Authors of a research review recently published in Pregnancy highlighted the ongoing challenges of managing hemolytic disease of the fetus and newborn (HDFN) due to red blood cell (RBC) alloimmunization during pregnancy.
RBC alloimmunization occurs when a pregnant woman develops antibodies against her baby’s red blood cells, which can happen if the fetus inherits a blood group antigen the mother doesn’t have. The authors noted that while RhD prophylaxis has drastically reduced Rh-related disease in many parts of the world, other antibodies, such as anti-c, anti-K and anti-E, continue to lead to other health issues, including fetal anemia, hydrops fetalis and perinatal death. In countries where Rh immunoglobulin is less available, RhD alloimmunization also remains a major risk.
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The authors outlined how care teams approach diagnosis and monitoring. Mothers are screened for antibodies early in pregnancy, and if they are detected, further testing determines whether the fetus carries the corresponding antigen. Non-invasive fetal genotyping using cell-free DNA from the mother’s blood is now making this process safer and easier.
Once an at-risk pregnancy is identified, doctors monitor for signs of fetal anemia, most often using Doppler ultrasounds to measure blood flow in the baby’s middle cerebral artery. This is a reliable, non-invasive way to detect anemia before symptoms appear.
If anemia becomes moderate or severe, intrauterine transfusions (IUTs) remain the standard treatment, helping restore fetal red cell levels and prevent heart failure or hydrops. These procedures have greatly improved survival rates but still carry risks, especially when performed before 20 weeks. Other treatments such as intravenous immunoglobulin (IVIG) or plasmapheresis can sometimes delay or reduce the need for transfusion. Emerging therapies, including drugs that block the neonatal Fc receptor (FcRn) to reduce antibody transfer, are currently being studied.
The review emphasizes the need for a coordinated, multidisciplinary care team including obstetricians, fetal medicine specialists, hematologists and transfusion experts. It also stresses the global health challenge posed by limited access to prophylaxis, screening and treatment in low-resource regions. The authors note that despite advances, HDFN remains a major cause of perinatal morbidity and mortality worldwide.
“Future research should focus on refining non-invasive screening techniques for fetal RBC genotype, improving therapeutic alternatives to donor-derived anti-D immunoglobulin, and expanding access to effective prophylaxis in resource-limited settings,” the authors wrote. “Additionally, increasing awareness of RBC alloimmunization through educational programs can empower healthcare providers and pregnant individuals to better understand the risks of HDFN, while also reducing unnecessary anxiety during pregnancy.”
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