Placental mRNA in maternal plasma: Prospects for fetal screening

Increasingly, over the past 30 years, couples at risk of bearing children with certain types of severe handicaps have had the option of fetal diagnosis, followed by selective termination of pregnancy, with the prospect of trying for a healthy baby later. In a society where financial and other help is seldom available to provide adequate support to the parent caring for a severely disabled infant, it is understandable that there is an increasing demand for obstetric services to provide prenatal screening to determine risks, and safe tests to confirm, or exclude, the diagnosis. Modern obstetric ultrasonography brings the fetus into sight and is one of the main screening tests for developmental malformations. Nuchal translucency is a measurable ultrasound feature associated with Down's syndrome and, when used in conjunction with maternal serum screening, increases the detection rate in the first trimester to >85% for a false-positive rate of 5% (1). The key maternal serum markers are the levels of the β subunit of human chorionic gonadotrophin (βhCG), and pregnancy-associated plasma protein-A (PAPP-A). Ultrasound bears no hazard for the fetus, but the procedures used for definitive diagnosis, namely chorion villus sampling (CVS) and amniocentesis, carry a risk of miscarriage of ≈1%. Almost all current tests for fetal chromosome, genetic, and biochemical disorders depend on either of these two invasive procedures to provide fetal cells for culture or DNA analysis.

The search for a noninvasive diagnostic procedure that avoids the risk of miscarriage has centered in recent years on attempts to isolate fetal cells from the maternal circulation and, more recently, on attempts to assay for free nucleic acids of fetal origin in maternal serum or plasma. In this issue of PNAS, Ng et al. (2), provide important new insight on mRNA levels in maternal plasma of the genes coding for βhCG and …