Guiding Light: How the Updated AAP Clinical Guidelines for Hyperbilirubinemia Impacted Management of a Case of Severe and Persistent Hemolytic Disease of the Newborn

A full-term newborn is found to have clinically significant hyperbilirubinemia in the first 24 hours of life secondary to maternal anti-Rhesus (Rh) (E) immunization in this illustrative case. Rh(E) is a minor non-Rh(D) antigen that is less commonly implicated in hemolytic disease of the fetus and newborn (HDFN). The infant had both a severe and prolonged course of HDFN and hemolytic anemia requiring a combination of phototherapy, intravenous immunoglobulin (IVIG), and blood transfusions during the course of 2 weeks. By following the 2022 American Academy of Pediatrics' Clinical Practice Guidelines for hyperbilirubinemia, we demonstrate that rapid identification and adjuvant therapy with IVIG successfully avoids exchange transfusion in a case of severe immune-mediated HDFN. This case also specifically highlights the importance of minor antigens, such as Rh(E) in newborn hemolytic conditions. <b>[<i>Pediatr Ann</i>. 2025;54(4):e125-e129.]</b>.