A study recently published in Prenatal Diagnosis provides an overview of the evolving landscape of hemolytic disease of the fetus and newborn (HDFN) detection, prevention and treatment, emphasizing the need for more standardized procedures to improve outcomes.
Routine anti-D prophylaxis is a treatment given to RhD-negative women to prevent their immune systems from destroying the red blood cells of an RhD-positive fetus. Some countries may give all RhD-negative women prophylactic treatment even when unnecessary, including cases where the child is also RhD-negative.
Fetal RhD genotyping, the authors explain, can help reduce the overuse of prophylaxis, which is especially important given current shortages of the drug. It is considered a noninvasive procedure, as it consists of analyzing traces of fetal DNA that are present in maternal blood samples. This would allow physicians to determine whether the child is RhD-positive or negative, and thus whether prophylaxis may be beneficial.
Many European countries have begun to implement routine RhD genotyping, with the United States following close behind.
Read more about HDFN testing and diagnosis
Even when anti-D prophylaxis is administered, though, some patients will still develop anti-D alloimmunizationAlloimmunization When a person’s immune system develops antibodies against foreign antigens from the same species—such as when an Rh-negative mother’s body forms antibodies against her baby’s Rh-positive red blood cells., which may lead to severe HDFN. In many cases, this occurs due to missed or delayed treatment or inadequate doses. Although patients who receive two doses of prophylactic treatment may have higher anti-D levels at delivery, this approach carries increased costs and lower compliance than the one-dose technique.
In the case that fetal anemiaAnemia A condition that occurs when the body doesn’t have enough healthy red blood cells to carry oxygen to its tissues. In HDFN, anemia occurs when maternal antibodies destroy fetal red blood cells. does arise, the study explains that doppler ultrasoundDoppler ultrasound A non-invasive scan that measures blood flow speed in the fetus' brain to diagnose anemia. Specifically, it checks the middle cerebral artery peak systolic velocity (MCA-PSV). is the safest and most accurate mode of detection and is used to determine whether a patient will require an intrauterine transfusionIntrauterine transfusion A procedure that delivers donor red blood cells to the fetus through the umbilical vein to treat severe anemia caused by HDFN. (IUTIntrauterine transfusion A procedure that delivers donor red blood cells to the fetus through the umbilical vein to treat severe anemia caused by HDFN.).
While IUT is a relatively safe procedure, it carries risks including bleeding and preterm birth. Additionally, there is significant international variation in IUT practices and outcomes, highlighting the pressing need for improved guidelines.
Intravenous immunoglobulinIntravenous immunoglobulin A therapy made from donated antibodies that may help reduce the mother’s immune response and protect the fetus. (IVIGIntravenous immunoglobulin A therapy made from donated antibodies that may help reduce the mother’s immune response and protect the fetus.) is another option for treating severe HDFN, both during pregnancy and after delivery. Although IVIG has been shown to delay the time of first IUT during pregnancy, the authors call for more research on the mechanisms of IVIG, the risks of the procedure and the impact on survival.
Lastly, the study discusses neonatal Fc receptor (FcRn) inhibitors, an emerging class of drug to prevent HDFN. Thus far, nipocalimab has shown promising results in clinical trials, with more data expected in the coming years.
“This review underscores the importance of continued innovation and multidisciplinary collaboration to enhance early detection, targeted prophylaxis, and therapeutic options for affected pregnancies,” the authors concluded.
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