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JOGC

No. 343-Routine Non-invasive Prenatal Prediction of Fetal RHD Genotype in Canada: The Time is Here

      Abstract

      The optimal management of the D-negative pregnant woman is now based on the non-invasive antenatal prediction of fetal D-blood group by cell-free DNA (cfDNA) in maternal plasma, with targeted prophylaxis for women carrying RHD-positive fetuses. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. This paper is the result of a consensus meeting of the Canadian National Rh Working Group, an interdisciplinary group formed to review the current status of fetal RHD genotyping based on cfDNA in Canada. The group, in collaboration with the SOGC Genetics committee, reviewed the benefits and challenges of implementing RHD genotyping with targeted prophylaxis in the context of the existing routine antenatal anti D prophylaxis program in Canada. The following summary statements and recommendations are based on this review.

      Summary Statements

      • 1.
        Non-invasive antenatal determination of fetal RHD genotype by cell-free DNA is highly accurate with sensitivities above 99% and very few false-negative results (II-2).
      • 2.
        While the risks of Rh immune globulin exposure are exceptionally low, it is no longer considered appropriate to treat all D-negative pregnant women with human plasma derivatives when there are no benefits to her or to the fetus in a substantial percentage of cases (II-2).
      • 3.
        Implementation of non-invasive fetal RHD genotyping with targeted routine antenatal anti-D prophylaxis would enable up to 40% of D-negative women to avoid use of Rh immune globulin (II-2).
      • 4.
        Fetal RHD genotyping is feasible as early as 10 weeks’ gestation and earlier testing is preferable as it allows for targeted prophylaxis for women with sensitizing events prior to 28 weeks’ gestation (II-2).
      • 5.
        Implementation of non-invasive fetal RHD genotyping with selective prophylaxis requires interdisciplinary collaboration (clinical and laboratory) as well as the endorsement of provincial ministries of health (III).

      Recommendations

      • 1.
        The current optimal management of the D-negative pregnant woman is based on the prediction of the fetal D-blood group by cell-free DNA in maternal plasma with targeted antenatal anti-D prophylaxis. This approach should be adopted in Canada (II-2A).
      • 2.
        While various algorithms of implementation of fetal RHD genotyping have been described, a model positioned in the first trimester appears to be most in alignment with the existing Canadian antenatal anti-D prophylaxis program and should be endorsed (II-2A).
      • 3.
        While the risk of a false-negative result with RHD genotyping is very small and the benefits of knowing the fetal RHD status in terms of compliance with prophylaxis seem to outweigh the risks, the chance of immunization is not zero. Quality control at a laboratory and clinical level should be of utmost priority in program planning (II-3A).

      Abbreviations:

      CBS (Canada blood sevices), cfDNA (cell-free DNA), FMH (fetomaternal hemorrhage), FN (false-negative), FP (false-positive), HDFN (Hemolytic disease of the fetus and newborn), PCR (polymerase chain reaction), RAADP (routine antenatal anti-D prophylaxis), RHD (the gene that determines the expression of the D antigen), RhD (Rhesus D antigen positive), RhIG (Rh (D) immunoglobulin)
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