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Updated: Jun 8, 2026

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
03:19

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes

Published on: June 28, 2024

Effects and safety of periconceptional folate supplementation for preventing birth defects

Luz Maria De-Regil1, Ana C Fernández-Gaxiola, Therese Dowswell

  • 1Micronutrients Unit, Department of Nutrition for Health and Development, World Health Organization, 20 Avenue Appia, Geneva, Geneva, Switzerland, 1211.

The Cochrane Database of Systematic Reviews
|October 8, 2010
PubMed

Insights

Daily folic acid supplementation effectively prevents neural tube defects (NTDs) in infants. While it significantly reduces NTD recurrence, evidence for preventing other birth defects remains unclear.

Area of Science:

  • Obstetrics and Gynecology
  • Public Health
  • Genetics

Background:

  • Periconceptional folic acid supplementation is known to prevent neural tube defects (NTDs).
  • The impact of various folate doses, forms, and supplementation schedules on other birth defects and maternal/infant outcomes requires further clarification.

Purpose of the Study:

  • To update and expand a previous Cochrane Review on periconceptional folic acid for NTD prevention.
  • To assess if folate supplementation before and during early pregnancy reduces neural tube and other birth defects, including cleft palate, without adverse maternal or infant outcomes.

Main Methods:

  • Searched Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010), international clinical trials registries, and contacted relevant organizations.
  • Included randomized or quasi-randomized trials of periconceptional folate supplementation (alone or with other vitamins/minerals) in women of any age or parity.
  • Assessed trial quality using Cochrane criteria; two authors independently assessed inclusion, with data extraction and accuracy checking.

Main Results:

  • Five trials with 6105 women were included. Daily folic acid significantly reduced NTDs (RR 0.28, 95% CI 0.15 to 0.52) compared to no folic acid.
  • Folic acid showed a significant protective effect against NTD recurrence (RR 0.32, 95% CI 0.17 to 0.60).
  • No statistically significant evidence of effect on cleft palate, cleft lip, cardiovascular defects, or miscarriages; no data on maternal folate or anemia; no short-term side effects observed.

Conclusions:

  • Folic acid supplementation, with or without other vitamins, is effective in preventing neural tube defects.
  • Current evidence does not demonstrate a clear effect of folic acid on preventing other types of birth defects.
Abstract

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