Am J Perinatol 2010; 27(8): 631-640
DOI: 10.1055/s-0030-1249366
© Thieme Medical Publishers

Maternal Serum Interleukin-6, C-Reactive Protein, and Matrix Metalloproteinase-9 Concentrations as Risk Factors for Preterm Birth <32 Weeks and Adverse Neonatal Outcomes

Yoram Sorokin1 , 2 , Roberto Romero3 , Lisa Mele4 , Ronald J. Wapner1 , 5 , Jay D. Iams1 , 6 , Donald J. Dudley1 , 7 , Catherine Y. Spong8 , Alan M. Peaceman1 , 9 , Kenneth J. Leveno1 , 10 , Margaret Harper1 , 11 , Steve N. Caritis1 , 12 , Menachem Miodovnik1 , 13 , 14 , Brian M. Mercer1 , 15 , John M. Thorp1 , 16 , Mary Jo O'Sullivan1 , 17 , Susan M. Ramin1 , 18 , Marshall W. Carpenter1 , 19 , Dwight J. Rouse1 , 20 , Baha Sibai1 , 21 for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
  • 1The Departments of Obstetrics and Gynecology at Wayne State University, Detroit, Michigan
  • 2Wayne State University, Detroit, Michigan
  • 3The Perinatology Research Branch, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, Michigan
  • 4The George Washington University Biostatistics Center, Washington, District of Columbia
  • 5Drexel University College of Medicine, Philadelphia, Pennsylvania
  • 6The Ohio State University, Columbus, Ohio
  • 7University of Utah, Salt Lake City, Utah
  • 8the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • 9Northwestern University, Chicago, Illinois
  • 10University of Texas Southwestern Medical Center, Dallas, Texas
  • 11Wake Forest University Health Sciences, Winston-Salem, North Carolina
  • 12University of Pittsburgh, Pittsburgh, Pennsylvania
  • 13Columbia University, New York, New York
  • 14University of Cincinnati, Cincinnati, Ohio
  • 15Case Western Reserve University, Cleveland, Ohio
  • 16University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • 17University of Miami, Miami, Florida
  • 18The University of Texas Health Science Center at Houston, Houston, Texas
  • 19Brown University, Providence, Rhode Island
  • 20University of Alabama at Birmingham, Birmingham, Alabama
  • 21University of Tennessee, Memphis, Tennessee
Further Information

Publication History

Publication Date:
01 March 2010 (online)

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ABSTRACT

Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery.

REFERENCES

Yoram SorokinM.D. 

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology

Hutzel Women's Hospital, 3990 John R, Mailbox 163, Detroit MI, 48201

Email: ysorokin@med.wayne.edu