Folic acid and primary prevention of neural tube defects: A review

Reprod Toxicol. 2018 Sep:80:73-84. doi: 10.1016/j.reprotox.2018.05.004. Epub 2018 May 16.


With 4 mg folic acid daily, it may take 20 weeks to reach red-blood-cell folate levels between 1050 and 1340 nmol/L, optimal for reduction of the neural tube defect risk. Therefore, folic acid supplementation should be started 5-6 months before conception. The residual risk with optimal red-blood-cell folate levels is reportedly 4.5 per 10,000 total births. The residual risk in pooled data from countries with mandatory folic acid fortification is 7.5 per 10,000 pregnancies, regardless of pre-fortification rates. European monitoring of folate intake with questionnaires should be replaced by periodic measurements of red-blood-cell folate. The risk of folate intake >1 mg/day does not outweigh the benefits of folic acid fortification, provided un-metabolized folic acid, RBC folate and vitamin B12 are monitored periodically. A European monitoring system, based on U.S. National Health and Nutrition Examination Surveys, should reside with the European Centre for Disease Prevention and Control.

Keywords: Folate; Folic acid; Fortification; Neural tube defect; Primary prevention; Supplementation.

Publication types

  • Review

MeSH terms

  • Drug Monitoring
  • Erythrocytes / metabolism
  • Europe
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / blood
  • Folic Acid / pharmacology*
  • Humans
  • Neural Tube Defects / blood
  • Neural Tube Defects / prevention & control*
  • Pregnancy
  • Primary Prevention / methods*


  • Folic Acid