Critically Appraised Topic Fetal RHD genotyping in maternal blood using cell-free fetal DNA

The discovery of cell-free fetal DNA (cffDNA) in maternal plasma has opened up new possibilities for non-invasive prenatal diagnosis (NIPD). Real-time PCR protocols as well as MALDI-TOF mass spectrometry techniques have been developed to determine fetal RHD genotype on maternal plasma. In several European centers, NIPD for fetal RHD has become the standard of care for evaluation of anti-D allo-immunized pregnant women. Several authors have also suggested the feasibility of fetal RHD genotyping in non-immunized women to determine the need for antenatal and perinatal anti-D immunoglobulin. However, up until now there are insufficient data of the cost-effectiveness of largescale implementation of this test. Most studies were organized in a research/experimental setting in which several replicates were analyzed and inconclusive or unobtainable results have systematically been excluded. In case of large-scale implementation, the number of analyzed replicates should be limited, and inconclusive or unobtainable results need to be taken into consideration. Moreover, up until today, there’s still no universal internal control for the presence of cell-free fetal DNA available. This is necessary to avoid false negative results. International guideline providers such as NICE, ICSI and BCSH await further studies on NIPD using cell-free fetal DNA to issue new guidelines considering the preand postnatal management of RhD negative non-immunized pregnant women.