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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.

BACKGROUND Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. METHODS Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. RESULTS Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. CONCLUSIONS High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.

BACKGROUND: Animal models have demonstrated that maternal nutrition can alter fetal vulnerability to prenatal alcohol exposure (PAE). Few human studies have examined the role of nutrition in fetal alcohol spectrum disorders (FASD). OBJECTIVES: Our objectives were to examine whether fetal vulnerability to PAE-related growth restriction is modified by: 1) rate of gestational weight gain; or prenatal dietary intakes of 2) energy, 3) iron, or 4) choline. METHODS: In a prospective longitudinal birth cohort in Cape Town, South Africa, 118 heavy-drinking and 71 abstaining/light-drinking pregnant women were weighed and interviewed regarding demographics, alcohol, cigarette/other drug use, and diet at prenatal visits. Infant length, weight, and head circumference were measured at 2 wk and 12 mo postpartum. RESULTS: Heavy-drinking mothers reported a binge pattern of drinking [Mean = 129 mL (∼7.2 drinks)/occasion on 1.3 d/wk). Rate of gestational weight gain and average daily dietary energy, iron, and choline intakes were similar between heavy-drinking women and controls. In regression models adjusting for maternal age, socioeconomic status, cigarette use, and weeks gestation at delivery, PAE [ounces (30 mL) absolute alcohol per day] was related to smaller 2-wk length and head circumference and 12-mo length, weight, and head circumference z-scores (β = −0.43 to −0.67; all P values

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).

Despite several decades of research and prevention efforts, fetal alcohol spectrum disorders (FASD) remain the most common preventable cause of neurodevelopmental disabilities worldwide. Animal and human studies have implicated fetal alcohol-induced alterations in epigenetic programming as a chief mechanism in FASD. Several studies have demonstrated fetal alcohol-related alterations in methylation and expression of imprinted genes in placental, brain, and embryonic tissue. Imprinted genes are epigenetically regulated in a parent-of-origin-specific manner, in which only the maternal or paternal allele is expressed, and the other allele is silenced. The chief functions of imprinted genes are in placental development, somatic growth, and neurobehavior-three domains characteristically affected in FASD. In this review, we summarize the growing body of literature characterizing prenatal alcohol-related alterations in imprinted gene methylation and/or expression and discuss potential mechanistic roles for these alterations in the teratogenic effects of prenatal alcohol exposure. Future research is needed to examine potential physiologic mechanisms by which alterations in imprinted genes disrupt development in FASD, which may, in turn, elucidate novel targets for intervention. Furthermore, mechanistic alterations in imprinted gene expression and/or methylation in FASD may inform screening assays that identify individuals with FASD neurobehavioral deficits who may benefit from early interventions.

OBJECTIVES: Imprinted genes are epigenetically regulated and play critical roles in placental development and fetal growth. We aimed to examine (1) the impact of maternal one-carbon (methyl donor) nutrition on placental imprinted gene expression, placental development, and fetal growth; (2) whether imprinted gene expression alterations mediate effects of one-carbon nutrition on placental development and fetal growth; (3) interaction effects between one-carbon nutrients and imprinted genes in placental development and fetal growth. METHODS: Histopathology and expression of 109 imprinted genes (Nanostring) were assessed in placentas from 101 women recruited at initiation of antenatal care in a prospective cohort study examining developmental effects of prenatal alcohol exposure in South Africa. Women were interviewed prenatally about demographics, alcohol, smoking, and drug use, and erythrocyte folate, serum vitamin B12, and plasma choline concentrations were assayed at recruitment. Infant weight and height were assessed at age 2 wk. RESULTS: In limma tests, women with plasma choline concentrations below the median had lower placental expression of EPS15, IGF2R, LINC00657, SGCE, ZC3H12C, and ZNF264 than women above the median (p

