Erin A S Clark1, Steven J Weiner2, Dwight J Rouse3, Brian M Mercer4,5, Uma M Reddy6, Jay D Iams7, Ronald J Wapner8, Yoram Sorokin9, Fergal D Malone10, Mary J O'Sullivan11, Alan M Peaceman12, Gary D V Hankins13, Donald J Dudley14, Steve N Caritis15. 1. Department of Obstetrics and Gynecology at the University of Utah Health Sciences Center, Salt Lake City, Utah. 2. The George Washington University Biostatistics Center, Washington, District of Columbia. 3. Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama. 4. Department of Obstetrics and Gynecology, MetroHealth Medical Center-Case Western Reserve University, Cleveland, Ohio. 5. Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee. 6. Department of Obstetrics and Gynecology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland. 7. Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio. 8. Department of Obstetrics and Gynecology, Thomas Jefferson University and Drexel University, Philadelphia, Pennsylvania. 9. Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan. 10. Department of Obstetrics and Gynecology, Columbia University, New York, New York. 11. Department of Obstetrics and Gynecology, University of Miami, Miami, Florida. 12. Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois. 13. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas. 14. Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. 15. Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
OBJECTIVE: To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. STUDY DESIGN: We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. RESULTS:Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). CONCLUSION: Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
RCT Entities:
OBJECTIVE: To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. STUDY DESIGN: We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. RESULTS: Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). CONCLUSION: Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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