How does research prevent birth defects? The story of a recent protective factor—folic acid—illustrates the transition from scientific discovery to clinical care and public health policy.

DEMOGRAPHICS GIVE FIRST CLUES

The story opened with the observation that neural tube defectsserious brain and spine abnormalitiesoccurred more commonly in low-income families. Suspecting nutritional factors might be responsiblein particular, lack of fresh vegetables that supply the B vitamin folic acidBritish researchers gave vitamins with folic acid to pregnant women who had prior babies with these conditions. There was an 87% reduction in recurrences.

PUZZLING RESULTS CLARIFIED

Scientists then turned their attention to first-time occurrences of neural tube defects. Interview studies from 1988-1993 showed convincing results: about a 50% risk reduction in North American women who took multivitamins with folic acid near the time they conceived. However, a study of California and Illinois women showed no benefit.

In 1995, a definitive California Birth Defects Monitoring Program study helped clarify these findings. While vitamin supplementation did lower risk in some women, there was less benefit in other groupsnamely, well educated White women and Latina mothers. Because these women make up much of California's population, folic acid's effect was blurred.

BENEFIT SEEN IN OTHER CONDITIONS

Our studies looked beyond neural tube defects, discovering that folic acidcontaining multivitamins lowered risk for oral clefts, limb defects and heart defects as well. These findings have since been confirmed in studies of other populations.

CLINICAL RECOMMENDATIONS ADOPTED

In 1992, strong cumulative evidence prompted the US Public Health Service to recommend that all women take 0.4 milligrams of folic acid daily. Healthcare providers echoed this message in clinical practice.

Despite widespread public education campaigns, however, surveys found many women still didn't get enough folic acid. Dietary sources alone are often inadequate. And about half of pregnancies are unplanned, so many women wouldn't have taken supplements around the time of conception, a critical period for fetal development.

PUBLIC POLICY INFLUENCED

With strong backing from the March of Dimes Foundation and the Centers for Disease Control, in 1998 the federal government mandated fortification of flour and other foods to bolster folic acid intake among all women of childbearing age.

Growing knowledge about folic acid and its role in lowering neural tube defects is likely to be one reason they have declined in the US over the last decade.