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Change in Mononuclear Leukocyte Responsiveness in Midpregnancy and Subsequent Preterm Birth

Harper, Margaret MD, MSc; Li, Liwu PhD; Zhao, Yuan MSc; Klebanoff, Mark A. MD, MPH; Thorp, John M. Jr MD; Sorokin, Yoram MD; Varner, Michael W. MD; Wapner, Ronald J. MD; Caritis, Steve N. MD; Iams, Jay D. MD; Carpenter, Marshall W. MD; Peaceman, Alan M. MD; Mercer, Brian M. MD; Sciscione, Anthony DO; Rouse, Dwight J. MD; Ramin, Susan M. MD; Anderson, Garland D. MD

doi: 10.1097/AOG.0b013e3182878a80
Original Research

OBJECTIVE: To estimate the associations of change in immune response with preterm delivery, omega-3 supplementation, and fish diet.

METHODS: This was an ancillary study to a randomized trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. In vitro maternal peripheral blood mononuclear leukocyte production of the anti-inflammatory cytokine, interleukin-10, and the proinflammatory cytokine, tumor necrosis factor-α, in response to stimulation with lipopolysaccharide, was measured at 16–22 weeks of gestation (baseline) and again at 25–28 weeks of gestation (follow-up) among women with prior spontaneous preterm birth. Changes in concentrations from baseline to follow-up ([INCREMENT]) were compared separately among groups defined by gestational age category at delivery, fish diet history, and omega-3 compared with placebo treatment assignment with Kruskal-Wallis tests.

RESULTS: Interleukin-10 [INCREMENT] differed by gestational age category among 292 women with paired assays. Concentrations increased less in women delivering between 35 and 36 6/7 weeks of gestation (48.9 pg/mL) compared with women delivering at term (159.3 pg/mL) and decreased by 65.2 pg/mL in women delivering before 35 weeks of gestation (P=.01). Tumor necrosis factor-α Δ also differed by gestational age category among 319 women, but the pattern was inconsistent. Those delivering between 35 and 36 6/7 weeks of gestation exhibited decreased concentrations of tumor necrosis factor-α at follow-up compared with baseline (−356.0 pg/mL); concentrations increased among women delivering before 35 weeks of gestation and those delivering at term, 132.1 and 86.9 pg/mL (P=.03). Interleukin-10 Δ and tumor necrosis factor-α Δ were unaffected by either omega-3 supplementation or fish diet.

CONCLUSION: Recurrent preterm birth was associated with decreased peripheral blood mononuclear leukocyte production of interleukin-10 in response to a stimulus during the second trimester.



Peripheral blood mononuclear leukocyte production of interleukin-10 is downregulated during the second trimester among women delivering preterm compared with women delivering at term.Supplemental Digital Content is Available in the Text.

Departments of Obstetrics and Gynecology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Wayne State University, Detroit, Michigan, University of Utah Health Sciences Center, Salt Lake City, Utah, Columbia University, New York, New York, University of Pittsburgh, Pittsburgh, Pennsylvania, The Ohio State University, Columbus, Ohio, Women and Infants Hospital, Brown University, Providence, Rhode Island, Northwestern University, Chicago, Illinois, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio, Drexel University College of Medicine, Philadelphia, Pennsylvania, the University of Alabama at Birmingham, Birmingham, Alabama, the University of Texas Health Science Center at Houston, Houston, Texas, and the University of Texas Medical Branch, Galveston, Texas; the Division of Inflammation Biology and Immunology, Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia; the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

Corresponding author: Margaret Harper, MD, MSc, Mountain Area Health Education Center, 119 Hendersonville Road, Asheville, NC 28803; e-mail:

The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD27860, HD27917, HD40560, HD34208, HD40485, HD21410, HD27915, HD40500, HD40512, HD40544, MO1-RR-000080, HD34136, HD27869, HD40545, HD36801, HD19897) and does not necessarily represent the official views of the NICHD or the National Institutes of Health.

Presented at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, February 7-12, 2011, San Francisco, California.

Financial Disclosure The authors did not report any potential conflicts of interest.

The authors thank Karen Dorman, RN, MS, for protocol development and coordination between clinical research centers, Elizabeth Thom, PhD, for protocol and data management and statistical analysis, and Catherine Y. Spong, MD, for protocol development and oversight.

*For a list of other members of the NICHD MFMU, see the Appendix online at

Dr. Spong and Dr. Rouse, Associate Editors of Obstetrics & Gynecology, were not involved in the review or decision to publish this article.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.