Obstetrics & Gynecology

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Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e3182878a80
Original Research

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; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network

Supplemental Author Material
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Abstract

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.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902.

LEVEL OF EVIDENCE: II

© 2013 The American College of Obstetricians and Gynecologists

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