High-Dose Folic Acid Supplement Use From Prepregnancy Through Midpregnancy Is Associated With Increased Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study

Periconceptional folic acid (FA) supplementation is widely recommended for substantial benefits on preventing neural tube defects (1), but concerns regarding the potential side effects on both mothers and their infants have been raised recently (2,3). Higher plasma folate was found to be associated with higher risk of gestational diabetes mellitus (GDM) (4). A Chinese cohort had reported association between FA supplement use in early pregnancy and increased GDM risk (5). However, no details on FA doses and durations had been addressed. To further understand the safe dose and duration of FA supplement use regarding GDM risk, for the first time, we evaluated the impact of FA supplement use on GDM with consideration of both doses and durations. Participants came from the Tongji Maternal and Child Health Cohort (TMCHC), a cohort investigating the role of maternal nutritional, environmental, and lifestyle influences on the outcomes of pregnant women and their offspring. Information on social-demographic status, reproductive factors, lifestyle factors, illnesses, and medical records was collected via questionnaire-based interviews at enrollment (<16 weeks of gestation) and follow-up visits. The study was approved by the ethics committee (Tongji Medical College of Huazhong University of Science and Technology, NO-201302). Among 8,649 women in TMCHC, after excluding those with diabetes/glucose intolerance prepregnancy, multiple pregnancies, and abortions and without reliable FA information (unclear doses/durations or varying doses) and/or oral glucose tolerance test (OGTT), 4,353 women were eligible for final analysis. The incidence of GDM was 8.6%. All participants were instructed to report at enrollment whether they used any FA or other supplements prepregnancy and in early pregnancy, and if so, the brand, dose, timing, and frequency …