A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition

Romero, Roberto; Gomez, Ricardo; Ghezzi, Fabio; Yoon, Bo Hyun; Mazor, Moshe; Edwin, Samuel S.; Berry, Stanley M.

doi:10.1016/s0002-9378(98)70271-6

Cited by 509 publications

(341 citation statements)

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“…Maternal infection is a common cause of preterm birth, [23][24][25] as well as CP. However, preterm birth may be associated with CP through other, noninflammatory mechanisms as well.…”

Section: Discussionmentioning

confidence: 99%

Maternal Infection and Risk of Cerebral Palsy in Term and Preterm Infants

et al. 2004

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We tested the hypothesis that term and preterm infants exposed to maternal infection at the time of delivery are at increased risk of developing cerebral palsy (CP). STUDY DESIGN:A population-based case-control study was conducted using Washington State birth certificate data linked to hospital discharge data. Cases (688) were children r6 years old, singleton births, hospitalized during 1987 to 1999 with an ICD-9 diagnosis code for CP. Controls were 3068 singleton birth infants randomly selected from birth records for the same years without CP-related hospitalizations. Infection information was available only for the birth hospitalization. RESULTS:Infants of women who had any infection during their hospitalization for delivery were at increased risk of CP (odds ratio (OR) 3.1, 95% confidence interval (CI) 2.3 to 4.2). This was observed for term deliveries (OR 1.8, 95% CI 1.1 to 2.8) and preterm deliveries (OR 2.3, 95% CI 1.3 to 4.2). CONCLUSIONS:Our results suggest that maternal infection is a risk factor for CP in both term and preterm infants.

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“…Maternal infection is a common cause of preterm birth, [23][24][25] as well as CP. However, preterm birth may be associated with CP through other, noninflammatory mechanisms as well.…”

Section: Discussionmentioning

confidence: 99%

Maternal Infection and Risk of Cerebral Palsy in Term and Preterm Infants

et al. 2004

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“…Although infection in amniotic fluid is common, systemic sepsis soon after birth is detected in only 2% of these preterm infants (2). However, ϳ50% of infants exposed to chorioamnionitis have a systemic inflammatory response, referred to as fetal inflammatory response syndrome (FIRS) 3 (3)(4)(5). Unlike the cytokine storm associated with the adult systemic inflammatory response, FIRS is often a more subtle inflammatory response (4,6).…”

Section: Pulmonary and Systemic Endotoxin Tolerance In Pretermmentioning

confidence: 99%

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Kallapur

Jobe

Ball

et al. 2007

The Journal of Immunology

108

139

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In a model of human chorioamnionitis, fetal sheep exposed to a single injection, but not repeated injections, of intra-amniotic endotoxin develop lung injury responses. We hypothesized that repeated exposure to intra-amniotic endotoxin induces endotoxin tolerance. Fetal sheep were given intra-amniotic injections of saline (control) or Escherichia coli LPS O55:B5 (10 mg) either 2 days (2-day group, single exposure), 7 days (7-day group, single exposure), or 2 plus 7 days (2- and 7-day repeat exposure) before preterm delivery at 124 days gestation (term = 150 days). Endotoxin responses were assessed in vivo in the lung and liver, and in vitro in monocytes from the blood and the lung. Compared with the single 2-day LPS exposure group, the (2 plus 7 days) repeat LPS-exposed lambs had: 1) decreased lung neutrophil and monocyte inducible NO synthase (NOSII) expression, and 2) decreased lung cytokine and liver serum amyloid A3 mRNA expression. In the lung, serum amyloid A3 mRNA expression decreased in the airway epithelial cells but not in the lung inflammatory cells. Unlike the single 7-day LPS exposure group, peripheral blood and lung monocytes from the repeat-LPS group did not increase IL-6 secretion or hydrogen peroxide production in response to in vitro LPS. Compared with controls, TLR4 expression did not change but IL-1R-associated kinase M expression increased in the monocytes from repeat LPS-exposed lambs. These results are consistent with the novel finding of endotoxin tolerance in preterm fetal lungs exposed to intra-amniotic LPS. The findings have implications for preterm infants exposed to chorioamnionitis for both responses to lung injury and postnatal nosocomial infections.

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“…Neutrophils involved in intrauterine inflammation are thought to be predominantly of fetal lineage, and Romero et al 5,13,14 have shown that the fetus may therefore play a role in preterm PROM. Amniotic fluid levels of MMP-8 obtained at the time of diagnosis of preterm PROM are elevated and are an indicator of intra-amniotic infection.…”

Section: Commentmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…Despite this similarity, it is, however, clear that patients with extreme elevations of MMP-8 levels are at increased risk for subsequent preterm PROM, reflecting a state of neutrophil activation as early as 16 weeks' gestation. The lack of elevation in MMP-8 levels in some subjects may reflect the multitude of pathophysiologic pathways, proteases, and collagenases that can be involved in preterm PROM or may simply reflect timing of sample collection.Neutrophils involved in intrauterine inflammation are thought to be predominantly of fetal lineage, and Romero et al 5,13,14 have shown that the fetus may therefore play a role in preterm PROM. Amniotic fluid levels of MMP-8 obtained at the time of diagnosis of preterm PROM are elevated and are an indicator of intra-amniotic infection.…”

mentioning

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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A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition

Cited by 509 publications

References 18 publications

Maternal Infection and Risk of Cerebral Palsy in Term and Preterm Infants

Maternal Infection and Risk of Cerebral Palsy in Term and Preterm Infants

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

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

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