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Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth.

ABSTRACT: Identification of pregnancies at risk of preterm birth (PTB), the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. We report a longitudinal multi-omics study coupled with a DREAM challenge to develop predictive models of PTB. The findings indicate that whole-blood gene expression predicts ultrasound-based gestational ages in normal and complicated pregnancies (r = 0.83) and, using data collected before 37 weeks of gestation, also predicts the delivery date in both normal pregnancies (r = 0.86) and those with spontaneous preterm birth (r = 0.75). Based on samples collected before 33 weeks in asymptomatic women, our analysis suggests that expression changes preceding preterm prelabor rupture of the membranes are consistent across time points and cohorts and involve leukocyte-mediated immunity. Models built from plasma proteomic data predict spontaneous preterm delivery with intact membranes with higher accuracy and earlier in pregnancy than transcriptomic models (AUROC = 0.76 versus AUROC = 0.6 at 27-33 weeks of gestation).

SUBMITTER: Tarca AL

PROVIDER: S-EPMC8233692 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth.

Tarca Adi L AL Pataki Bálint Ármin BÁ Romero Roberto R Sirota Marina M Guan Yuanfang Y Kutum Rintu R Gomez-Lopez Nardhy N Done Bogdan B Bhatti Gaurav G Yu Thomas T Andreoletti Gaia G Chaiworapongsa Tinnakorn T Hassan Sonia S SS Hsu Chaur-Dong CD Aghaeepour Nima N Stolovitzky Gustavo G Csabai Istvan I Costello James C JC

Cell reports. Medicine 20210615 6

Identification of pregnancies at risk of preterm birth (PTB), the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. We report a longitudinal multi-omics study coupled with a DREAM challenge to develop predictive models of PTB. The findings indicate that whole-blood gene expression predicts ultrasound-based gestational ages in normal and complicated pregnancies (r = 0.83) and, using data collected before 37 weeks of gestation, also predicts the delive ...[more]

PMID: 34195686

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Project description:ImportanceAdverse birth outcomes, including preterm birth, small for gestational age (SGA), and large for gestational age (LGA) are associated with increased risks of hypertension, ischemic heart disease, stroke, and heart failure, but knowledge regarding their associations with atrial fibrillation (AF) is limited and inconsistent.ObjectiveTo investigate whether preterm birth, SGA, or LGA are associated with increased risks of AF later in life.Design, setting, and participantsThis multinational cohort study included Danish, Swedish, and Finnish national health registries. Live singleton births in Denmark from 1978 through 2016, in Sweden from 1973 through 2014, and in Finland from 1987 through 2014, who were followed up until December 31, 2016, in Denmark, December 31, 2021, in Sweden, and December 31, 2014, in Finland were included. Data analyses were performed between January 2021 and August 2022.ExposuresPreterm birth (less than 37 gestational weeks), SGA (less than 10th percentile birth weight for gestational age), and LGA (more than 90th percentile birth weight for gestational age) identified from medical birth registers.Main outcomes and measuresDiagnosis of AF obtained from nationwide inpatient and outpatient registers. The study team ran multivariable Cox proportional hazard models and flexible parametric survival models to estimate hazard ratios (HRs) and 95% CIs for AF according to preterm birth, SGA, and LGA. Sibling analyses were conducted to control for unmeasured familial factors.ResultsThe cohort included 8 012 433 study participants (maximum age, 49 years; median age, 21 years; male, 51.3%). In 174.4 million person-years of follow-up, 11 464 participants had a diagnosis of AF (0.14%; median age, 29.3 years). Preterm birth and LGA were associated with increased AF risk in both the full population cohort and in the sibling analyses; the multivariate HRs from the cohort analyses were 1.30 (95% CI, 1.18-1.42) and 1.55 (95% CI, 1.46-1.63), respectively. Preterm birth was more strongly associated with AF in childhood than in adulthood. Children born SGA had an increased risk of AF in the first 18 years of life but not afterwards.Conclusions and relevancePreterm births and LGA births were associated with increased risks of AF up to middle age independently of familial confounding factors. Individuals born SGA had an increased AF risk only during childhood.

Dataset Information

Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth.

Publications

Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth.

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