* Abbreviations: COVID-19 — : coronavirus disease 2019 MIS-C — : multisystem inflammatory syndrome in children PCR — : polymerase chain reaction SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Current data suggest lower rates of severe coronavirus disease 2019 (COVID-19) in children compared with adults.1,2 Although severe respiratory disease has rarely been described,3 new data suggest the emergence of a COVID-19–related multisystem inflammatory syndrome in children (MIS-C).4,5 Describing the temporal variation of pediatric COVID-19 presentations across the course of a high-prevalence outbreak may help elucidate the epidemiology and biology of these manifestations in children. We conducted a retrospective chart review of children (age ≤20 years) presenting to the New York-Presbyterian Morgan Stanley Children’s Hospital pediatric emergency department from March 13, 2020 (date of first known case), to May 19, 2020, who tested positive for severe acute respiratory syndrome coronavirus … Address correspondence to Nazreen Jamal, MD, Department of Emergency Medicine, Irving Medical Center, Columbia University, CH-N 116, 3959 Broadway, New York, NY 10032. E-mail: nk176{at}columbia.edu

Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs (exmiRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed exmiRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of exmiRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered exmiRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant exmiRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.

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.

Background Although animal and human studies have demonstrated interactions between dietary choline and fetal alcohol spectrum disorders, dietary choline deficiency in pregnancy is common in the US and worldwide. We sought to develop and validate a quantitative food frequency questionnaire (QFFQ) to estimate usual daily choline intake in pregnant mothers. Methods A panel of nutrition experts developed a Choline-QFFQ food item list, including sources with high choline content and the most commonly consumed choline-containing foods in the target population. A data base for choline content of each item was compiled. For reliability and validity testing in a prospective longitudinal cohort, 123 heavy drinking Cape Coloured pregnant women and 83 abstaining/light-drinking controls were recruited at their first antenatal clinic visit. At 3 prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use, and administered a 24-hour recall interview and the Choline-QFFQ. Results Across all visits and assessments, > 78% of heavy drinkers and controls reported choline intake below the Dietary Reference Intakes adequate intake level (450 mg/day). Women reported a decrease in choline intake over time on the QFFQ. Reliability of the QFFQ across visits was good-to-acceptable for 2 of 4 group-level tests and 4 of 5 individual-level tests for both drinkers and controls. When compared with 24-hr recall data, validity of the QFFQ was good-to-acceptable for 3 of 4 individual-level tests and 3 of 5 group-level tests. For controls, validity was good-to-acceptable for all 4 individual-level tests and all 5 group-level tests. Conclusions To our knowledge, this is the first quantitative choline food frequency screening questionnaire to be developed and validated for use with both heavy and non-drinking pregnant women and the first to be used in the Cape Coloured community in South Africa. Given the high prevalence of inadequate choline intake and the growing evidence that maternal choline supplementation can mitigate some of the adverse effects of prenatal alcohol exposure, this tool may be useful for both research and future clinical outreach programs.

Background A growing body of evidence in animal models has implicated alcohol-induced alterations in epigenetic programming as an important mechanism in fetal alcohol spectrum disorders (FASD). Imprinted genes, a subset of epigenetically regulated genes that are sensitive to the prenatal environment, are chiefly involved in growth and neurobehavior. We tested the hypothesis that alterations in placental imprinted gene expression mediate fetal alcohol growth restriction. Methods Placental expression of 109 genes previously shown to be imprinted and expressed in the placenta was assessed using the NanoString™ nCounter Analysis System in flash-frozen samples from 34 heavy drinkers and 31 control women in Cape Town, South Africa, from whom prospective pregnancy alcohol consumption data had been obtained. Length/height, weight, and head circumference were measured at 6.5 and 12 months and at an FASD diagnostic clinic (at ages 1.1 to 4.6 years) that we organized. Imprinted gene expression between exposed and control placentas was compared using the limma R package. The relation of alcohol exposure to World Health Organization length-for-age z-scores was examined before and after inclusion of expression for each alcohol-related imprinted gene, using hierarchical mixed regression models with repeated measures. Results Heavy drinkers averaged 8 standard drinks on 2 to 3 days/wk (vs. 0 for controls). Prenatal alcohol exposure was associated with smaller length/height and weight during the postnatal period. Heavy exposure was related to alterations in expression of 11 of 93 expressed imprinted genes, including increased expression of 5 genes found to be negatively associated with growth and decreased expression of 3 genes positively associated with growth. Alcohol-related alterations in expression of 5 genes statistically mediated the effect of prenatal alcohol exposure on length. Conclusions These findings identify alcohol-related alterations in placental imprinted gene expression as potential biomarkers of adverse effect in FASD and suggest that these alterations may play a mechanistic role in fetal alcohol growth restriction. Future studies are needed to determine whether alterations in imprinted gene expression also mediate FASD neurobehavioral deficits and whether such alterations are amenable to intervention.

