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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.

SUBMITTER: Heng YJ

PROVIDER: S-EPMC4917227 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.

Heng Yujing J YJ Pennell Craig E CE McDonald Sheila W SW Vinturache Angela E AE Xu Jingxiong J Lee Mary W F MW Briollais Laurent L Lyon Andrew W AW Slater Donna M DM Bocking Alan D AD de Koning Lawrence L Olson David M DM Dolan Siobhan M SM Tough Suzanne C SC Lye Stephen J SJ

PloS one 20160622 6

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 Calga ...[more]

PMID: 27333071

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Project description:ObjectiveWe sought to describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route, and type of cesarean incision.Study designTrained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing one third of deliveries across 25 US hospitals over 3 years (n = 115,502). All women delivering nonanomalous singletons between 23-33 weeks' gestation were included. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including nonreassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe and unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage), infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening, or unexpected procedure), intensive care unit admission, or death. Delivery route was categorized as classic cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery. Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery.ResultsOf 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23-27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of vaginal delivery, 23.0% of CCD (aRR, 3.54; 95% confidence interval (CI), 2.29-5.48), 12.1% of LTCD (aRR, 2.59; 95% CI, 1.77-3.77), and 10.3% of LVCD (aRR, 2.27; 95% CI, 0.68-7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR, 1.37; 95% CI, 0.95-1.97) or between CCD and LVCD (aRR, 1.56; 95% CI, 0.48-5.07).ConclusionThe risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection, and intensive care unit admission for early preterm births requiring cesarean delivery.

Project description:BackgroundPreterm labour prediction has been relied on history of previous preterm birth and cervical length of current pregnancy. However, universal cervical length measurement has some limitation. We aim to find a surrogate marker of cervical length to close the gap in preterm prevention program and lower uterine wall thickness seems promising. We generate the nomogram of lower uterine wall thickness during 18-22 weeks of gestation and evaluate the accuracy of LUW thickness as a predictor of preterm delivery before 37 weeks.MethodsThis prospective cohort study included 524 Thai singleton pregnant women at 18-22 weeks of gestation between November 2016 and October 2017. After signing informed consent, transabdominal ultrasonography was performed to examine fetal anatomical structures and to measure LUW thickness. The results were blinded to the caregivers. The outcomes of all pregnancies were followed. The LUW thickness at 10th percentiles was established and was correlated with the outcomes of pregnancy. The performance of LUW thickness at 10th percentile as a predictor of preterm delivery was calculated. The intra-observer and inter-observer reliability of measurement were assessed by intraclass correlation coefficient and Bland-Altman plot.ResultsOf the 524 pregnant women, 64 (12.2%) delivered before 37 weeks of gestation. The reference value of lower uterine wall thickness at 18-22 weeks was established. Mean and 10th percentile of LUW thickness were 6.2 and 4.5 mm respectively. The inter-observer and intra-observer variation of measurement were small (intraclass correlation coefficient = 0.926 and 0.989 respectively). Using LUW thickness at less than 4.5 mm as a predictor of preterm delivery, we found a 2.37 folds increased risk of preterm delivery after adjustment of other factors (p = 0.037). Sensitivity, specificity, positive predictive value and negative predictive value were 14% (95% CI: 6.64-25.02), 92.8% (95% CI: 90.06-95.12), 22.5% (95% CI: 12.66-36.76) and 88% (95% CI: 86.92-89.08) respectively.ConclusionsThe measurement of LUW thickness by transabdominal ultrasonography is feasible and reproducible. The risk of delivery before 37 weeks of gestation is increased significantly if the LUW thickness at 18-22 weeks is less than 4.5 mm.Trial registrationThe study protocol was approved by institutional ethical committee (COA No. Si 657/2016).

Project description:It is now recognized that preterm infants ?28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial.This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2???0.30 at an age ?6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2???0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017.Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation.Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.

Dataset Information

Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.

Publications

Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.

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