Moderate Prenatal Alcohol Exposure Research Articles

Moderate-level prenatal alcohol exposure induces sex differences in dopamine d1 receptor binding in adult rhesus monkeys.

We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on (D1 R) binding in a non human primate model. The dopamine D1 R is involved in executive function, and it may play a role in cognitive behavioral deficits associated with prenatal alcohol and/or stress exposure. Little is known, however, about the effects of prenatal alcohol and/or stress exposure on the D1 R. We expected that prenatal insults would lead to alterations in D1 R binding in prefrontal cortex (PFC) and striatum in adulthood. Rhesus macaque females were randomly assigned to moderate alcohol exposure and/or mild prenatal stress as well as a control condition during pregnancy. Thirty-eight offspring were raised identically and studied as adults by noninvasive in vivo neuroimaging using positron emission tomography with the D1 antagonist radiotracer [(11) C]SCH 23390. Radiotracer binding in PFC and striatum was evaluated by 2 (alcohol)×2 (stress)×2 (sex) analysis of variance. In PFC, a significant alcohol×sex interaction was observed with prenatal alcohol exposure leading to increased [(11) C]SCH 23390 binding in male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was observed. These results suggest that prenatal alcohol exposure results in long-term increases in prefrontal dopamine D1 R binding in males. This may help explain gender differences in the prevalence of neurodevelopmental disorders consequent to prenatal alcohol exposure.

Study protocol: Asking QUestions about Alcohol in pregnancy (AQUA): a longitudinal cohort study of fetal effects of low to moderate alcohol exposure

BackgroundDespite extensive research, a direct correlation between low to moderate prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders has been elusive. Conflicting results are attributed to a lack of accurate and detailed data on PAE and incomplete information on contributing factors. The public health effectiveness of policies recommending complete abstinence from alcohol during pregnancy is challenged by the high frequency of unplanned pregnancies, where many women consumed some alcohol prior to pregnancy recognition. There is a need for research evidence emphasizing timing and dosage of PAE and its effects on child development.Methods/DesignAsking QUestions about Alcohol (AQUA) is a longitudinal cohort aiming to clarify the complex effects of low to moderate PAE using specifically developed and tested questions incorporating dose, pattern and timing of exposure. From 2011, 2146 pregnant women completed a questionnaire at 8-18 weeks of pregnancy. Further prenatal data collection took place via a questionnaire at 26-28 weeks and 35 weeks gestation. Extensive information was obtained on a large number of risk factors to assist in understanding the heterogeneous nature of PAE effects. 1571 women (73%) completed all three pregnancy questionnaires. A biobank of DNA from maternal and infant buccal cells, placental biopsies and cord blood mononuclear cells will be used to examine epigenetic state at birth as well as genetic factors in the mother and child. Participants will be followed up at 12 and 24 months after birth to assess child health and measure infant behavioural and sensory difficulties, as well as family environment and parenting styles. A subgroup of the cohort will have 3D facial photography of their child at 12 months and a comprehensive developmental assessment (Bayley Scales of Infant & Toddler Development, Bayley-III) at two years of age.DiscussionUsing detailed, prospective methods of data collection, the AQUA study will comprehensively examine the effects of low to moderate alcohol consumption throughout pregnancy on child health and development, including the role of key mediators and confounders. These data will ultimately contribute to policy review and development, health professional education and information about alcohol consumption for pregnant women in the future.

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15–17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics analysis. This study is the first to use chronic low to moderate PAE, to more accurately reflect maternal alcohol consumption, and subsequent neural progenitor cell culture to demonstrate that PAE throughout gestation alters expression of genes involved in neural development and embryonic neurogenesis.

Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats

Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure – MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment.