BACKGROUND: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this paper, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure on infant growth and cognitive function. METHODS: 69 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 prenatal alcohol exposure 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.

Objectives Prenatal exposure to methamphetamine is associated with a range of neuropsychological, behavioural and cognitive deficits. A small number of imaging studies suggests that these may be mediated by neurostructural changes, including reduced volumes of specific brain regions. This study investigated potential volumetric changes in the brains of neonates with prenatal methamphetamine exposure. To our knowledge no previous studies have examined methamphetamine effects on regional brain volumes at this age. Study design Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy. Mothers in the exposure group reported using methamphetamine ≥ twice/month during pregnancy; control infants had no exposure to methamphetamine or other drugs and minimal exposure to alcohol. MRI scans were performed in the first postnatal month, following which anatomical images were processed using FreeSurfer. Subcortical and cerebellar regions were manually segmented and their volumes determined using FreeView. Pearson correlations were used to analyse potential associations between methamphetamine exposure and regional volumes. The associations between methamphetamine exposure and regional volumes were then examined adjusting for potential confounding variables. Results Methamphetamine exposure was associated with reduced left and right caudate and thalamus volumes. The association in the right caudate remained significant following adjustment for potential confounding variables. Conclusions Our findings showing reduced caudate and thalamus volumes in neonates with prenatal methamphetamine exposure are consistent with previous findings in older exposed children, and demonstrate that these changes are already detectable in neonates. Continuing research is warranted to examine whether reduced subcortical volumes are predictive of cognitive, behavioural and affective impairment in older children.

OBJECTIVES: Prenatal alcohol exposure is the most common preventable cause of neurodevelopmental deficits worldwide and causes growth restriction that worsens in the first year of life. Fetal alcohol growth restriction has been shown to be a marker for severity of alcohol-related neurocognitive deficits. However, the role of postnatal nutrition in fetal alcohol growth restriction remains unknown. The aims of this study were to compare infant feeding practices (e.g., breastfeeding, formula feeding, complementary foods) between heavy drinkers and controls and to examine whether these practices play confounding roles in fetal alcohol growth restriction. METHODS: 123 heavy drinking pregnant women and 86 controls were recruited at their first antenatal clinic visit in Cape Town, South Africa. Demographic background and alcohol, cigarette, marijuana, and methamphetamine use during pregnancy were assessed prenatally. Infant feeding practices were assessed at 6.5 mo postpartum using the USDA Infant Feeding Questionnaire. Infant weight, length and head circumference were measured at 2 wk and 6.5 and 12 mo. Potential confounders were those related to growth outcomes at p

Background Despite known risks of prenatal nutritional deficiencies and studies documenting increased prevalence of poor dietary intake among non-pregnant alcohol abusers, the nutritional status of heavy drinking pregnant women remains largely unstudied. Animal models have found interactions between prenatal ethanol exposure and micronutrients, such as choline, folate, B12, and iron, and human studies have reported that lower maternal weight and body mass confer increased fetal alcohol-related risk. Methods 123 heavy drinking Cape Coloured pregnant women and 83 abstaining controls were recruited at their first antenatal clinic visit. At three prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use and weight, height, and arm skinfolds were measured. Dietary intakes of energy, protein, fat, and 25 major micronutrients were assessed from three 24-hour recall interviews. Results The majority of women gained less than the recommended 0.42 kg/week during pregnancy. While methamphetamine use was associated with smaller biceps skinfolds, an indicator of body fat, alcohol consumption was not related to any anthropometric indicator. Alcohol was related to higher intake of phosphorous, choline, and vitamins B12 and D. Alcohol, cigarette, and methamphetamine use were related to lower vitamin C intake. Insufficient intake was reported by >85% of women for 10 of 22 key nutrients, and >50% for an additional 3 nutrients. Conclusions Alcohol consumption during pregnancy was not associated with meaningful changes in diet or anthropometric measures in this population, suggesting that poor nutrition among drinkers does not confound the extensively reported effects of prenatal alcohol exposure on growth and neurobehavior. The poor gestational weight gain and high rates of insufficient intake for several nutrients in both the alcohol-exposed and control groups are also of public health importance. This article is protected by copyright. All rights reserved.

