Skip to main content
Premium Trial:

Request an Annual Quote

Preeclampsia Linked to MicroRNA Markers in Maternal Blood

NEW YORK – A team from the University of California, San Diego has tracked down extracellular microRNAs in maternal blood samples that coincide with the development or severity of preeclampsia, a pregnancy complication marked by placental dysfunction that increases the risk of preterm birth and maternal death.

Preeclampsia "is an important cause of fetal and maternal morbidity and mortality, for which there are currently no highly accurate methods for early diagnosis or prognostic assessment," senior and corresponding author Louise Laurent, an investigator at UCSD's obstetrics, gynecology, and reproductive medicine department, and her colleagues wrote in Science Advances on Wednesday.

While the pregnancy complication may be marked by symptoms such as headaches, hypertension, proteinuria, and abdominal pain, atypical forms of it may lack such symptoms, the team explained. The condition can also impact the liver, kidney, or blood platelet levels, they noted, and sometimes progresses to symptoms such as seizure, cerebral edema, or placental separation from the uterus inner wall.

Though such symptoms tend to turn up in the second half of pregnancy, preeclampsia outcomes are typically worse when it is not diagnosed in a timely manner, prompting the investigators to search for biomarkers that show up early.

"Given the broad array of clinical presentations for [preeclampsia], it can be difficult to differentiate the early signs and symptoms of [preeclampsia] from other conditions," the authors explained, noting that "early diagnosis of and/or risk assessment for the later development of [preeclampsia] is problematic due to the lack of assays that are highly specific for this disease."

In an effort to uncover maternal blood markers for early-stage preeclampsia or prognosis of the disease, the researchers used small RNA sequencing and machine learning. Specifically, they searched for preeclampsia-associated miRNAs in blood samples from 82 pregnant participants, including 48 women who were diagnosed with preeclampsia and 34 who were not.

The search highlighted 110 extracellular miRNA biomarkers in maternal blood that coincided with early preeclampsia. In an email, Laurent explained that so-called bivariate biomarkers, made up of a ratio of two distinct miRNAs, outperformed individual miRNA biomarkers.

After validating the most promising miRNAs in another 23 preeclampsia cases and 18 controls, the team ultimately narrowed in on three bivariate miRNA biomarker sets: miR-522-3p/miR-4732-5p, miR-516a-5p/miR-144-3p, and miR-27b-3p/let-7b-5p.

"Sequential application of three bivariate miRNA biomarkers was able to not only detect early preeclampsia but also distinguish between patients who will develop preeclampsia with different levels of severity," Laurent wrote.

Using iterative bivariate biomarker analyses that involved the sequential use of each bivariate miRNA ratio, the researchers found preeclampsia cases with 93 percent sensitivity and 79 percent specificity, at positive and negative predictive values of 55 percent and 89 percent, respectively, further teasing out severity clues from the ratios identified.

When the team applied its assay, based on three bivariate miRNA biomarkers, to a subset of 70 individuals who had both small RNA-seq and preeclampsia protein marker data available, the sensitivity for detecting preeclampsia came in at 89.3 percent with nearly 74 percent specificity. The sensitivity and specificity increased to 89.4 percent and more than 91, respectively, when combing the miRNA biomarkers with information on the ratio between two previously described protein markers, sFlt1 and PlGF.

"Prior to this study, the state-of-the-art molecular test for early diagnosis of preeclampsia was the recently FDA-approved sFlt1:PlGF ratio," Laurent explained, "which in our population had a sensitivity of 74.5 percent and specificity of 91.3 percent."

Laurent noted that additional research will be needed to understand the role of the miRNA biomarkers in placental function or preeclampsia pathogenesis to not only learn more about the condition but also make progress toward new treatment strategies.

"We plan to conduct future studies to validate the combined protein/miRNA assay and to determine how it can best be implemented for clinical diagnosis and management of preeclampsia," she explained, "including determining which patients should be managed in the hospital versus as outpatients, and determining the optimal time for delivery."