title: Microbial invasion and histological chorioamnionitis upregulate neutrophil-gelatinase associated lipocalin in preterm prelabor rupture of membranes.
abstract: Our recent exploratory proteomic study suggested increased levels of neutrophil-gelatinase associated lipocalin (P80188, NGAL_HUMAN) due to microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes. In this study, we verified the proteomics findings by assessing the amniotic fluid NGAL by ELISA in the original exploratory cohort. The NGAL level was significantly higher in women positive for both MIAC and HCA compared to women with both conditions ruled out (median 75.1 ng/ml versus 27.9 ng/ml; p < 0.0001). For independent validation and to assess NGALs potential to stratify women positive for both MIAC and HCA from women in whom at least one of these conditions was absent, we subsequently designed a retrospective replication cohort. Significantly higher NGAL levels were found in women positive for both MIAC and HCA (median 65.9 ng/ml versus 34.2 ng/ml; p = 0.0061). Significantly higher levels of NGAL were confirmed only in strata below 32 weeks of gestation. Based on the observed likelihood ratio, the best predictive cutoff level (47.1 ng/ml) was evaluated in both cohorts. Data from the verification cohort implied that NGAL is a valuable clinical marker for revealing MIAC leading to HCA; however, this potential was not replicated in the replication cohort.
authors.affiliation: a Department of Molecular Pathology and Biology, Faculty of Military Health Sciences , University of Defence , Hradec Kralove , Czech Republic .
authors.forename: Marie
authors.initials: M
authors.lastname: Vajrychova
authors.affiliation: b Biomedical Research Center, University Hospital , Hradec Kralove , Czech Republic .|c Department of Obstetrics and Gynecology, Faculty of Medicine , Charles University in Prague , Hradec Kralove , Czech Republic , and.
authors.forename: Marian
authors.initials: M
authors.lastname: Kacerovsky
authors.affiliation: b Biomedical Research Center, University Hospital , Hradec Kralove , Czech Republic .
authors.forename: Vojtech
authors.initials: V
authors.lastname: Tambor
authors.affiliation: d Fingerland's Department of Pathology, University Hospital and Faculty of Medicine , Charles University in Prague , Hradec Kralove , Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Hornychova
authors.affiliation: a Department of Molecular Pathology and Biology, Faculty of Military Health Sciences , University of Defence , Hradec Kralove , Czech Republic .
authors.forename: Juraj
authors.initials: J
authors.lastname: Lenco
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism* / Q000382:microbiology; D015415:Biomarkers / Q000378:metabolism; D002821:Chorioamnionitis / Q000378:metabolism* / Q000382:microbiology; D015331:Cohort Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
keywords: Amniotic fluid; histological chorioamnionitis; microbial invasion of the amniotic cavity; neutrophil-gelatinase associated lipocalin; preterm prelabor rupture of membranes