Association between Glyburide Dose and Adverse Neonatal Outcomes in Women with Gestational Diabetes

Abstract

Glyburide is used to treat women with gestational diabetes (GDM). However, recent data has demonstrated that it crosses the placenta, and concerns about the neonatal effects of glyburide treatment including fetal overgrowth and neonatal hypoglycemia persist. We sought to assess if there are subsets of women treated with glyburide who are at increased risk for adverse neonatal outcomes compared to women treated with medical nutritional therapy (MNT) alone using a retrospective cohort of 1,012 women with GDM. We collected characteristics including glucose values and pregnancy outcomes. We used bivariate and multivariable logistic regression analyses to assess the association between GDM treatment and pregnancy outcomes. Treatment was divided into categories of MNT (n=343), glyburide <7.5 mg (n=495), and glyburide ≥7.5 mg/day (n=173). When compared to women treated with MNT or glyburide <7.5 mg, those treated with glyburide ≥7.5 mg/day were more likely to be obese (28.5 vs. 48.3 vs. 63.2%, p<0.001), gain excessive weight (35.2 vs. 42.9 vs. 56.4%, p<0.0001), and had higher mean glucose (106.4 vs. 114.3 vs. 121.9, p<0.001). Higher glyburide doses were associated with an increased risk for large for gestational age (LGA) and neonatal hypoglycemia. After adjusting for covariates including nulliparity, prepregnancy BMI, gestational weight gain, prematurity, and maternal glucose, women treated with ≥7.5 mg/day were 2.6-fold more likely to deliver an LGA infant, but there was no increased risk for hypoglycemia. Our findings suggest that neonatal outcomes in women on lower glyburide doses are similar to those treated with MNT, but higher doses are associated with fetal overgrowth. Further studies are needed to determine optimal management of women receiving glyburide, specifically the maximal dose for use in pregnancy and identification of women who respond well to lower doses. Disclosure M.N. Feghali: None. S. Caritis: None. J.M. Catov: None. C.M. Scifres: None.