Predictors of small-for-gestational-age infants in gestational diabetes mellitus: the impact of metformin use

Introduction: Gestational diabetes mellitus (GDM) affects 3%–25% of pregnancies worldwide, posing risks to maternal, fetal, and neonatal health. GDM is often associated with macrosomia and large-for-gestational-age (LGA) infants. However, the association between GDM and small-for-gestational-age (SGA) infants is less understood. This study aimed to identify predictors of SGA in women with GDM. Methods: This retrospective study included GDM patients (GDMA1 and A2) admitted to the fetal–maternal unit between 2014 and 2023. The study population was divided into those who delivered an appropriate for gestational age (AGA) neonate and those who delivered an SGA neonate (defined as birthweight < 10th percentile. Women with pregestational diabetes mellitus were excluded. Obstetric and neonatal outcomes were compared between the groups. A subgroup analysis focused on GDMA2 patients, comparing maternal and neonatal outcomes and treatment regimens (insulin and metformin use). Results: The study included 894 GDM patients. Compared to the AGA group (n = 712), the SGA group (n = 182) had lower maternal BMI (p = 0.02). Maternal age was comparable between groups. Rates of GDMA2 (30.2% vs. 23.4%, p = 0.07), and hypertensive disorders (7.1% vs. 5%, p = 0.21) did not differ significantly between the groups. The neonatal birthweight of the SGA infants was 2375 ± 432 g vs. 3021 ± 165 g in the AGA infants, (p = 0.005). The SGA group had a higher rate of CD due to NRFHR (27.4% vs. 18.4%, p < 0.01). Among GDMA2 patients (n = 222), more women in the SGA group (n = 55) were treated with metformin as compared to the AGA group (n = 167) (72.7% vs. 23.9%, p < 0.001). Multivariate regression analysis revealed that among GDMA2 patients metformin treatment was independently associated with SGA neonates OR 1.7, CI 1.18–1.35, p < 0.01). Conclusion: Metformin use in GDMA2 pregnancies may be linked to SGA neonates. The impact of metformin on fetal growth highlights the need for careful monitoring and individualized treatment strategies in managing GDMA2.