Front Endocrinol (Lausanne). 2026 Sep 16;17:1904624. doi: 10.3389/fendo.2026.1904624. eCollection 2026.
ABSTRACT
BACKGROUND: Gestational diabetes mellitus (GDM) affects 14-17% of pregnancies globally, imposing long-term public health burdens beyond pregnancy. Maternal hyperglycaemia increases offspring risk of metabolic disorders through epigenetic, hormonal and developmental programming. Growing evidence connects prenatal GDM exposure to childhood and adult metabolic diseases, yet the consistency and magnitude of these associations across different metabolic conditions remains unclear.
METHODS: We systematically searched PubMed, Cochrane CENTRAL and Embase. Eligible studies included observational cohorts exploring associations between in-utero GDM exposure and offspring metabolic outcomes, and RCTs assessing maternal antenatal interventions. Bias risk was evaluated with Cochrane RoB 2 (for RCTs) and the Newcastle-Ottawa Scale (NOS) (for observational studies). Separate outcome-based pooled analyses were conducted, given the distinct clinical questions addressed by the two study designs. All meta-analyses used the random-effects inverse-variance model. Heterogeneity was assessed via I² and Cochran's Q statistic, and Egger's linear regression test was used to detect publication bias.
RESULTS: Sixteen studies (n=9 RCTs, n=7 observational cohorts) involving diverse populations across 11 countries were included. In observational cohorts, GDM-exposed offspring showed higher BMI (MD = 1.42 kg/m2, 95% CI: 0.94-1.89) and greater estimates for overweight/obesity in adulthood (OR = 2.09, 95% CI: 1.25-3.50, I² = 80.7%). The analysis of fasting glucose results displayed high variability (I² = 80.7%) yet produced no meaningful combined impact (MD = -0.016 mmol/L, 95% CI: -1.52 to 1.49). In RCTs, active antenatal GDM management was associated with a non-significant trend towards lower HOMA-IR (MD = -0.30, 95% CI: -0.61 to 0.01; I² = 68.2%) and HbA1c (MD = -0.41%, 95% CI: -0.85 to 0.03; I² = 99.1%) relative to usual care. There were no statistically significant combined effects found for 2-hour OGTT glucose levels total cholesterol levels triglyceride levels or HDL-C levels. Egger's test revealed no significant publication bias for either glucose (t = 0.82, p = 0.43) or lipid outcomes (t = -0.08, p = 0.94).
CONCLUSION: In-utero GDM exposure confers metabolic risks from childhood to adulthood; lifelong persistence requires verification via extended longitudinal research GDM interventions including diet, exercise and pharmacotherapy may lower offspring risk, although heterogeneity necessitates cautious interpretation.
PMID:42819227 | PMC:PMC13623741 | DOI:10.3389/fendo.2026.1904624