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The Pathologist / Issues / 2025 / Feb / Early Prediction of Preeclampsia via Liquid Biopsy
Liquid biopsy Precision medicine Technology and innovation Screening and monitoring

Early Prediction of Preeclampsia via Liquid Biopsy

How the PEARL framework seeks signals of placental and endothelial dysfunction in cell-free DNA

02/21/2025 News 1 min read

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A study published in Nature Medicine has demonstrated that prenatal cell-free DNA (cfDNA) sequencing can predict preeclampsia risk months before clinical onset, offering a non-invasive approach to early detection. The researchers developed a computational framework –  preeclampsia early assessment of risk from liquid biopsy (PEARL) – which analyzes nucleosome accessibility in cfDNA to identify early signs of placental and endothelial dysfunction.

Preeclampsia, a hypertensive disorder affecting two to eight percent of pregnancies, remains a major cause of maternal and fetal morbidity, particularly when diagnosed late. Traditional screening methods rely on clinical risk factors or serum biomarkers but have limited predictive accuracy. The new study explored whether cfDNA, already used for routine aneuploidy screening, could also serve as an early biomarker for preeclampsia.

The researchers analyzed 1,854 cfDNA samples obtained from pregnant individuals at up to 16 weeks’ gestation. Low-coverage whole-genome sequencing was used to examine tissue-specific nucleosome profiles. The model was trained on 450 samples, then validated in 831 clinical cases and externally tested on 141 samples from independent cohorts. The PEARL framework achieved 81 percent sensitivity at 80 percent specificity for predicting preterm preeclampsia. External validation yielded 79 percent sensitivity at 80 percent specificity, confirming the model’s robustness.

A key finding was that pregnant individuals who later developed preeclampsia had less DNA from the placenta in their blood and more DNA from damaged blood vessel cells. This pattern suggests that problems with blood vessel function start early in pregnancy, well before any symptoms appear.

PEARL also integrates two clinical parameters – blood pressure and body mass index (BMI) – to refine predictions, improving its clinical applicability while avoiding the need for additional sampling or specialized assays. The model's performance in routine prenatal screening datasets suggests it could be seamlessly integrated into existing workflows, providing an early warning system for high-risk pregnancies.

Corresponding author, Swati Shree, said, “Although using liquid biopsies for human diseases is largely used in the cancer area, given the frequency at which cell-free DNA screening is performed, prenatal biology truly has incredible opportunities for the discovery and application of innovative tools.”

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