Discoveries and Data: Exposures and Risk Factors


Following the first reports that taking folic acid reduced risk for neural tube defects, the California Birth Defects Monitoring Program pioneered research looking at folic acid use in a variety of birth defects.

Folic acid is a B vitamin used by cells as they grow and divide. The naturally occurring form, folate, is found in spinach and leafy green vegetables, dried beans, liver and citrus fruits. Folic acid is also found in fortified foods such as breakfast cereal. It is estimated that diet supplies the average woman only about 0.2 milligrams of folate daily (about half the recommended amount).

Because dietary sources are often inadequate, research concentrates on women’s use of multivitamin supplements containing folic acid. Our studies look at vitamin use around the time of conception and in early pregnancy—the critical period for fetal development.


Our studies showed reduced risk for many types of birth defects in mothers taking multivitamins containing folic acid around the time of conception. Among women who did not take multivitamins, those consuming fortified cereal daily also had lower risk.

bullet-1862808 Neural tube defects: 35% lower risk, but college-educated women and Latina mothers had much less benefit than other groups. ref_book-6045713 pdf_logo-6595714 English Spanish
bullet-1862808 Oral clefts: 25%-50% risk reduction, depending on type of cleft. ref_book-6045713 pdf_logo-6595714
bullet-1862808 Heart defects: 30% risk reduction for conotruncal heart defects. ref_book-6045713 pdf_logo-6595714
bullet-1862808 Limb defects: 36% lower risk for reduction-type defects, particularly longitudinal defects (those affecting a lengthwise segment of the arm/leg). There was no effect for transverse (amputation-type) defects. ref_book-6045713 pdf_logo-6595714
bullet-1862808 Multiple birth defects: about a 60% risk reduction. No particular organ system was uniquely affected by multivitamin use. ref_book-6045713


Taking vitamins does not eliminate the risk for birth defects-why do some pregnancies benefit while others do not? The search to understand how supplementation alters risk has focused on a number of genes that influence the developing baby’s folic acid metabolism. Variant forms of these genes can lower folic acid levels, particularly if the mother does not take multivitamins containing folic acid. We determined which babies inherited double doses of variant genes and whose mothers did not use multivitamins, and found:

bullet-1862808 MTHFR: About 1 in 6 babies has the genetic type “TT” of methylenetetrahydrofolate reductase (MTHFR); this variant is more common in Latino infants. Babies with type “TT” had a modest increase in neural tube defect risk. Their risk for oral clefts was not affected. ref_book-6045713 ref_book-6045713 ref_book-6045713
bullet-1862808 TGFalpha-6392151: If their mothers did not take multivitamins, infants with the less common A2 form of the transforming growth factor-alpha (TGFalpha-6392151) gene were at 2-8 times higher risk, depending on the type of cleft. ref_book-6045713