OBJECTIVE: The aim of this study was to identify early proteomic biomarkers of spontaneous preterm delivery (PTD) in mid-trimester amniotic fluid from asymptomatic women. METHODS: This is a case-cohort study. Amniotic fluid from mid-trimester genetic amniocentesis (14-19 weeks of gestation) was collected from 2008 to 2011. The analysis was conducted in 24 healthy women with subsequent spontaneous PTD (cases) and 40 randomly selected healthy women delivering at term (controls). An exploratory phase with proteomics analysis of pooled samples was followed by a verification phase with ELISA of individual case and control samples. RESULTS: The median (interquartile range (IQR: 25th; 75th percentiles) gestational age at delivery was 35+5 (33+6-36+6) weeks in women with spontaneous PTD and 40+0 (39+1-40+5) weeks in women who delivered at term. In the exploratory phase, the most pronounced differences were found in C-reactive protein (CRP) levels, that were approximately two-fold higher in the pooled case samples than in the pooled control samples. However, we could not verify these differences with ELISA. The median (25th; 75th IQR) CRP level was 95.2 ng/mL (64.3; 163.5) in women with spontaneous PTD and 86.0 ng/mL (51.2; 145.8) in women delivering at term (p = 0.37; t-test). CONCLUSIONS: Proteomic analysis with mass spectrometry of mid-trimester amniotic fluid suggests CRP as a potential marker of spontaneous preterm delivery, but this prognostic potential was not verified with ELISA.

BCNatal Barcelona Center for Maternal Fetal and Neonatal Medicine University of Barcelona Barcelona Spain

Biomedical Research Center University Hospital Hradec Kralove Hradec Kralove Czech Republic

Centro de Investigaciones Biomedicas en Enfermedades Raras Barcelona Spain

Department of Genetics and Bioinformatics Area of Health Data and Digitalisation Institute of Public Health Oslo Norway

Department of Molecular Pathology and Biology Faculty of Military Health Sciences University of Defense Hradec Kralove Czech Republic

Department of Neurochemistry Sahlgrenska University Hospital Gothenburg Sweden

Department of Obstetrics and Gynecology Charles University Prague Faculty of Medicine in Hradec Kralove Hradec Kralove Czech Republic

Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Department of Obstetrics and Gynecology Sahlgrenska University Hospital Gothenburg Sweden

Mathematical Sciences Chalmers University of Technology Gothenburg Sweden

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