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.

Objective: With increasingly prevalent folic acid consumption in early pregnancy, concerns about its potentially negative effect on maternal metabolism have been raised. Recent findings regarding folic acid levels in the first trimester and the risk of gestational diabetes mellitus have been inconclusive. The aim of this study was to investigate the association of folic acid status in early pregnancy with gestational diabetes mellitus as well as examine whether glucose levels can be modulated by folic acid status during the same first trimester.

Methods: This was a retrospective cohort study based on 27 128 Chinese pregnant women who 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 of gestational diabetes mellitus by using the serum folic acid levels quartiles with adjustment for major confounders. To investigate the potential effect of modifying key risk factors for gestational diabetes mellitus, we established subgroups, in which analyses were stratified by age (<25, 25-29, 30-34, and ≥35 y), parity (nulliparous and parous), prepregnancy body mass index (< 18.5, 18.5-23.9, and ≥ 24 kg/m), and family history of diabetes (yes and no).

Results: The positive association between maternal folate concentrations and fasting blood glucose was observed: the risk for hyperglycemia was higher in those in the middle (Q3) and higher (Q4) quartiles compared with those in Q1 and Q2. A higher risk for gestational diabetes mellitus was found in hyperglycemia of early pregnant women with high folate concentrations (Q3: odds ratio = 5.63; 95% CI, 4.56-6.95, and Q4: odds ratio = 5.57; 95% CI, 4.68-6.64) compared with normal fasting glucose mothers with folate concentrations in Q1 and Q2 after accounting for multiple covariables. Similar patterns were observed for different subgroups. Restricted cubic spline plots had a positive correlation of serum folic acid level with fasting blood glucose concentration as well as risk of gestational diabetes mellitus in a nonlinear pattern, with 32.5 nmol/L as the cutoff point for folic acid level.

Conclusions: Our findings underscore the importance of maintaining an appropriate folic acid concentration for preserving a lower risk of gestational diabetes mellitus, especially in women with relatively higher blood glucose in early pregnancy. Additionally, folic acid concentration > 32.5 nmol/L may be considered a risk factor for gestational diabetes mellitus. This research suggested that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent adverse effects of excessive folic acid intake.