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Currently there are strong recommendations and advisories for adequate intake of the B-vitamin, folic acid, among women of childbearing age to prevent neural tube defects. Government mandated folate fortification of cereal grain products has been in place since 1998. Many current studies continue to evaluate use of nutritional supplements to reduce the risk of birth defects. A recent case-control study carried out by researchers at Harvard and Boston Universities evaluated the effect of periconceptual multivitamin supplementation on risk of specific birth defects.

Methods:

This evaluation was part of a large case-control birth defects study carried out in the Boston area. Births of infants with major malformations detected prior to 5 months (cases) were ascertained in birth and tertiary care hospitals. Cases also included pregnancies terminated due to malformations. There were 8 case groups (with N's ranging from 31 to 186): cleft lip with or without cleft palate, cleft palate only, conotruncal defects, ventricular septal defects, urinary tract defects, limb reduction defects, congenital hydrocephaly, and pyloric stenosis. Control groups were infants totally without birth defects (N=521) and those with birth defects other than those in the case groups (N=442). Mothers were interviewed in their homes regarding factors under study. Daily multivitamin supplementation was evaluated according to gestational timing categories including periconceptual. A multivitamin was defined as a supplement that contained at least 2 water soluble and 2 fat soluble vitamins. 90% of non-prenatal and 100% of prenatal vitamins contained folic acid.

Subjects were divided into groups based on quintile level of the lipid-standardized plasma vitamin E levels. Adjusted Odd's Ratios were computed, (adjusting for age, sex education, BMI, diabetes, smoking, and various cardiovascular parameters), using the lowest quintile as the reference group. After multivariate adjustment, lipid-standardized vitamin E was inversely associated with risk.

Results:

When Cases with limb reduction and urinary tract defects were compared with non-malformation controls, use of multivitamins during the periconceptual period (28 days before through 28 days after last menstruation) was higher among controls. The percent decrease in risk for each of these 2 defects is shown in the figure. Results were similar when cases were compared with malformed controls (defects other than the ones under study - a method of protecting against recall-bias in the interview).

The investigators also found a substantial decreased risk of cleft palate alone (no cleft lip) and of urinary tract defects when multivitamins were initiated in the second lunar month of pregnancy. The authors concluded that periconceptual vitamin supplementation may extend benefits beyond a reduction in neural tube defect risk. In this study, specific nutrient or nutrient combinations of benefit could not be discerned.

Reference

1. Werlar MM, Hayes C, Louik C et al. Multivitamin Supplementation and Risk of Birth Defects. Am J Epidemiol 1999;150:675-682.