41: Fetal metabolic biomarkers after late preterm betamethasone and their association with neonatal hypoglycemia

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Late preterm betamethasone significantly reduced neonatal respiratory morbidity, but also increased neonatal hypoglycemia through an uncertain mechanism. Our objective was to define the fetal metabolic effects of antenatal late preterm betamethasone. Secondary analysis of a randomized trial of antenatal betamethasone versus placebo in women with threatened late preterm birth (2010-2015). Mother-neonate dyads with stored umbilical cord blood plasma were included. Major congenital anomalies were excluded. Magnetic bead-based multiplex assays were used to measure metabolic biomarkers C-peptide, insulin, leptin and insulin-like growth factor binding protein 1 (IGFBP-1) in umbilical cord blood plasma. Baseline characteristics and biomarker levels were compared between betamethasone and placebo groups. Multivariable generalized linear regression estimated the association between betamethasone and biomarker levels, adjusting for BMI, GDM, hours from study drug exposure to delivery, and hospital as a random effect. Subsequently, the associations between the fetal biomarkers and neonatal hypoglycemia (glucose< 40mg/dL) were investigated. Of 2831 women in the primary trial, 203 met inclusion criteria for this analysis: 106 (52%) exposed to betamethasone and 97 (48%) exposed to placebo. A total of 173 (85%) women delivered preterm and 23 (11%) had GDM. Overall, 61 (30%) neonates had hypoglycemia. Betamethasone was associated with higher adjusted mean C-peptide, insulin, and leptin levels (Figure). There was no difference in IGFBP-1. Fetal C-peptide and insulin levels >90th percentile were associated with 3- to 6-fold higher odds of neonatal hypoglycemia (Table). Betamethasone given in late preterm is associated with altered fetal metabolic pathways, and these alterations are associated with neonatal hypoglycemia. Further studies are needed to confirm whether fetal hyperinsulinemia is the cause of neonatal hypoglycemia after late preterm betamethasone exposure, and if this outcome can be prevented.View Large Image Figure ViewerDownload Hi-res image Download (PPT)