Soothill et al. have provided us with a prospective evaluation of circulating cell-free fetal DNA (ccffDNA) RHD testing to help determine which RhD-negative patient should receive antenatal anti–D prophylaxis (AADP). Based on their findings, these authors propose that the practice be extended to the National Health Service in the UK. Screening of RhD-negative pregnant patients to determine whether AADP should be undertaken is routinely practiced in Denmark and the Netherlands, as well as in some regions in Sweden and France. In some of these situations, ccffDNA screening was implemented as part of a new AADP programme because of limited availability of Rhesus-immune globulin (RHIG); however, in the USA and in the UK plasma collected from sensitised male volunteer donors in the US is used to manufacture RHIG. As such, there is currently no restriction on the availability of RHIG. Thus, the argument that ccffDNA screening should be employed because of limited resources does not appear to be valid. Kent et al. (BMC Pregnancy and Childbirth 2014;14:87–90) have argued that it is unethical to subject the 38% of RhD-negative pregnant women with an RhD-negative fetus to exposure of a blood product with the potential for infectious morbidity from prions and new viruses. Similarly, male volunteers who undergo plasma donation to make RHIG are also exposed to red cell aliquots for the initial sensitization and subsequent enhancement of their titers. Costs must clearly play a major role in the implementation of a nationwide ccffDNA screening programme to guide AADP. Szczepura and co–workers (BMC Pregnancy and Childbirth 2011;11:5–12) calculated a break-even test cost of £18.43. This is considerably less than £40, which the authors of the current study calculated as the cost of ccffDNA screening. A similar cost analysis in the US (Hawk et al. Obstet Gynecol 2013;122:579–85) indicated that the break-even cost of a test was $119 (£71.29). Finally, one must evaluate the impact of this potential new policy on new cases of alloimmunization. A false-positive ccffDNA test will not prove problematic, as the patient will receive RHIG; however, a false-negative test would result in a missed opportunity for AADP, with an estimated risk for alloimmunisation of 1%. This risk has been estimated to be 1 : 86 000 patients (Finning et al. BMJ 2008;336:816–8.) Clearly, a ‘checks and balances’ continuation of the serologic evaluation of cord blood at the time of delivery would virtually eliminate these false-negative ccffDNA cases. Cord testing would allow for postpartum RHIG administration: a time when the incidence of alloimmunisation is increased 14 times over antenatal alloimmunisation. If one assumes a sensitivity of 99.7%, as previously reported by the authors (Finning et al. BMJ 2008;336:816–9), such a policy has been estimated to result in only three new cases of Rhesus alloimmunisation annually in England and Wales (Szczepura et al. BMC Pregnancy and Childbirth 2011;11:5–12). In the end, do these arguments fall on the side of widespread adoption of ccffDNA RHD screening to guide AADD programmes? I believe the final answer will be related to cost, as long as we as a society are willing to accept a slight increase in new cases of Rhesus alloimmunisation. KJM receives royalty payments for chapter authorship from UpToDate, Inc. He also serves as a consultant to LabCorp, Inc. There is no financial conflict with the views presented in this commentary.
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Aug 31, 2024
Tae-Shin Kim + 6
Open Access