title: The relationship of circulating proteins in early pregnancy with preterm birth.
abstract: BACKGROUND
  Preterm birth (PTB) (< 37 completed weeks' gestation) is a pathological outcome of pregnancy and a major global health problem. Babies born preterm have an elevated risk for long-term adverse medical and neurodevelopmental sequelae. Substantial evidence implicates intrauterine infection and/or inflammation in PTB. However, these are often relatively late findings in the process, when PTB is inevitable. Identification of earlier markers of PTB may make successful intervention possible. Although select proteins, notably those related to the inflammatory pathways, have been associated with PTB, there has been a lack of research into the role of other protein pathways in the development of PTB. The purpose of this study was to investigate, using a previously described biomarker discovery approach, a subset of circulating proteins and their association with PTB focusing on samples from early pregnancy.
  
  
  OBJECTIVE
  The objectives of the study were as follows: (1) to perform a large-scale biomarker discovery, utilizing an innovative platform to identify proteins associated with preterm birth in plasma taken between 10 and 15 weeks' gestation and, (2) to determine which protein pathways are most strongly associated with preterm birth. To address these aims, we measured 1129 proteins in a plasma sample from early pregnancy using a multiplexed aptamer-based proteomic technology developed in Colorado by SomaLogic.
  
  
  METHODS
  Using a nested case-control approach, we measured proteins at a single time point in early pregnancy in 41 women who subsequently delivered preterm and 88 women who had term uncomplicated deliveries. We measured 1129 proteins using a multiplexed aptamer-based proteomic technology developed by SomaLogic. Logistic regressions and random forests were used to compare protein levels.
  
  
  RESULTS
  The complement factors B and H and the coagulation factors IX and IX ab were the highest-ranking proteins distinguishing cases of preterm birth from term controls. The top 3 pathways associated with preterm birth were the complement cascade, the immune system, and the clotting cascade.
  
  
  CONCLUSIONS
  Using a discovery approach, these data provide further confirmation that there is an association of immune- and coagulation-related events in early pregnancy with preterm birth. Thus, plasma protein profiles at 10-15 weeks of gestation are related to the development of preterm birth later in pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado, National Jewish Health, Denver, CO. Electronic address: Anne.Lynch@ucdenver.edu.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Lynch
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, National Jewish Health, Denver, CO.
authors.forename: Brandie D
authors.initials: BD
authors.lastname: Wagner
authors.affiliation: Department of Pediatric Pulmonology, University of Colorado, National Jewish Health, Denver, CO.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Deterding
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, National Jewish Health, Denver, CO.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Giclas
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado, National Jewish Health, Denver, CO.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Gibbs
authors.affiliation: Department of Medicine and Infectious Disease, University of Colorado, National Jewish Health, Denver, CO.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
authors.affiliation: Department of Medicine and Immunology, University of Colorado, National Jewish Health, Denver, CO.
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado, National Jewish Health, Denver, CO.
authors.forename: Nanette F
authors.initials: NF
authors.lastname: Santoro
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D047928:Premature Birth / Q000097:blood*; D040901:Proteomics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: coagulation cascade; complement system; early pregnancy; preterm birth