron homeostasis that are consistent with changes seen in the setting of inflammation. We hypothesized that PAE leads to alterations in the placental expression of genes related to iron metabolism and inflammation that play functional roles in the teratogenic effects of alcohol on iron homeostasis. A total of 126 heavy-drinking women (≥1 oz (30 mL) absolute alcohol/day (~1.67 standard drinks/day) or women reporting binge drinking (≥2 drinks/occasion)) and 80 control women (<0.5 oz AA per day, no binging) in Cape Town, South Africa were interviewed prenatally regarding demographics, and alcohol, smoking, and drug use around conception and during pregnancy. Prenatal/maternal and infant hemoglobin and ferritin were measured. Whole-transcriptome RNA sequencing analysis was performed on flash-frozen transplacental tissue samples. Gene sets related to iron metabolism (n = 398) and inflammation (n = 467) were constructed by searching the Molecular Signatures Database for related ontology terms. Principal component analysis (PCA) yielded 59 factors for each theme. In multivariable regression models, PAE was related to 2 iron metabolism PCA factors (PCs) and 5 inflammation PCs, among which 2 iron metabolism and 4 inflammation factors were related to at least 1 key maternal or infant iron outcome. In causal inference analyses based on marginal structural models and the product method, the alterations in the expression profile of genes with functions in immune cell regulation, cytokine activity, angiogenesis, hematopoiesis, and ubiquitous cell processes appeared to partially mediate the relation of prenatal drinking frequency (days/week) around conception to a lower maternal hemoglobin-to-log(ferritin) ratio (proportion mediation = 51.35%). These findings suggest that placental inflammation may be partly responsible for the differences in alcohol-related iron homeostasis patterns between pregnant and non-pregnant adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]