Intended for healthcare professionals

Practice Uncertainties

Who should consume high-dose folic acid supplements before and during early pregnancy for the prevention of neural tube defects?

BMJ 2022; 377 doi: (Published 07 June 2022) Cite this as: BMJ 2022;377:e067728
  1. Erin Rose Dwyer, research scientist1,
  2. Kristian B Filion, associate professor2,
  3. Amanda J MacFarlane, research scientist and adjunct professor3,
  4. Robert W Platt, professor3,
  5. Azar Mehrabadi, assistant professor4
  1. 1Departments of Obstetrics and Gynecology and Urology, University of Washington, Seattle, Washington, USA
  2. 2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  3. 3Nutrition Research Division, Health Canada, Ottawa, Ontario, Canada
  4. 4Departments of Obstetrics & Gynaecology and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
  1. Correspondence to: A Mehrabadi azar.mehrabadi{at}

What you need to know

  • Guidelines recommend 0.4 mg of folic acid per day in the periconceptional period, and certain guidelines recommend high doses (4-5 mg/day) in women at higher risk for neural tube defects such as those with diabetes, body mass index ≥30, or taking antiepileptic medications or other folate antagonists

  • For those who had a previous pregnancy affected by neural tube defect, high quality evidence from a large randomised clinical trial supports using 4 mg per day of folic acid

  • We lack evidence to suggest that high doses have additional benefit in preventing neural tube defects in women with other risk factors

  • Discuss with your patient their preference considering risk factors and the lack of evidence on benefits or harms of high dose folic acid to choose an appropriate dose

Neural tube defects are fatal or disabling birth defects resulting from failure of the neural tube to close approximately 21-28 days after conception.1 Neural tube defects, which include spina bifida, anencephaly and encephalocele, are common congenital anomalies estimated to affect 18.6 per 10 000 live births worldwide; 50% of cases result in elective terminations or stillbirths.2 Folic acid supplementation and fortification of foods are established interventions for the prevention of neural tube defects.1

Guidelines in many countries recommend 0.4 mg (400 µg) of folic acid per day (standard dose) for all individuals of childbearing age capable of becoming pregnant, with supplementation started 2-3 months before the intended pregnancy until the 12th week of pregnancy.3456 High doses (4-5 mg per day of folic acid) are commonly recommended for those with certain underlying risk factors for neural tube defects.

Uncertainty as to which high risk groups benefit from high dose folic acid use has led to variations in guidelines internationally. Most guidelines include women who had a previous pregnancy affected by a neural tube defect …

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