Loke CTR members Sung Gong, Gordon Smith and Steve Charnock-Jones, alongside colleagues in Obstetrics and Gynaecology, and collaborators at Illumina, have shown that raised Leptin and Pappalysin2 cell-free RNAs are hallmarks of pregnancies complicated by preeclampsia with fetal growth restriction.
In this study, published in Nature Communications, researchers have shown that sequencing cell-free RNA from maternal blood can be used to predict pregnancy complications before the onset of disease.
Preeclampsia (PE) and fetal growth restriction (FGR) complicate 5-10% of pregnancies and are major causes of maternal and fetal morbidity and mortality. This study used 751 plasma samples collected at four time points in pregnancy as part of the Pregnancy Outcome Prediction study (POPS). A customised RNA purification method was used and the resulting cell-free RNA sequenced. Eleven machine learning models were developed in a discovery cohort and their predictive performances evaluated in a separate set of samples.
The key finding was that surprisingly, the measurement of only 2 mRNAs was sufficient to give accurate prediction. Circulating leptin (LEP) and pappalysin2 (PAPPA2) cell-free RNAs were the strongest predictors of complicated pregnancies and in the replication sample set the area under the receiver operating characteristic curve (AUC) was ~0.82. The predictive model was evaluated in an independent set of samples collected after the time of diagnosis these two predictors were even more strongly associated with disease (AUC ~0.95).
This work opens a new window of liquid biopsy by using cfRNAs for monitoring complications of human pregnancy.