It is of great importance that physicians and public health professionals endeavor to prevent sensitization and hemolytic disease of the fetus and newborn (HDFN) by implementing certain health policies across the world, particularly in countries and regions in which high rates of morbidity and mortality are reported, researchers stated in a review published recently in the Journal of Perinatal Medicine.
The need exists to explore new therapeutic and diagnostic strategies that consider the physiopatholology of HDFN and focus on the immune systems of both the pregnant patient and the fetus. In other words, this implies that the fetus should be viewed as a patient.
Although a safe, effective technique for preventing HDFN was discovered more than 50 years ago, the disorder nonetheless continues to be a key cause of perinatal morbidity and mortality.
Traditionally, the treatment for HDFN comprises intrauterine transfusion (IUT) and neonatal transfusion. Transfusion tackles anemia, however—a recognized cause of HDFN—rather than attempting to solve the actual cause of HDFN. Further a pregnant patient’s antibody titers are a “universally accepted method of screening.” This technique, however, is imprecise and focuses only on the immune system of the pregnant patient, despite the fact that the actual responsibility for fetal hemolysis and/or anemia rests with the fetal immune system.
Read more about symptoms and risks of HDFN
The need exists to investigate new diagnostic and therapeutic strategies that take into account both the pregnant person’s immune system and the fetal immune system. From this vantage point, an anti-neonatal Fc receptor (FcRn) blocking antibody known as nipocalimab, with a binding affinity that is more than 1000 times that of immune globulin, has been developed. The agent was shown to delay or prevent fetal anemia and thus IUTs.
Further, the capacity of fetal phagocyctosis remains unknown, with new immunologic tools becoming available that might permit us to predict which fetal immune systems might develop HDFN.
Three key factors allow contribute to the current global epidemiology of HDFN, the researchers stated:
- From a clinical perspective, the most important blood groups antigens are D, K, and c, although 50 additional antigens are capable of triggering HDFN as well
- Overall, 2% of the general population and one in 80 pregnant patients carry antibodies that are considered clinically significant. Thus, one in 362 live births across the globe experience HDFN
- The use of immunoprophylaxis fails in one in every 1000 procedures. This is due mainly to a lack of access to immunoprophylaxis or to the administration of a dose that is deemed to be insufficient
A profound inequity exists in access to immunoprophylaxis between regions and continents, which leads to a major difference in the prevalence, incidence, and mortality linked to HDFN between high-income and low-income countries.
From an immunohematologic perspective, pregnancy denotes an extraordinary situation. It implies the existence of two immune systems in one body—that is, the fetal and the pregnant person’s immune systems. Not only do both of these immune systems exist within one body, but they also interact with one another, thus attaining a particular balance.
Based on the findings presented above, some of the goals to strive for, in an effort to prevent sensitization and HDFN, are needed to ensure the following health policies across the globe—particularly in those countries in which high rates of morbidity and mortality are reported:
- Equity in access to immunoprophylaxis with anti-D
- Equity in access to monoclonal antibodies as they become more readily available
- Equity in access to antenatal care
- Interdisciplinary approach used for pregnant patients, fetuses, and newborns
- Blood transfusions that are as compatible as possible
According to the authors, “[The] fetal immune system’s role in HDFN could benefit from more evidence-based support.”
