Reaffirmed Guideline No. 343: Prediction of Fetal RHD Genotype by Routine Noninvasive Prenatal Testing

Statement summaries1. Fetal RHD genotyping using a noninvasive test performed on cell-free DNA has a high degree of accuracy: it has a sensitivity consistently above 99% and produces very few false negatives (II-2).2. Although the risk of exposure to Rh immune globulin is extremely low, routine administration of human plasma derivatives to Rh-negative pregnant women is no longer indicated, since in a significant number of cases this practice is of no benefit to either the mother or the fetus (II-2).3. With noninvasive fetal RHD genotyping combined with routine targeted anti-D antenatal prophylaxis, up to 40% of Rh-negative women may not receive anti-RH immunoglobulin (II-2).4. Fetal RHD genotyping is available as early as 10 weeks of pregnancy; early is preferable to offer targeted prophylaxis before 28 weeks of pregnancy to women who have experienced a sensitizing event (II-2).5. The implementation of non-invasive fetal RHD genotyping combined with selective prophylaxis requires interdisciplinary collaboration (clinical and laboratory) and endorsement by provincial ministries of health (III).Recommendations1. Currently, the best way to manage Rh-negative pregnant women is to predict the presence or absence of D antigen in the fetus using a noninvasive test that analyzes cell-free DNA (aDNA) in the mother's plasma, and to administer targeted antenatal anti-D prophylaxis. This approach should be adopted in Canada (II-2A).2. Although different modalities for fetal RHD genotyping have been described, first-trimester testing appears to be the most compatible with the existing Canadian routine anti-D antenatal prophylaxis program and should be preferred (II-2A).3. The risk of false-negative RHD genotyping is very low, and the benefits of adherence to prophylaxis practices based on knowledge of the fetal RHD genotype appear to outweigh the risks, but the potential for immunization is not zero. Quality control in the laboratory and clinical settings should be a high priority in program planning (II-3A).