Premature labor: a state of platelet activation?

Romero

et al. 2010

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Objective: Previous studies reported that the clinical significance of intra-amniotic inflammation with a negative amniotic fluid (AF) culture is similar to that of intra-amniotic inflammation with microbiologically-proven AF infection. However, the magnitude of the fetal inflammatory response in these two conditions is different as gauged by umbilical cord C-reactive protein (CRP) concentrations. We undertook this study to determine if the frequency of oligohydramnios is different in these two conditions. Methods: The amniotic fluid index (AFI) was measured in 205 patients with preterm premature rupture of membranes (PROM) (F35 weeks). AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 (MMP-8) concentration ()23 ng/mL). Patients were divided into three groups according to the results of AF culture and the presence or absence of intraamniotic inflammation: 1) without intra-amniotic inflammation and a negative culture (ns109); 2) with intra-amniotic inflammation and a negative culture (ns44); and 3) a positive culture (ns52). Results: Patients with a positive culture had a higher frequency of oligohydramnios and a lower median AFI than those with a negative culture but with intra-amniotic inflammation (P-0.01). However, there was no significant difference in the median AFI or in the frequency of oligohydramnios according to the presence or absence of intraamniotic inflammation among patients with a negative culture (P)0.1). Conclusion: Oligohydramnios was more frequent in patients with culture-proven AF infection than in those with intraamniotic inflammation and a negative AF culture.

Section: Commentmentioning

confidence: 71%

Amniotic fluid volume in intra-amniotic inflammation with and without culture-proven amniotic fluid infection in preterm premature rupture of membranes

Romero

et al. 2010

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“…Each of these pathways is central in the deployment of an inflammatory response: cytokine-cytokine receptor interaction, Jak-STAT signaling, the complement and coagulation pathway, NOD-like receptor signaling, systemic lupus erythematosus (specifically the complement C1q complex), and chemokine signaling. Interestingly, components of these pathways have been previously linked to both normal parturition [57, 75, 76, 159, 180, 201, 213, 221, 226–228, 235, 271, 274, 308] and the “Great Obstetrical Syndromes” [32, 33, 64, 79–82, 84, 85, 89, 238, 267, 291, 295, 307, 320], including preterm labor [28, 58, 74, 77, 83, 86–88, 119, 120, 164, 165, 211, 223, 246, 252, 254, 290, 292, 293, 316–319]. Indeed, our group has reported an association between activation of the NALP3 inflammasome and the common pathway of parturition [119].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

Mittal¹,

Romero²,

Tarca³

et al. 2010

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142

113

Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term. Methods: Myometrium was obtained from women with (ns19) and without labor (ns20). Illumina ᭨ HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set. Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.

“…Intra-amniotic inflammation (regardless of the presence or absence of proven intra-amniotic infection) is associated with adverse pregnancy outcome [9, 23, 38, 48]. Recent studies revealed that various chemokines [11, 14, 16, 18, 21, 29, 30], as well as traditional proinflammatory cytokines such as the interleukin family [3, 13, 19, 45] and MMPs [4, 10, 27, 32], play a role in the pathogenesis of intra-amniotic infection/inflammation and preterm parturition.…”

Section: Commentmentioning

confidence: 99%

Detection of ureaplasmas by the polymerase chain reaction in the amniotic fluid of patients with cervical insufficiency

Jung

et al. 2010

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140

107

Aims The purpose of this study was to determine the clinical significance of detecting microbial footprints of ureaplasmas in amniotic fluid (AF) using specific primers for the polymerase chain reaction (PCR) in patients presenting with cervical insufficiency. Methods Amniocentesis was performed in 58 patients with acute cervical insufficiency (cervical dilatation, ≥1.5 cm) and intact membranes, and without regular contractions (gestational age, 16–29 weeks). AF was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) were detected by PCR using specific primers. Patients were divided into three groups according to the results of AF culture and PCR for ureaplasmas: those with a negative AF culture and a negative PCR (n=44), those with a negative AF culture and a positive PCR (n = 10), and those with a positive AF culture regardless of PCR result (n=4). Results 1) Ureaplasmas were detected by PCR in 19.0% (11/58) of patients, by culture in 5.2% (3/58), and by culture and/or PCR in 22.4% (13/58); 2) Among the 11 patients with a positive PCR for ureaplasmas, the AF culture was negative in 91% (10/11); 3) Patients with a negative AF culture and a positive PCR for ureaplasmas had a significantly higher median AF matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count than those with a negative AF culture and a negative PCR (P<0.001 and P<0.05, respectively); 4) Patients with a positive PCR for ureaplasmas but a negative AF culture had a higher rate of spontaneous preterm birth within two weeks of amniocentesis than those with a negative AF culture and a negative PCR (P<0.05 after adjusting for gestational age at amniocentesis); 5) Of the patients who delivered within two weeks of amniocentesis, those with a positive PCR for ureaplasmas and a negative AF culture had higher rates of histologic amnionitis and funisitis than those with a negative AF culture and a negative PCR (P<0.05 after adjusting for gestational age at amniocentesis, for each); (6) However, no significant differences in the intensity of the intra-amniotic inflammatory response and perinatal outcome were found between patients with a positive AF culture and those with a negative AF culture and a positive PCR. Conclusions 1) Cultivation techniques for ureaplasmas did not detect most cases of intra-amniotic infection caused by these microorganisms (91% of cases with cervical insufficiency and microbial footprints for ureaplasmas in the amniotic cavity had a negative AF culture); 2) Patients with a negative AF culture and a positive PCR assay were at risk for intra-amniotic and fetal inflammation as well as spontaneous preterm birth.