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      Prenatal Alcohol Exposure and Congenital Heart Defects: A Meta-Analysis

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          Abstract

          Background

          There are still inconsistent conclusions about the association of prenatal alcohol drinking with congenital heart defects (CHDs). We conducted this meta-analysis to investigate the association between prenatal alcohol exposure and the risk of overall CHDs and the CHDs subtypes.

          Methods

          Case-control and cohort studies published before March 2015 were searched through PubMed and Embase. Two authors independently extracted data and scored the study quality according to the Newcastle-0ttawa Scale. The pooled ORs and 95%CI were estimated using the random-effects model and heterogeneity was assessed by the Q test and I 2 statistic.

          Results

          A total of 20 studies were finally included. The results provided no evidence of the association between prenatal alcohol exposure and the risk of overall CHDs (OR = 1.06, 95%CI = 0.93–1.22), ventricular septal defects (VSDs) (OR = 1.04, 95%CI = 0.86–1.25), or atrial septal defects (ASDs) (OR = 1.40, 95%CI = 0.88–2.23). However, prenatal alcohol drinking was marginally significantly associated with conotruncal defects (CTDs) (OR = 1.24, 95%CI = 0.97–1.59) and statistically significantly associated with d-Transposition of the Great Arteries (dTGA) (OR = 1.64, 95%CI = 1.17–2.30). Moreover, both prenatal heavy drinking and binge drinking have a strong association with overall CHDs (heavy drinking: OR = 3.76, 95%CI = 1.00–14.10; binge drinking: OR = 2.49, 95%CI = 1.04–5.97), and prenatal moderate drinking has a modest association with CTDs (OR = 1.35, 95%CI = 1.05–1.75) and dTGA (OR = 1.86, 95%CI = 1.09–3.20).

          Conclusions

          In conclusion, the results suggested that prenatal alcohol exposure was not associated with overall CHDs or some subtypes, whereas marginally significant association was found for CTDs and statistically significant association was found for dTGA. Further prospective studies with large population and better designs are needed to explore the association of prenatal alcohol exposure with CHDs including the subtypes in specific groups.

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          Most cited references33

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          Dose-response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight, preterm birth and small for gestational age (SGA)-a systematic review and meta-analyses.

          Descriptions of the effects of moderate alcohol consumption during pregnancy on adverse pregnancy outcomes have been inconsistent. To review systematically and perform meta-analyses on the effect of maternal alcohol exposure on the risk of low birthweight, preterm birth and small for gestational age (SGA). Using Medical Subject Headings, a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science between 1 January 1980 and 1 August 2009 was performed followed by manual searches. Case-control or cohort studies were assessed for quality (STROBE), 36 available studies were included. Two reviewers independently extracted the information on low birthweight, preterm birth and SGA using a standardised protocol. Meta-analyses on dose-response relationships were performed using linear as well as first-order and second-order fractional polynomial regressions to estimate best fitting curves to the data. Compared with abstainers, the overall dose-response relationships for low birthweight and SGA showed no effect up to 10 g pure alcohol/day (an average of about 1 drink/day) and preterm birth showed no effect up to 18 g pure alcohol/day (an average of 1.5 drinks/day); thereafter, the relationship showed a monotonically increasing risk for increasing maternal alcohol consumption. Moderate consumption during pre-pregnancy was associated with reduced risks for all outcomes. Dose-response relationship indicates that heavy alcohol consumption during pregnancy increases the risks of all three outcomes whereas light to moderate alcohol consumption shows no effect. Preventive measures during antenatal consultations should be initiated. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.
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            Recognition of the fetal alcohol syndrome in early infancy.

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              Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies.

              Classification and analysis of congenital heart defects (CHD) in etiologic studies is particularly challenging because of diversity of cardiac phenotypes and underlying developmental mechanisms. We describe an approach to classification for risk assessment of CHD based on developmental and epidemiologic considerations, and apply it to data from the National Birth Defect Prevention Study (NBDPS). The classification system incorporated the three dimensions of cardiac phenotype, cardiac complexity, and extracardiac anomalies. The system was designed to facilitate the assessment of simple isolated defects and common associations. A team with cardiologic expertise applied the system to a large sample from the NBDPS. Of the 4,703 cases of CHDs in the NBDPS with birth years 1997 through 2002, 63.6% were simple, isolated cases. Specific associations of CHDs represented the majority of the remainder. The mapping strategy generated relatively large samples for most cardiac phenotypes and provided enough detail to isolate important subgroups of CHDs that may differ by etiology or mechanism. Classification of CHDs that considers cardiac and extracardiac phenotypes is practically feasible, and yields manageable groups of well-characterized phenotypes. Although best suited for large studies, this approach to classification and analysis can be a flexible and powerful tool in many types of etiologic studies of heart defects.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 June 2015
                2015
                : 10
                : 6
                : e0130681
                Affiliations
                [1 ]Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
                [2 ]Nutrition and Food Safety Engineering Research Center of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China
                Tabriz University of Medical Sciences, ISLAMIC REPUBLIC OF IRAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JY LZ HY. Performed the experiments: JY HQ PQ RZ. Analyzed the data: JY HQ. Contributed reagents/materials/analysis tools: JY HQ PQ RZ. Wrote the paper: JY LZ HY.

                Article
                PONE-D-15-14179
                10.1371/journal.pone.0130681
                4482023
                26110619
                872e908b-7191-4fac-a460-6e28430f3ba2
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 7 April 2015
                : 2 May 2015
                Page count
                Figures: 5, Tables: 2, Pages: 15
                Funding
                This work was supported by National Natural Science Foundation of China (grant number: 81230016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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