Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes

Yoon, Bo Hyun; Romero, Roberto; Moon, Jeong Mi; Shim, So Yeon; Kim, Miha; Kim, Gilja; Jun, Jong Kwan

doi:10.1067/mob.2001.117680

Cited by 567 publications

(518 citation statements)

References 25 publications

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“…It is more frequent at the lowest gestational age (GA) 10,11 ( Table 1), but it also complicates 1%-13% of term births. 6 The diagnosis of CA can be made on clinical, histopathological, biochemical, or microbiological grounds, but disagreement in the criteria for diagnosis is common.…”

Section: Introductionmentioning

confidence: 99%

Chorioamnionitis and neonatal morbidity: current perspectives

Henríquez¹,

Rodrigo²

2017

RRN

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Abstract:The term chorioamnionitis (CA) is commonly used to refer to different clinical or pathological conditions characterized by an infectious and/or inflammatory process that affects primarily the chorioamniotic membranes, but also the amniotic fluid, vessels of the chorionic plate, and, eventually, the umbilical cord (funisitis) and the fetus. Its incidence is higher at lower gestational ages, and the main mechanism is believed to be the ascending bacterial infection from the maternal genital tract. It can be diagnosed by clinical criteria, amniotic fluid examination for inflammatory mediators, and/or isolation of microorganisms, or by histopathological examination of the placenta. CA is an important cause of stillbirth and is related to an increased incidence of premature rupture of membranes, preterm delivery, and adverse maternal and neonatal outcomes such as early-onset neonatal sepsis and necrotizing enterocolitis. An independent causal association to other neonatal morbidities is more controversial. The heterogeneity in the diagnostic criteria and in the operative definitions for morbidity makes comparison of studies difficult, and results are inconsistent. In addition, the intensity and duration of the process are usually not considered. For all these reasons, evidence-based recommendations for the management of mother and infant under these circumstances are difficult to establish, and clinical practice varies widely.

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Section: Introductionmentioning

confidence: 99%

Chorioamnionitis and neonatal morbidity: current perspectives

Henríquez¹,

Rodrigo²

2017

RRN

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“…The Asp299Gly polymorphism, a variant of the human TLR4 gene, has been associated with PTB (8). However, despite these associations, it remains unclear what exact role microbial infection has in PEC as microbial products are rarely detected in the maternal circulation, and furthermore it has been estimated that only 30% of PTB cases demonstrate evidence of microbial infection (9). To further this discrepancy, antibiotic treatment has never been shown to decrease rates of preterm delivery (10).…”

mentioning

confidence: 99%

TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal Loss in Preterm Birth and Preeclampsia

Scharfe-Nugent

Corr

Carpenter

et al. 2012

The Journal of Immunology

151

173

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Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflammation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in spontaneous preterm birth. Fetal DNA activates NF-κB, shown by IκBα degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 μg/dam) on gestational day 10–14. In contrast, TLR9−/− mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of pregnancy.

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“…6 Recently, a study demonstrated that inflammatory cytokines in cervicovaginal fluid and in amniotic fluid, but not in plasma, are strongly associated with spontaneous PTD in women, suggesting that inflammation at the maternal-fetal interface, rather than systemic inflammation, may play a major role in the etiology of PTD. 7 Despite the growing association between inflammation and PTD, the mediators, receptors, and cellular participants in triggering cervical changes remain unclear.…”

mentioning

confidence: 99%

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

González

Franzke

Yang

et al. 2011

The American Journal of Pathology

Self Cite

157

177

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Inflammation is frequently linked to preterm delivery (PTD). Here, we tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS) and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophages infiltration and increased serum C3adesArg and C5adesArg levels were observed in both models when compared to gestational age matched controls. A significant increase in collagen degradation, matrix metalloproteinase 9 (MMP-9) activity and tissue distensibility was observed in the cervix in both models. Mice deficient in complement receptor C5a did not show increased MMP-9 activity and cervical remodeling and did not deliver preterm in response to LPS or RU486, suggesting a role for C5aR in the cervical changes that precede PTD. In vitro studies show that macrophages release MMP-9 in response to C5a. Progesterone diminished the amount of C5aR on the macrophages surface, inhibited the release of MMP-9 and prevented PTD. In addition, macrophages depletion also prevented cervical remodeling and PTD in LPS-treated mice. Our studies show that C5a-C5aR interaction is required for MMP-9 release from macrophages, and the cervical remodeling that leads to PTD. Complement inhibition and supplementation with progesterone may be good therapeutic options to prevent this serious pregnancy complication. Premature birth/delivery (PTD) is one of the most significant causes of perinatal mortality and morbidity in developed countries. Preterm infants suffer morbidities including respiratory distress, intraventricular hemorrhage, and cerebral palsy, among other serious diseases.1 These outcomes can have a life-long impact and more than $25 billion is spent each year to take care of these infants. Investigations to define the causes of PTD remain a challenge in the obstetrical field. Preterm labor is a multistage biochemical and biophysical process, during which changes in the myometrium and the cervix occur.The uterine cervix is a complex organ that undergoes extensive changes through gestation and parturition. These changes are a common first step in preterm parturition.2 As a gatekeeper for pregnancy, the cervix is a structural barrier that keeps the fetus inside the uterus until the end of gestation. Collagens, elastin, proteoglycans, and hyaluronate are responsible for the full tensile strength of the cervix.2 Ripening of the cervix is an important biological and clinical event required for a normal parturition. The process is gradual during pregnancy, with a fast final remodeling of the cervix before parturition. Increased collagen degradation and synthesis, and high activity of collagenases have been observed in the human cervix during final ripening.

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Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes

Cited by 567 publications

References 25 publications

Chorioamnionitis and neonatal morbidity: current perspectives

Chorioamnionitis and neonatal morbidity: current perspectives

TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal Loss in Preterm Birth and Preeclampsia

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

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