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Association between folic acid and gestational diabetes mellitus; a systematic review and Meta-analysis

Pijush Sarker, Andrew Joabe, Shishir Sarker, Zhang Jiayue, Tan Hongzhuan

Coronary despite beneficial outcomes in preventing neurogenic defects in fetus, folic-acid significant correlation with gestational diabetes mellitus have recently been demonstrated by a number of published studies. Therefore, our aim was to compare women taking low versus high folic-acid supplements before/during pregnancy period in association to the development of Gestational Diabetes Mellitus (GDM) in the second/third trimester, by systematic review of literature and meta-analysis. PubMed, EMBASE and Clinical Trials.gov were systematically searched for observational studies assessing clinical outcome in terms of GDM diagnosis, between women taking high folic-acid supplements doses versus low folic-acid supplements doses before/during pregnancy. High folic-acid supplement dose was defined as >400 ug/day of folic acid supplements for >90 days prior/during conception, while low folic-acid supplement dose was defined as consuming <400 ug/day of folic-acid supplements for <30 days prior/during pregnancy. Main outcome was development of GDM during second/third trimester. The outcome/dependent variable was treated as a dichotomous-nominal variable (i.e. developed/not-developed GDM). Risk ratio was the outcome measures for each comparison group, while Odds Ratio was used as overall-effect measure for two comparison groups. Overall effect was diagrammatically illustrated by forest-plots and funnel-plots utilizing computer software, Review Manager Version 5.3. Fixed-effect model was used when I² was <50% and random-effect model was used if I² was >50%. Thirteen (13) studies reported a total of 42,780 participants, of which, 27,278 had taken adequate folate while 15,502 had taken inadequate folate. Eight (62%), three (23%) and two (15%) included studies showed increased risk, reduced risk and no association, respectively, between comparison groups. The risk of developing GDM was 70% higher in women taking higher/adequate folic acid supplements than those taking lower/inadequate folate doses; OR=1.70, p-value=0.03, at 95%; C.I:1.04-2.78. Therefore, high/adequate folate intake before or during pregnancy positively correlates with increased risk of GDM in the second and third trimester.