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.
Highlights
Preterm birth (PTB; birth before 37 weeks of gestation) is the greatest challenge facing contemporary obstetrics in both high and low resource settings
Term delivery controls (n = 114, power = 0.84) were matched to spontaneous preterm birth (SPTB) cases drawn from baseline survey at
Eleven clinical variables were significantly associated with SPTB (Table 1)
Summary
Preterm birth (PTB; birth before 37 weeks of gestation) is the greatest challenge facing contemporary obstetrics in both high and low resource settings. The current screening tools to identify asymptomatic women at high risk of spontaneous PTB (SPTB) include clinical risk factor assessment [11], measuring cervical length [12, 13] and screening for fetal fibronectin (fFN) [14, 15]. These tools are limited by their low sensitivities (
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