Objectives: To determine the prevalence and load of Ureaplasma spp. DNA in the cervical fluid of women with singleton pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to intra-amniotic infection, sterile intra-amniotic inflammation, and colonization of the amniotic fluid. Methods: A total of 217 women with PPROM between gestational ages 24 + 0 and 33 + 6 weeks were included in this study. Paired amniotic and cervical fluid samples were collected at the time of admission via transabdominal amniocentesis and using a Dacron polyester swab, respectively. Microbial invasion of the amniotic cavity was diagnosed using a combination of culture and molecular biology methods. Intra-amniotic inflammation was determined based on the concentration of interleukin-6 in the amniotic fluid. Based on the presence or absence of these conditions, the women were stratified into the following subgroups: intra-amniotic infection (with both), sterile intra-amniotic inflammation (with inflammation only), colonization (with microorganisms only), and negative amniotic fluid (without either). The Ureaplasma spp. DNA load in the cervical fluid was assessed using PCR. Results: Ureaplasma spp. DNA in the cervical fluid was found in 61% (133/217) of the women. Women with negative amniotic had similar prevalence of Ureaplasma spp. DNA in cervical fluid (55%) to those with sterile intra-amniotic inflammation (54%) but lower than those with intra-amniotic infection (73%) and colonization (86%; p < 0.0001). Women with negative amniotic fluid had a lower load of Ureaplasma spp. DNA in their cervical fluid (median: 4.7 × 103 copies of DNA/ml) than those with intra-amniotic infection (median: 2.8 × 105 copies DNA/ml), sterile intra-amniotic inflammation (median: 5.3 × 104 copies DNA/ml), and colonization (median: 1.2 × 105 copies DNA/mL; p < 0.0001). Conclusion: In conclusion, in PPROM at <34 weeks, the presence of intra-amniotic infection, sterile intra-amniotic inflammation, or colonization of the amniotic fluid was associated with a higher prevalence and/or load of Ureaplasma spp. DNA in the cervical fluid than the absence of intra-amniotic complications.

• Keywords
• genital mycoplasma, intra-amniotic inflammation, microbial invasion of the amniotic cavity, non-invasive sample, preterm delivery,
• Publication type
• Journal Article MeSH

To determine the main clinical characteristics of preterm prelabor rupture of membranes (PPROM) complicated by colonization of the amniotic cavity (microbial invasion of the amniotic cavity without intra-amniotic inflammation). A total of 302 women with PPROM were included. Transabdominal amniocentesis was performed and amniotic fluid was assessed. Based of microbial invasion of the amniotic cavity and intra-amniotic inflammation (interleukin-6 ≥ 3000 pg/mL), the women were divided into following groups: intra-amniotic infection, sterile intra-amniotic inflammation, colonization of the amniotic cavity, and negative amniotic fluid. Colonization was found in 11% (32/302) of the women. The most common bacteria identified in the amniotic fluid were Ureaplasma spp. with a lower burden than those with intra-amniotic infection (p = 0.03). The intensity of intra-amniotic inflammatory response measured by interleukin-6 was higher in women with colonization than in those with negative amniotic fluid (medians: 961 pg/mL vs. 616 pg/mL; p = 0.04). Women with colonization had higher rates of acute inflammatory placental lesions than those with negative amniotic fluid. In PPROM, colonization, caused mainly by microorganisms from the lower genital tract, might represent an early stage of microbial invasion of the amniotic cavity with a weak intra-amniotic inflammatory response.

• MeSH
• Chorioamnionitis * microbiology   MeSH
• Interleukin-6 MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Placenta MeSH
• Amniotic Fluid microbiology   MeSH
• Fetal Membranes, Premature Rupture MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Inflammation complications   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interleukin-6 MeSH

A prelabor rupture of membranes (PROM) and its subtypes, preterm PROM (pPROM) and term PROM (tPROM), are associated with disturbances in the hemostatic system and angiogenesis. This study was designed to demonstrate the role of single nucleotide polymorphisms (SNPs), localized in CSF2 (rs25881), FLT1 (rs722503), TFPI (C-399T) and TLR9 (rs352140) genes, in PROM. A population of 360 women with singleton pregnancy consisted of 180 PROM cases and 180 healthy controls. A single-SNP analysis showed a similar distribution of genotypes in the studied polymorphisms between the PROM or the pPROM women and the healthy controls. Double-SNP TT variants for CSF2 and FLT1 polymorphisms, CC variants for TLR9 and TFPI SNPs, TTC for CSF2, FLT1 and TLR9 polymorphisms, TTT for FLT1, TLR9 and TFPI SNPs and CCCC and TTTC complex variants for all tested SNPs correlated with an increased risk of PROM after adjusting for APTT, PLT parameters and/or pregnancy disorders. The TCT variants for the CSF2, FLT1 and TLR9 SNPs and the CCTC for the CSF2, FLT1, TLR9 and TFPI polymorphisms correlated with a reduced risk of PROM when corrected by PLT and APTT, respectively. We concluded that the polymorphisms of genes, involved in hemostasis and angiogenesis, contributed to PROM.

