Supplementary Material for: Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants

<strong><em>Background:</em></strong> 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 polymorphisms in the glucocorticoid receptor <i>(GR)</i> gene. <b><i>Objectives:</i></b> To assess the impact of <i>GR</i> polymorphisms <i>N363S</i> (rs56149945), <i>R23K</i> (rs6190), and <i>BclI</i> (rs41423247) on neonatal outcome. <b><i>Methods:</i></b> The <i>GR</i> polymorphisms <i>N363S, R23K,</i> and <i>BclI</i> were examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome. <b><i>Results:</i></b> Infants carrying the <i>BclI</i> genotype were at higher risk to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per <i>BclI</i> 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 betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. <i>N363S</i> and <i>R23K</i> did not show any stable association with neonatal outcome parameters. <b><i>Conclusion:</i></b> Except for a slightly higher risk of BPD in carriers of the <i>GR</i><i>BclI</i> variant, the <i>GR</i> gene polymorphisms <i>BclI, N363S,</i> and <i>R23K</i> did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants.