The battle against Rh disease is about to get a lot easier

April 15, 2006

With the help of PCR analysis, cell-free fetal RhD antigen can be detected in maternal serum, offering the promise of detecting mother/child incompatibilities long before any clinical damage can occur. Here's a brief overview of the technology and why it's still not ready for prime time in the U.S.

While modern medicine is sometimes accused of providing band-aid treatments for complex disorders, the history of Rh disease represents one of medicine's genuine success stories. When the erythrocyte's rhesus D antigen was first discovered in the 1950s, about one out of every two Rh-negative women who became sensitized to the antigen lost her baby. But by 1986, with the help of amniocentesis, amniotic fluid analysis, and intrauterine transfusions, the odds of a child surviving such an immunological nightmare had vastly improved, with mortality dropping to 2% to 3%.1

The real victory, however, will come when all these mother/child immunological incompatibilities are detected long before they become nightmares. Middle cerebral artery Doppler is helping physicians achieve that goal, but even more impressive is the technology that allows clinicians to noninvasively determine the presence of fetal Rh antigen in maternal blood.

With the assistance of polymerase chain reaction analysis, noninvasive cell-free fetal RhD genotyping has become a routine part of prenatal care in several European countries. Our purpose here is to briefly describe the technology, discuss its advantages and disadvantages, and answer the question on the minds of many clinicians: Why isn't it part of the prenatal workup in the United States?

There are two clinical situations in which cell-free fetal DNA testing of an Rh-negative mother holds the potential for being a major breakthrough. John T. Queenan, MD, a well-respected expert in Rh disease, points out that the Rh-negative immunized mother with a heterozygous Rh-positive father has a 50-50 chance of having an Rh-negative fetus.2 If the fetus turns out to be Rh negative, there's no risk of hemolytic disease and testing can be stopped. If, on the other hand, the fetus tests Rh positive, then appropriate diagnostic tests, and therapy, if needed, can proceed.

The second situation in which fetal genotyping holds promise is in the Rh-negative, nonimmunized mother who is a candidate for 28-week Rh immunization (Rh immunoglobulin). By testing the mother for fetal Rh antigen, the clinician can determine if the fetus is Rh positive, which would mean immunoglobulin is indicated. Of course, if the fetus is Rh negative, the clinician "can eliminate the expensive and wasteful practice of administering Rh immune globulin at 28 weeks to those who subsequently deliver Rh-negative babies."1

Eventually enough DNA is synthesized-the amplification process. Because the chain reaction has generated enough RhD antigen molecules, a discrete pattern emerges, which can then be displayed graphically to signal the presence of the DNA fingerprint for the antigen.