Noninvasive Prenatal Diagnosis: Past, Present, and Future

The presence of fetal cells in the maternal circulation was first noted by Georg Schmorl when he documented the presence of multinucleated syncytial giant cells of placental origin in the lung tissue of women who had died from complications of eclampsia. In the intervening century, advances in cellular and molecular biology further elucidated both the physiology and pathophysiology of communication within the fetomaternal unit. This concept is at the foundation of the rapidly expanding field of noninvasive prenatal diagnosis. However, the clinical utility of this phenomenon had been limited until the presence of cell‐free fetal DNA circulating in the maternal plasma was reported in 1997 and fetal messenger RNA was demonstrated to circulate in the maternal plasma in 2000. These circulating nucleic acids are found free‐floating in the maternal plasma, unencumbered by a surrounding fetal cell. The analysis of these 3 fetal markers (fetal cells, cell‐free fetal DNA, and fetal messenger RNA) for diagnostic and screening purposes is now being developed. The scope of noninvasive prenatal diagnosis is not limited to only the diagnosis of fetal genetic traits and aneuploidies. Recently, researchers have focused their investigations on the role of cell‐free fetal DNA and fetal messenger RNA in preeclampsia, intrauterine growth restriction, and preterm labor. These biomarkers, the result of inherent placental dysfunction or the byproducts of placental trophoblastic apoptosis, may allow for improvements in the diagnosis and management of high‐risk pregnancies. Mt Sinai J Med 76:521‐528, 2009. © 2009 Mount Sinai School of Medicine