Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age neonates: a population study, systematic review and meta-analysis

BJOG. 2015 Mar;122(4):478-90. doi: 10.1111/1471-0528.13202. Epub 2014 Nov 26.


Objectives: To assess the effect of timing of folic acid (FA) supplementation during pregnancy on the risk of the neonate being small for gestational age (SGA).

Design: A population database study and a systematic review with meta-analysis including the results of this population study.

Setting and data sources: A UK regional database was used for the population study and an electronic literature search (from inception until August 2013) for the systematic review.

Participants and included studies: Singleton live births with no known congenital anomalies; 111,736 in population study and 188,796 in systematic review.

Outcome measures, data extraction and analysis: The main outcome was SGA based on customised birthweight centile. Associations are presented as odds ratios (OR) and adjusted odds ratios (aOR), adjusted for maternal and pregnancy-related characteristics.

Results: Of 108,525 pregnancies with information about FA supplementation, 92,133 (84.9%) had taken FA during pregnancy. Time of commencement of supplementation was recorded in 39,416 pregnancies, of which FA was commenced before conception in 10,036, (25.5%) cases. Preconception commencement of FA supplementation was associated with reduced risk of SGA <10th centile (aOR 0.80, 95% CI 0.71-0.90, P < 0.01) and SGA <5th centile (aOR 0.78, 95% CI 0.66-0.91, P < 0.01). This result was reproduced when the data were pooled with other studies in the systematic review, showing a significant reduction in SGA (<5th centile) births with preconception commencement of FA (aOR 0.75, 95% CI 0.61-0.92, P < 0.006). In contrast, postconception folate had no significant effect on SGA rates.

Conclusion: Supplementation with FA significantly reduces the risk of SGA at birth but only if commenced preconceptually independent of other risk factors.

Systematic review registration: This systematic review was prospectively registered with PROSPERO number CRD42013004895.

Keywords: Fetal growth; folic acid; growth restriction; small for gestational age.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Birth Weight
  • Dietary Supplements
  • Female
  • Fetal Development
  • Folic Acid / administration & dosage*
  • Health Knowledge, Attitudes, Practice
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Pregnancy
  • Pregnancy Outcome
  • Prenatal Nutritional Physiological Phenomena*
  • Risk Factors
  • United Kingdom / epidemiology


  • Folic Acid