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Innovative Cell-Free RNA Biomarkers Enable Early Prediction of Preterm Birth

Innovative Cell-Free RNA Biomarkers Enable Early Prediction of Preterm Birth

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New research demonstrates that circulating cell-free RNA signatures in maternal blood can predict preterm birth over four months before delivery, offering a breakthrough in early intervention and prevention strategies.

3 min read

Preterm birth, defined as delivery before 37 weeks of gestation, poses significant health risks to infants, with increased chances of mortality and long-term health complications. Children born prematurely are at a higher risk for respiratory issues, jaundice, feeding difficulties, infections, and neurodevelopmental disorders such as cerebral palsy and epilepsy. Globally, approximately 13.4 million babies are born prematurely each year, and nearly one million of these infants die early due to complications related to early birth.

Recent advancements in molecular diagnostics have opened new horizons in predicting preterm birth well in advance of delivery. Researchers have identified that signatures in cell-free RNA (cfRNA) circulating in maternal blood can forecast preterm birth more than four months before the expected delivery date. This groundbreaking study was presented at the European Society of Human Genetics annual conference.

The study involved analyzing blood plasma samples from 851 pregnancies, including 299 preterm cases and 552 controls, at around 16 weeks of gestation. The team, led by Dr. Wen-Jing Wang of BGI Research in Shenzhen and Professor Chemming Xu from Fudan University, uncovered significant differences in cfRNA profiles between women who terminated their pregnancies prematurely and those delivering at term. These differences were observed even in cases with intact membranes as well as premature rupture of membranes (when the water breaks early). Notably, fewer than 3% of the subjects had a history of preterm birth, highlighting the predictive power of early cfRNA markers.

Dr. Wang emphasized that the ability to detect these signals so early suggests a biological priming for preterm labor, providing a crucial window for intervention—far earlier than current clinical detection methods. The findings have profound implications, as preterm births are responsible for a significant proportion of neonatal mortality and long-term disabilities.

Since preterm infants have underdeveloped organs, they face higher risks of complications such as respiratory problems, infections, and feeding issues. Long-term health impacts include cerebral palsy, disabilities, and vision problems, which also place emotional and financial strain on families.

The potential of this cfRNA-based approach lies in its practicality and compatibility with existing prenatal testing routines. The same blood sample taken for non-invasive prenatal testing (NIPT) can be utilized for cfRNA analysis, making it a cost-effective and accessible method for early risk assessment. Although current sequencing costs are comparable to NIPT, future developments could further reduce costs, making widespread screening feasible.

Unlike static genetic markers, circulating RNA provides dynamic insights into tissue-specific processes, including inflammation, infection, metabolism, and trophoblast function, that are involved in preterm labor. The researchers observed distinct molecular patterns associated with different subtypes of preterm birth, offering pathways for targeted interventions.

However, before this technology can be integrated into routine clinical practice, standardized protocols for sample handling and analysis need to be developed, given the fragile nature of RNA. Additionally, studies across diverse populations and further understanding of the different mechanisms leading to preterm birth are essential.

Advances in sequencing technology and analysis are paving the way for new diagnostic possibilities. As Professor Alexandre Reymond from the conference noted, sequencing readouts can now evaluate pregnancy risk dynamically, shifting from traditional genetic predisposition assessments to real-time molecular risk profiling. The ongoing research and collaboration efforts aim to bring this promising technology from the laboratory to widespread clinical use, ultimately improving pregnancy outcomes worldwide.

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