CELL-FREE DNA patterns detectable during the first trimester could help identify patients at increased risk of pregnancy complications before clinical warning signs emerge, according to new research.\u00a0<\/p>\n
The study suggests that information already contained within prenatal blood samples could provide a new way to stratify\u00a0high-risk pregnancies\u00a0and potentially allow clinicians to intensify monitoring and care earlier.\u00a0<\/p>\n
Researchers\u00a0in Belgium\u00a0analysed 1,910 first-trimester blood samples from pregnant individuals, including low-risk pregnancies and those considered at higher risk of adverse pregnancy outcomes because of twin pregnancy, pre-existing immune-mediated disease, or cytomegalovirus infection.\u00a0<\/p>\n
Rather than focusing only on the genetic sequence of cell-free DNA (cfDNA), the researchers examined its fragmentome: characteristics of how DNA molecules circulating in the blood have been fragmented.\u00a0\u00a0<\/p>\n
Their analysis incorporated multiple features, including DNA fragment length profiles, frequencies of sequences found at fragment ends, and estimates of the cell types contributing cfDNA.\u00a0<\/p>\n
Using these features, the team developed models capable of distinguishing the high-risk pregnancy group<\/a>s from low-risk controls, with the exception of diabetes.\u00a0<\/p>\n One of the most striking findings emerged among patients with immune-mediated diseases. The researchers identified a distinct cfDNA fragmentomic profile associated with adverse pregnancy outcomes,\u00a0even among patients whose disease was clinically quiescent and serologically inactive during early pregnancy.\u00a0<\/p>\n At a fixed 10% false-positive rate, fragmentomic analysis correctly identified 54% of patients with systemic immune-mediated disease who subsequently experienced an adverse pregnancy outcome. Detection reached 38% for thyroid-related immune disease, 73% for Crohn\u2019s disease, and 90% for psoriasis.\u00a0<\/p>\n Importantly, the researchers validated their findings in an independent cohort of pregnant patients with immune-mediated diseases from an external centre, strengthen<\/a>ing evidence that the observed signal was not restricted to the original study population.\u00a0<\/p>\n The fragmentomic information also provided predictive value independent of, and additional to, established clinical risk factors and fetal fraction measurements, indicating that it may capture biological information that conventional assessments miss.\u00a0<\/p>\n Cell-free DNA testing is already widely used during pregnancy for non-invasive prenatal screening. These findings raise the possibility that the same type of blood sample could eventually provide information not only about fetal chromosomal abnormalities, but also about the wider biological state of the pregnancy and risk of later complications.\u00a0<\/p>\nHidden Risk in Immune-Mediated Disease<\/b>\u00a0<\/h2>\n
Potential for Earlier Pregnancy Triage<\/b>\u00a0<\/h2>\n