Treatment Versus Observation in Early Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract Purpose Early gestational diabetes mellitus (eGDM) refers to elevated blood glucose levels not meeting the criteria for overt diabetes before 20 weeks gestation. Observational studies link eGDM to adverse outcomes, but randomized controlled trial (RCT) evidence on early intervention benefits remains inconclusive. To address this, we performed a systematic review and meta-analysis (SRM) of RCTs on this subject. Methods We searched electronic databases to identify RCTs comparing early treatment versus observation for eGDM. The primary neonatal outcomes analyzed were large-for-gestational-age (LGA) and macrosomia. The primary maternal outcome was pregnancy-related hypertension. Secondary neonatal outcomes included neonatal respiratory distress (NRD), neonatal intensive-care unit (NICU) admission, small-for-gestational-age (SGA), cord-blood C-peptide ≥90th percentile, and neonatal hypoglycemia. Secondary maternal outcomes were cesarean section (CS), emergency CS, labor induction, preeclampsia, and preterm birth. Results Seven RCTs involving 4,427 pregnancies were analyzed. The studies differed in their timing and methods of inclusion. Six studies used a combination of lifestyle and pharmaceutical interventions, while one relied solely on lifestyle modifications. Early treatment did not reduce LGA [OR 0.84 (95%CI: 0.53–1.32); P=0.44], macrosomia [OR 0.68 (95%CI: 0.43–1.06); P=0.09], or pregnancy-related hypertension [OR 1.04 (95%CI: 0.68–1.57); P=0.87]. Among the secondary outcomes, only NRD was significantly reduced in the treatment arm [OR 0.52 (95%CI: 0.34–0.80); P=0.003]. However, sensitivity analysis, omitting the lifestyle-only study, demonstrated a lower risk of macrosomia with early intervention [OR 0.55 (95%CI: 0.34–0.91); P=0.02]. Conclusion The SRM demonstrates early intervention does not improve most pregnancy outcomes, except NRD. Sensitivity analysis, excluding the lifestyle-only study, additionally revealed a reduction in macrosomia. The findings must be interpreted cautiously due to the variability in study designs. Replication in well-designed multicenter trials is required before clinical application.