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

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 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.