Misclassification of RhD variants among pregnant women: a systematic review

The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus and newborn. This systematic review discusses the prevalence of RhD variants among pregnant women and the importance of including RhD genotyping for prenatal testing to detect RhD variants and prevent anti-D alloimmunization. A comprehensive literature search was conducted using scientific search engines, including PubMed and MEDLINE databases, with the keywords 'anti-D alloimmunization', 'RhD variant', and 'pregnant women.' The review adhered to the PRISMA guidelines. Meta-analysis was performed using MedCalc version 20. A significance level of p≤0.05 was considered statistically significant for all two-tailed tests. The meta-analysis included four articles that met the inclusion criteria. The total prevalence of RhD positivity (RhD+) was 61% (95% CI:34%–85%). The prevalence ranged from 22% to 82%, indicating a high degree of heterogeneity between studies (I2=98.71%, p<0.0001). The overall prevalence of D variants was 15% (95% CI, 9%–23%) with a prevalence of 0.05% to 100%, showing a high degree of heterogeneity between studies (I2=99.89%, p<0.0001). Anti-D alloimmunization could occur in pregnant women with some types of RhD variants. All four studies focused on molecular testing of samples showing inconsistent or weak results with at least two anti-D antibodies using serological methods.