During pregnancy, fetal growth causes an increase in the total number of rapidly dividing
cells, which leads to increased requirements for folate. Inadequate folate intake
leads to a decrease in serum folate concentration, resulting in a decrease in erythrocyte
folate concentration, a rise in homocysteine concentration, and megaloblastic changes
in the bone marrow and other tissues with rapidly dividing cells
To assess the effectiveness of oral folic acid supplementation alone or with other
micronutrients versus no folic acid (placebo or same micronutrients but no folic acid)
during pregnancy on haematological and biochemical parameters during pregnancy and
on pregnancy outcomes.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December
2012) and we contacted major organisations working in micronutrient supplementation,
including UNICEF Nutrition Section, World Health Organization (WHO) Maternal and Reproductive
Health, WHO Nutrition Division, and National Center on Birth defects and Developmnetal
Disabilities, US Centers for Disease Control and Prevention (CDC).
All randomised, cluster-randomised and cross-over controlled trials evaluating supplementation
of folic acid alone or with other micronutrients versus no folic acid (placebo or
same micronutrients but no folic acid) in pregnancy.
Two review authors independently assessed trials for inclusion, assessed risk of bias
and extracted data. Data were checked for accuracy.
Thirty-one trials involving 17,771 women are included in this review. This review
found that folic acid supplementation has no impact on pregnancy outcomes such as
preterm birth (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.38; three
studies, 2959 participants), and stillbirths/neonatal deaths (RR 1.33, 95% CI 0.96
to 1.85; three studies, 3110 participants). However, improvements were seen in the
mean birthweight (mean difference (MD) 135.75, 95% CI 47.85 to 223.68). On the other
hand, the review found no impact on improving pre-delivery anaemia (average RR 0.62,
95% CI 0.35 to 1.10; eight studies, 4149 participants; random-effects), mean pre-delivery
haemoglobin level (MD -0.03, 95% CI -0.25 to 0.19; 12 studies, 1806 participants),
mean pre-delivery serum folate levels (standardised mean difference (SMD) 2.03, 95%
CI 0.80 to 3.27; eight studies, 1250 participants; random-effects), and mean pre-delivery
red cell folate levels (SMD 1.59, 95% CI -0.07 to 3.26; four studies, 427 participants;
random-effects). However, a significant reduction was seen in the incidence of megaloblastic
anaemia (RR 0.21, 95% CI 0.11 to 0.38, four studies, 3839 participants).
We found no conclusive evidence of benefit of folic acid supplementation during pregnancy
on pregnancy outcomes.