U-shaped Association Between Folic Acid Supplementation and the Risk of Gestational Diabetes Mellitus in Chinese Women

Objective Our aim in this study was to assess the association between folic acid (FA) supplementation before and during pregnancy and risk of gestational diabetes mellitus (GDM) in Chinese women. Methods This case–control study was conducted at 2 hospitals in central China. A total of 1,300 pregnant women, including 396 GDM patients and 904 controls, participated in the study. Information on the dose and duration of FA supplementation was collected using a self-report questionnaire at enrolment (24 to 28 weeks of gestation). Results We observed a U-shaped association between FA supplementation and GDM risk that demonstrated a 228% increased risk of GDM among women who never took FA supplements, a 28% increased risk among women who took supplements containing <400 μg/day FA or took FA supplements for <1 month and a 188% increased risk among women who took supplements containing ≥800 μg/day FA for an adequate duration (>1 month before pregnancy and >3 months during pregnancy) compared with women who took supplements containing 400 to 799 μg/day FA for an adequate duration (all p<0.05). For women who took supplements containing ≥800 μg/day FA for an adequate duration, the association between FA supplementation and GDM risk appeared to be stronger among those women with a prepregnancy body mass index (BMI) of ≥25 kg/m2 than among those with a prepregnancy BMI of <25 kg/m2 (p=0.006 for interaction). Conclusions There was a U-shaped association of FA supplementation with GDM risk; that is, FA supplementation both below and above the recommended levels may increase the risk of GDM.