This year in the United States, between 5 and 10 percent of pregnant people will face a hypertensive disorder related to their pregnancy. Although these conditions will often subside after giving birth, the most severe complications can lead to death of the fetus or the mother, according to Contemporary Ob/Gyn. The most common of these disorders is called preeclampsia, which presents as elevated blood pressure and protein levels (proteinuria) both during pregnancy and for some time after giving birth. If this isn’t monitored, it may lead to eclampsia, a more severe progression of the disease characterized by frequent seizures in addition to worsening of the preeclampsia symptoms.
At times, it has been difficult to diagnose these diseases in a timely manner. Symptoms may not present until late in a gestational period, and it is also necessary to receive consistent and reliable clinical monitoring. It is crucial to make a diagnosis as soon as possible so that patients can be monitored and treatment can be administered accordingly.
Another challenge to diseases like preeclampsia is that there is no guaranteed treatment. The general consensus among medical providers is that the best treatment option currently available is delivery of the baby. Symptoms can be monitored, diet and lifestyle changes are recommended, and in more severe cases, magnesium sulfate may be administered to alleviate seizures. However, these are generally the only options, and treatment research is difficult given the obvious ethical constraints of testing therapeutics on pregnant people, as stated in a 2016 paper from Advances in Clinical Chemistry.
The researchers discovered the RNA patterns of pregnancy progression by analyzing the cf-RNA from a single, noninvasive blood draw.
Enter: RNA. The once overlooked sibling of DNA has recently been involved in key biomedical developments, including gene editing therapies and the COVID-19 vaccines. It may also extend a hand in providing more accurate diagnoses and monitoring of hypertensive diseases. Already, RNA plays a key role in developmental pathology, identifying fetal blood genotypes and common chromosomal abnormalities. Now, a 2022 Nature transcriptomic study, using an RNA library of over 1,800 patients, reveals that cell-free RNA (cf-RNA) displays signature patterns of normal and abnormal pregnancies. In other words, the researchers discovered the RNA patterns of pregnancy progression by analyzing the cf-RNA from a single, noninvasive blood draw.
This potential molecular diagnostic may enable doctors to diagnose this disease well before symptoms begin.
This potential molecular diagnostic may enable doctors to diagnose this disease well before symptoms begin so that they can advise at-risk patients. Consequently, this tool has the potential to alleviate a facet of racial and socioeconomic disparities within maternal healthcare. Many Black patients and those with lower socio-economic status are less likely to be accurately diagnosed, according to the American Academy of Family Physicians. As a result, they are more likely to suffer from worse complications during their pregnancies. This Nature study included the most diverse maternal cohort population to date and found that the pregnancy profiles and cf-RNA signatures are highly generalizable to all races and ethnicities. This means that an objective diagnostic is available for those who are most vulnerable to the severest disease.
In addition to the diagnostic tool, this transcriptomic study also uncovered some potential biomarkers for the onset of disease. Some confirmed previous speculations and genetic analyses, like the upregulation of PAPPA2, which is a key regulator of placental development. Other genes like SNORD14A, PLEKHH1, and MAGEA10 are still being explored to determine their function. They likely hold key information about how maternal and fetal genetic material collaborate during pregnancy.
In exploring RNA data from early stages of gestation, this study took a novel approach in mapping preeclampsia disease pathology. It exposes new molecular mechanisms that previous analyses of confirmed cases failed to discover. This model gives hope for reduced mortality, as well as a better and more equitable diagnosis paradigm for this disease. There’s promise that RNA transcriptomics can elucidate other diseases in the future.
Source:
Advances in Clinical Chemistry (2016). DOI: 10.1016/bs.acc.2015.12.004
Nature (2022). DOI: 10.1038/s41586-021-04249-w
Image courtesy of Wikimedia Commons
