The Association of Cord Serum Cytokines with Neurodevelopmental Outcomes

Michael W. Varner; Nicole E. Marshall; Dwight J. Rouse; Kathleen A. Jablonski; Kenneth J. Leveno; Uma M. Reddy; Brian M. Mercer; Jay D. Iams; Ronald J. Wapner; Yoram Sorokin; John M. Thorp; Fergal D. Malone; Marshall Carpenter; Mary J. O'Sullivan; Alan M. Peaceman; Gary D. V. Hankins; Donald J. Dudley; Steve N. Caritis; ; for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network

doi:10.1055/s-0034-1376185

American Journal of Perinatology, Table of Contents

Am J Perinatol 2015; 32(02): 115-122
DOI: 10.1055/s-0034-1376185

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Association of Cord Serum Cytokines with Neurodevelopmental Outcomes

Michael W. Varner

¹Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah

,

Nicole E. Marshall

²Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon

,

Dwight J. Rouse

³Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama

,

Kathleen A. Jablonski

⁴Department of Biostatistics, George Washington University Biostatistics Center, Washington, District of Columbia

,

Kenneth J. Leveno

⁵Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas

,

Uma M. Reddy

⁶Department of Obstetrics and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development

,

Brian M. Mercer

⁷Department of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio

⁸Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee

,

Jay D. Iams

⁹Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio

,

Ronald J. Wapner

¹⁰Department of Obstetrics and Gynecology, Thomas Jefferson University and Drexel University, Philadelphia, Pennsylvania

,

Yoram Sorokin

¹¹Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan

,

John M. Thorp

¹²Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

,

Fergal D. Malone

¹³Department of Obstetrics and Gynecology, Columbia University, New York, New York

,

Marshall Carpenter

¹⁴Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island

,

Mary J. O'Sullivan

¹⁵Department of Obstetrics and Gynecology, University of Miami, Miami, Florida

,

Alan M. Peaceman

¹⁶Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois

,

Gary D. V. Hankins

¹⁷Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas

,

Donald J. Dudley

¹⁸University of Texas Health Science Center at San Antonio, San Antonio, Texas

,

Steve N. Caritis

¹⁹Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania

,

; for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network

› Author Affiliations

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.

Keywords

cytokines - cerebral palsy - neurodevelopmental outcomes - prematurity - magnesium sulfate

Full Text

References

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