Limiting RHIG prophylaxis based on prenatal determination of fetal Rh status
W. John Judd, FIBMS, MIBiol, Professor of Immunohematology at the Department of Pathology of University of Michigan Medical Center (attribution used with permission) reports that counterparts in the UK and Holland are limiting antepartum RhIG prophylaxis (because RhIG is in short supply) based on determination of fetal Rh status using maternal plasma. See Bianchi DW, Avent ND, Costa JM, van der Schoot E. Noninvasive prenatal diagnosis of fetal Rhesus D: Ready for Prime(r) Time. Obstertics and Gynecology 2005;106:841-4. On page 682 of that issue, there is an accompanying editorial by JT Queenan (Editor in Chief) essentially stating that the US needs to get its act together on this issue (i.e., doing the testing and limiting antepartum RhIG prophylaxis to women carrying an Rh-positive fetus). Professor Judd acknowledges that he and colleagues have recently published a feasability study on this issue. However, he qualifies their report by adding that "While results were positive, we were limited in our study design by Institutional Review Board issues". [Zhou L, Thorson JA, Nugent C, Davenport RD, Butch SH, Judd WJ. Noninvasive prenatal RHD genotyping by real-time polymerase chain reaction using plasma from D-negative pregnant women. Am J Obstet Gynecol. 2005 Dec;193(6):1966-71. "However, we will not proceed further even with additional validation data because of the fear of litigation". He wonders "What would be the FDA's position on this?" He also wonders if there will be a shortage of anti-D for RhIG manufacture, and if anyone is planning on offering this kind of testing in the USA for the purpose of limiting RhIG prophylaxis."
The following comments have been received.
ADDENDA Jan. 2, 2006
- A scientist in Europe who is very familiar with molecular methods for determination of Rh typing cautions that a certain (presumably low) failure rate will occur if one relies on molecular typing methods such as prenatal RHD genotyping by real-time polymerase chain reaction using plasma from D-negative pregnant women. These failures will in all likelihood cause a few primary anti-D alloimmunizations each year in pregnant women. Even the most eager proponents acknowledge a failure rate of, at least, 1 or 2 in 10,000. Of course, according to the European scientist, the rate of inadvertant lack of RhIG prophylaxis or of failure of RhIG prophylaxis may be as high or even higher. The difference and the catch is - and will remain - that it might be risky for an immunohematologist to recommend dropping the RhIG prophylaxis, especially if it is later most straightforwardly proved in court that exactly this individual's recommendation initiated a chain of events leading to primary anti-D immunization. S/he adds that within the US setting there is a much higher rate of African and Asian dys-functional alleles like the RHD pseudogene and K409K. This issue can be dealt with, of course, but may complicate the testing significantly. It renders the extrapolation of the European failure rate into the US population shaky, at best. S/he assumes that no definite answer may or should be accepted for the applicability within the US before a feasibility study would have established the actual and hopefully (legal and otherwise) acceptable failure rate in critical US regions, like southern US (African-American) and California (Asian-American). It might be noted that the proposed procedure is not standard practice in any European country, neither is it implemented in any guideline of any European country to date.
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