Presymptomatic Noninvasive Assessment of Fetal Well-being by Genome-wide RNA Sequencing.

Abstract

Spontaneous preterm birth with preterm delivery (before week 37) and other high prevalence pregnancy-associated diseases, including early-onset preeclampsia, late-onset preeclampsia, and fetal intrauterine growth restriction, form the “Big 4” of pregnancy complications. Until now, truly effective methods to screen, prevent, or manage these complications have been lacking. A major obstacle is the fact that many of these diseases have an early placental origin with late clinical presentation in the mother. Methods that allow presymptomatic screening or diagnosis are urgently needed to overcome the time disparities between disease origin and presentation for the benefit of the mothers and babies involved. In a recent issue of Science , Quake and colleagues have demonstrated 1 of the first prerequisites to reach this goal (1). Their approach was based on their previous work and that of another pioneering group in the field of noninvasive prenatal screening, both of which clearly showed the possibility of maternal plasma sequencing using circulating cell-free fetal nucleic acids. Applying this approach, they identified by maternal plasma RNA sequencing of 38 women (23 full-term and 15 preterm deliveries) that a set of 7 cell-free fetal RNA (cffRNA) transcripts permitted classification of women who delivered preterm up to 2 months in advance of labor (1, 2). Although these results certainly require validation in larger, blinded clinical trials, their proof of principle indicates the potential of the approach used and generates exciting new perspectives, both for preterm delivery and other diseases of the Big 4. A …