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Aubrey Milunsky, MBBCh, DSc, FRCP, DCH; Hershel Jick, MD; Susan S. Jick, MPH; Carol L. Bruell, MS; Dean S. MacLaughlin, PhD; Kenneth J. Rothman, DrPH; Walter Willett, MD

JAMA. 1989;262(20):2847-2852.

Abstract
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 -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.

(JAMA. 1989;262:2847-2852)

Author Affiliations
From the Center for Human Genetics (Dr Milunsky and Ms Bruell) and the Departments of Medicine and Epidemiology (Dr Rothman), Boston (Mass) University School of Medicine; Boston Collaborative Drug Surveillance Program, Boston University Medical Center (Drs Jick and MacLaughlin and Ms Jick); and the Departments of Epidemiology and Nutrition, Harvard School of Public Health, Channing Laboratory, Harvard Medical School, and the Brigham and Women's Hospital, Boston (Dr Willett).

Footnotes
Reprint requests to the Center for Human Genetics, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118-2394 (Dr Milunsky).

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