Periconceptional folate and gestational diabetes mellitus: a systematic review and meta-analysis of cohort studies

Objective To examine the relationship between periconceptional folate exposure and risk of gestational diabetes mellitus (GDM). Methods Several electronic databases, including PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Cochrane Library, were searched for all relevant cohort studies by January 2021. Studies on relationship between folate exposure (intake or status) and GDM risk were included. Quality of included studies was assessed using Newcastle-Ottawa Scale. Random effects meta-analysis was performed to estimate overall odds ratio (OR) and 95% confidence intervals (CIs) by Stata software (Stata Corp., College Station, TX). Results Ten cohort studies with 40,244 pregnancies were eligible for quantitative meta-analysis. Significant association was observed between folate exposure and risk of GDM (OR = 1.24, p=.036, 95% CI: 1.01-1.52). Subgroup analysis revealed that periconceptional folate exposure of population in China (OR = 1.35, 95% CI: 1.09-1.67) but not in western countries, folate exposure during pregnancy (OR = 1.49, 95% CI: 1.22-1.81) but not before pregnancy, and internal folate exposure (OR = 1.36, 95% CI: 1.10-1.67), were significantly associated with increased GDM risk. Conclusions Overall, periconceptional folate exposure is positively associated with GDM risk, especially the exposure during pregnancy and exposure in Chinese populations.