Abstract
Background: Haemolytic disease of the fetus and newborn arises from maternal allo-antibodies to red cell antigens, crossing the placenta. The most frequent antibodies after RhD, are Kell, Duffy and RhCE antigens. Liquid biopsy in pregnancy management is concerned with the detection of cell-free fetal DNA (cffDNA) circulating in the maternal plasma. The accuracy for fetal RHD genotyping is well established. Aim: To evaluate a maternal blood test to predict the fetal, non-RhD, blood group status. Methods: A clinical collaborative study assessed the accuracy for a suite of assays to predict fetal Kell, Duffy, Rhc/C and Rhe/E status for women with respective antibodies (n=90, gestation age 8–37 weeks). Droplet digital PCR technology, ddPCR, tested for single nucleotide variants (SNVs) associated with these blood group antigens. Infant cord blood serotypes were used as the primary outcome measure. Results: Fetal specific signals were detected as early as 8 weeks gestation. Genotyping matched all available infant cord outcomes 45/45. Accuracy is 100% (95% confidence interval 91.96–100%). Discussion: A clinical demand exists for liquid biopsy of maternal blood for fetal blood group genotyping. Droplet digital PCR is accurate and provides an evidence base to guide clinical care for at-risk pregnancies.
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