FOLIC ACID SUPPLEMENT USE DECREASES RELATIVE RISK OF FIRST- TIME NTDs BY 60%
This article was originally published in The Tan Sheet
FOLIC ACID SUPPLEMENT USE DECREASES RELATIVE RISK OF FIRST- TIME NTDs BY 60%, according to a study published in the March 10 issue of the Journal of the American Medical Association. Conducted by Martha Werler, Boston University School of Medicine, et al., the study found that, when taking daily multivitamins containing folic acid during the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk of first-occurrence neural tube defects (NTDs) was reduced to .4 from 1 (in the general population). The researchers noted that their study is the first to provide direct evidence that NTD risk can be reduced with daily consumption of .4 mg of folic acid, the dose most commonly contained in OTC multivitamins. The multicenter case control study was undertaken to determine whether "periconceptional folic acid supplementation reduces the risk of occurrent [first] NTDs" and at what dose; whether "dietary folate intake affects the risk; and whether the reduction in risk varies according to the location of the defect." With regard to the second question, Werler, et al. observed that "there was a statistically significant trend of decreasing risk with increasing intake" of dietary folate. Reduced risk also did "not appear to vary according to the site of the defect," the group noted. Werler's conclusions complement previous study findings that consumption of folic acid supplements before and during early pregnancy reduces the risk of recurrent NTDs. However, the researchers pointed out, "less than 10% of NTDs are recurrent," and it was more important to determine whether folic acid decreases the risk of the first occurrence of an NTD. Carried out from 1988 through 1991, the study was part of an ongoing case-control surveillance program of drugs and environmental factors and their relation to risk of major malformations. Study subjects (liveborn and stillborn fetuses and therapeutic abortuses) were enrolled by systematic contact at hospitals in the Boston, Philadelphia and Toronto areas. Mothers were interviewed within six months of delivery about demographic and health behavior factors, reproductive history, family history of birth defects, occupation, and use of alcohol, cigarettes and medications, and asked detailed questions about use of vitamin supplements during the six months before their last menstrual period. The final case group was comprised of 436 subjects (84 with anencephaly, 44 with encephalocele and 308 with spina bifida). A final series of 2,615 controls with other "major malformations" was used. Daily use of folic acid supplements in the periconceptional period was reported by mothers of 8% of cases and mothers of 18% of controls, with crude and multivariate relative risk estimates being .5 and .6, respectively. Relative risk was estimated based on knowledge of the hypothesis: 75 case mothers (17%) and 65 control mothers (3%) reported that folic acid reduces the risk of NTDs. Among these women, multivariate relative risk was .8; relative risk was .4 (60% reduction) for women who did not know the hypothesis. The researchers acknowledged that "recall may have been biased" among women who knew the hypothesis and therefore excluded them from the primary conclusion of the study. Among women using daily supplements, all case mothers and 98% of control mothers obtained their folic acid in a multivitamin. Of 34 case mothers and 220 control mothers who reported less than daily use, 94% and 83%, respectively, took supplements for fewer than four days per week. "No appreciable reductions in risk were observed for less than daily use," the Boston University group concluded. Regardless of the dose of folic acid consumed, all relative risk estimates "were less than 1," Werler, et al. emphasized. "In the absence of a randomized clinical trial," the authors suggested "it is difficult to separate with certainty the respective roles of folic acid, multivitamins and life-style factors in the studies of occurrent NTDs." Nevertheless, the authors concluded, "taken as a whole, the evidence to date strongly suggests that it is the folic acid that confers the protection" against NTDs. Werler, et al. noted that the benefits of daily supplementation with folic acid may be achieved with amounts as low as the .4 mg dose found in most OTC multivitamins, but may only be achieved with "a relatively high dietary intake" of folic acid. In an accompanying JAMA editorial, Godfrey Oakley, MD, Centers for Disease Control and Prevention, agreed that "even though rates of" NTDs in the U.S. "have fallen considerably in the last 50 years, the proportion of [spina bifida and anencephaly] that could be prevented by folic acid supplementation remains substantial." Oakley, who heads CDC's Division of Birth Defects and Developmental Disabilities, gave a presentation on "Primary Prevention of Neural Tube Defects" Implications Regarding Folic Acid Intake" at a March 12 March of Dimes conference in Seattle. In September 1992, the Public Health Service issued a recommendation that all women of childbearing age should consume .4 mg of folic acid to reduce their risk of conceiving a child with NTDs. In carrying out this suggestion, FDA said in its Jan. 6 Nutrition Labeling & Education Act final rule that it would consider fortifying the food supply with folic acid but did not recommend the use of dietary supplements. Organizations, including the Council for Responsible Nutrition, have since urged the agency to adopt an interim policy of allowing health claims for folic acid on certain dietary supplements ("The Tan Sheet" March 1, p. 10).
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