PraenaRhD
The prenatal rhesus test
Non-invasive prenatal RhD genotyping from maternal blood
Now you have the option of determining the fetal Rhesus factor non-invasively from the blood of the RhD-negative mother (PraenaRhD), with a high level of diagnostic reliability. As a result, you can decide whether anti-D prophylaxis is indicated in order to use it specifically only for those RhD-negative pregnant women who are actually expecting an RhD-positive child.
Benefits of the PraenaRhD
According to the German Society of Gynecology and Obstetrics (DGGG), you avoid the following adverse effects in those pregnant women in whom prophylaxis is not indicated:4
- Potential infection through the transmission of pathogens with the administration of the anti-D prophylaxis (human immunoglobulin)
- Allergoid/anaphylactic reactions
Also, inpatient hospitalization for RhD-negative mothers can be shortened, since they can receive anti-D prophylaxis immediately after delivery if the test result is positive. In addition, the anti-D immunoglobulin is currently obtained from immunized donors and imported.
Anti-D prophylaxis in pregnant women is not necessary if the fetus was determined to be RhD-negative using a validated method. After delivery, the RhD characteristic is to be determined, preferably from umbilical cord blood.
Hemotherapy guideline, overall amendment 2017
Methods and diagnostic quality
In the PraenaRhD, cell-free DNA from the placenta is tested. Using qPCR, the exons 5, 7 and 10 of the RhD gene are amplified and evaluated. If the test result is positive for all three exons, the analyzed sample is classified as RhD-positive. If the test result is positive for only one or two exons, the overall result is evaluated as being not diagnostically conclusive. All test results of the three exons must be negative in order for the overall result of the sample to be classified as RhD-negative.
IQWiG final report (March 2018)
The Institute for Quality and Efficiency in Health Care (IQWiG) certifies that the non-invasive prenatal determination of the fetal Rhesus factor has a very high level of sensitivity and specificity. Because of the high level of sensitivity of the test, only very few cases of anti-D prophylaxis which were erroneously not administered antepartum can be expected. In addition, the postnatal tests also yielded false-negative results at rates similar to those of the prenatal tests. The prenatal test is therefore equivalent to the postnatal test.
IQWiG: The prenatal test is equivalent to postnatal test.
Limits of the test
- False-positive test results are possible in the case of a rare genotype, non-functional RhD variant5 or a bone marrow donation6
- A test result cannot be reported if the mother is a carrier of the RhD gene
- False-negative results are also fundamentally possible7,8
Literatur
- Instruction manual: Institut de Biotechnologies Jaques Boy. Free DNA Fetal KitR RhD. Noninvasive fetal RHD genotyping from free fetal DNA in maternal RhD-Negative pregnant women blood (Real-Time PCR). Product identification: 502080233. Manual version 16/03/2018.
- Rouillac-Le Sciellour C et al. (2007). Noninvasive fetal RHD genotyping from maternal plasma. Use of a new developed Free DNA Fetal Kit RhDR. Transfus Clin Biol, 2007 Dec;14(6):572-7. doi: 10.1016/j.tracli.2008.01.003.
- Mackie FL et al. (2017). The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. BJOG, 2017 Jan;124(1): 32-46. doi: 10.1111/1471-0528.14050.
- 237. Stellungnahme der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG). Nichtinvasive Bestimmung des fetalen Rhesusfaktors zur Vermeidung einer mütterlichen Rhesus-Sensibilisierung im Rahmen der Vorsorgeuntersuchung gemäß Mutterschafts-Richtlinien (Mu-RL). www.dggg.de/leitlinienstellungnahmen/stellungnahmen/nichtinvasive-bestimmung-des-fetalen-rhesusfaktors-413, abgerufen am 21.01.2019.
- Flegel WA (2007). Genetik des Rhesus-Blutgruppensystems. Dtsch Ärztebl 2007, 104(10): A-651-657/B-573/C-549.
- Thurik FF et al. (2016). Fetal RHD genotyping after bone marrow transplantation. Transfusion, 56: 2122-2126. doi :10.1111/ tr f.13669.
- Clausen FB et al. (2014). Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women – 2 years of screening experience from Denmark. Prenat Diagn, 34:1000-1005. doi: 10.1002/pd.4419.
- de Haas, M et al. (2012). A nation‐wide fetal RHD screening programme for targeted antenatal and postnatal anti‐D. ISBT Science Series, 7: 164-167. doi:10.1111/j.1751-2824.2012.01600.x.