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.

* Abbreviation: FASD — : fetal alcohol spectrum disorder Fetal alcohol spectrum disorders (FASD) comprise the most common preventable cause of neurodevelopmental disabilities worldwide, with prevalence estimates of 1.1% to 5.0% in the United States and Western Europe1 and 13.6% to 20.9% in South Africa.2 Although children with FASD often phenotypically resemble children with other disorders, the neural underpinnings of FASD neurobehavioral deficits are unique and, therefore, require specifically targeted interventions. Accordingly, a growing number of evidence-based programs tailored to FASD are being studied, targeting arithmetic, maladaptive social behaviors, attention and self-regulation, language development, and literacy.3,4 However, the promise of these interventions is limited by diagnostic challenges in clinical practice because children with FASD are most difficult to identify in infancy and early childhood, when neurocognitive interventions may be most effective. In “Early-Life Predictors of Fetal Alcohol Spectrum Disorders” in this issue of Pediatrics , Kalberg et al5 address the issue of early diagnosis in a prospective longitudinal cohort in the Western Cape province of South Africa by examining the degree to which growth, dysmorphology, and neurobehavioral measures are predictive of FASD diagnosis at age 5 years. Although … Address correspondence to R. Colin Carter, MD, MMSc, Departments of Emergency Medicine and Pediatrics, Columbia University Medical Center, 3959 Broadway, CHN-1-116, New York, NY 10032. E-mail: rcc2142{at}cumc.columbia.edu

BACKGROUND Magnetic resonance imaging (MRI) studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure (PAE) but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate PAE effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC). METHODS Forty-three nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost 2-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and fetal alcohol spectrum disorders diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains. RESULTS CC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy. CONCLUSIONS Given that midline craniofacial anomalies have been recognized as a hallmark of fetal alcohol syndrome in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence.

BACKGROUND: 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. METHODS: 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 RESULTS: 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. CONCLUSIONS: 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.

Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. 107 Cape Coloured, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, socio-demographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and IQ and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. By contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver.

BACKGROUND: Animal studies have demonstrated adverse effects of prenatal alcohol exposure on placental development, but few studies have examined these effects in humans. Little is known about effects of prenatal exposure to methamphetamine, marijuana, and cigarette smoking on placental development. METHODS: Placentas were collected from 103 Cape Coloured (mixed ancestry) pregnant women recruited at their first antenatal clinic visit in Cape Town, South Africa. Sixty-six heavy drinkers and 37 nondrinkers were interviewed about their alcohol, cigarette smoking, and drug use at 3 antenatal visits. A senior pathologist, blinded to exposure status, performed comprehensive pathology examinations on each placenta using a standardized protocol. In multivariable regression models, effects of prenatal exposure were examined on placental size, structure, and presence of infections and meconium. RESULTS: Drinkers reported a binge pattern of heavy drinking, averaging 8.0 drinks/occasion across pregnancy on 1.4 d/wk. 79.6% smoked cigarettes; 22.3% used marijuana; and 17.5% used methamphetamine. Alcohol exposure was related to decreased placental weight and a smaller placenta-to-birthweight ratio. By contrast, methamphetamine was associated with larger placental weight and a larger placenta-to-birthweight ratio. Marijuana was also associated with larger placental weight. Alcohol exposure was associated with increased risk of placental hemorrhage. Prenatal alcohol, drug, and cigarette use were not associated with chorioamnionitis, villitis, deciduitis, or maternal vascular underperfusion. Alcohol and cigarette smoking were associated with a decreased risk of intrauterine passing of meconium, a sign of acute fetal stress and/or hypoxia; methamphetamine, with an increased risk. CONCLUSIONS: This is the first human study to show that alcohol, methamphetamine, and marijuana were associated with distinct patterns of pathology, suggesting different mechanisms mediating their effects on placental development. Given the growing body of evidence linking placental abnormalities to neurodevelopmental deficits, these findings may be important in the long-term teratogenic effects of prenatal alcohol and drug exposure.Copyright © 2016 by the Research Society on Alcoholism. Language: en

OBJECTIVE: To determine the separate effects of zinc and multivitamin supplementation on infant hematologic status. METHODS: In a double-blind RCT, infants born to HIV-negative women (n=2400) in Da...

