Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth Weight Preterm Infants

Background: Induction of lung maturation by prenatal steroid treatment has become the standard of care for pregnant women at risk for preterm birth. In addition to the beneficial effects on lung maturation, prenatal steroids have been shown to reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. However, little is known about the role of interindividual differences in corticoid sensitivity arising from polynnorphisms in the glucocorticoid receptor (GR) gene. Objectives: To assess the impact of GR polymorphisnns N3635 (rs56149945), R23K (rs6190), and Bc/1(rs41423247) on neonatal outcome. Methods: The GR polymorphisnns N3635,R23K, and BO were examined in 10,490 very-low-birth-weight (VLBW) preternn infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome. Results: Infants carrying the 8d/ genotype were at higher risk to develop bronchopulnnonary dysplasia (BPD) (OR 1.12 per Bcll allele, 95% CI: 1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational age, mechanical ventilation, and small for gestational age status. A similar relative risk was seen in the children (89.4%) who received antenatal betannethasone treatment (OR 1.16, 95% CI: 1.051.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. N3635 and 62]K did not show any stable association with neonatal outcome parameters. Conclusion: Except for a slightly higher risk of BPD in carriers of the GR Bcll variant, the G8 gene polynnorphisms Bcll, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants. (C) 2016 S. Karger AG, Basel.