Fetal Cells in Maternal Blood

Prenatal genetic diagnosis has advanced immensely over the last several decades. In the 1950s. genetic counseling was the only modality available. Couples could be provided recurrence risk figures for the few recognized Mendelian conditions, but otherwise no diagnosis could be made, and no intervention was possible. This changed abruptly in 1968 when diagnosis in utero became possible through amniocentesis. In 1982 to 1984, first-trimester prenatal diagnosis was shown to be feasible through chorionic villus sampling, a first-trimester procedure later shown to be as safe and effective as amniocentesis.' Despite these notable advances, shortcomings remain in prenatal genetic diagnosis. Specifically, both chorionic villus sampling and amniocentesis are invasive procedures that carry a low but finite risk of pregnancy loss. Therefore, these tests cannot be offered to the entire population, but rather only to women at increased risk for genetic disorders. Examples include those with previously affected offspring (e.g., with a Mendelian trait) or advanced maternal age (235 years at delivery). Noninvasive methods would be highly desirable. Methods currently available to clinical geneticists include ultrasonographic assessment and maternal serum analyte screening. Unfortunately, noninvasive tests lack the sensitivity of invasive tests. Although certain studies have suggested that a relatively high proportion of structural anomalies are detectable by ultrasound, this did not prove to be the case in a large, recent, randomized trial of low-risk women in the United States. In this trial,* 15,151 low-risk patients were randomized between those receiving routine ultrasound and those receiving ultrasound only for specific indications. In the indicated ultrasound arm, 35% of anomalies were detected, whereas only 11% were detected in the control (routine ultrasound) arm. Unfortunately, only slightly less than half the anomalies detected were recognized earlier than 24 weeks of gestation (i.e., 31 out of 187 in the routine ultrasound arm). Pregnancy outcome was thus not often altered. Maternal serum analyte screening is also less than optimal. Screening in women less than 35 years of age will detect perhaps 60% of Down syndrome cases, although the rate rises to approximately 90% in women over the age of 35 years.3 Because neither ultrasound nor serum screening approaches the sensitivity of invasive screening, attention has continued to focus on the idea of recovering fetal