Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids

K. S. Borowski*, E. A.S. Clark, Y. Lai, R. J. Wapner, Y. Sorokin, Alan M Peaceman, J. D. Iams, K. J. Leveno, M. Harper, S. N. Caritis, M. Miodovnik, B. M. Mercer, J. M. Thorp, M. J. O'Sullivan, S. M. Ramin, M. W. Carpenter, D. J. Rouse, B. Sibai

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Original languageEnglish (US)
Pages (from-to)1126-1132
Number of pages7
JournalAmerican journal of perinatology
Volume32
Issue number12
DOIs
StatePublished - May 8 2015

Fingerprint

Adrenal Cortex Hormones
Alleles
Steroids
Gestational Age
Mechanical Ventilators
Single Nucleotide Polymorphism
Genes
Continuous Positive Airway Pressure
Placenta
Randomized Controlled Trials
Logistic Models
Newborn Infant
DNA
Serum
Therapeutics

Keywords

  • antenatal corticosteroids
  • candidate gene
  • respiratory distress syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Borowski, K. S. ; Clark, E. A.S. ; Lai, Y. ; Wapner, R. J. ; Sorokin, Y. ; Peaceman, Alan M ; Iams, J. D. ; Leveno, K. J. ; Harper, M. ; Caritis, S. N. ; Miodovnik, M. ; Mercer, B. M. ; Thorp, J. M. ; O'Sullivan, M. J. ; Ramin, S. M. ; Carpenter, M. W. ; Rouse, D. J. ; Sibai, B. / Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids. In: American journal of perinatology. 2015 ; Vol. 32, No. 12. pp. 1126-1132.
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title = "Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids",
abstract = "Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.",
keywords = "antenatal corticosteroids, candidate gene, respiratory distress syndrome",
author = "Borowski, {K. S.} and Clark, {E. A.S.} and Y. Lai and Wapner, {R. J.} and Y. Sorokin and Peaceman, {Alan M} and Iams, {J. D.} and Leveno, {K. J.} and M. Harper and Caritis, {S. N.} and M. Miodovnik and Mercer, {B. M.} and Thorp, {J. M.} and O'Sullivan, {M. J.} and Ramin, {S. M.} and Carpenter, {M. W.} and Rouse, {D. J.} and B. Sibai",
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Borowski, KS, Clark, EAS, Lai, Y, Wapner, RJ, Sorokin, Y, Peaceman, AM, Iams, JD, Leveno, KJ, Harper, M, Caritis, SN, Miodovnik, M, Mercer, BM, Thorp, JM, O'Sullivan, MJ, Ramin, SM, Carpenter, MW, Rouse, DJ & Sibai, B 2015, 'Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids', American journal of perinatology, vol. 32, no. 12, pp. 1126-1132. https://doi.org/10.1055/s-0035-1549217

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids. / Borowski, K. S.; Clark, E. A.S.; Lai, Y.; Wapner, R. J.; Sorokin, Y.; Peaceman, Alan M; Iams, J. D.; Leveno, K. J.; Harper, M.; Caritis, S. N.; Miodovnik, M.; Mercer, B. M.; Thorp, J. M.; O'Sullivan, M. J.; Ramin, S. M.; Carpenter, M. W.; Rouse, D. J.; Sibai, B.

In: American journal of perinatology, Vol. 32, No. 12, 08.05.2015, p. 1126-1132.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids

AU - Borowski, K. S.

AU - Clark, E. A.S.

AU - Lai, Y.

AU - Wapner, R. J.

AU - Sorokin, Y.

AU - Peaceman, Alan M

AU - Iams, J. D.

AU - Leveno, K. J.

AU - Harper, M.

AU - Caritis, S. N.

AU - Miodovnik, M.

AU - Mercer, B. M.

AU - Thorp, J. M.

AU - O'Sullivan, M. J.

AU - Ramin, S. M.

AU - Carpenter, M. W.

AU - Rouse, D. J.

AU - Sibai, B.

PY - 2015/5/8

Y1 - 2015/5/8

N2 - Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

AB - Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

KW - antenatal corticosteroids

KW - candidate gene

KW - respiratory distress syndrome

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JF - American Journal of Perinatology

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