• Keywords
• angiogenesis, genotyping, hemostasis, pPROM, pregnancy, prelabor rupture of membranes (PROM), restriction fragment length polymorphism (RFLP), single nucleotide polymorphism (SNP), tPROM,
• MeSH
• Adult MeSH
• Granulocyte-Macrophage Colony-Stimulating Factor genetics   MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Association Studies MeSH
• Polymorphism, Single Nucleotide * MeSH
• Humans MeSH
• Lipoproteins genetics   MeSH
• Young Adult MeSH
• Fetal Membranes, Premature Rupture genetics   MeSH
• Vascular Endothelial Growth Factor Receptor-1 genetics   MeSH
• Case-Control Studies MeSH
• Pregnancy MeSH
• Toll-Like Receptor 9 genetics   MeSH
• Maternal Age MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CSF2 protein, human MeSH Browser
• Granulocyte-Macrophage Colony-Stimulating Factor MeSH
• FLT1 protein, human MeSH Browser
• lipoprotein-associated coagulation inhibitor MeSH Browser
• Lipoproteins MeSH
• Vascular Endothelial Growth Factor Receptor-1 MeSH
• TLR9 protein, human MeSH Browser
• Toll-Like Receptor 9 MeSH

BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. OBJECTIVE: The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. RESULTS: A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). CONCLUSION: Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.

• Keywords
• 16S ribosomal RNA, Ureaplasma, amniocentesis, amniotic fluid, bacteria, benzylpenicillin, biomarker, chorioamnionitis, clarithromycin, funisitis, genital mycoplasmas, great obstetrical syndromes, inflammation, interleukin-6, intraamniotic infection, microbial invasion of the amniotic cavity, neonatal outcome, neonatal sepsis, nucleic acid, polymerase chain reaction, pregnancy, prematurity, preterm birth, rapid point of care test, sterile intraamniotic inflammation,
• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Bacterial Infections etiology   prevention & control   MeSH
• Chorioamnionitis etiology   prevention & control   MeSH
• DNA, Bacterial analysis   MeSH
• Adult MeSH
• Interleukin-6 analysis   MeSH
• Clarithromycin therapeutic use   MeSH
• Clindamycin therapeutic use   MeSH
• Cohort Studies MeSH
• Humans MeSH
• Penicillin G therapeutic use   MeSH
• Amniotic Fluid chemistry   MeSH
• Fetal Membranes, Premature Rupture * MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Ureaplasma genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• DNA, Bacterial MeSH
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH
• Clarithromycin MeSH
• Clindamycin MeSH
• Penicillin G MeSH

OBJECTIVE: To evaluate the association between cervical human papillomavirus (HPV) infection at the time of admission and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI) in women with preterm prelabor rupture of membranes (PPROM) and to determine the association between cervical HPV infection and short-term neonatal morbidity. METHODS: One hundred women with singleton pregnancies complicated by PPROM between the gestational ages of 24+0 and 36+6 weeks were included in the study. The presence of HPV DNA was evaluated in scraped cervical cells using polymerase chain reaction (PCR). Amniotic fluid samples were obtained by transabdominal amniocentesis. RESULTS: The rate of cervical HPV infection in women with PPROM was 24%. The rates of MIAC and IAI were not different between women with cervical HPV infection and those without cervical HPV infection [MIAC: with HPV: 21% (5/24) vs. without HPV: 22% (17/76), p = 1.00; IAI: with HPV: 21% (5/24) vs. without HPV: 18% (14/76), p = 0.77]. There were no differences in the selected aspects of short-term neonatal morbidity between women with and without cervical HPV infection. CONCLUSIONS: In women with PPROM, the presence of cervical HPV infection at the time of admission is not related to a higher risk of intra-amniotic infection-related and inflammatory complications or worse short-term neonatal outcomes.

• MeSH
• Cervix Uteri virology   MeSH
• Adult MeSH
• Papillomavirus Infections complications   MeSH
• Infant MeSH
• Infant Mortality MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Papillomaviridae physiology   MeSH
• Amniotic Fluid virology   MeSH
• Fetal Membranes, Premature Rupture virology   MeSH
• Patient Admission MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH