Journal article
RNA profiles reveal signatures of future health and disease in pregnancy
Nature (London), Vol.601(7893), pp.422-427
01/2022
DOI: 10.1038/s41586-021-04249-w
PMCID: PMC8770117
PMID: 34987224
Abstract
Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden
. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method
. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.
Details
- Title: Subtitle
- RNA profiles reveal signatures of future health and disease in pregnancy
- Creators
- Morten Rasmussen - AbbVieMitsu Reddy - AbbVieRory Nolan - AbbVieJoan Camunas-Soler - AbbVieArkady Khodursky - AbbVieNikolai M Scheller - Statens Serum InstitutDavid E Cantonwine - Brigham and Women's HospitalLine Engelbrechtsen - Herlev HospitalJia Dai Mi - St Thomas' HospitalArup Dutta - Human KineticsTiffany Brundage - AbbVieFarooq Siddiqui - AbbVieMainou Thao - AbbVieElaine P S Gee - AbbVieJohnny La - AbbVieCourtney Baruch-Gravett - Global Alliance to Prevent Prematurity and StillbirthMark K Santillan - University of IowaSaikat Deb - Human KineticsShaali M Ame - Public Health Laboratory Ivo de CarneriSaid M Ali - Public Health Laboratory Ivo de CarneriMelanie Adkins - Michigan State UniversityMark A DePristo - BigHat Biosciences, Inc., San Mateo, CA, USA.Manfred Lee - AbbVieEugeni Namsaraev - AbbVieDorte Jensen Gybel-Brask - Zealand University HospitalLillian Skibsted - Zealand University HospitalJames A Litch - Global Alliance to Prevent Prematurity and StillbirthDonna A Santillan - University of Iowa Hospitals and ClinicsSunil Sazawal - Human KineticsRachel M Tribe - St Thomas' HospitalJames M Roberts - Magee-Womens Research InstituteManeesh Jain - AbbVieEstrid Høgdall - Herlev HospitalClaudia Holzman - Michigan State UniversityStephen R Quake - Chan Zuckerberg InitiativeMichal A Elovitz - University of PennsylvaniaThomas F McElrath - Brigham and Women's Hospital
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.601(7893), pp.422-427
- DOI
- 10.1038/s41586-021-04249-w
- PMID
- 34987224
- PMCID
- PMC8770117
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- P50 HD103556 / NICHD NIH HHS
- Language
- English
- Date published
- 01/2022
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984318223902771
Metrics
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