A Prospective Cohort Study of the Prevalence of Growth, Facial, and Central Nervous System Abnormalities in Children with Heavy Prenatal Alcohol Exposure

Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 07/2012; 36(10):1811-9. DOI: 10.1111/j.1530-0277.2012.01794.x
Source: PubMed


Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited.
This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status.
One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome.
After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure.

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    • "Alcohol (ethanol) is a systemic toxin and a teratogen; gestational exposure to ethanol has been associated with a wide variety of adverse effects on developing embryos and fetuses (Kuehn et al., 2012; Lipinski et al., 2012). The irreversible arrays of developmental anomalies associated with embryonic ethanol exposure are now described as fetal alcohol spectrum disorder (FASD) (Riley and McGee, 2005). "
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    ABSTRACT: We aimed to investigate the impact of the epigenome in inducting fetal alcohol spectrum disorder (FASD) phenotypes in Japanese rice fish embryogenesis. One of the significant events in epigenome is DNA methylation which is catalyzed by DNA methyltransferase (DNMT) enzymes. We analyzed DNMT enzyme mRNA expressions in Japanese rice fish development starting from fertilized eggs to hatching and also in embryos exposed for first 48h of development either to ethanol (300mM) or to 5-azacytidine (5-azaC; 2mM), an inhibitor of DNMT enzyme activity. As observed in FASD phenotypes, 5-azaC exposure was able to induce microcephaly and craniofacial cartilage deformities in Japanese rice fish. Moreover, we have observed that expression of DNMTs (dnmt1, dnmt3aa, and dnmt3bb.1) are developmentally regulated; high mRNA copies were found in early stages (1-2 day-post-fertilization, dpf), followed by gradual reduction until hatched. In ethanol-treated embryos, compared to controls, dnmt1 mRNA is in reduced level in 2 dpf and in enhanced level in 6dpf embryos. While dnmt3aa and 3bb.1 remained unaltered. In contrast, embryos exposed to 5-azaC have an enhanced level of dnmt1 and dnmt3bb.1 mRNAs both in 2 and 6 dpf embryos while dnmt3aa is enhanced only in 6 dpf embryos. Moreover, endocannabinoid receptor 1a (cnr1a) mRNA which was found to be reduced by ethanol remained unaltered and cnr1b and cnr2 mRNAs, which were remained unaltered by ethanol, were increased significantly by 5-azaC in 6 dpf embryos. This study indicates that the craniofacial defects observed in FASD phenotypes are the results of dysregulations in DNMT expressions. Copyright © 2015. Published by Elsevier Inc.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 07/2015; 176-177. DOI:10.1016/j.cbpc.2015.07.002 · 2.30 Impact Factor
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    • "Accurate automated cerebellar segmentation would be valuable in the study of clinical samples, such as fetal alcohol spectrum disorders (FASD). Although not all children with histories of prenatal exposure to alcohol meet the diagnostic criteria for fetal alcohol syndrome (FAS) (Kuehn et al., 2012), many with heavy exposure exhibit functional abnormalities. Children with FASD show difficulties with cognitive processes that may be related to alcohol-induced cerebellar dysfunction , including memory, verbal learning, and executive functions (Mattson et al., 2011, 2013; Vaurio et al., 2011). "
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    ABSTRACT: Objective To validate an automated cerebellar segmentation method based on active shape and appearance modeling and then segment the cerebellum on images acquired from adolescents with histories of prenatal alcohol exposure (PAE) and non-exposed controls (NC). Methods Automated segmentations of the total cerebellum, right and left cerebellar hemispheres, and three vermal lobes (anterior, lobules I-V; superior posterior, lobules VI-VII; inferior posterior, lobules VIII-X) were compared to expert manual labelings on 20 subjects, studied twice, that were not used for model training. The method was also used to segment the cerebellum on 11 PAE and 9 NC adolescents. Results The test-retest intraclass correlation coefficients (ICCs) of the automated method were greater than 0.94 for all cerebellar volume and mid-sagittal vermal area measures, comparable or better than the test-retest ICCs for manual measurement (all ICCs > 0.92). The ICCs computed on all four cerebellar measurements (manual and automated measures on the repeat scans) to compare comparability were above 0.97 for non-vermis parcels, and above 0.89 for vermis parcels. When applied to patients, the automated method detected smaller cerebellar volumes and mid-sagittal areas in the PAE group compared to controls (p < 0.05 for all regions except the superior posterior lobe, consistent with prior studies). Discussion These results demonstrate excellent reliability and validity of automated cerebellar volume and mid-sagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.
    Clinical neuroimaging 01/2014; 4. DOI:10.1016/j.nicl.2014.01.002 · 2.53 Impact Factor
  • JAMA The Journal of the American Medical Association 08/2012; 308(8):753c-753. DOI:10.1001/2012.jama.10699 · 35.29 Impact Factor
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