Can folic acid protect against congenital heart defects in Down syndrome?
BACKGROUND
Several studies have suggested a protective effect of folic acid (FA) on congenital heart anomalies. Down syndrome (DS) infants are known to have a high frequency of heart anomalies. Not all children with DS suffer from heart anomalies, which raises the question whether maternal factors might affect the risk of these anomalies. Our objectives were to investigate whether first-trimester FA use protects against heart anomalies among DS children.


METHODS
Women with liveborn DS children participating in the Slone Epidemiology Center Birth Defects Study between 1976 and 1997 were included. We performed case-control analyses using DS, with heart anomalies as cases and DS, without heart anomalies as controls. Subanalyses were performed for defects that have been associated with FA in non-DS populations (conotruncal, ventricular septal [VSD]) and for those that are associated with DS (ostium secundum type atrial septal defects [ASD] and endocardial cushion defects [ECD]). Exposure was defined as the use of any FA-containing product for an average of at least 4 days per week during the first 12 weeks of pregnancy, whereas no exposure was defined as no use of FA in these 12 weeks.


RESULTS
Of the 223 cases, 110 (49%) were exposed versus 84 (46%) of the 184 controls. After adjustment for possible confounders, no protective effect of FA was found on heart anomalies overall (OR 0.95, 95% CI: 0.61-1.47) nor separately for conotruncal defects, VSDs, ASDs, or ECDs.


CONCLUSIONS
Our study does not show a protective effect of FA on heart anomalies among infants with DS.
Meijer
Willemijn M
WM
Slone Epidemiology Center, Boston University, Boston, Massachusetts 02215-1201, USA.
Werler
Martha M
MM
Louik
Carol
C
Hernandez-Diaz
Sonia
S
de Jong-van den Berg
Lolkje T W
LT
Mitchell
Allen A
AA
D019587:Dietary Supplements; D004314:Down Syndrome / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D005492:Folic Acid; D005527:Food, Fortified; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012189:Retrospective Studies
D005492:Folic Acid