92. Does maternal folic acid supplementation reduce the risk of preeclampsia? A systematic review and meta-analysis of observational studies

Abstract

Introduction Preeclampsia contributes significantly to maternal and neonatal morbidity and mortality worldwide. Maternal folic acid supplementation is recommended peri-conceptionally for the prevention of neural tube defects. Research suggests an association between folic acid supplementation during pregnancy and a reduced risk of preeclampsia. Objective A systematic review and meta-analysis was conducted to review the evidence of an association between maternal folic acid supplementation during pregnancy and preeclampsia risk. Methods The protocol for this review was prospectively registered with PROSPERO (CRD42015029310). Multiple scientific databases and unpublished literature were searched for relevant studies. Two reviewers independently reviewed studies against a priori inclusion and exclusion criteria. Study data was extracted and quality of each included study assessed. Meta-analysis was conducted to examine the effect of maternal folic acid supplementation on preeclampsia risk. Sub-group analysis was used to explore any sub-group differences between folic acid taken alone or in/alongside a multivitamin, on preeclampsia risk. Results Meta-analysis of eight cohort studies showed a significantly lower risk of preeclampsia with folic acid supplementation in comparison to no folic acid (Odds Ratio = 0.78 [95% CI = 0.63–0.98]). Heterogeneity between studies was moderately high (I-squared = 67%). No significant subgroup difference was found between folic acid taken alone vs folic acid taken in or with a multivitamin on the risk of preeclampsia (Chi-squared = 0.34 (p = 0.56); I-squared = 0%). Discussion This systematic review and meta-analysis found a modest association between maternal folic acid supplementation and reduction in preeclampsia risk, however the overall level of available evidence for the association is low. Further, well-designed prospective studies investigating this relationship are required. These should clearly define the duration and regularity of supplementation, control for the presence of multivitamins, measure folate biomarkers to validate maternal self-report of supplementation, and differentiate between preeclampsia sub-types in their outcomes.