The impact of glucocorticoid polymorphisms on markers of neonatal respiratory disease after antenatal betamethasone administration

• Published in: American journal of obstetrics and gynecology 2013-03, Vol.208 (3), p.215.e1-215.e6
• Main Authors: Haas, David M., MD, MS, Dantzer, Jessica, BS, Lehmann, Amalia S., BS, Philips, Santosh, MS, Skaar, Todd C., PhD, McCormick, Catherine L., RN, Hebbring, Scott J., PhD, Jung, Jeesun, PhD, Li, Lang, PhD
• Format: Article
• Language: English
• Subjects: Adult; antenatal corticosteroid; betamethasone; Betamethasone - pharmacology; Betamethasone - therapeutic use; Female; Genotype; Gestational Age; Glucocorticoids - therapeutic use; Humans; Infant, Newborn; Obstetrics and Gynecology; pharmacogenetics; Polymorphism, Single Nucleotide; Pregnancy; Pulmonary Surfactants - therapeutic use; Respiratory Distress Syndrome, Newborn - drug therapy; Respiratory Distress Syndrome, Newborn - genetics
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2012.12.031

Objective We previously demonstrated that maternal and fetal genotypes are associated independently with neonatal respiratory distress syndrome. The objective of the current study was to determine the impact of maternal and fetal single-nucleotide polymorphisms (SNPs) in key betamethasone pathways on respiratory outcomes that serve as markers for severity of disease. Study Design DNA was obtained from women who were given betamethasone and from their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis that controlled for relevant clinical variables to determine SNP impact on bronchopulmonary dysplasia (BPD), the need for respiratory support, and surfactant therapy use was performed. Results Data from 109 women who delivered 117 infants were analyzed: 14.5% of the infants experienced BPD; 70.8% of the infants needed some respiratory support after birth, and 27.5% of the infants needed surfactant therapy. In a multivariable regression analysis, gestational age at delivery was associated with most neonatal respiratory outcomes ( P ≤ .01), and chorioamnionitis was associated with BPD ( P < .03). The following genotypes were associated with respiratory severity outcomes: BPD–fetal Importin 13 gene ( IPO13 ; rs4448553; odds ratio [OR], 0.01; 95% confidence interval [CI], 0.00–0.92); surfactant use–maternal IPO13 (rs2428953 and 2486014; OR, 13.8; 95% CI, 1.80–105.5; and OR, 35.5; 95% CI, 1.71–736.6, respectively). Conclusion Several discrete maternal and fetal SNPs in the IPO13 family may be associated with neonatal respiratory outcomes after maternal antenatal corticosteroid treatment for anticipated preterm birth.