Objective To examine the effects of prenatal alcohol exposure ascertained prospectively on infant visual acuity across a range of exposures and factors that mediate or moderate these effects. Study design Infant visual acuity was examined in 131 Cape Coloured (mixed ancestry) maternal-infant pairs in Cape Town, South Africa. Drinking patterns were documented by maternal reporting during pregnancy. Grating acuity was assessed with Teller Acuity Cards (TAC) at 6.5 months after term. Data were analyzed by correlation, multiple regression, and analysis of variance. Results Greater average daily prenatal alcohol exposure was related to poorer acuity, as indicated by lower TAC scores. The effect of alcohol on acuity was significant primarily for infants born to mothers ≥30 years of age at delivery, in comparison to infants born to younger mothers. This effect was not mediated by gestational age or birth size or attributable to alcohol-related neurocognitive deficits. Conclusions This study linked prenatal alcohol exposure ascertained prospectively to poorer visual acuity in infancy. The results are consistent with clinical and animal evidence of alcohol-related disruption of the visual system.

The relationship between early parental practices and school readiness described by Gibbs and Forste provides a new and original perspective on the impact of breastfeeding on development.1 Their study used direct indicators of parenting practices not used in previous studies and examined school readiness (math and reading) rather than child IQ as the outcome measure at age 4 years. Using data from the Early Childhood Longitudinal Study survey of early childhood (n = 7500), Gibbs and Forste found that reading to an infant every day as early as age 9 months and sensitivity to the child’s cues during social interactions, rather than breastfeeding per se, were significant predictors of reading readiness at age 4 years. In contrast, other practices, such as early introduction of solid foods and putting an infant to bed with a bottle, were unrelated to child cognitive outcomes. Based on these findings, the authors concluded that the association between breastfeeding and cognitive outcome “is better understood as a proxy for parenting practices that foster cognitive development in early childhood.” Although not noted explicitly, the data show that children who were breastfed for 6 months or longer performed best on the age 4 year reading assessment, which is consistent with their also having experienced the most optimal parenting practices. Numerous previous studies have documented better performance on IQ tests in children who were breastfed compared with those who were not.2-4 This intellectual advantage has been demonstrated in several cultures for full-term infants and even more strongly for preterm and low birthweight infants. The IQ advantage for full-term infants is small, roughly 3-4 points, but remarkably consistent across studies. Moreover, the controversy is not about whether there is enhanced cognitive function among the breastfed children, but whether this difference reflects a direct nutritional advantage from breastfeeding or a difference in maternal intellectual competence and socioenvironmental factors, which generally are more optimal among women who breastfeed. It is well established that women who breastfeed are also more likely to provide a more enriched and cognitively stimulating environment for their children, which could be responsible for these children’s more optimal cognitive performance. The Gibbs and Forste study is the first to directly evaluate specific and discrete measures of parenting, such as frequency of reading to the infant and maternal sensitivity, instead of more distal measures, such as socioeconomic status (SES) and maternal education, to examine this association. Based on data demonstrating a positive relationship between breastfeeding and childhood IQ after controlling statistically for SES and maternal education, previous authors have inferred a nutritional benefit from breastfeeding above and beyond the benefit of a more optimal rearing environment.2 In our cohort of Michigan children (n = 323), we confirmed previous findings showing a positive association between breastfeeding and higher childhood IQ at age 4 and 11 years, after statistical adjustment for SES and maternal education.4,5 However, when we controlled for 2 more direct indicators of parental cognitive stimulation—maternal vocabulary IQ and the Home Observation for Measurement of the Environment (HOME), a semistructured interview and behavioral observation measure that provides an assessment of quality of intellectual stimulation and emotional support provided by the parents—the association between breastfeeding and childhood IQ was no longer evident. Gibbs and Forste extend this finding by identifying 2 specific aspects of parenting practices—early reading and sensitivity—that account, at least in part, for the beneficial effects of breastfeeding on children’s cognitive outcomes. Der et al6 reported that among 9 indicators (including breastfeeding) in their regression analysis, maternal IQ was clearly the strongest predictor of child IQ. The importance of including maternal IQ was demonstrated by their demonstration that the association of breastfeeding with child cognitive performance declined from 4.7 points to 0.5 point after adjustment