Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: A report from the National Down Syndrome Project

Abstract

BACKGROUND 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. METHODS As part of the population-based case-control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of folic acid-containing supplements. These data were used to determine whether 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/ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (OR=1.69; 95% 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/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). CONCLUSIONS Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome.

Is maternal smoking during pregnancy associated with an increased risk of congenital heart defects among offspring? A systematic review and meta-analysis of observational studies

“…multiple imputation, regression imputation, or last observation carry forward). Two studies restricted the study population to children with Down's syndrome [29,31], which compromised generalizability. Moreover, these researches were conducted within a wide time span, and socioeconomic heterogeneity across the eras could hardly be handled by statistical models.…”

Maternal Alcohol Consumption before and during Pregnancy and the Risks of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis

“…All of the studies were published between 1991 and 2013. There were 19 casecontrol studies [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and four cohort studies. [35][36][37][38] The main characteristics of the included studies are presented in Table 1.…”

Folate supplementation during the preconception period, pregnancy and puerperium. Polish Society of Gynecologists and Obstetricians Guidelines

“…An increased demand for folate, which is not synthesized in the human body, during pregnancy can be met only partially by the supply of foods rich in folate -about 150-250 µg [1]. Folate deficiency is associated with a higher risk of neural tube defects in the fetus, as well as cleft lip and palate and Down syndrome [2]. Disorders of folate metabolism can lead to hyperhomocysteinaemia and more frequent complications of pregnancy, such as recurrent miscarriage, intrauterine growth restriction (IUGR) and preeclampsia [3,4].…”