Although screening for the Rhesus (Rh)D antigen and the use of Rh immune globulin (RhIG) in RhD-negative women has been linked to dramatic reductions in the occurrence of hemolytic disease of the fetus and newborn (HDFN) in high-income countries, the clinical burden of the disorder in low-income and middle-income nations nonetheless remains high, according to a recent study published in The Lancet.
It has been estimated by the Worldwide Initiative for Rh Disease Eradication (WIRhE) and the International Federation of Gynecology and Obstetrics (FIGO) that each year, perinatal deaths and perinatal-related disabilities linked to HDFN total approximately 160,000 and 100,000, respectively. In fact, in sub-Saharan Africa, the burden of HDFN remains unknown because of the lack of population-based data, but it is likely substantial in scope.
Rh disease, which is a known type of HDFN, is reported when a pregnant woman’s immune system mounts a response to the red blood cells of her unborn baby. Typically, such a response is observed when a mother and her fetus have different blood types. HDFN, if left untreated, can be associated with severe anemia, jaundice, brain damage and death in an unborn child.
Several initiatives, including the AFRICA RhE project, have responded to the call to action by WIRhE and FIGO to eradicate HDFN from the continent of Africa. A monoclonal RhIG produced by a mouse-human heterohybridoma cell line—that is, Rhoclone (Bharat Serums and Vaccines; Navi Mumbai, India)—is known to be available on a widespread scale in a number of African nations, but the efficacy of the product has not yet been investigated in a robust fashion.
Read more about HDFN testing and diagnosis
Notably, only two clinical trials of women treated with postpartum Rhoclone, which were conducted in 110 women and 105 women, respectively, have been published in the international literature. Despite the fact that no alloimmune sensitization was observed in the 186 patients who were not lost to follow-up and received monoclonal RhIG, no data were available on fetal-maternal ABO compatibility or on parity.
Further, it was thought that nonresponders to blood group alloimmunization might have been recruited preferentially. There was no follow-up reported regarding subsequent pregnancies, which is especially significant here since primary immunization to RhD may be recognized only following a secondary immune response.
Polyclonal RhIG is used for the prevention of HDFN in high-income nations. In fact, in the United States, the RhIG utilized is prepared mainly with plasma from hyperimmunized male donors. Such immunoprophylaxis is highly efficacious, but it is insufficient to fulfill the needs of all at-risk women globally. An unlimited supply of monoclonal RhIG would thus prove to be ideal.
Many factors have hindered the production of monoclonal RhIG, including insufficient funding, lack of an RhD animal model, and the belief that some monoclonal antibodies might actually increase the risk for alloimmunization. Ethical considerations might have played a role as well, because it is quite challenging to conduct a clinical trial in which a highly efficacious polyclonal RhIG is being withheld from pregnant women in need.
“[A]lthough preliminary findings suggest that monoclonal RhIG might be a useful alternative to polyclonal RhIG, we believe that more extensive and rigorous trials are needed to establish its efficacy,” the authors indicated. “Such a trial should first be performed in a setting with access to antenatal treatment, including intrauterine transfusion for severe HDFN, in case prophylaxis fails.”
