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 Sorokin, Roberto Romero, Lisa Mele, Ronald J. Wapner, Jay D. Iams, Donald J. Dudley, Catherine Y. Spong, Alan M. Peaceman, Kenneth J. Leveno, Margaret Harper, Steve N. Caritis, Menachem Miodovnik, Brian M. Mercer, John M. Thorp, Mary Jo O'Sullivan, Susan M. Ramin, Marshall W. Carpenter, Dwight J. Rouse, Baha Sibai

Research output: Contribution to journalArticle

96 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalAmerican Journal of Perinatology
Volume27
Issue number8
DOIs
StatePublished - 2010

Fingerprint

Matrix Metalloproteinase 9
Premature Birth
Interleukin-6
Mothers
C-Reactive Protein
Serum
Proteins
Odds Ratio
Confidence Intervals
Random Allocation
Logistic Models
Regression Analysis
Morbidity
Membranes
Therapeutics

Keywords

  • cytokines
  • Maternal serum
  • neonatal morbidity
  • preterm birth

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Maternal serum interleukin-6, c-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes. / Sorokin, Yoram; Romero, Roberto; Mele, Lisa; Wapner, Ronald J.; Iams, Jay D.; Dudley, Donald J.; Spong, Catherine Y.; Peaceman, Alan M.; Leveno, Kenneth J.; Harper, Margaret; Caritis, Steve N.; Miodovnik, Menachem; Mercer, Brian M.; Thorp, John M.; O'Sullivan, Mary Jo; Ramin, Susan M.; Carpenter, Marshall W.; Rouse, Dwight J.; Sibai, Baha.

In: American Journal of Perinatology, Vol. 27, No. 8, 2010, p. 631-639.

Research output: Contribution to journalArticle

Sorokin, Y, Romero, R, Mele, L, Wapner, RJ, Iams, JD, Dudley, DJ, Spong, CY, Peaceman, AM, Leveno, KJ, Harper, M, Caritis, SN, Miodovnik, M, Mercer, BM, Thorp, JM, O'Sullivan, MJ, Ramin, SM, Carpenter, MW, Rouse, DJ & Sibai, B 2010, 'Maternal serum interleukin-6, c-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes', American Journal of Perinatology, vol. 27, no. 8, pp. 631-639. https://doi.org/10.1055/s-0030-1249366
Sorokin, Yoram ; Romero, Roberto ; Mele, Lisa ; Wapner, Ronald J. ; Iams, Jay D. ; Dudley, Donald J. ; Spong, Catherine Y. ; Peaceman, Alan M. ; Leveno, Kenneth J. ; Harper, Margaret ; Caritis, Steve N. ; Miodovnik, Menachem ; Mercer, Brian M. ; Thorp, John M. ; O'Sullivan, Mary Jo ; Ramin, Susan M. ; Carpenter, Marshall W. ; Rouse, Dwight J. ; Sibai, Baha. / Maternal serum interleukin-6, c-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes. In: American Journal of Perinatology. 2010 ; Vol. 27, No. 8. pp. 631-639.
@article{1310afe721b34a3396f069e3c83e8450,
title = "Maternal serum interleukin-6, c-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes",
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.",
keywords = "cytokines, Maternal serum, neonatal morbidity, preterm birth",
author = "Yoram Sorokin and Roberto Romero and Lisa Mele and Wapner, {Ronald J.} and Iams, {Jay D.} and Dudley, {Donald J.} and Spong, {Catherine Y.} and Peaceman, {Alan M.} and Leveno, {Kenneth J.} and Margaret Harper and Caritis, {Steve N.} and Menachem Miodovnik and Mercer, {Brian M.} and Thorp, {John M.} and O'Sullivan, {Mary Jo} and Ramin, {Susan M.} and Carpenter, {Marshall W.} and Rouse, {Dwight J.} and Baha Sibai",
year = "2010",
doi = "10.1055/s-0030-1249366",
language = "English (US)",
volume = "27",
pages = "631--639",
journal = "American Journal of Perinatology",
issn = "0735-1631",
publisher = "Thieme Medical Publishers",
number = "8",

}

TY - JOUR

T1 - Maternal serum interleukin-6, c-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes

AU - Sorokin, Yoram

AU - Romero, Roberto

AU - Mele, Lisa

AU - Wapner, Ronald J.

AU - Iams, Jay D.

AU - Dudley, Donald J.

AU - Spong, Catherine Y.

AU - Peaceman, Alan M.

AU - Leveno, Kenneth J.

AU - Harper, Margaret

AU - Caritis, Steve N.

AU - Miodovnik, Menachem

AU - Mercer, Brian M.

AU - Thorp, John M.

AU - O'Sullivan, Mary Jo

AU - Ramin, Susan M.

AU - Carpenter, Marshall W.

AU - Rouse, Dwight J.

AU - Sibai, Baha

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - cytokines

KW - Maternal serum

KW - neonatal morbidity

KW - preterm birth

UR - http://www.scopus.com/inward/record.url?scp=77955540389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955540389&partnerID=8YFLogxK

U2 - 10.1055/s-0030-1249366

DO - 10.1055/s-0030-1249366

M3 - Article

C2 - 20195952

AN - SCOPUS:77955540389

VL - 27

SP - 631

EP - 639

JO - American Journal of Perinatology

JF - American Journal of Perinatology

SN - 0735-1631

IS - 8

ER -