The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: To determine the impact of maternal and fetal single nucleotide polymorphisms in key betamethasone pathways on neonatal outcomes. Study Design: DNA was obtained from women given betamethasone and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway single nucleotide polymorphisms. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome was performed. Results: One hundred nine women delivering 117 infants were analyzed. Sixty-four infants (49%) developed respiratory distress syndrome. Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6). Conclusion: Maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome after treatment with betamethasone for preterm labor.

Original languageEnglish
JournalAmerican Journal of Obstetrics and Gynecology
Volume206
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Betamethasone
Single Nucleotide Polymorphism
Adrenal Cortex Hormones
Odds Ratio
Confidence Intervals
Newborn Respiratory Distress Syndrome
Mothers
Enzymes
Pharmaceutical Preparations
Genotype
Cytochrome P-450 CYP3A
Premature Obstetric Labor
Glucocorticoids
Logistic Models
Regression Analysis
DNA
Therapeutics

Keywords

  • betamethasone
  • neonatal respiratory distress syndrome
  • pharmacogenetics
  • preterm birth

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use. / Haas, David; Lehmann, Amalia S.; Skaar, Todd; Philips, Santosh; McCormick, Catherine L.; Beagle, Kyle; Hebbring, Scott J.; Dantzer, Jessica; Li, Lang; Jung, Jeesun.

In: American Journal of Obstetrics and Gynecology, Vol. 206, No. 5, 05.2012.

Research output: Contribution to journalArticle

Haas, David ; Lehmann, Amalia S. ; Skaar, Todd ; Philips, Santosh ; McCormick, Catherine L. ; Beagle, Kyle ; Hebbring, Scott J. ; Dantzer, Jessica ; Li, Lang ; Jung, Jeesun. / The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use. In: American Journal of Obstetrics and Gynecology. 2012 ; Vol. 206, No. 5.
@article{622b8f1acd1a4826a47b265862e8b5e9,
title = "The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use",
abstract = "Objective: To determine the impact of maternal and fetal single nucleotide polymorphisms in key betamethasone pathways on neonatal outcomes. Study Design: DNA was obtained from women given betamethasone and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway single nucleotide polymorphisms. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome was performed. Results: One hundred nine women delivering 117 infants were analyzed. Sixty-four infants (49{\%}) developed respiratory distress syndrome. Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95{\%} confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95{\%} CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95{\%} CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95{\%} CI, 1.33-420.6). Conclusion: Maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome after treatment with betamethasone for preterm labor.",
keywords = "betamethasone, neonatal respiratory distress syndrome, pharmacogenetics, preterm birth",
author = "David Haas and Lehmann, {Amalia S.} and Todd Skaar and Santosh Philips and McCormick, {Catherine L.} and Kyle Beagle and Hebbring, {Scott J.} and Jessica Dantzer and Lang Li and Jeesun Jung",
year = "2012",
month = "5",
doi = "10.1016/j.ajog.2012.02.016",
language = "English",
volume = "206",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",
number = "5",

}

TY - JOUR

T1 - The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use

AU - Haas, David

AU - Lehmann, Amalia S.

AU - Skaar, Todd

AU - Philips, Santosh

AU - McCormick, Catherine L.

AU - Beagle, Kyle

AU - Hebbring, Scott J.

AU - Dantzer, Jessica

AU - Li, Lang

AU - Jung, Jeesun

PY - 2012/5

Y1 - 2012/5

N2 - Objective: To determine the impact of maternal and fetal single nucleotide polymorphisms in key betamethasone pathways on neonatal outcomes. Study Design: DNA was obtained from women given betamethasone and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway single nucleotide polymorphisms. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome was performed. Results: One hundred nine women delivering 117 infants were analyzed. Sixty-four infants (49%) developed respiratory distress syndrome. Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6). Conclusion: Maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome after treatment with betamethasone for preterm labor.

AB - Objective: To determine the impact of maternal and fetal single nucleotide polymorphisms in key betamethasone pathways on neonatal outcomes. Study Design: DNA was obtained from women given betamethasone and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway single nucleotide polymorphisms. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome was performed. Results: One hundred nine women delivering 117 infants were analyzed. Sixty-four infants (49%) developed respiratory distress syndrome. Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6). Conclusion: Maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome after treatment with betamethasone for preterm labor.

KW - betamethasone

KW - neonatal respiratory distress syndrome

KW - pharmacogenetics

KW - preterm birth

UR - http://www.scopus.com/inward/record.url?scp=84862803948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862803948&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2012.02.016

DO - 10.1016/j.ajog.2012.02.016

M3 - Article

C2 - 22445700

AN - SCOPUS:84862803948

VL - 206

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

IS - 5

ER -