for mother’s cognitive competence and other socioenvironmental measures in their National Longitudinal Survey of Youth cohort study (n = 5475). They identified maternal IQ, attributable at least in part to heritability, as the principal variable accounting for the apparent association between breastfeeding and child performance. They included only 2 of the HOME subscales in their analysis, however. In our study, which included the complete HOME inventory, maternal verbal IQ and the HOME score contributed equally to the predicted IQ score at age 11 years.5 Taken together, these data suggest that both heritability and rearing environment play important roles in explaining the apparent association between breastfeeding and children’s cognitive performance.6,7 Gibbs and Forste contrasted the nutritional benefits of breastfeeding with maternal education, IQ, and quality of parenting, questioning which constitutes the primary pathway through which breastfeeding influences child cognitive outcome. They did not consider the role of maternal IQ (both genetically contributing to child cognitive ability and as an indicator of a potentially more enriched and stimulating environment), because this measure was not available in their dataset. In several studies that attempted to show that the link between breastfeeding and cognitive outcome was not attributable to social factors, failure to include maternal IQ led to underestimation of a critically important factor4-6; however, in the Gibbs and Forste study, in which the authors demonstrated that their direct measures of parenting practices are sufficient to explain the association between breastfeeding and child academic achievement, inclusion of maternal IQ was not necessary. It is noteworthy that the Gibbs and Forste study is the third study to show that, in contrast to maternal IQ and quality of child rearing, maternal depression did not mediate the relation between breastfeeding and later child cognitive achievement. Both our Michigan study4,5 and the study of Der et al6 also found that maternal depression did not mediate this association on child IQ. The importance of the nutritional benefits of breastfeeding for a broad range of health outcomes should not be underestimated, however. These include reduced rates of asthma, allergies, and atopy; improved body mass index and reduced obesity rates; reduced rates of cardiovascular disease; and marked decreases in mortality, particularly in resource-poor settings.8 The Lancet Child Survival Series estimates that exclusive breastfeeding through age 6 months would prevent 13% of all deaths in children under age 5 years worldwide.9 Moreover, a large body of research has demonstrated protective effects of breastfeeding against infectious diseases, particularly gastrointestinal and respiratory illnesses, in both resource-rich and resource-poor settings.8 In areas with a high infectious disease burden, repeated infections have been associated with poor growth and cognitive deficits. Thus, improved immunity may be a mechanism through which breastfeeding confers cognitive benefits, particularly in resource-poor settings. Gibbs and Forste examined infants in the US, where federal programs, such as the Special Supplemental Nutrition Program for Women Infants, and Children, ensure that most infants who are not breastfed have access to commercial formula that is designed to closely approximate the nutritional content of breast milk and often contains even higher concentrations of key nutrients known to impact cognitive and emotional development, including iron,10,11 choline,12,13 and long-chain polyunsaturated fatty acids.14 In contrast, commonly used alternatives to breastfeeding in resource-poor settings include lower quality and/or diluted formulas, cow’s milk (also often diluted), and adult foods too complex for the immature digestive tract. In addition, breastfeeding may promote more secure and less-disorganized infant–mother attachment,15 thereby fostering better parenting behaviors, such as maternal sensitivity, which was associated with both math and reading skills in the regression models in the study of Gibbs and Forste. Their findings have led Gibbs and Forste to conclude that more emphasis is needed on fostering better parenting behaviors rather than on encouraging breastfeeding to promote school readiness, especially for disadvantaged children. Parents often do not recognize how early an infant responds to being read to. For the practitioner, these data may beparticularly relevant when caring for a mother who may be considering foregoing or curtailing breastfeeding for various reasons, such as the need to take antiseizure or antidepression medication or undergo chemotherapy that might be transferred to the infant via breast milk or the need to resume employment. These data indicate that one consideration—a potential adverse long-term impact on the child’s cognitive function—need not be of concern. Nonetheless, when there is no risk to the infant or major inconvenience for the mother, encouragement of breastfeeding for other reasons, including health benefits to the infant and enhancement of mother–infant attachment, should not be underemphasized and warrants attention from pediatricians and other health care providers. There is considerable merit to the recommendation that both breastfeeding and good parenting practices should be promoted.

