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      Prevention of Neural-Tube Defects with Folic Acid in China

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          Abstract

          Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

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          Most cited references 11

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          Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects.

          We examined the relation of multivitamin intake in general, and folic acid in particular, to the risk of neural tube defects in a cohort of 23,491 women undergoing maternal serum alpha-fetoprotein screening or amniocentesis around 16 weeks of gestation. Complete questionnaires and subsequent pregnancy outcome information was obtained in 22,776 pregnancies, 49 of which ended in a neural tube defect. The prevalence of neural tube defect was 3.5 per 1000 among women who never used multivitamins before or after conception or who used multivitamins before conception only. The prevalence of neural tube defects for women who used folic acid-containing multivitamins during the first 6 weeks of pregnancy was substantially lower--0.9 per 1000 (prevalence ratio, 0.27; 95% confidence interval, 0.12 to 0.59 compared with never users). For women who used multivitamins without folic acid during the first 6 weeks of pregnancy and women who used multivitamins containing folic acid beginning after 7 or more weeks of pregnancy, the prevalences were similar to that of the nonusers and the prevalence ratios were close to 1.0.
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            Periconceptional folic acid exposure and risk of occurrent neural tube defects.

            A recent controlled trial has established that use of a 4-mg folic acid supplement before and during early pregnancy reduces the risk of recurrent neural tube defects (NTDs) by 72%. The present study was designed to determine whether folic acid also reduces the risk of first (occurrent) NTDs. Case-control study. Tertiary and birth hospitals in metropolitan areas of Boston, Mass, Philadelphia, Pa, and Toronto, Ontario. Mothers of 436 occurrent cases with NTDs and mothers of 2615 controls with other major malformations. The prevalence of use of multivitamins containing folic acid was compared between mothers of cases and controls. The mothers of 17% of cases and 3% of controls reported knowledge of the folic acid-NTD hypothesis and were excluded from further analysis. For daily use of a multivitamins containing folic acid in the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk (RR) (and 95% confidence interval) was 0.4 (0.2 to 0.6). The most commonly used dose of folic acid was 0.4 mg, and the RR estimate was 0.3 (95% confidence interval, 0.1 to 0.6). For dietary folate, there was a dose-related decline in risk according to the quintile of intake (P for trend = .02). These findings suggest that daily periconceptional intake of 0.4 mg of folic acid (the dose most commonly contained in over-the-counter multivitamin preparations) reduces the risk of occurrent NTDs by approximately 60%. A relatively high dietary intake of folate may also reduce the risk.
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              Periconceptional use of multivitamins and the occurrence of neural tube defects.

              We studied the association between multivitamin use during the periconceptional period and the occurrence of neural tube defects using data from the Atlanta Birth Defects Case-Control Study. There were 347 babies with neural tube defects who were live born or stillborn to residents of metropolitan Atlanta from 1968 through 1980. The 2829 control-babies born without birth defects were randomly selected through birth certificates. Periconceptional multivitamin use was defined as reported use for each of the three months before conception through the first three months of pregnancy. Mothers who reported not using multivitamins any time during the six-month period were defined as nonusers. Fourteen percent of mothers reported periconceptional multivitamin use and 40% reported nonuse. Multivitamin users were different from nonusers in a number of demographic, health-related, and life-style characteristics. We found an overall apparent protective effect of periconceptional multivitamin use on the occurrence of neural tube defects, with a crude estimated relative risk of 0.40 (95% confidence interval, 0.25 to 0.63). At this time, it is not possible to determine whether this apparently lower risk is the direct result of multivitamin use or the result of other characteristics of women who use multivitamins.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                November 11 1999
                November 11 1999
                : 341
                : 20
                : 1485-1490
                Article
                10.1056/NEJM199911113412001
                10559448
                © 1999

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