Lack of Maternal Folic Acid Supplementation Is Associated with Heart Defects in Down Syndrome: A Report from the National Down Syndrome Project

Department of Human Genetics, Emory University, Atlanta, Georgia, USA.
Birth Defects Research Part A Clinical and Molecular Teratology (Impact Factor: 2.09). 10/2011; 91(10):885-93. DOI: 10.1002/bdra.22848
Source: PubMed


Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism.
As part of the population-based case-control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception.
Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08-2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11-2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85-1.87; p = 0.124).
Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.

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    • "Thus, the dysregulation of pathways involved in heart development may cause the cardiac defects observed in DS. A second hypothesis implicating both environmental and genetic factors in DS phenotypes is supported by epidemiological studies of DS: specific cardiac defects were associated with smoking mothers (AVSD, TOF) [17], [18], folate pathways and folate supplementation have been proposed to interfere with the incidence of AVSD [19], [20], and an association between DS and CHD with global hypomethylation status has been found in a Dutch population-based case-control study [21]. "
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