Effects of moderate prenatal ethanol exposure and age on social behavior, spatial response perseveration errors and motor behavior

Persistent deficits in social behavior are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked deficits in social behavior following moderate prenatal alcohol exposure (PAE) in the rat to functional alterations in the ventrolateral frontal cortex [21]. In addition to social behaviors, the regions comprising the ventrolateral frontal cortex are critical for diverse processes ranging from orofacial motor movements to flexible alteration of behavior in the face of changing consequences. The broader behavioral implications of altered ventrolateral frontal cortex function following moderate PAE have, however, not been examined. In the present study we evaluated the consequences of moderate PAE on social behavior, tongue protrusion, and flexibility in a variant of the Morris water task that required modification of a well-established spatial response. PAE rats displayed deficits in tongue protrusion, reduced flexibility in the spatial domain, increased wrestling, and decreased investigation, indicating that several behaviors associated with ventrolateral frontal cortex function are impaired following moderate PAE. A linear discriminant analysis revealed that measures of wrestling and tongue protrusion provided the best discrimination of PAE rats from saccharin-exposed control rats. We also evaluated all behaviors in young adult (4–5 months) or older (10–11 months) rats to address the persistence of behavioral deficits in adulthood and possible interactions between early ethanol exposure and advancing age. Behavioral deficits in each domain persisted well into adulthood (10–11 months), however, there was no evidence that aging enhances the effects of moderate PAE within the age ranges that were studied.

Impact of Moderate Prenatal Alcohol Exposure on Problem Behaviors in Preschool and School Children

Data on the relation between moderate prenatal alcohol exposure (PAE) and behavioral disorders are inconsistent, and this raises new questions. We examined (1) the association between moderate PAE and problem behaviors and (2) whether these associations differed by levels of socioeconomic status (SES), fetal smoke exposure, or exposure to environmental tobacco smoke (ETS). Data were taken from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study. Parents evaluated children’s behaviors using the Strengths and Difficulties Questionnaire (SDQ). Results showed a slight, but insignificant, increase of problem behaviors in children with moderate PAE. In 3- to 6-year-olds, PAE had a stronger effect on hyperactivity/inattention in combination with fetal smoke exposure (odds ratio = 2.82), than did PAE alone. Effects were not stronger in low-SES children, but they were stronger in children with ETS. We conclude that moderate PAE might have adverse effects on neurodevelopment, with stronger effects in disadvantaged populations. To confirm our preliminary findings, further research should be conducted.

Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

Fetal alcohol spectrum disorders (FASDs) are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE), specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

Adolescents' Use of Alcohol, Tobacco and Illicit Drugs in Relation to Prenatal Alcohol Exposure: Modifications by Gender and Ethnicity

The study aimed to investigate (a) the association between low to moderate prenatal alcohol exposure (PAE) and the use of alcohol, tobacco and illicit drugs in adolescence and (b) whether the associations are modified by gender and ethnicity. The subjects of the study were 5922 children and adolescents, aged from 11 to 17 years, enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents (the KiGGS study). Information on PAE is based on parental self-report questionnaires. Use of alcohol, tobacco and illicit drugs was assessed through self-report questionnaires for adolescents. Low to moderate PAE was associated with an increased risk of drinking alcohol (adjusted odds ratio (OR) 1.73, 95% confidence interval (CI) 1.34, 2.18) and also of illicit drug use (adjusted OR 1.62, 95% CI 1.23, 2.14). The associations between PAE and the use of alcohol, tobacco and illicit drugs differed according to gender and ethnicity. Gender-stratified analyses resulted in adverse effects of PAE on drinking alcohol, smoking and illicit drug use in females; however, in German males, the associations disappeared. Stronger associations between PAE and the outcome measures were found in non-Germans. Our findings indicate that low to moderate levels of maternal alcohol intake during pregnancy are a risk factor for use of alcohol, tobacco and illicit drugs by the offspring, with stronger associations in females and non-Germans.

Fate Analysis of Adult Hippocampal Progenitors in a Murine Model of Fetal Alcohol Spectrum Disorder (FASD)

Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreERT2/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access “drinking-in-the-dark” model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A–B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population.

