Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications.

Circulating nucleic acids have revolutionized prenatal diagnosis in the last decade, allowing non-invasive screening for single gene or chromosomal defects using a single sample of maternal blood. In addition to DNAs, RNAs from the placenta are released into the maternal blood from early in pregnancy and may reflect changes in gene expression occurring within the placenta. Measuring circulating RNA may therefore provide insights into the placental transcriptome without the need for invasive testing. Combined with advances in next-generation sequencing and molecular analyses, it may be possible to measure circulating RNA to improve our understanding of placental pathology and develop novel non-invasive biomarkers for pregnancy complications and monitoring high-risk pregnancies. This review summarizes the current technologies available and the studies that have measured circulating placental RNA to predict and/or monitor pregnancies complicated by preeclampsia, fetal growth restriction, preterm birth, early pregnancy complications, invasive placentation and twin-twin transfusion syndrome. Prospective cohort studies are now required to validate these findings to determine the clinical applicability of measuring circulating placental RNA to develop novel biomarkers for a wide spectrum of pregnancy complications.