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.

© 2014 Royal College of Obstetricians and Gynaecologists.