Association between Early Pregnancy Maternal Folate and Glycemic Indices at Oral Glucose Tolerance Test: A Systematic Review and Meta-analysis

Journal article

Background Folate plays a crucial role in foetal development, but its relationship with maternal glucose metabolism remains inconclusive. Recent meta-analyses have suggested a correlation between high folate and the risk of GDM in pregnancy, however its association with different glycaemic parameters have not yet been explored. Objective To comprehensively synthesise evidence and test the association between early pregnancy circulating folate (<16 weeks of gestation) and glycaemic indices measured during oral glucose tolerance testing (OGTT) at 24-28 weeks. Methods We conducted a systematic search of databases up to 25th June 2025 examining the relationship between early pregnancy folate and maternal glycaemic indices. Study quality was assessed by Newcastle-Ottawa Scale (NOS). Standardised effect sizes (std. β coefficients) for serum/plasma folate were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to account for between- study heterogeneity. Results Ten studies were included in this meta-analysis. Early pregnancy maternal folate levels were positively associated with glycaemic indices measured at the time of OGTT. One standard deviation (SD nmol/l) increase in early pregnancy serum folate was associated with 0.01 (95% CI: -0.001, 0.01) mmol/l higher fasting, 0.17 (95% CI: 0.15; 0.18) mmol/l higher 1-hour glucose, and 0.10 (95% CI: 0.05, 0.15) mmol/l higher 2-hour glucose levels during OGTT Subgroup analyses revealed similar positive association between mid-pregnancy circulating folate and glucose levels measured at the time of OGTT despite substantial between-study heterogeneity (I2>70%). Conclusions Our analysis suggests a possible association between higher early pregnancy folate levels and higher glucose levels at the time of OGTT. However, these findings should be interpreted cautiously given the methodological limitations and limited number of studies included in this review

Authors: Periyathambi, N; Sampathkumar, S; Sukumar, N; Ghebremichael-Weldeselassie, Y; Saravanan, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Current Developments in Nutrition
• Volume: 9
• Issue: 9
• Pages: 107531-107531
• Publication date: 2025-08-23
• DOI: 10.1016/j.cdnut.2025.107531
• EISSN: 2475-2991
• ISSN: 2475-2991
• Language: English
• Keywords: Test (biology); Internal medicine; Biology; Obstetrics; Association (psychology); Meta-analysis; Psychology; Pregnancy; Medicine