The impact of metformin therapy for gestational diabetes on fetal growth in women with risk factors for fetal growth restriction- a registry-based study from Qatar

Background

Gestational diabetes mellitus (GDM) has been the most prevalent medical condition in pregnancy, often managed by a multidisciplinary team. Numerous studies have demonstrated that metformin therapy for GDM offers advantages including a reduced risk of macrosomia, neonatal hypoglycemia, and admission to neonatal intensive care units (NICU). However, its use has been linked to fetal growth restriction (FGR) as well. Our study aims to investigate the effect of metformin when given to women with GDM and additional risk factors for FGR like hypertension, inherited or acquired thrombophilia, anemia, and autoimmune disorders such as anti-phospholipid syndrome, lupus erythematosus.

Methods

Women who had singleton live births and diagnosed with gestational diabetes (GDM) were selected. They were divided into two groups based on the presence of additional risk factors for FGR during their pregnancies. Each of these groups were further divided based on use of metformin for the management of GDM- resulting in four comparison groups. The outcomes were birthweight (BW), birthweight centiles, small for date baby (SFD), low birth weight (LBW), preterm birth (PTB), large for date baby (LGA), macrosomia, admission to NICU and mode of delivery.

Results

Of the 4,290 women included in the study, 18% had risk factors for FGR, 27% of whom took metformin for GDM. Among the women with no risk factors, 29% took metformin. In women who were taking metformin, those having risk factors had lower mean BW (3015± 608.1 gms vs 3179.2± 506.2 grams; p<0.001), higher risk of PTD (20% vs 10.2%; p<0.001), LBW (16.5% vs 7.2%. p<0.001), SFD (8.0% vs 3.6%; p=0.006), and admission to NICU (19.5% vs 11.3%; p<0.001) and cesarean (48.0% vs 36.8%; p<0.001) compared to those who without risk factors. These risks were also higher than women not taking metformin, regardless of their risk factors status. The birthweight centiles were lower in women with risk factors compared to those without (57.5±30.5 vs 60.2±28.2). However, the centiles were higher in those who took metformin compared to those who did not. Regardless of risk factor status, women taking metformin had higher risk of LFD (p=0.001), but no difference in risk of macrosomia.

Conclusion

The results of this study suggest that in women with additional risk factors for FGR, the concurrent use of metformin significantly decreases the birthweight and increases the risk for LBW, SFD, PTB and admission to NICU. The use of metformin in these women should be judicious and increased fetal surveillance during pregnancy is warranted.