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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. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated maternal C-reactive protein (CRP) as a predictor of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes (PPROM) before and after 32 weeks of gestation. Methods: This study was a prospective observational cohort study of 386 women. Maternal serum CRP concentrations were evaluated, and amniotic fluid samples were obtained via transabdominal amniocentesis at the time of admission. Placentas underwent histopathological examination after delivery. MIAC was defined based on a positive PCR for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive 16S rRNA gene amplification. HCA was defined based on the Salafia classification. Results: Maternal CRP was significantly higher in women with MIAC and HCA (median 9.0 mg/l) than in women with HCA alone (median 6.9 mg/l), MIAC alone (median 7.4 mg/l) and without MIAC or HCA (median 4.5 mg/l) (p<0.0001). CRP was a weak predictor of the occurrence of MIAC and HCA before and after 32 weeks of gestation. Only the 95th percentile of CRP and PPROM before 32 weeks exhibited a false-positive rate of 1%, a positive predictive value of 90% and a positive likelihood ratio of 13.2 to predict MIAC and HCA. However, the low sensitivity of 15% limits the clinical utility of this detection. Conclusion: CRP is a poor predictor of the occurrence of MIAC and HCA, even at early gestational ages. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between the presence of oligohydramnios, determined as an amniotic fluid index ≤ 5 cm and the intra-amniotic inflammatory response, fetal inflammatory response and neonatal outcomes in actively managed preterm prelabor rupture of membranes (PPROM). Methods: Women with singleton pregnancies complicated by PPROM at a gestational age of between 24+0 and 36+6 weeks were included in the study. Ultrasound assessments of the amniotic fluid index and evaluation of the amniotic fluid interleukin (IL)-6 levels were performed at admission. The umbilical cord blood IL-6 levels were evaluated after delivery. Results: In total, 74 women were included. The women with oligohydramnios did not have different amniotic fluid IL-6 levels [with oligohydramnios: median 342 pg/mL, interquartile range (IQR) 110-1809 vs. without oligohydramnios: median 256 pg/mL, IQR 122–748; p = 0.71] or umbilical cord blood IL-6 levels (with oligohydramnios: median 8.2 pg/mL, IQR 3.8–146.9 vs. without oligohydramnios: median 5.9 pg/mL, IQR 2.1–27.9; p = 0.14) than those without oligohydramnios. No association between oligohydramnios and neonatal morbidity was found. A correlation between the amniotic fluid index and the interval from rupture of membranes to amniocentesis was observed (rho = −0.34; p = 0.003). Conclusion: The presence of oligohydramnios is not associated with an adverse outcome in actively managed PPROM in singleton pregnancies in the absence of other complications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate umbilical cord interleukin (IL)-6 and funisitis as independent predictors of early-onset neonatal sepsis (EONS) in preterm prelabor rupture of membranes (PPROM). Design: Prospective cohort study. Setting: Evaluation of umbilical cord IL-6 and funisitis as predictors of early-onset neonatal sepsis in PPROM. Population: 176 women with PPROM between 23+0−36+6 weeks of gestation. Methods: Umbilical cord IL-6 was assayed by ELISA. Funisitis was defined according to the Salafia classification. Data was adjusted by gestational age at delivery and prenatal administration of corticosteroids and antibiotics. Main Outcome Measures: Binary logistic regression was performed to assess the independence of umbilical cord IL-6 and funisitis to predict EONS in women complicated with PPROM. Results: The rate of EONS was 7%. Funisitis was present in 18% of women. Umbilical cord IL-6 was significantly higher in women complicated with EONS than without [median (range) 389.5 pg/mL (13.9–734.8) vs 5.2 (0.1–801–4), p<0.001]. Umbilical cord IL-6 was the only independent predictor of early-onset neonatal sepsis (odds ratio 13.6, p = 0.004). Conclusion: Umbilical cord IL-6 was the only predictor of early-onset neonatal sepsis in PPROM. Contrary to what is reported, funisitis was not. [ABSTRACT FROM AUTHOR]

Background: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the magnitude of intra-amniotic inflammatory response in preterm prelabor rupture of membranes (PPROM). Methodology/Principal Finding:A prospective cohort study was performed in 107 women with PPROM between 23.0 and 36.6 weeks of gestational age. Twenty- six proteins were assayed by multiple immunoassay in amniotic fluid. The policy for PPROM in Czech Republic is active, and 90% of the women were delivered within 96 hours of membrane rupture. Histopathological placental findings were evaluated based on the Salafia classification. Data were analyzed in four subgroups of population according to the presence of MIAC and/or HCA. Results were stratified by gestational age at PPROM (< or ≥34.0 weeks). The rates of MIAC and HCA were 44% and 57%, respectively. Regardless of gestational age at PPROM, intra-amniotic inflammatory response was higher when MIAC and HCA were both present. There were no differences in the intra-amniotic inflammatory response between women with MIAC or HCA alone and women without infection. Conclusion: A higher intra-amniotic inflammatory response was identified when both HCA and MIAC were detected. [ABSTRACT FROM AUTHOR]

Background: Preterm prelabor rupture of membranes (PPROM) complicated by microbial invasion of the amniotic cavity (MIAC) leading to histological chorioamnionitis (HCA) significantly impacts perinatal morbidity. Unfortunately, no wellestablished tool for identifying PPROM patients threatened by these disorders is available. Methodology/Principal Findings: We performed an unbiased exploratory analysis of amniotic fluid proteome changes due to MIAC and HCA. From among the top five proteins that showed the most profound and significant change, we sought to confirm results concerning cathelicidin (P49913, CAMP•HUMAN), since an ELISA kit was readily available for this protein. In our exploratory proteomic study, cathelicidin showed a ∼6-fold higher concentration in PPROM patients with confirmed MIAC and HCA. We verified significantly higher levels of cathelicidin in exploratory samples (women without both MIAC and HCA: median 1.4 ng/ml; women with both conditions confirmed: median 3.6 ng/ml; p = 0.0003). A prospective replication cohort was used for independent validation and for assessment of cathelicidin potential to stratify women with MIAC leading to HCA from women in whom at least one of these conditions was ruled out. We confirmed the association of higher amniotic fluid cathelicidin levels with MIAC leading to HCA (the presence of both MIAC and HCA: median 3.1 ng/ml; other women: median 1.4 ng/ml; p<0.0001). A cathelicidin concentration of 4.0 ng/ml was found to be the best cut-off point for identifying PPROM women with both MIAC and HCA. When tested on the validation cohort, a sensitivity of 48%, a specificity of 90%, a likelihood ratio of 5.0, and an area under receiver-operating characteristic curve of 71% were achieved for identification of women with MIAC leading to HCA. Conclusions: Our multi-stage study suggests cathelicidin as a candidate marker that should be considered for a panel of amniotic fluid proteins permitting identification of PPROM women with MIAC leading to HCA. [ABSTRACT FROM AUTHOR]