Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus

Abstract

Highlights• Higher folate and lower vitamin B 12 levels were associated with higher glucose and a higher risk of gestational diabetes mellitus (GDM). • The association between folate and vitamin B 12 imbalance and GDM risk can be further modified by maternal risk factors. Abstract Background: This study examined whether folate and vitamin B 12 imbalance is associated with gestational diabetes mellitus (GDM) and explored interactions between B vitamin imbalance and maternal risk factors for GDM. Methods: A cross-sectional study was performed in 406 Chinese pregnant women. Serum folate, vitamin B 12 , and blood glucose concentrations were measured at 24 to 28 weeks gestation during GDM screening. A diagnosis of GDM was made based on International Association of Diabetes and Pregnancy Study Groups criteria (fasting plasma glucose [FPG] ≥5.1 mM, 1-hour plasma glucose ≥10.0 mM, or 2-hour plasma glucose ≥8.5 mM). Binary logistic regression was used to obtain odds ratios (ORs) after controlling for different confounders. Results: Higher folate levels were associated with higher glucose concentrations and a higher risk of GDM (OR 1.98; 95% confidence interval [CI] 1.00-3.90), whereas higher vitamin B 12 levels were associated with lower FPG and a lower risk of GDM (OR 0.30; 95% CI 0.15-0.60). A higher folate: vitamin B 12 ratio was associated with higher glucose and a higher risk of GDM (OR 3.08; 95% CI 1.63-5.83). The presence of both a higher folate: vitamin B 12 ratio and advanced age further increased the OR to 2.13 (95% CI 1.09-4.15) with a significant additive interaction. Furthermore, a higher folate: vitamin B 12 ratio and a higher prepregnancy body mass index (pp-BMI) were synergistically associated with an increased risk of GDM (OR 3.03; 95% CI 1.40-6.57). Conclusions: An imbalance between folate and vitamin B 12 , represented by a higher folate: vitamin B 12 ratio, was highly associated with GDM risk, and this association could be further modified by maternal age and pp-BMI. K E Y W O R D S folate, gestational diabetes mellitus, pregnancy, synergistic effect, vitamin B 12

Association between maternal folate status and gestational diabetes mellitus

“…In the end, 17 studies met the selection criteria, 5 of which (Cheng et al., 2019; Huang et al., 2019; Li, Li, et al., 2019; Zhu et al., 2016) used FA supplement or intake instead of folate level as the standard of maternal folate status (Table S1). Therefore, we only included the remaining 12 studies (Barzilay et al., 2018; Berglund et al., 2016; Guven & Cetinkaya, 2005; Idzior‐Waluś et al., 2008; Krishnaveni et al., 2009; Lai et al., 2018; Li, Hou, et al., 2019; Liu et al., 2020; Seghieri et al., 2003; Sukumar et al., 2016; Tarim et al., 2004; Xie et al., 2019) for qualitative and quantitative (meta‐analysis) synthesis.…”

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

“…Percentile ratios were categorized into tertiles for the association analyses with the GDM risk. According to previous studies (19), the folate/ vitamin B 12 ratio was also calculated based on their raw data. Moreover, the restricted cubic spline (RCS) regression model with assumed three knots was used to outline the potential nonlinear relations among continuous RBC folate, vitamin B 12 , and GDM risk.…”

“…Increasing concerns have risen about supplementing high doses of folic acid to women of reproductive age with low vitamin B 12 intake, although this issue has not been well investigated yet (5). Several casecontrol studies demonstrated that higher serum folate/vitamin B 12 ratio was positively associated with GDM risk (18,19). However, to our knowledge, no studies have investigated the relationship between maternal vitamin B 12 in early pregnancy and GDM.…”

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

“…Second, we did not measure the serum concentration of FA before pregnancy or early in pregnancy. Higher FA level in serum was associated with a higher risk of GDM and lower risks of adverse birth outcomes [25,52]. Third, the total FA intake is unknown because we did not consider the FA intake from diet.…”

“…The potential confounders included maternal age, education, average monthly household income, postpartum BMI, parity, passive smoking, family history of diabetes, iron supplementation, multivitamin supplementation, gestational dietary intake, and alcohol use. We assessed the interaction between the duration of FA supplementation and multivitamin supplementation on GDM [25]. Generalized linear models were also used to assess the effects of GDM on adverse birth outcomes compared with non-GDM, as well as the effects of FA supplementation for <3 months on adverse birth outcomes.…”