Abstract
BackgroundPreterm 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 well-established tool for identifying PPROM patients threatened by these disorders is available.Methodology/Principal FindingsWe 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.ConclusionsOur 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.
Highlights
Preterm prelabor rupture of membranes (PPROM) occurs in one third of all preterm deliveries and represents a specific subset of spontaneous preterm deliveries
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 microbial invasion of the amniotic cavity (MIAC) leading to histological chorioamnionitis (HCA)
Three distinct histone proteins (P62805; Q71DI3; Q99880) showed the highest concentration change, followed by cathelicidin (P49913) and myeloperoxidase (P05164). These proteins represent five biomarker candidates with the most promising diagnostic potential for identifying MIAC leading to HCA
Summary
Preterm prelabor rupture of membranes (PPROM) occurs in one third of all preterm deliveries and represents a specific subset of spontaneous preterm deliveries It is defined as spontaneous rupture of the membranes with the leakage of amniotic fluid at least two hours before the onset of regular uterine activity in the gestational age below 37 weeks [1]. Specific motifs on the bacterial surface as well as endogenous molecules, released from damaged tissue and cells, are recognized by pattern recognition receptors Their activation leads to increasing levels of inflammatory mediators in the amniotic fluid followed by the recruitment of neutrophils and other immune cells from the uterine wall to the placenta and fetal membranes. Preterm prelabor rupture of membranes (PPROM) complicated by microbial invasion of the amniotic cavity (MIAC) leading to histological chorioamnionitis (HCA) significantly impacts perinatal morbidity. No wellestablished tool for identifying PPROM patients threatened by these disorders is available
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
