Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis

OBJECTIVES: We aimed to systematically assess the relationship between folic acid supplementation in pregnancy and risk of preeclampsia and gestational hypertension. METHODS: The relevant studies were included by retrieving the Embase, PubMed and Cochrane library databases. Data extraction was conducted by two investigators independently. The risk ratio (RR) and 95% confidence interval (CI) were used as effect indexes to evaluate the relationship between folic acid supplementation and risk of gestational hypertension or preeclampsia. A subgroup analysis was performed according to the supplementation patterns of folic acid. The homogeneity of the effect size was tested across the studies, and publication biases were examined. RESULTS: In total, 13 cohort studies and 1 randomized controlled trial study was included, containing 160,562 and 149,320 women with and without folic acid supplementation during pregnancy. Pooled results showed that risk of gestational hypertension was not associated with the supplementation of folic acid. However, folic acid supplementation during pregnancy could significantly reduce the risk of preeclampsia. Moreover, the results of subgroup analysis showed that the decreased preeclampsia risk was associated with supplementation of multivitamins containing folic acid rather than folic acid alone. CONCLUSIONS: Our findings indicate that the supplementation of multivitamins containing folic acid during pregnancy could significantly lower preeclampsia risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00404-018-4823-4) contains supplementary material, which is available to authorized users.