Leber congenital amaurosis (LCA, MIM 204001) is a clinically and genetically heterogeneous retinal disorder characterized by severe visual loss from birth, nystagmus, poor pupillary reflexes, retinal pigmentary or atrophic changes, and a markedly diminished electroretinogram (ERG). Purpose: To examine 100 consecutive patients with LCA in order to assess the relative burden of the three known genes involved in LCA, namely retinal guanylyl cyclase ( GUCY2D ), retinal pigment epithelium protein ( RPE65 ), and the cone-rod homeobox ( CRX ), and to define their clinical correlates. Methods: Mutational analysis and detailed clinical examinations were performed in patients diagnosed with LCA at the Johns Hopkins Center for Hereditary Eye Diseases and the Montreal Children’s Hospital. Results: Mutations were identified in 11% of our patients: GUCY2D mutations accounted for 6%, while RPE65 and CRX gene mutations accounted for 3% and 2%, respectively. The clinical presentation was variable; however, the visual evol...

Day and colleagues have presented the first data showing that the behavioral effects of low to moderate prenatal alcohol exposure seen in childhood and adolescence persist into adulthood. Using the Achenbach Adult Self-Report, they found dose-dependent effects of prenatal exposure on internalizing, externalizing, and attention problems that persist in young adults and, thus, appear to be permanent. To date, few studies have attempted to identify thresholds at which prenatal alcohol exposure is harmful, although the animal literature suggests that even 1 to 2 binge episodes can result in adverse effects in the offspring. Four prospective longitudinal studies have reported adverse effects at what can be characterized as moderate exposure levels based on NIAAA criteria, but moderate drinking women often concentrate their alcohol use on 1 to 2 days per week, thereby engaging in binge drinking. In this study, binge drinking was not a strong predictor of adverse outcome when average daily dose was held constant, a conclusion that the authors note runs “counter to studies that have reported that binge drinking has a greater effect.” This inconsistency may be due to the difficulty of allocating variance that is shared (overlapping) between average daily dose and binge drinking (i.e., dose/occasion). Data from laboratory animal studies, in which dosage can be manipulated experimentally, demonstrate that a higher dose per occasion, the key feature of binge drinking, leads to more severe adverse effects. Day and colleagues’ findings of adverse effects at low levels of exposure provides clear evidence that there is no safe level of drinking during pregnancy and that, even at low levels, drinking results in irreversible behavioral impairment. On the other hand, given the evidence from the animal and most human studies, it is important for all women who drink during pregnancy, even at light to moderate levels, to recognize that minimizing their intake per occasion and refraining from binge drinking can reduce risk to the fetus.

Background: Polychlorinated biphenyls (PCBs), methylmercury (MeHg), and lead (Pb) are environmental contaminants known for their adverse effects on cognitive development. Objectives: In this study we examined the effects of prenatal exposure to PCBs, MeHg, and Pb on cognitive development in a sample of Inuit infants from Arctic Québec. Methods: Mothers were recruited at local prenatal clinics. PCBs, mercury (Hg), Pb, and two seafood nutrients—docosahexaenoic acid (DHA) and selenium (Se)—were measured in umbilical cord blood. Infants (n = 94) were assessed at 6.5 and 11 months of age on the Fagan Test of Infant Intelligence (FTII), A-not-B test, and Bayley Scales of Infant Development–2nd Edition (BSID-II). Results: Multiple regression analyses revealed that higher prenatal PCB exposure was associated with decreased FTII novelty preference, indicating impaired visual recognition memory. Prenatal Hg was associated with poorer performance on A-not-B, which depends on working memory and is believed to be a precursor of executive function. Prenatal Pb was related to longer FTII fixation durations, indicating slower speed of information processing. Conclusions: PCBs, MeHg, and Pb each showed specific and distinct patterns of adverse associations with the outcomes measured during infancy. By contrast, none of these exposures was associated with performance on the BSID-II, a global developmental measure. The more focused, narrow band measures of cognitive function that appeared to be sensitive to these exposures also provide early indications of long-term impairment in specific domains that would otherwise not likely be evident until school age. Citation: Boucher O, Muckle G, Jacobson JL, Carter RC, Kaplan-Estrin M, Ayotte P, Dewailly É, Jacobson SW. 2014. Domain-specific effects of prenatal exposure to PCBs, mercury, and lead on infant cognition: results from the Environmental Contaminants and Child Development Study in Nunavik. Environ Health Perspect 122:310–316; http://dx.doi.org/10.1289/ehp.1206323