The Association of Mild, Moderate, and Binge Prenatal Alcohol Exposure and Child Neuropsychological Outcomes: A Meta-Analysis

The objective of this review is to evaluate the literature on the association between mild, moderate, and binge prenatal alcohol exposure and child neurodevelopment. Meta-analysis with systematic searches of MEDLINE (1970 through August 2012), EMBASE (1988 through August 2012), and PsycINFO(®) (1970 through August 2012) and examination of selected references. From 1,593 articles, we identified 34 presenting data from cohort studies that met our inclusion criteria. Information on study population, outcomes, measurement instruments, timing and quantification of alcohol exposure, covariates, and results was abstracted. Outcomes included academic performance, attention, behavior, cognition, language skills, memory, and visual and motor development. The quality of each article was assessed by 2 researchers using the Newcastle-Ottawa Scale. Based on 8 studies of 10,000 children aged 6 months through 14 years, we observed a significant detrimental association between any binge prenatal alcohol exposure and child cognition (Cohen's d [a standardized mean difference score] -0.13; 95% confidence interval [CI], -0.21, -0.05). Based on 3 high-quality studies of 11,900 children aged 9 months to 5 years, we observed a statistically significant detrimental association between moderate prenatal alcohol exposure and child behavior (Cohen's d -0.15; 95% CI, -0.28, -0.03). We observed a significant, albeit small, positive association between mild-to-moderate prenatal alcohol exposure and child cognition (Cohen's d 0.04; 95% CI, 0.00, 0.08), but the association was not significant after post hoc exclusion of 1 large study that assessed mild consumption nor was it significant when including only studies that assessed moderate alcohol consumption. None of the other completed meta-analyses resulted in statistically significant associations between mild, moderate, or binge prenatal alcohol exposure and child neuropsychological outcomes. Our findings support previous findings suggesting the detrimental effects of prenatal binge drinking on child cognition. Prenatal alcohol exposure at levels less than daily drinking might be detrimentally associated with child behavior. The results of this review highlight the importance of abstaining from binge drinking during pregnancy and provide evidence that there is no known safe amount of alcohol to consume while pregnant.

Commentary on Day and Colleagues : The Association Between Prenatal Alcohol Exposure and Behavior at 22 Years of Age-Adverse Effects of Risky Patterns of Drinking Among Low to Moderate Alcohol-Using Pregnant Women

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.

Moderate Prenatal Alcohol Exposure Reduces Plasticity and Alters NMDA Receptor Subunit Composition in the Dentate Gyrus

Although it is well documented that heavy consumption of alcohol during pregnancy impairs brain development, it remains controversial whether moderate consumption causes significant damage. Using a limited access, voluntary consumption paradigm, we recently demonstrated that moderate prenatal alcohol exposure (MPAE) is associated with dentate gyrus-dependent learning and memory deficits that are manifested in adulthood. Here, we identified a novel mechanism that may underlie this effect of MPAE. We found that MPAE mice exhibit deficits in NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) in the dentate gyrus. Further, using semiquantitative immunoblotting techniques, we found that the levels of GluN2B subunits were decreased in the synaptic membrane, while levels of C2'-containing GluN1 and GluN3A subunits were increased, in the dentate gyrus of MPAE mice. These data suggest that MPAE alters the subunit composition of synaptic NMDARs, leading to impaired NMDAR-dependent LTP in the dentate gyrus.

Danish studies suggesting low and moderate prenatal alcohol exposure has no adverse effects on children aged 5 years did not use appropriate or effective measures of executive functioning

BJOG: An International Journal of Obstetrics & GynaecologyVolume 119, Issue 13 p. 1669-1670 Correspondence Danish studies suggesting low and moderate prenatal alcohol exposure has no adverse effects on children aged 5 years did not use appropriate or effective measures of executive functioning G Powell, G Powell Retired Diplomate American Board of Psychiatry and Neurology and also American Board of Clinical and Anatomic Pathology, Fort Mill, SC, USASearch for more papers by this author G Powell, G Powell Retired Diplomate American Board of Psychiatry and Neurology and also American Board of Clinical and Anatomic Pathology, Fort Mill, SC, USASearch for more papers by this author First published: 19 November 2012 https://doi.org/10.1111/1471-0528.12005Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume119, Issue13December 2012Pages 1669-1670 RelatedInformation

The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-old children.

