title: Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.
abstract: The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17-23 (sampling time point 1, T1) and 27-33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care.
authors.affiliation: Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.|Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
authors.forename: Yujing J
authors.identifier: http://orcid.org/0000-0002-8930-817X
authors.initials: YJ
authors.lastname: Heng
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, WA, Australia.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.affiliation: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Sheila W
authors.initials: SW
authors.lastname: McDonald
authors.affiliation: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.|Departments of Obstetrics & Gynaecology and Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, AB, Canada.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Vinturache
authors.affiliation: Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.|Dalla Lana School of Public Health, University of Toronto, ON, Canada.
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Mary W F
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.|Dalla Lana School of Public Health, University of Toronto, ON, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Briollais
authors.affiliation: Department of Pathology and Lab Medicine, University of Saskatchewan, St Paul's Hospital, Saskatoon Health Region, Saskatoon, SK, Canada.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lyon
authors.affiliation: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.|Departments of Obstetrics & Gynaecology and Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, AB, Canada.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Slater
authors.affiliation: Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Bocking
authors.affiliation: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.|Calgary Laboratory Services, Calgary, AB, Canada.|Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Lawrence
authors.initials: L
authors.lastname: de Koning
authors.affiliation: Departments of Obstetrics & Gynecology, Physiology and Pediatrics, University of Alberta, Edmonton, AB, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Olson
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health (Reproductive Genetics), Albert Einstein College of Medicine, Bronx, NY, United States of America.
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Dolan
authors.affiliation: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.|Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Tough
authors.affiliation: Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003710:Demography; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007743:Labor, Obstetric; D008957:Models, Genetic; D015999:Multivariate Analysis; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood* / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results