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Evidence summaries

Folic Acid Supplementation during Pregnancy for Pregnancy Outcomes other Than Neural Tube Defects

Higher maternal folate levels and folic acid supplementation during pregnancy may decrease the risk of preterm birth. Level of evidence: "C"

Summary

A Cochrane review [Abstract] 1 included 31 studies with a total of 17771 subjects. Inclusion criteria were 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.

Folic acid supplementation had no impact on pregnancy outcomes such as preterm birth (RR 1.01, 95% 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). Improvements were seen in the mean birthweight (MD 135.75, 95% CI 47.85 to 223.68). No impact on improving pre-delivery anaemia was found (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 (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). 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).

A meta-analysis 2 including 562 068 participants assessed folic acid and risk of preterm birth. 10 (6 prospective cohort studies and 4 case-control studies) were included on folate concentrations, 13 cohort studies were included about folic acid supplementation, and 4 cohort studies were included regarding dietary folate intake. Higher maternal folate levels were associated with a 28% reduction in the risk of preterm birth (OR 0.72, 95% CI 0.56 to 0.93; 10 trials). Higher folic acid supplementation (400 μg vs over 1000 μg daily) was associated with 10% lower risk of preterm birth (OR 0.90, 95% CI 0.85 to 0.95; 20 trials). In addition, a significant negative association was observed between dietary folate intake and the risk of preterm birth (OR 0.68, 95% CI 0.55 to 0.84). To initiate taking folic acid supplementation early before conception was adversely associated with preterm birth risk (OR 0.89, 95% CI 0.83 to 0.95).

Clinical comments

Date of latest search:2020-01-20

    References

    • Lassi ZS, Salam RA, Haider BA et al. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev 2013;3():CD006896. [PubMed]
    • Li B, Zhang X, Peng X et al. Folic Acid and Risk of Preterm Birth: A Meta-Analysis. Front Neurosci 2019;(13):1284.[PubMed]

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