To examine the effects of low to moderate maternal alcohol consumption during early pregnancy on children's intelligence (IQ) at age 5 years. Prospective follow-up study. Neuropsychological testing in four Danish cities 2003-2008. A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R). Parental education, maternal IQ, maternal smoking in pregnancy, the child's age at testing, gender, and tester were considered core confounding factors, whereas the full model also controlled for maternal binge drinking, age, BMI, parity, home environment, postnatal smoking in the home, health status, and indicators for hearing and vision impairments. The WPPSI-R. No differences in test performance were observed between children whose mothers reported consuming between one and four or between five and eight drinks per week at some point during pregnancy, compared with children of mothers who abstained. For women who reported consuming nine or more drinks per week no differences were observed for mean differences; however, the risks of low full-scale IQ (OR 4.6; 95% CI 1.2-18.2) and low verbal IQ (OR 5.9; 95% CI 1.4-24.9) scores, but not low performance IQ score, were increased. Maternal consumption of low to moderate quantities of alcohol during pregnancy was not associated with the mean IQ score of preschool children. Despite these findings, acceptable levels of alcohol use during pregnancy have not yet been established, and conservative advice for women continues to be to avoid alcohol use during pregnancy.

Moderate Prenatal Alcohol Exposure and Serotonin Genotype Interact to Alter CNS Serotonin Function in Rhesus Monkey Offspring

Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine (DA) metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from 4 groups of females were assessed: (i) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 50; (ii) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 50 to 135; (iii) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 135; and (iv) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 to 50, 50 to 135, or 0 to 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l vs. homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, whereas 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared with monkeys homozygous for the long allele. Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle-to-late gestation alcohol-exposed monkeys and reduced HVA at baseline. These findings that prenatal alcohol exposure altered central 5-HT activity in genetically sensitive monkeys raise questions about whether abnormal serotonin biological pathways could underlie some of the psychiatric disorders reported in fetal alcohol spectrum disorder.

Prenatal Alcohol Exposure and Risk of Birth Defects

The term alcohol-related birth defects (ARBDs) refers to a wide range of birth defects included in the Institute of Medicine (IOM) diagnostic guidelines on prenatal alcohol exposure (PAE). Evidence for many of the ARBDs included in the IOM guidelines was derived from animal studies and high-risk populations, and many of the ARBDs occur rarely, and can have other potential causes. Information on dose, pattern, and timing of PAE is also important for the diagnosis of ARBDs, but is not always available. For these reasons, it can be difficult to confidently attribute a defect to PAE. Population-based evidence for the association between PAE and birth defects is limited. This population-based study investigated the associations between dose, pattern, and timing of PAE (before pregnancy, in the first trimester, and in late pregnancy) and ARBDs according to IOM criteria. Between 1995 and 1997, data from a randomly selected cohort of nonindigenous women in Western Australia (WA) (n = 4714), who gave birth to a live infant (n = 4714), were linked to birth information recorded in the WA Midwives' Notification System and the WA Birth Defects Registry. Information about alcohol use before and during pregnancy was collected retrospectively from the participating women within 3 months of giving birth. Alcohol use was categorized as low, moderate, or heavy; the comparison group consisted of women who abstained from drinking alcohol. Multivariate logistic regression analysis was used to estimate the associations between PAE in each time period and the birth defects. There was a low prevalence of birth defects classified as ARBDs according to IOM criteria. As compared to the abstinent group, heavy PAE in the first trimester was associated with an increased likelihood of having an infant with a birth defect classified as an ARBD; the adjusted odds ratio was 4.57, with a 95% confidence interval of 1.46–14.26). The association was similar (adjusted odds ratio: 4.56) after bootstrap analysis. In contrast, no association was found between low or moderate PAE and any ARBD classified according to IOM criteria. These findings show a greater than 4-fold increase in the risk of birth defects classified as ARBD after heavy PAE in the first trimester. Many of the individual birth defects classified as ARBDs according to IOM criteria were not present in the cohort or were not related to PAE.

