Is Maternal Plasma Transcriptome Analysis a New Tool for Monitoring High-Risk Pregnancies?

The analysis of circulating nucleic acids has been accepted for more than a decade as a novel noninvasive tool for prenatal diagnosis and monitoring of pregnancy-associated disorders, as well as for monitoring other diseases such as cancer and diabetes (1–3). In this issue of Clinical Chemistry , Tsui et al. present a study in which they successfully investigated the complete maternal plasma transcriptome during pregnancy by the use of RNA sequencing (RNA-seq)2 (4). The authors analyzed circulating RNA for first-, second-, and third-trimester pregnancies and found an increasing fetal contribution to maternal plasma RNAs during pregnancy of up to more than 11% during late gestation. Fetal- and maternal-specific alleles were detected on the basis of single nucleotide polymorphisms in RNA-seq reads specific for the paternal or the maternal genome to estimate the fetal and maternal contribution to the circulating transcripts in maternal plasma, respectively. Genes containing informative single nucleotide polymorphisms were identified by the use of exome-enriched genomic DNA library sequencing of samples from the fetal part of the placenta and from maternal white blood cells. Furthermore, the ratio of fetal- and maternal-specific alleles to the common allele was used to find genes with a high fetal or maternal contribution, which correspond to genes specifically expressed from …