Periconceptional folic acid exposure and risk of occurrent neural tube defects.
OBJECTIVE
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.


METHODS
Case-control study.


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


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


METHODS
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 a 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).


CONCLUSIONS
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.
Werler
M M
MM
Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA 02146.
Shapiro
S
S
Mitchell
A A
AA
D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D007231:Infant, Newborn; D009436:Neural Tube Defects / Q000453:epidemiology / Q000517:prevention & control*; D016742:Preconception Care; D011247:Pregnancy; D011256:Pregnancy Outcome; D011295:Prenatal Care; D012307:Risk Factors; D014815:Vitamins
D014815:Vitamins; D005492:Folic Acid