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folic acid
heart defects
limb defects
neural tube defect
oral clefts

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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 Neural tube defects: 35% lower risk, but college-educated women and Latina mothers had much less benefit than other groups. reference information PDF file English Spanish
bullet Oral clefts: 25%-50% risk reduction, depending on type of cleft. reference information PDF file
bullet Heart defects: 30% risk reduction for conotruncal heart defects. reference information PDF file
bullet 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. reference information PDF file
bullet Multiple birth defects: about a 60% risk reduction. No particular organ system was uniquely affected by multivitamin use. reference information


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 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. reference information reference information reference information
bullet TGF: If their mothers did not take multivitamins, infants with the less common A2 form of the transforming growth factor-alpha (TGF) gene were at 2-8 times higher risk, depending on the type of cleft. reference information


bullet 19% of mothers who had normal infants took multivitamins before conception.
bullet By the end of the second month of pregnancy, 69% were taking multivitamins.
bullet 90% of women taking vitamins reported daily use.
bullet About 10% of women who did not take multivitamins ate vitamin-fortified cereal daily. (A bowl of fortified cereal contains at least 0.1 milligrams of folic acid.)

Most studies of vitamins and birth defects have focused on folic acid. Yet few women take folic acid alone; most get it from multivitamins. We can't say whether the reduced risk is solely due to folic acid, another component of multivitamins or some other health behavior common in vitamin users.

reference information

bullet Diet and nutrition
bullet Vitamin A
bullet More on foic acid
- The folic acid story
- Folic acid resources
bullet Downloadable study summaries
  PDF file Vitamins and Neural
Tube DefectsWho
  PDF file Los Defectos del Tubo
Cerebromedular y Las
Vitaminas-¿ A Quién
  PDF file Multivitamin use and Oral
  PDF file Multivitamin Use and Heart
and Limb Defects


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