Periconceptional Multivitamin Folic Acid Use, Dietary Folate, Total Folate, and Risk of Neural Tube Defects in South Carolina

Abstract

Studies have established that daily folate supplements in the periconceptional period lower the risk of both first and recurrent neural tube defects (NTDs). There also are indications that dietary folate is effective, butthis is less definite than is the case for supplementation. This population-based case-control study, carried out in 1992 to 1997, enrolled 179 women having NTD-affected pregnancies and 288 randomly chosen control women. They completed a food frequency questionnaire, and also were interviewed in person about their reproductive history, lifestyle, and multivitamin use. The interval of interest extended from 3 months before conception through the first trimester. Nearly 60% of affected pregnancies were terminated electively. A large majority of NTDs were spina bifida or anencephaly. The case and control groups were comparable demographically and behaviorally except that more case women were white and had been exposed to cigarette smoke. Barring inconsistent users, 68.8% of case women and 90.7% of control subjects took multivitamins, including folic acid, on a daily basis. Fewer than 10% of women in either group had low dietary folate intake and also did not use multivitamins. After adjusting for age, race, body mass index, smoke exposure, and the use of multivitamin folic acid, a protective effect was evident only in the highest quartile of dietary folate; the odds ratio (OR) was 0.4. Using 0.4 mg or more of multivitamin folic acid at least 3 times a week did not significantly lower the risk of an NTD (adjusted OR, 0.55). The OR for NTDs in the top quartile of combined dietary folate and daily multivitamin folic acid (total folate) was 0.35 (95% confidence interval, 0.17-0.72). This translates into a 65% reduction in risk. The OR figures for the other quartiles of total folate, although not statistically significant, were in the expected direction. There was a trend toward increasing use of multivitamin folic acid over the 5-year study period. Further studies in large populations are needed to be sure that current food fortification practices and multivitamin supplementation will in fact raise folate levels to the point where most NTDs are prevented without adverse effects.