Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma

Background The ability to determine fetal RhD status noninvasively is usefu l in the treatment of RhD-sensitized pregnant women whose partners are hete rozygous for the RhD gene. The recent demonstration of fetal DNA in materna l plasma raises the possibility that fetal RhD genotyping may be possible w ith the use of maternal plasma. Methods We studied 57 RhD-negative pregnant women and their singleton fetus es. DNA extracted from maternal plasma was analyzed for the RhD gene with a fluorescence-based polymerase-chain-reaction (PCR) test sensitive enough t o detect the RhD gene in a single cell. Fetal RhD status was determined dir ectly by serologic analysis of cord blood or PCR analysis of amniotic fluid . Results Among the 57 RhD-negative women, 12 were in their first trimester o f pregnancy, 30 were in their second trimester, and 15 were in their third trimester. Thirty-nine fetuses were RhD-positive, and 18 were RhD-negative. In the samples obtained from women in their second or third trimester of p regnancy, the results of RhD PCR analysis of maternal plasma DNA were compl etely concordant with the results of serologic analysis. Among the maternal plasma samples collected in the first trimester, 2 contained no RhD DNA, b ut the fetuses were RhD-positive; the results in the other 10 samples were concordant (7 were RhD-positive, and 3 RhD-negative). Conclusions Noninvasive fetal RhD genotyping can be performed rapidly and r eliably with the use of maternal plasma beginning in the second trimester o f pregnancy. (N Engl J Med 1998;339:1734-8.) (C) 1998, Massachusetts Medica l Society.