Mid-trimester amniotic fluid proteome’s association with spontaneous preterm delivery and gestational duration
Journal article, 2020
Background Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery. Objective The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort. Methods Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls. Results Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort. Conclusions Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.
Author
Maria Hallingström
Sahlgrenska University Hospital
University of Gothenburg
Petra Zedníková
University of Pardubice
University Hospital Hradec Kralove
V. Tambor
University Hospital Hradec Kralove
Malin Barman
Chalmers, Biology and Biological Engineering, Food and Nutrition Science
M. Vajrychova
University of Defence in Brno Faculty of Military Health Sciences
University Hospital Hradec Kralove
J. Lenco
Charles University
University Hospital Hradec Kralove
Felicia Viklund
Sahlgrenska University Hospital
Stockholm South General Hospital
Linda Tancred
Sahlgrenska University Hospital
University of Gothenburg
Hardis Rabe
University of Gothenburg
Daniel Jonsson
University of Gothenburg
Sahlgrenska University Hospital
Alisa Kachikis
University of Washington
Staffan Nilsson
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
University of Gothenburg
Marian Kacerovský
Charles University
University Hospital Hradec Kralove
Kristina M. Adams Waldorf
University of Washington
University of Gothenburg
Bo Jacobsson
Sahlgrenska University Hospital
Norwegian Institute of Public Health
University of Gothenburg
PLoS ONE
1932-6203 (ISSN) 19326203 (eISSN)
Vol. 15 5 e0232553Subject Categories
Clinical Laboratory Medicine
Biomedical Laboratory Science/Technology
Obstetrics, Gynecology and Reproductive Medicine
DOI
10.1371/journal.pone.0232553