Revolutionizing preeclampsia risk prediction: Study examines RNA biotypes | Image Credit: © ktsdesign - © ktsdesign - stock.adobe.com.
RNA biotypes can be used to predict preeclampsia risk, according to a recent study published in the American Journal of Obstetrics & Gynecology.
- The study suggests that RNA biotypes can be utilized as predictors for preeclampsia (PE) risk in pregnant women, offering a potentially noninvasive method for assessing pregnancy-related complications.
- Preeclampsia affects 2% to 4% of pregnant women worldwide, leading to a substantial number of maternal and fetal deaths annually. The study emphasizes the significance of finding accurate predictive measures for PE due to its impact on maternal and fetal health.
- The research identifies 2 stages in the development of preeclampsia: abnormal placental development in early pregnancy and systemic maternal endothelial dysregulation and inflammation later on. Understanding these stages is crucial for developing effective predictive models.
- The investigators conducted a comprehensive study involving 917 pregnancies to evaluate the cell-free RNA (cfRNA) transcriptomic landscape associated with PE. The study used polyadenylation ligation-mediated sequencing on plasma samples collected from pregnant women between 12- and 33-weeks’ gestation.
- The study developed predictive models for preterm PE and early-onset PE, incorporating 13 genes along with in vitro fertilization (IVF) and mean arterial pressure (MAP). These models demonstrated high accuracy, indicating the potential of RNA biotypes in enhancing the precision of PE risk prediction.
Between 2% and 4% of pregnant women worldwide experience preeclampsia (PE), with approximately 46,000 maternal deaths and 500,000 fetal and newborn deaths from PE reported annually. PE is defined as, “the onset of new hypertension and proteinuria or other end-organ damage, such as the liver or brain, after 20 weeks of pregnancy.”
Early-onset PE increases risks of placental dysfunction, and both early-onset PE and preterm PE are associated with potentially severe maternal and fetal complications. PE development occurs in 2 stages, the first being abnormal placental development in early pregnancy and the second systemic maternal endothelial dysregulation and inflammation.
It is difficult to predict PE risk because of the disease’s heterogeneity and complexity, but cell-free RNA (cfRNA) may allow for noninvasive research of pregnancy-related complications. Investigators conducted a study to evaluate PE-associated cfRNA transcriptomic landscape in plasma using polyadenylation ligation-mediated sequencing.
There were 917 pregnancies recruited from 2 hospitals in China, 202 of which developed preterm PE and 715 were healthy. Plasma samples were collected from January 1, 2018, to March 1, 2022, with all patients between 12- and 33-weeks’ gestation when samples were collected. Investigators obtained antenatal blood samples before diagnosis.
Uncomplicated pregnancies reaching full term were considered noninvasive. Healthy control samples from full-term pregnancies without complications were collected.
Exclusion criteria included chronic hypertension, pregestational diabetes, autoimmune diseases, kidney-related diseases, alcohol consumption during pregnancy, smoking history, pregnancy termination, and pregnancies with aneuploidies and major fetal abnormalities.
BD Vacutainer spray coated K2EDTA tubes (BD, catalog number 367863, Jinan, China) were used to collect whole blood. Plasma separation occurred at 1600g for 20 minutes at 4°C within 6 hours of blood collection. Plasma samples were stored at −80°C.
American College of Obstetricians and Gynecologists guidelines were used to determine PE, with diagnostic criteria including new-onset hypertension at 20 weeks of gestation or more and new-onset proteinuria.
If proteinuria was not present, the following could be used as diagnostic criteria alongside new-onset hypertension: thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or cerebral or visual disturbances. Early-onset PE was defined as PE before 34 weeks’ gestation, and preterm PE as PE before with delivery before 37 weeks’ gestation.
Body mass index, parity, and maternal age did not significantly differ between patients with PE and controls. However, in vitro fertilization (IVF) and mean arterial pressure (MAP) were significantly higher in patients with PE.
Mothers who later developed early-onset PE developed preterm compared to normotensive mothers and delivered earlier than mothers with preterm PE. Lower fetal weights were also observed among infants of mothers with early-onset PE or preterm PE compared to normotensive mothers.
In PE samples, increased mRNA expression levels associated with skeletal muscle, bone marrow, the liver, lymphoid tissue, brain, and kidney were observed. There were 77 differentially expressed genes (DEGs) observed when comparing mothers who later developed preterm PE with normotensive mothers.
When comparing normotensive mothers with those who later developed early-onset PE, 94 DEGs were observed. Additionally, DEGs were associated with known etiologies of PE. Using this data, investigators developed models to identify mothers at risk of preterm PE and early-onset PE.
The model predicting preterm PE included 13 genes combined with IVF and MAP, which had an area under the receiver operating characteristic curve (AUC) of 0.91 and specificity of 93%. The model predicting early-onset PE also included 13 genes combined with IVF and MAP and had an AUC of 0.93 and specificity of 99%.
These results indicated RNA biotypes are associated with higher accuracy when predicting PE risk. Investigators concluded RNA biotypes may be used as a new avenue for reducing pregnancy complications and fetal morbidity.
Zhou S, Li J, Xue P, et al. Noninvasive preeclampsia prediction using plasma cell–free RNA signatures. Am J Obstet Gynecol. 2023;229:553.e1-16. doi:10.1016/j.ajog.2023.05.015