Background Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother–infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother–infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother–infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother–infant interaction, infant temperament, or other socioemotional aspects of the infant's environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS.

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.

Prenatal alcohol exposure has been associated with pre- and postnatal growth restriction, but little is known about the natural history of this restriction throughout childhood or the effects of prenatal alcohol on body composition. The objective of this study was to examine the effects of heavy prenatal alcohol exposure on longitudinal growth and body composition.Eighty-five heavy drinking pregnant women (≥2 drinks/d or ≥4 drinks/occasion) and 63 abstaining and light-drinking controls (1 drink/d, no binging) were recruited at initiation of prenatal care in an urban obstetrical clinic in Cape Town, South Africa and prospectively interviewed during pregnancy about alcohol, smoking, drug use, and demographics. Among their children, length/height, weight, and head circumference were measured at 6.5 and 12 months and at 5 and 9 years. Percent body fat (BF) was estimated at age 9 years using bioelectric impedance analysis.In multiple regression models with repeated measures (adjusted for confounders), heavy alcohol exposure was associated with reductions in weight (0.6 SD), length/height (0.5 SD), and head circumference (0.9 cm) from 6.5 months to 9 years that were largely determined at birth. These effects were exacerbated by iron deficiency in infancy but were not modified by iron deficiency or measures of food security at 5 years. An alcohol-related postnatal delay in weight gain was seen at 12 months. Effects on head circumference were greater at age 9 than at other age points. Although heavy alcohol exposure was not associated with changes in body composition, children with fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) had lower percent BF than heavy exposed nonsyndromal and control children.Heavy prenatal alcohol exposure is related to prenatal growth restriction that persists through age 9 years and an additional delay in weight gain during infancy. FAS and PFAS diagnoses are associated with leaner body composition in later childhood.

Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. 107 Cape Coloured, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, socio-demographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and IQ and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. By contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver.

OBJECTIVES. Our goals were to determine whether prenatal alcohol exposure is associated with an increased incidence of iron-deficiency anemia in infancy and to compare effects of fetal alcohol exposure and iron-deficiency anemia on infant growth. We also tested whether effects of fetal alcohol exposure on growth are mediated or moderated by iron-deficiency anemia.METHODS. A total of 96 infants born to mothers from the Coloured (mixed ancestry) community in Cape Town, South Africa, were recruited prenatally; 42 mothers drank heavily during pregnancy, and 54 abstained or drank small amounts of alcohol. Growth was assessed at birth and 6.5 and 12 months, and iron-deficiency anemia was assessed at 6.5 or 12 months.RESULTS. Infants whose mothers binge drank during pregnancy (≥4 drinks per occasion) were 3.6 times more likely to be diagnosed with iron-deficiency anemia at 12 months than were infants whose mothers did not binge drink. Prenatal alcohol exposure was associated with reduced weight at birth, 6.5 months, and 12 months and with shorter length at 6.5 and 12 months. Iron-deficiency anemia was related to reduced 12-month weight and head circumference and to slower growth velocity between 6 and 12 months. The effects of prenatal alcohol on weight were not mediated by iron-deficiency anemia; however, they were seen primarily in infants with iron-deficiency anemia.CONCLUSIONS. The association of maternal binge drinking with an increased incidence of iron-deficiency anemia may reflect disruption of accumulation of fetal iron stores or postnatal deficiencies in iron uptake, absorption, or intake. Moreover, iron deficiency seems to exacerbate the prenatal alcohol effects on growth.