Michael W Varner1, Nicole E Marshall2, Dwight J Rouse3, Kathleen A Jablonski4, Kenneth J Leveno5, Uma M Reddy6, Brian M Mercer7, Jay D Iams8, Ronald J Wapner9, Yoram Sorokin10, John M Thorp11, Fergal D Malone12, Marshall Carpenter13, Mary J O'Sullivan14, Alan M Peaceman15, Gary D V Hankins16, Donald J Dudley17, Steve N Caritis18. 1. Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah. 2. Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon. 3. Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama. 4. Department of Biostatistics, George Washington University Biostatistics Center, Washington, District of Columbia. 5. Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas. 6. Department of Obstetrics and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development. 7. Department of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio. 8. Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio. 9. Department of Obstetrics and Gynecology, Thomas Jefferson University and Drexel University, Philadelphia, Pennsylvania. 10. Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan. 11. Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 12. Department of Obstetrics and Gynecology, Columbia University, New York, New York. 13. Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island. 14. Department of Obstetrics and Gynecology, University of Miami, Miami, Florida. 15. Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois. 16. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas. 17. University of Texas Health Science Center at San Antonio, San Antonio, Texas. 18. Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
OBJECTIVE: To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). STUDY DESIGN: Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. RESULTS: Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. CONCLUSION:Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
RCT Entities:
OBJECTIVE: To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). STUDY DESIGN: Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. RESULTS: Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. CONCLUSION: Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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