Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation

N Engl J Med. 1992 Dec 24;327(26):1832-5. doi: 10.1056/NEJM199212243272602.


Background: The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing such during the periconceptional period. The extent to which folic acid supplementation can reduce the first occurrence of defects is not known.

Methods: We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later.

Results: Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetus or infant had a neural-tube defect or congenital malformation) was known in 2104 women who received the vitamin supplement and in 2052 who received the trace-element supplement. Congenital malformations were significantly more prevalent in the group receiving the trace-element supplement than in the vitamin-supplement group (22.9 per 1000 vs. 13.3 per 1000, P = 0.02). There were six cases of neural-tube defects in the group receiving the trace-element supplement, as compared with none in the vitamin-supplement group (P = 0.029). The prevalence of cleft lip with or without cleft palate was not reduced by periconceptional vitamin supplementation.

Conclusions: Periconceptional vitamin use decreases the incidence of a first occurrence of neural-tube defects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Cleft Lip / prevention & control
  • Congenital Abnormalities / prevention & control
  • Female
  • Folic Acid / administration & dosage
  • Humans
  • Neural Tube Defects / prevention & control*
  • Parity
  • Preconception Care
  • Pregnancy
  • Pregnancy Outcome
  • Prenatal Care
  • Trace Elements / administration & dosage
  • Vitamins / administration & dosage*


  • Trace Elements
  • Vitamins
  • Folic Acid