Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21

Background; The recent discovery of the presence of circulating cell-free f etal DNA in maternal plasma opens up new prenatal diagnostic applications a nd provides new avenues for clinical investigation. It is of research and p otential diagnostic interest to determine whether fetal trisomy 21 may be a ssociated with quantitative abnormalities of circulating fetal DNA in mater nal plasma. Methods: Maternal plasma samples were prospectively collected from two cent ers situated in Hong Kong and Boston. Samples collected from Boston consist ed of 7 women carrying male trisomy 21 fetuses, 19 carrying euploid male fe tuses, and 13 carrying female fetuses. Samples collected from Hong Kong con sisted of 6 women carrying male trisomy 21 fetuses, 18 carrying euploid mal e fetuses, and 10 carrying female fetuses. Male fetal DNA in maternal plasm a was measured using real-time quantitative Y-chromosomal PCR. Results: For patients recruited from Boston, the median circulating fetal D NA concentrations in women carrying trisomy 21 and euploid male fetuses wer e 46.0 genome-equivalents/mL and 23.3 genome-equivalents/mL, respectively ( P = 0.028). For patients recruited from Hong Kong, the median circulating f etal DNA concentrations in women carrying trisomy 21 and euploid male fetus es were 48.2 genome-equivalents/mL and 16.3 genome-equivalents/mL, respecti vely (P = 0.026). None of the samples from women carrying female fetuses ha d detectable Y-chromosomal signals. Conclusions: Abnormally high concentrations of circulating fetal DNA are fo und in a proportion of women carrying fetuses with trisomy 21. The robustne ss and reproducibility of real-time PCR analysis of maternal plasma makes i t a valuable tool for cross-institutional collaboration involving centers l ocated in different parts of the world. (C) 1999 American Association for C linical Chemistry.