Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery

Wenstrom, Katharine D.; Andrews, William; Hauth, John C.; Goldenberg, Robert L.; DuBard, Mary B.; Cliver, Suzanne P.

doi:10.1016/s0002-9378(98)70436-3

Cited by 207 publications

(107 citation statements)

References 14 publications

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“…Intra-amniotic inflammation has been repeatedly associated with spontaneous preterm labor and preterm premature rupture of membranes (PROM). [4][5][6] The migration of fetal neutrophils into the amniotic cavity and their subsequent activation and release of proteolytic enzymes, including MMP-8, characterizes the intraamniotic inflammatory response. Previously Maymon et al [7][8][9] reported an increase in amniotic fluid MMP-8 levels in the setting of both preterm labor with intact membranes and preterm PROM.…”

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confidence: 99%

“…Previously Maymon et al [7][8][9] reported an increase in amniotic fluid MMP-8 levels in the setting of both preterm labor with intact membranes and preterm PROM. Because markers of intrauterine inflammation at the time of midtrimester genetic amniocentesis have been associated with preterm delivery and pregnancy loss, 4,7 we hypothesized that MMP-8 levels measured in amniotic fluid obtained from asymptomatic women at the time of midtrimester genetic amniocentesis would be associated with subsequent preterm PROM because of its effect on weakening the extracellular matrix of the fetal membranes.…”

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confidence: 99%

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Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes

Biggio

Ramsey

Cliver

et al. 2005

American Journal of Obstetrics and Gynecology

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Objective-We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes.Study design-We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks' gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed.Results-The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03).Conclusions-The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. KeywordsPresented at the 23rd Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, Calif, Feb 3-8, 2003 Collagens are a family of proteins responsible for the maintenance of tissue tensile strength. Each collagen molecule is composed of 3 polypeptide chains in a triple helical configuration with the specific composition of the monomeric chains defining the collagen subtype. The predominant collagens of the chorioamnion extracellular matrix are types I and III, but types IV, V, and VI have been localized to the amnion as well. 1,2 Matrix metalloproteinases (MMP), a family of potent enzymes capable of ...

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confidence: 99%

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes

Biggio

Ramsey

Cliver

et al. 2005

American Journal of Obstetrics and Gynecology

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“…However, assessment of very specific inflammatory biochemical markers of preterm birth, such as interleukin 6 require both an invasive procedure (amniocentesis) and costly, sophisticated laboratory facilities. 27 While others have suggested the predictive value of PAPP-A in preterm labor, 6-13 this work was primarily based on PAPP-A values obtained at an early gestational age, most often in the first trimester. Interestingly, the structural sequence of PAPP-A is characterized by five short consensus repeats seen in components of the complement system.…”

Section: Discussionmentioning

confidence: 99%

PAPP-A levels as an early marker of idiopathic preterm birth: a pilot study

et al. 2007

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Objective: To evaluate late PAPP-A levels as predictive of preterm birth in symptomatic women.Study Design: Prospective cohort study of singleton gestations, 23 to 34 weeks, and symptoms of preterm labor. PAPP-A, IGF-I and IGF-III analysis were performed. Primary end point was delivery p7 days. Accuracy and optimally predictive PAPP-A values were based on receiver operator characteristic (ROC) curves.Result: In all, 26 women (51%) delivered p7 days post-admission (Group 1); 25 women (49%) >7 days (Group 2). Group 1 mean PAPP-A ¼ 38 000 vs 55 333 for Group 2 (P<0.04). Group 1 mean gestational age at delivery ¼ 29 weeks vs 37 weeks for Group 2 (P<0.00014). PAPP-A level p30 000 mU l À1 had highest specificity (88%), sensitivity (50%), and positive predictive (81%) and negative predictive (62%) values for delivery p7 days. ROC area under curve ¼ 0.703.Conclusion: PAPP-A levels p30 000 mU l À1 at admission was associated with increased risk for preterm birth p7 days, supporting active management and therapeutic approach in these women.

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“…Despite considerable effort, the incidence of preterm birth is still rising. [4] We have proposed that spontaneous preterm parturition is a syndrome [1]resulting from multiple pathological processes including intrauterine infection [5][6][7][8][9][10][11][12], uterine overdistension [13][14][15][16], allergic-like reaction [17][18][19], cervical disease [20][21][22], endocrine disorders [23][24][25][26], maternal or fetal stress[27-31]and uterine ischemia. Evidence in support for a role of utero-placental ischemia as a mechanism of disease leading to preterm labor (PTL) includes: 1) an experimental study showed that, after induced uterine ischemia (designed to generate a primate model for preeclampsia), a proportion of animals went into PTL and delivery [32]; 2) patients with PTL and preterm PROM who delivered preterm had a higher percentage of failure of physiologic transformation in myometrial segment of the spiral arteries than women who delivered at term [33,34]; 3) increased impedance to flow in uterine artery in the second trimester increased risk of preterm delivery [35].…”

Section: Introductionmentioning

confidence: 99%

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

Chaiworapongsa¹,

Romero²,

Tarca³

et al. 2009

DJMF

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OBJECTIVE-An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction, and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and antiangiogenic factors different from normal pregnant women.STUDY DESIGN-This longitudinal nested case-control study included normal pregnant women (n=208) and patients with PTL leading to preterm delivery (n=52). Maternal blood samples were collected at 6 gestational age intervals from 6-36.9 weeks of gestation. The end point (time of diagnosis) of the study, "True PTL", was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. RESULTS-1)Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of "true NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript PTL". 2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of "true PTL"; and 3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patents diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. CONCLUSION-The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition.

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Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery

Cited by 207 publications

References 14 publications

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes

PAPP-A levels as an early marker of idiopathic preterm birth: a pilot study

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

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