Association of serum folic acid levels in response to fasting blood glucose in early pregnancy with the risk of gestational diabetes mellitus: A retrospective cohort study

With increasingly prevalent FA consumption in early pregnancy, concerns about its potentially negative effect on maternal metabolism have been raised. Recent findings regarding the folic acid levels in the first trimester and the risk of GDM were inconclusive. The aim of this study was to investigate the association of FA status in early pregnancy with GDM, as well as examine whether glucose level can be modulated by FA status during the same first trimester. This was a retrospective cohort study based on 27,128 Chinese pregnant women that registered during their first prenatal visit from January 2015 to December 2019. Serum folic acid and fasting blood glucose concentrations were measured during the 9th to 13th gestational weeks. Binary logistic regression was applied to estimate the odds ratios (ORs) of GDM by using the serum FA levels quartiles with adjustment for major confounders. To investigate the potential impact modification by main risk factors for GDM, we established subgroups in which analyses were stratified by age (<25, 25-29, 30-34, ≥35 years), parity (nulliparous and parous), pre-pregnancy BMI (<18.5, 18.5-23.9, ≥24kg/m2) and family history of diabetes (yes and no). The positive association between maternal folate concentrations and fasting blood glucose was observed: the risk for hyperglycemia was higher among those in the middle(Q3) and higher(Q4) quartiles as compared with those in Q1 through Q2. The higher risk for GDM was found among hyperglycemia of early pregnant women with high folate concentrations (Q3: OR, 5.63, 95% CI, 4.56-6.95 and Q4: OR, 5.57, 95% CI, 4.68-6.64) compared with normal fasting glucose mothers with folate concentrations in Q1 through Q2 after accounting for multiple covariables. Similar patterns were observed for different subgroups. Restricted cubic spline plots showed a positive correlation of serum FA level with the FBG concentration as well as the risk of GDM in a non-linear pattern, with 32.5nmol/L as the cut-off point for FA level. Our findings underscore the importance of maintaining an appropriate FA concentration for preserving the lower risk of GDM, especially among women with relatively higher blood glucose in early pregnancy. Additionally, FA concentration with higher than 32.5 nmol/L may be considered as a risk factor of GDM. This research suggested that FA levels should be monitored during the first trimester from the first prenatal check-up to prevent adverse effects of excessive FA intake.