Prepregnancy Habitual Intakes of Total, Supplemental, and Food Folate and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study

Abstract

To identify novel modifiable risk factors of gestational diabetes mellitus (GDM) by examining the association between prepregnancy habitual folate intake and GDM risk. RESEARCH DESIGN AND METHODS The study included 14,553 women in the Nurses' Health Study II who reported at least one singleton pregnancy between the 1991 and 2001 questionnaires. Prepregnancy intakes of total folate, supplemental folate, and food folate were assessed using a food frequency questionnaire administered every 4 years. Incident GDM was ascertained from a self-reported physician diagnosis. Relative risks (RRs) of GDM were estimated using log-binomial models, with adjustment for demographic, lifestyle, and dietary factors. RESULTS Over the study follow-up, 824 incident GDM cases were reported among 20,199 pregnancies. Women with adequate total folate intake (‡400 mg/day) had an RR of GDM of 0.83 (95% CI 0.72, 0,95, P = 0.007) compared with women with inadequate intake (<400 mg/day). This association was entirely driven by supplemental folate intake. The RRs of GDM for 1-399, 400-599, and ‡600 mg/day of supplemental folate intake were 0.83, 0.77, and 0.70, respectively, compared with no supplemental folate intake (P trend = 0.002). The association between supplemental folate intake and GDM risk largely persisted after additional adjustment for intake of multivitamins and other micronutrients, as well as among women who likely planned for the pregnancy. CONCLUSIONS Higher habitual intakes of supplemental folate before pregnancy were significantly associated with lower GDM risk. If confirmed, these findings indicate that prepregnancy folic acid supplementation could offer a novel and low-cost avenue to reduce GDM risk.

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

“…Folate is one of the key nutrients for pregnant women for its protective effect in preventing birth defects. Two large studies have assessed the association of periconceptional FAS with subsequent GDM risk ( 11 , 12 ) but with inconsistent findings. While preconception FAS was associated with reduced GDM risk in the Nurses’ Study ( 11 ), opposite findings were found for FAS during early pregnancy in the China-Anhui Birth Cohort ( 12 ).…”

“…Two large studies have assessed the association of periconceptional FAS with subsequent GDM risk ( 11 , 12 ) but with inconsistent findings. While preconception FAS was associated with reduced GDM risk in the Nurses’ Study ( 11 ), opposite findings were found for FAS during early pregnancy in the China-Anhui Birth Cohort ( 12 ). However, due to variations in individual folate metabolism, periconceptional folate status evaluated by FAS via questionnaire cannot directly reflect the folate levels in the body.…”

“…Nevertheless, the relationship between folate and GDM risk with inconsistent findings has emerged as a field of interest. The Nurses’ Health Study II including 14,533 women has observed that FAS before pregnancy is associated with a lower risk of GDM ( 11 ); in contrast, another cohort study gave opposite conclusions that daily folic acid intake in early pregnancy increased the risk of GDM ( 12 ), reminding us that the association of folate with GDM is still equivocal.…”

Gestational Diabetes Mellitus and Folic Acid Supplementation in Pregnant Women: A Systematic Review

“…7 were cohort [13] [23], one had a case-control design [24] and only one was an interventional randomized controlled trial (RCT) [23]. 8 studies were conducted in China [13] [17] [19]- [24], and only one in USA [25]. All studies were published and written in English.…”

Adequate maternal pre-conceptional folate status may reduce the risk of gestational diabetes mellitus

“…Rates of GDM are rising worldwide and associated with adverse perinatal outcomes and long-term cardiometabolic risk in mothers and their offspring 1. This large prospective cohort study investigates the association between pre-pregnancy habitual folate intake and the risk GDM 2…”