FP11-3 Glucocorticoid Receptor Gene Polymorphisms and Neonatal Outcome of VLBW Preterm Infants: Preliminary Results from a German Multicenter Study

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP11-Pediatric Endocrinology
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:10 AM
Room 104 (Moscone Center)

Poster Board SAT-600
Felix Schreiner*1, Christine Poralla1, Christoph Haertel2, Matthias Heckmann3, Joachim F Woelfle1, Peter Bartmann1, Egbert Herting2, Wolfgang Goepel2 and (GNN) German Neonatal Network4
1Children's Hospital, University of Bonn, Bonn, Germany, 2Children's Hospital, University of Luebeck, Luebeck, Germany, 3Children's Hospital, University of Greifswald, Greifswald, Germany, 4GNN, Luebeck, Germany
Background: Apart from its beneficial effects on lung maturation, prenatal betamethasone administration has been shown to reduce the incidence of necrotizing enterocolitis, sepsis, and intraventricular hemorrhage in preterm infants. However, little is known about the role of endogenous differences in corticoid sensitivity arising from polymorphisms in the glucocorticoid receptor (GR) gene.

Study design: We analyzed GR polymorphisms BclI, N363S and R23K with respect to recorded neonatal outcome parameters in a German Neonatal Network (GNN) multicenter cohort comprising 2.211 very low birth weight preterm (VLBW)  infants.

Results:  Birth parameters were not different between genotype groups. Variants BclI and R23K were associated with a significantly higher risk of culture-positive neonatal sepsis (Bcll homozygosity: OR 1.85, p=0.002; R23K-carrier: OR 2.08, p=0.016; adj. for gestational age). In addition, infants carrying BclI alleles were more likely to develop bronchopulmonary dysplasia (OR 1.41 per allele [95% CI 1.14-1.75], p < 0.01 adj. for gestational age and mechanical ventilation). A similar relative risk was seen in the subcohort of infants with antenatal betamethasone treatment (OR 1.44, p < 0.01), whereas no such effect was detectable in the small subgroup without steroid treatment (n=185, OR 1.03, n.s.). N363S-carrier tended to have lower mean arterial blood pressure at the first day of life (total cohort: beta=-0.050, p=0.010; BclI-/R23K-wildtype subcohort: beta -0.055, p=0.074) and were more likely to require catecholamine treatment (p<0.01). However, none of the analyzed GR variants significantly influenced incidence rates of intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), or retinopathy (ROP).

Conclusion: This study supports the hypothesis that endogenous differences in glucocorticoid sensitivity mediated by GR gene polymorphisms affect the neonatal outcome of VLBW preterm infants. In order to confirm the observed associations, analysis of a replication cohort is ongoing.

Nothing to Disclose: FS, CP, CH, MH, JFW, PB, EH, WG, G

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm