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

Abstract

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. We searched electronic databases to identify RCTs comparing early treatment vs 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 admission, small-for-gestational age, cord-blood C-peptide ≥90th percentile, and neonatal hypoglycemia. Secondary maternal outcomes were cesarean section (CS), emergency CS, labor induction, preeclampsia, and preterm birth. Seven RCTs involving 4427 pregnancies were analyzed. The studies differed in their timing and methods of inclusion. Six studies used a combination of lifestyle and pharmaceutical interventions, while 1 relied solely on lifestyle modifications. Early treatment did not reduce LGA [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.53-1.32; P = .44], macrosomia (OR 0.68; 95% CI: 0.43-1.06; P = .09), or pregnancy-related hypertension (OR 1.04; 95% CI: 0.68-1.57; P = .87). Among the secondary outcomes, only NRD was significantly reduced in the treatment arm (OR 0.52; 95% CI: 0.34-0.80; P = .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 = .02). 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.