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

David Haas, Jessica Dantzer, Amalia S. Lehmann, Santosh Philips, Todd Skaar, Catherine L. McCormick, Scott J. Hebbring, Jeesun Jung, Lang Li

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Obstetrics and Gynecology
Volume208
Issue number3
DOIs
StatePublished - Mar 2013

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Infant, Newborn, Diseases
Betamethasone
Bronchopulmonary Dysplasia
Glucocorticoids
Mothers
Single Nucleotide Polymorphism
Surface-Active Agents
Odds Ratio
Confidence Intervals
Genotype
Regression Analysis
Karyopherins
Newborn Respiratory Distress Syndrome
Chorioamnionitis
Premature Birth
Gestational Age
Adrenal Cortex Hormones
Therapeutics
Logistic Models
Parturition

Keywords

  • antenatal corticosteroid
  • betamethasone
  • pharmacogenetics

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

The impact of glucocorticoid polymorphisms on markers of neonatal respiratory disease after antenatal betamethasone administration. / Haas, David; Dantzer, Jessica; Lehmann, Amalia S.; Philips, Santosh; Skaar, Todd; McCormick, Catherine L.; Hebbring, Scott J.; Jung, Jeesun; Li, Lang.

In: American Journal of Obstetrics and Gynecology, Vol. 208, No. 3, 03.2013.

Research output: Contribution to journalArticle

Haas, David ; Dantzer, Jessica ; Lehmann, Amalia S. ; Philips, Santosh ; Skaar, Todd ; McCormick, Catherine L. ; Hebbring, Scott J. ; Jung, Jeesun ; Li, Lang. / The impact of glucocorticoid polymorphisms on markers of neonatal respiratory disease after antenatal betamethasone administration. In: American Journal of Obstetrics and Gynecology. 2013 ; Vol. 208, No. 3.
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abstract = "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.",
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AB - 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.

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