High folic acid concentration during early pregnancy risk factor for gestational diabetes: Study

Hefeng Huang, Shanghai Jiao Tong University, Shanghai, China, and colleagues found that higher serum folic acid levels were significantly correlated with elevated fasting blood glucose concentration in the first trimester and subsequent risk of GDM diagnosed later in pregnancy.

The findings underscore the importance of maintaining an inadequate FA concentration for preserving a reduced risk of gestational diabetes, particularly in women with women with relatively higher blood glucose in early pregnancy. Furthermore, folic acid concentration > 32.5 nmol/L could be a risk factor for GDM.

'This research indicates that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent negative effects of excessive folic acid intake," the researchers wrote.

There has been an increasing prevalence of folic acid consumption in early pregnancy, concerns have been raised about its potentially negative effect on maternal metabolism. Recent findings on folic acid levels and the first trimester and GDM risk have been inconclusive. Therefore, the research team aimed to examine the association of FA status in early pregnancy with GDM and to examine whether glucose levels can be modulated by folic acid status during the same first trimester.

For this purpose, the researcher performed a retrospective cohort study based on 27,128 Chinese pregnant women who registered during the first prenatal visit from 2015 to 2019. During the 9th to 13th gestational weeks, serum folic acid and FBG concentrations were measured.

Binary logistic regression was applied to estimate odds ratios of GDM by using the serum FA levels quartiles with adjustment for major confounders. To investigate the potential effect of modifying key risk factors for gestational diabetes, the investigators established subgroups, in which analyses were stratified by prepregnancy body mass index (< 18.5, 18.5–23.9, and ≥ 24 kg/m2), age (<25, 25–29, 30–34, and ≥35 y), parity (nulliparous and parous), and family history of diabetes (yes and no).

The study revealed the following findings:

• A positive association was observed between maternal folate concentrations and fasting blood glucose: 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 was found in hyperglycemia of early pregnant women with high folate concentrations (Q3: odds ratio = 5.63, and Q4: odds ratio = 5.57) 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 and the risk of gestational diabetes mellitus in a nonlinear pattern, with 32.5 nmol/L as the cutoff point for folic acid level.

In conclusion, serum FA in early pregnancy is positively linked with early pregnant fasting blood glucose. GDM prevalence is significantly higher in pregnant women with folic acid levels > 32.5 nmol/L compared with < 32.5 nmol/L. For women with FBG ≥ 5.1 mmol/L, FA is significantly positively associated with GDM.

"Therefore, it is suggested that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent adverse effects of excessive FA intake," the researchers wrote.

Reference:

Zhang, C., Liu, Z., Sun, K., Zhao, J., Huang, H., & Zhang, C. (2024). 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. Nutrition, 122, 112383. https://doi.org/10.1016/j.nut.2024.112383