K S Borowski1, E A S Clark2, Y Lai3, R J Wapner4, Y Sorokin5, A M Peaceman6, J D Iams7, K J Leveno8, M Harper9, S N Caritis10, M Miodovnik11, B M Mercer12, J M Thorp13, M J O'Sullivan14, S M Ramin15, M W Carpenter16, D J Rouse17, B Sibai18. 1. Departments of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa. 2. University of Utah, Salt Lake City, Utah. 3. The George Washington University Biostatistics Center, Washington, District of Columbia. 4. Drexel University, Philadelphia, Pennsylvania. 5. Wayne State University, Detroit, Michigan. 6. Departments of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois. 7. Departments of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio. 8. Departments of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas. 9. Departments of Obstetrics and Gynecology, Wake Forest University Health Sciences, Winston-Salem, North Carolina. 10. Departments of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania. 11. Columbia University, New York, New York. 12. Departments of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio. 13. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 14. University of Miami, Miami, Florida. 15. The University of Texas Health Science Center at Houston, Houston, Texas. 16. Departments of Obstetrics and Gynecology, Brown University, Providence, Rhode Island. 17. University of Alabama at Birmingham, Birmingham, Alabama. 18. Departments of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee.
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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
RCT Entities:
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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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