Early prediction of preeclampsia using a blood-derived biomarker

September 02, 2023 09:15 pm | Updated 09:15 pm IST

A liquid-biopsy approach that measures DNA-methylation levels in the blood may improve the detection of pregnancies at risk of developing preeclampsia at early stages, a study published in Nature Medicine shows.

Preeclampsia is a major cause of morbidities during gestation. Early-onset preeclampsia — occurring before 34 weeks of gestation — is associated with a higher risk of severe disease and foetal mortality.

Among the few interventions available, low-dose aspirin at early stages of the disease (before 16 weeks of gestation) can reduce the risk of developing preeclampsia, but early identification of the disease is needed to initiate this intervention. Previous studies have shown that widespread methylation changes in the placenta occur at delivery. Liquid biopsy is a promising emerging tool for non-invasive diagnostics, and it is increasingly being used to detect disease and monitor progression and treatment response.

Bernard Thienpont from the Department of Human Genetics, KU Leuven, Leuven, Belgium and colleagues profiled blood DNA-methylation data from 498 pregnant women, about one third of whom developed preeclampsia. The authors detected differences in DNA methylation in the control pregnancies versus the pregnancies that developed preeclampsia. Using these data, they developed a model that enabled risk stratification not only when preeclampsia was diagnosed but also presymptomatically, at around 12 weeks of gestation. In a further analysis involving 197 of these women, they showed that this model, in combination with clinical and demographic risk factors, generated a risk score that correctly predicted 72% of patients with early-onset preeclampsia.

An accompanying News & Views piece cautions on overestimating the pre-eclampsia cases in the general population. It says that though the authors validated the screening tool in populations beyond the discovery cohort, they had used a case-control design in all populations. This would “inflate the relative proportions of pre-eclampsia cases far above what is seen in the general population (preterm pre-eclampsia has only a 1% population incidence).”

“The preliminary results suggest that cell-free DNA methylation profiling is a promising tool for presymptomatic PE risk assessment, and has the potential to improve treatment and follow-up in the obstetric clinic,” the authors. 

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