Investigation of discrepancies obtained during 15 years of non‐invasive fetal RHD genotyping in apparent serologic RhD‐negative pregnant women. (22nd August 2022)

• Record Type: Journal Article
• Authors: Dufour, Patrice; Gerard, Christiane; Chantraine, Frédéric; Minon, Jean‐Marc
• Is Part Of: Prenatal diagnosis. Volume 42:Number 10(2022)
• Page Start: 1262
• Page End: 1272
• Publication Date: 2022-08-22
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.6219
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objectives: In some European countries, non‐invasive fetal RHD genotyping is the first step of anti‐D allo‐immunized pregnant women management but presence of RHD variant alleles may interfere with the results accuracy. We developed an algorithm allowing solving discordant results (due to the presence of RHD variant) in fetal RHD genotyping assay. Method: This study gathered the results of fetal RHD genotyping performed between 2006 and 2020 in the Medicine Laboratory of CHR Liège. Exons 4, 5 and 10 of the fetal RHD were profiled in maternal plasma using real time polymerase chain reaction (PCR). When the results were discrepant, maternal RHD variant was further explored by sequence‐specific primer PCR on maternal buffy coat. Results: A total of 11, 630 pregnant women (mainly of both Caucasian and African origins) were tested during the study period and RHD variant alleles were detected in 247 women. The most frequent variant was RHD*08N.01 found in 66 women mainly of Black African origin. We identified 45 women with weak RHD variant type 1, 2 or 3. Conclusion: Women with weak RHD variant type 1, 2 or 3 can safely be considered as RhD positive in terms of RhIg prophylaxis and/or transfusion of blood components. Therefore, identification of RHD allele variants in women with discordant fetal RHD genotyping results contributes to save RhIg prophylaxis and RhD negative blood components. Key points: What is already known about this topic? In Belgium as in some other European countries, non‐invasive fetal RHD genotyping is the first step of anti‐D allo‐immunized pregnant women management. Presence of RHD variant alleles in the pregnant woman may interfere with fetal RHD genotyping accuracy. What does this study add? We developed an algorithm to explore non‐conclusive or inconsistent results in fetal RHD genotyping. With this algorithm, we identified 45 women with weak RHD variant type 1, 2 or 3 whom can be safely considered as RhD positive. We discovered and described a new mutation of the RHD gene associated with a silent phenotype.