Anti-D in pregnant women with the RHD(IVS3+1G>A)-associated DEL phenotype

BACKGROUND: Pregnant women with the DEL phenotype appear to be D- by routine serology. Women with DEL phenotypes that show a partial D-like epitope loss may develop anti-D. It has been proposed that this alloantibody could have a deleterious effect with respect to hemolytic disease in the fetus and newborn. CASE REPORTS: Two pregnant women, one in Australia and one in Germany, were serotyped as D- and were sensitized to the D antigen. Noninvasive fetal RHD genotyping was performed to plan pregnancy management. RESULTS: In both cases the fetal RHD status could not be assigned due to the presence of a maternal DEL allele. This was suspected through detection of high RHD amplicon levels during quantitative polymerase chain reaction. For both cases extended molecular typing of the maternal genomic DNA revealed a RHD(IVS3+1G>A) allele. For case one, the D+ infant developed a mild hemolytic disease requiring phototherapy. In the second case a D- (or DEL) newborn was unaffected. CONCLUSION: Fetal genotyping from maternal plasma reveals RHD variants in pregnant women with anti-D. Fetuses and newborns of sensitized pregnant women carrying the RHD(IVS3+1G>A) allele are at risk of hemolytic disease.