Non-invasive prenatal testing for sub-saharan Africa: Tailoring approaches for foetal RHD genotyping in RHD-negative pregnant women to manage African-associated RHD Alleles

Abstract

BACKGROUND Non-invasive prenatal testing (NIPT) for cell-free foetal (cff) RHD genotyping has clinical value to guide pregnancy management for alloimmunised RhD-negative pregnant women and guide antenatal anti-D prophylaxis needs for all D-negative women to prevent alloimmunisation. This assay assumes there is a maternal RHD gene deletion and genotyping is challenged where the mother carries RHD alleles such as RHD*Ψ and RHD-CE-Ds which are frequent in Sub-Saharan Africa.
AIM AND OBJECTIVE This paper reviews the range of RHD alleles reported in sub-Saharan African populations and strategies in managing African-associated RHD alleles to ensure the accuracy of cffRHD genotyping.
STUDY DESIGN/MATERIALS AND METHODS Online literature searches using Google, Google Scholar and PubMed, textbooks and International Society of Blood Transfusion Blood Group Tables.
RESULTS A NIPT assay design for cffRHD, tailored with the SAFE recommended RHD exon 5 and 7 approach, can provide foetal D-positive or D-negative predictions when a maternal RHD*Ψ and RHD-CE-Ds is present. Inclusion of RHD exon 4 in NIPT is a tool for increasing confidence in D-phenotype prediction.
CONCLUSIONS A strategic approach to NIPT cffRHD genotyping can overcome challenges with maternal RHD interference from RHD*Ψ and RHDCE- Ds alleles in D-negative pregnant women. Accommodating for these RHD alleles provides knowledge for clinical management to minimise maternal anti-D alloimmunisation and haemolytic disease of the foetus and newborn. Continuing study of RHD alleles, including those that are novel and low-frequency, is important in future approaches to NIPT cffRHD genotyping in sub- Saharan African populations.