RhD alloimmunization in pregnancy and hemolytic disease of the fetus and newborn in Africa: A systematic review and meta-analysis

Abstract

Although hemolytic disease of the fetus and newborn (HDFN), caused by maternal alloimmunization against fetal erythrocytes, has been nearly eliminated in high-income settings, it likely remains a significant public health problem in low-resource settings in Africa and elsewhere. We performed a comprehensive literature review across six major databases to determine the proportion of RhD-negativity, anti-D immunoprophylaxis utilization, RhD-alloimmunization prevalence, and the burden of RhD-mediated HDFN among pregnant women in Africa. A random-effects model was used to determine pooled estimates. We included 74 studies from 17 countries (42 from Nigeria), published between 1960 and 2024, involving 245,046 pregnancies, mostly from tertiary centers. The proportion of RhD negativity was 4.8 % (95 % CI: 4.1–5.7 %). The proven RhD alloimmunization rate was 5.8 % (95 % CI: 4.1–8.2 %). In multigravida women, the proportion of RhD alloimmunization was 5.7 % (95 % CI: 3.1–10.4 %). Anti-D immunoprophylaxis utilization after a previous pregnancy, reported in 18 studies (1490/3756 women), was 29.7 % (95 % CI: 18.0–45.0 %), with no effect on alloimmunization rate. Nine studies (including 50 neonates from 168 alloimmunized women) provided data on HDFN, with a pooled prevalence of 36.2 % (95 % CI: 16.8–61.4 %). In many papers, the specificity of the alloantibodies was not determined. Data on gravidity and the clinical definition of HDFN were incomplete. We conclude that there is a lack of robust data from Africa, thereby hampering HDFN prevention efforts. To eliminate HDFN in Africa, integrated strategies are urgently needed, including universal RhD typing and antibody screening, access to polyclonal anti-D immunoprophylaxis, and population-based surveillance.