Predictive screening for inflammatory disorders of pregnancy using targeted maternal cell-free RNA assays: proof-of-principle data from large animal and human cohorts

In a proof-of-principle study we used targeted cell-free RNA analyses of maternal plasma samples from large animal (sheep) and human pregnancy cohorts to develop a minimally invasive screening test for inflammatory disorders of pregnancy, namely chorioamnionitis and pre-eclampsia.

Research overview

The management and prevention of key inflammatory-associated pregnancy complications such as chorioamnionitis and pre-eclampsia is hampered by a lack of early gestation risk screening tools.

In a proof-of-principle study we used targeted cell-free RNA (cfRNA) analyses of maternal plasma samples from large animal (sheep) and human pregnancy cohorts to develop a minimally invasive screening test for these inflammatory disorders.

Key findings

  • In a sheep model of pregnancy, targeted analysis of maternal plasma cfRNA accurately predicts both sterile and infectious chorioamnionitis.
  • Findings were validated in a human cohort of women with late onset pre-eclampsia demonstrating translatability of cfRNA to predict other inflammatory disorders of pregnancy.

Why this project is important

Pathological inflammation in pregnancy is responsible for a material percentage of early births and is strongly associated with multi-system disease (notably the brain, lungs and GI tract) in preterm infants.

At present, we lack accurate, rapidly deployable screening tools for the early detection of inflammation-associated pregnancy disorders, hampering our ability to deliver effective interventions in a timely manner

This study demonstrates that targeted analysis of maternal plasma cfRNA has the potential to act as a novel, rapid, highly-accurate and minimally-invasive test for inflammatory disorders of pregnancy prior to the onset of overt clinical symptoms.

Further development of this technology may serve as a scalable, rapid and cost-effective means for predicting major inflammatory conditions in pregnancy.

Project researchers

Dr Sean Carter
Dr Haruo Usuda
Ms Erin Fee
Ms Hannah Watson
Professor Matt Kemp

Partners

Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research, Singapore
School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong , China
Division of Obstetrics and Gynaecology, University of Western Australia, Australia
Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Reproductive Biology Program, Center for Biomedical Research and Innovation, Universidad de los Andes, Santiago, Chile.
IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.

Funders

The Channel 7 Telethon Trust
The Department of Health, Government of Western Australia
The Stan Perron Charitable Foundation
The National University of Singapore NUHSRO/2021/075
The Ministry of Education, Government of Singapore, NUHSRO/2021/109/T1/Seed-Sep/02 General Sir John Monash Foundation

Project timeline

Completed 2025

Publication

Predictive Screening for Inflammatory Disorders of Pregnancy Using Targeted Maternal Cell-Free RNA Assays: Proof-of-Principle Data from Large Animal and Human Cohorts, Springer Nature, 4 June 2025.

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