Sex-Specific Genetic Susceptibility to Adverse Neurodevelopmental Outcome in Offspring of Pregnancies at Risk of Early Preterm Delivery
Year: 2019
Type: article
Abstract: Objective To evaluate sex-specific genetic susceptibility to adverse neurodevelopmental outcome (ANO, defined as cerebral palsy [CP], mental, or psychomotor delay) at risk for early preterm birth (EPTB, < 32 weeks). Study Design Secondary case–control analysis of a trial of magnesium sulfate (MgSO4) before anticipated EPTB for CP prevention. Cases are infants who died by the age of 1 year or developed ANO. Controls, matched by maternal race and infant sex, were neurodevelopmentally normal survivors. Neonatal DNA was evaluated for 80 polymorphisms in inflammation, coagulation, vasoregulation, excitotoxicity, and oxidative stress pathways using Taqman assays. The primary outcome for this analysis was sex-specific ANO susceptibility. Conditional logistic regression estimated each polymorphism's odds ratio (OR) by sex stratum, adjusting for gestational age, maternal education, and MgSO4-corticosteroid exposures. Holm–Bonferroni corrections, adjusting for multiple comparisons (p < 7.3 × 10−4), accounted for linkage disequilibrium between markers. Results Analysis included 211 cases (134 males; 77 females) and 213 controls (130 males; 83 females). An interleukin-6 (IL6) polymorphism (rs2069840) was associated with ANO in females (OR: 2.6, 95% confidence interval [CI]: 1.5–4.7; p = 0.001), but not in males (OR: 0.8, 95% CI: 0.5–1.2; p = 0.33). The sex-specific effect difference was significant (p = 7.0 × 10−4) and was unaffected by MgSO4 exposure. No other gene–sex associations were significant. Conclusion An IL6 gene locus may confer susceptibility to ANO in females, but not males, after EPTB.
Source: American Journal of Perinatology
Authors: Michael W. Varner, Maged M. Costantine, Kathleen A. Jablonski, Dwight J. Rouse, Brian M. Mercer, Kenneth J. Leveno, Uma M. Reddy, Catalin Buhimschi, Ronald J. Wapner, Yoram Sorokin, John M. Thorp, Susan M. Ramin, Fergal D. Malone, Marshall Carpenter, Mary J. O'sullivan, Alan M. Peaceman, Donald J. Dudley, Steve N. Caritis, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
Institutions: University of Utah, The University of Texas Medical Branch at Galveston, George Washington University, University of Alabama at Birmingham, MetroHealth Medical Center, Case Western Reserve University, The University of Texas Southwestern Medical Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development, The Ohio State University, Thomas Jefferson University, Drexel University, Wayne State University, University of North Carolina at Chapel Hill, The University of Texas Health Science Center at Houston, Columbia University, Brown University, University of Miami, Northwestern University, The University of Texas at San Antonio Health Science Center, University of Pittsburgh
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1212214770, G1414004571, General Clinical Research Center, Maternal Fetal Medicine Network: Data Coordinating Cent*, Eunice Kennedy Shriver NICHD Maternal Fetal Medicine Units Network, Maternal Fetal Medicine Units Network, NICHD Maternal Fetal Medicine Units Network, NICHD Maternal-Fetal Medicine Units (MFMU) Network, Maternal-Fetal Medicine Units Network, NICHD Maternal Fetal Medicine Units Network, G3234702349, G3345784204, Eunice Kennedy Shriver NICHD Maternal Fetal Medicine Units Network, Cooperative Multicenter Maternal Fetal Medicine Units Networks, Co-Operative Multicenter Trials in Obstetrics & Maternal Fetal Medicine, Data Coord Ctr-NICHD Cooperative Multicenter Maternal Medicine Units Research Net, MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS, MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS, Multicenter Network of Maternal Fetal Medicine Units, G5410992165, G5983902235, G6217874022, G6353120905, G6357807977, Eunice Kennedy Shriver NICHD Maternal Fetal Medicine Units Network (U10), G6652527080, Brown/WIH Eunice Kennedy Shriver NICHD MFM Units Network Site, G686192456, MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS, G6965387750, G7108069461, Maternal Fetal Medicine Network, G7274870677, Carolina Population Center, G7525158495, G7592277339, G7626983559, NICHD NETWORKS: DATA COORDINATING CENTER, G8003220005, NICHD Materal Fetal Medicine Units Network, MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS, G8402760467, G8597359909, G8856729796, G8884496267, G8943511676, UofU Maternal-Fetal Medicine Units (MFMU) Network: Clinical Centers, NICHD Maternal-Fetal Medicine Units (MFMU) Network: Data CoordinatingCenter, Brown University/Women & Infants Hospital of Rhode Island (WIH) Center Application for the Eunice Kennedy Shriver NICHD Maternal Fetal Medicine Units Network, Maternal Fetal Medicine Units Network - Northwestern Study Center, Maternal-Fetal Medicine Units (MFMU) Network, Yale Clinical and Translational Science Award, Case Western Reserve University Center of the NICHD MFMU Network, Columbia University Maternal-Fetal Medicine Units Network Clinical Center, NICHD maternal fetal medicine units network, UNC MFMU: Advancing Perinatal Health via Definitive, Multi-Site Clinical Studies, Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units (MFMU) Network (UG1)
OpenAlex ID: W2914233056