The Associations between the Duration of Folic Acid Supplementation, Gestational Diabetes Mellitus, and Adverse Birth Outcomes based on a Birth Cohort

Abstract

This study aimed to examine the associations between the duration of folic acid (FA) supplementation, gestational diabetes mellitus (GDM), and adverse birth outcomes. A total of 950 mother-offspring pairs participated in the cohort study during 2015 in Changsha, China. The data were collected through home visits and perfected by maternal and child healthcare handbooks. Generalized linear models and stratified analyses were used for statistical analyses. The incidence of GDM in our cohort was 10.2%. FA supplementation for ≥3 months before pregnancy was associated with an increased risk of GDM (adjusted relative risk (aRR): 1.72; 95% CI: 1.17–2.53) and decreased risk of small-for-gestational-age (SGA) birth (aRR: 0.40; 95% CI: 0.18–0.88). In the group of FA supplementation for ≥3 months during pregnancy, GDM was associated with an increased risk of cesarean delivery (aRR: 1.36; 95% CI: 1.06–1.75) and macrosomia (aRR: 2.11; 95% CI: 1.06, 4.20), but the aRRs were lower than the RRMH 1.53 (95% CI: 1.01–2.34) and 2.43 (95% CI: 1.27–4.66). Our study suggested that the longer duration of FA supplementation before pregnancy might increase the risk of GDM, but decrease the risk of SGA birth. Longer duration of FA supplementation during pregnancy had beneficial effects on birth outcomes in women with GDM. Further studies should consider a larger sample size to confirm these findings.

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.…”

“…Folic acid interferes with metabolism, as some studies found that alterations in the ratio between folate and vitamin B 12 can lead to fetal insulin resistance and increased risk of obesity [12]. Interestingly, several studies suggested that increased supplementation of folic acid imposed a higher risk of developing GDM [13]- [20]. However, no systematic review was ever published regarding folate use during pregnancy.…”

“…Supplementation Some studies targeted the duration and the doses of FA supplementation. Cheng et al proved that pre-pregnancy FA supplementation for a duration of 3 months or longer was associated with an increased risk of GDM (adjusted relative risk (aRR): 1.72; 95% CI: 1.17 -2.53) [13]. Another study showed an increase risk of GDM with both higher doses and longer duration.…”

“…The novel cohort study suggesting that a daily FA dose of 800 mg increased the risk of GDM can push towards a revision of the recommendations of daily doses higher than 400 mg [17]. Two studies discussing the duration of use of FA [13] [14] also proved the need for folic acid supplementation as it not only can decrease the risk of neural tube defects, but also can decrease the risk of GDM compared to no use; however, this vitamin should not be taken for more than 3 months prior to conception [13] and for a duration less than 90 days post-conception [14]. It is important to note that diet alone was not sufficient in providing the needed levels of micronutrients for pregnant women, including folate which was scarcely taken from food, as shown by Kozlowska A.…”

Nutrition in Reproductive Health: Nutritional Conditioning Factors during Pregnancy and Its Impact on Health

“…This advice must be adapted to the real needs of each woman [65,76,77]. However, folic acid supplementation by all pregnant women from the preconception stage for preventing neural tube defects does have support, although it has also been associated with adverse effects during pregnancy [78,79].…”