Periconceptional Folic Acid Exposure and Risk of... : JAMA: The Journal of the American Medical Association (original) (raw)

Periconceptional Folic Acid Exposure and Risk of Occurrent Neural Tube Defects.

Martha M. Werler
Samuel Shapiro
Allen A. Mitchell

JAMA: The Journal of the American Medical Association

269

(

)

1257

1261

Mar 10, 1993

Objectives

A recent controlled trial has established that use of a 4-mg folic acid supplement before and during early pregnancy reduces the risk of recurrent neural tube defects (NTDs) by 72%. The present study was designed to determine whether folic acid also reduces the risk of first (occurrent) NTDs.

Design

Case-control study.

Setting

Tertiary and birth hospitals in metropolitan areas of Boston, Mass, Philadelphia, Pa, and Toronto, Ontario.

Participants

Mothers of 436 occurrent cases with NTDs and mothers of 2615 controls with other major malformations.

Main Outcome Measures

The prevalence of use of multivitamins containing folic acid was compared between mothers of cases and controls.

Results

The mothers of 17% of cases and 3% of controls reported knowledge of the folic acid-NTD hypothesis and were excluded from further analysis. For daily use of multivitamins containing folic acid in the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk (RR) (and 95% confidence interval) was 0.4 (0.2 to 0.6). The most commonly used dose of folic acid was 0.4 mg, and the RR estimate was 0.3 (95% confidence interval, 0.1 to 0.6). For dietary folate, there was a dose-related decline in risk according to the quintile of intake (P for trend=.02).

Conclusion

These findings suggest that daily periconceptional intake of 0.4 mg of folic acid (the dose most commonly contained in over-the-counter multivitamin preparations) reduces the risk of occurrent NTDs by approximately 60%. A relatively high dietary intake of folate may also reduce the risk.

(JAMA. 1993;269:1257-1261).