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.) has historically been the standard of care for severe 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. due to hemolytic disease of the fetus and newborn (HDFN). However, 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.) and emerging treatments may delay the need for an IUT, according to a review recently published in the Journal of Obstetrics and Gynaecology Canada.
IUT carries a survival rate of 97% to 98% and a low complication rate of 1.2%. Some patients, though, may be unable to receive the treatment for a number of reasons. These range from personal preference to difficulty delivering treatment due to technical challenges.
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Several alternatives may exist for those who cannot undergo IUT. Early delivery of the fetus at a gestational age of at least 35 weeks may be acceptable in some cases, allowing neonatologists to directly treat the newborn. In more mild cases, physicians may take a “watch and wait approach,” monitoring the fetus carefully for signs of severe anemia. As the authors explain, the risk of severe HDFN is generally lowest during the first pregnancy and rises with subsequent pregnancies.
Limited evidence exists to support the use of plasmapheresis, the process by which the mother’s blood is filtered to remove harmful antibodiesAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. that attack fetal red blood cells. Scattered case reports and case series, the largest of which was published in 1980, are insufficient to support widespread use of plasmapheresis in HDFN.
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IVIG, on the other hand, is a well-established treatment option for HDFN. The therapy works by preventing the breakdown of fetal red blood cells. A 2023 meta-analysis supported the use of IVIG in pregnancies impacted by red blood cell 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.. Across eight studies and 194 pregnancies, IVIG reduced the risk of severe complications and delayed the need for IUT.
Nipocalimab, a newer drug that helps to destroy maternal antibodies before they can reach the fetal circulation, showed promise in a phase 2 clinical trial. While not yet approved for use in HDFN, findings from the phase 3 AZALEA study (NCT05912517) will further explore the efficacy of nipocalimab in HDFN.
“The future is looking brighter for those affected by alloimmunization with possible alternatives to IUT on the horizon,” the authors concluded.
