Abstract
delivery in women with preterm labor: analysis of multiple proteins in maternal serum Panagiotis Tsiartas, Rose-Marie Holst, Ulla-Britt Wennerholm, Henrik Hagberg, David Hougaard, Kristin Skogstrand, Brad Pearce, Marian Kacerovsky, Bo Jacobsson Papageorgiou University Hospital of Thessaloniki, Obstetrics and Gynecology, Thessaloniki, Greece, Sahlgrenska University Hospital, Department of Obstetrics and Gynecology, Gothenburg, Sweden, Sahlgrenska University Hospital, East, Obstetrics and Gynecology, Gothenburg, Sweden, Queen Charlottes and Chelsea Hospital, Institute of Reproductive and Developmental Biology, London, United Kingdom, Statens Serum Institut, Department of Clinical Biochemistry and Immunology, Copenhagen, Denmark, Statens Serum Institut, 3Department of Clinical Biochemistry and Immunology, Copenhagen, Denmark, Rollins School of Public Health, Epidemiology, Atlanta, GA, Univerzita Karlova Praha, Porodnicka a gynekologicka klinika FN Hradec Kralova, Praha, Czech Republic OBJECTIVE: To analyze whether specific proteins in maternal serum and the cervical length, alone or in combination, can identify the likelihood that women in preterm labor with intact membranes will deliver spontaneously within 7 days of sampling. STUDY DESIGN: We used in our study two independent cohorts of women, an exploratory cohort from 1995-2005 and a confirmatory cohort from 2008-2010 admitted to the Sahlgrenska University Hospital, Gothenburg, Sweden in preterm labor. In the exploratory cohort of 142 women in preterm labor between 22 and 33 weeks of gestation, maternal serum was collected and tested for twenty-seven proteins using multiplex xMAP technology. The women in the study provided serum samples at admission to the hospital for xMAP analysis. Individual levels of each protein were compared and calculations performed to find associations among different proteins, cervical length, and spontaneous preterm delivery within 7 days of sampling. Prediction models were created based on stepwise logistic regression. We have in a second stage applied our multivariable model in order to confirm its predictive capacity to an independent confirmatory cohort of 42 women between 23 and 33 weeks of gestation, who were admitted to the hospital in preterm labor and provided serum samples for xMAP analysis. RESULTS: We found one multivariable model through the data analysis of the exploratory cohort of women that predicts spontaneous preterm delivery within 7 days. This model was based on serum IL-10, RANTES and cervical length (sensitivity 73.8%, specificity 87.3%, positive predictive value 75.6%, negative predictive value 86.3%, likelihood ratio 5.8 and area under the curve 0.89). From the application of the multivariable model to the confirmatory cohort we found that the model had a sensitivity of 66.6%, specificity 66.6%, positive predictive value 35.3%, negative predictive value 88%, likelihood ratio 2 and area under the curve 0.66. CONCLUSION: A combination of maternal serum proteins and cervical length might help to determine whether women with preterm labor will deliver within 7 days.
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