Low–Moderate Prenatal Alcohol Exposure and Risk to Child Behavioral Development: A Prospective Cohort Study

ABSTRACTThe detrimental effects of fetal exposure to extreme levels of alcohol during pregnancy, such as the subsequent occurrence of childhood physical, cognitive, and behavioral deficits, are well known. Some investigators have suggested that there is a dose-response effect, with light drinking du

Prenatal Alcohol Exposure and Risk of Birth Defects

The goal was to examine the associations between dose, pattern, and timing of prenatal alcohol exposure (PAE) and birth defects. Data from a randomly selected, population-based cohort of nonindigenous women who gave birth to a live infant in Western Australia (WA) between 1995 and 1997 (N=4714) were linked to WA Midwives Notification System and WA Birth Defects Registry data. We assessed the associations of PAE before pregnancy, in the first trimester, and in late pregnancy with any birth defect and with birth defects classified as alcohol-related birth defects (ARBDs) by the Institute of Medicine (IOM), by using logistic regression. The prevalence of birth defects classified as ARBDs by the IOM was low. Compared with abstinence, heavy PAE in the first trimester was associated with increased odds of birth defects classified as ARBDs (adjusted odds ratio: 4.6 [95% confidence interval: 1.5-14.3]), with similar findings after validation through bootstrap analysis. There was no association between low or moderate PAE and birth defects. A fourfold increased risk of birth defects classified as ARBDs was observed after heavy PAE in the first trimester. Many individual birth defects included in the IOM classification for ARBDs either were not present in this cohort or were not associated with PAE. Large, population-based studies are needed to strengthen the evidence base for ARBDs.

Caudate asymmetry: A neurobiological marker of moderate prenatal alcohol exposure in young adults

This study identified structural changes in the caudate nucleus in offspring of mothers who drank moderate levels of alcohol during pregnancy. In addition, the effect of duration of alcohol use during pregnancy was assessed. Young adults were recruited from the Maternal Health Practices and Child Development Project. Three groups were evaluated: prenatal alcohol exposure (PAE) during all three trimesters (3T), PAE during the first trimester only (1T), and controls with no PAE (0T). Magnetic resonance images were processed using the automated labeling pathway technique. Volume was measured as the number (gray + white) and relative percentage (caudate count/whole brain count × 100) of voxels. Asymmetry was calculated by subtracting the caudate volume on the left from the right and dividing by the total (L − R/L + R). Data analyses controlled for gender, handedness, and prenatal tobacco and marijuana exposures. There were no significant differences between the groups for whole brain, left, or right volumes. There was a dose–response effect across the three exposure groups both in terms of magnitude and direction of asymmetry. In the 3T group, the left caudate was larger relative to the right caudate compared to the 0T group. The average magnitude of caudate asymmetry for the 1T group was intermediate between the 0T and 3T groups. Subtle anatomical changes in the caudate are detected at the moderate end of the spectrum of prenatal alcohol exposure.

Low–moderate prenatal alcohol exposure and risk to child behavioural development: a prospective cohort study

Please cite this paper as: Robinson M, Oddy W, McLean N, Jacoby P, Pennell CE, de Klerk N, Zubrick S, Stanley F, Newnham J. Low–moderate prenatal alcohol exposure and risk to child behavioural development: a prospective cohort study. BJOG 2010;117:1139–1152.Objective To examine the association of fetal alcohol exposure during pregnancy with child and adolescent behavioural development.Design The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnancies (1989–91) and the 14‐year follow up was conducted between 2003 and 2006.Setting Tertiary obstetric hospital in Perth, Western Australia.Population The women in the study provided data at 18 and 34 weeks of gestation on weekly alcohol intake: no drinking, occasional drinking (up to one standard drink per week), light drinking (2–6 standard drinks per week), moderate drinking (7–10 standard drinks per week), and heavy drinking (11 or more standard drinks per week).Methods Longitudinal regression models were used to analyse the effect of prenatal alcohol exposure on Child Behaviour Checklist (CBCL) scores over 14 years, assessed by continuous z‐scores and clinical cutoff points, after adjusting for confounders.Main outcome measure Their children were followed up at ages 2, 5, 8, 10 and 14 years. The CBCL was used to measure child behaviour.Results Light drinking and moderate drinking in the first 3 months of pregnancy were associated with child CBCL z‐scores indicative of positive behaviour over 14 years after adjusting for maternal and sociodemographic characteristics. These changes in z‐score indicated a clinically meaningful reduction in total, internalising and externalising behavioural problems across the 14 years of follow up.Conclusions Our findings do not implicate light–moderate consumption of alcohol in pregnancy as a risk factor in the epidemiology of child behavioural problems.