AABB 2026: Investigational Therapy Shows Promise for Severe HDFN

An investigational therapy targeting the transfer of maternal antibodies across the placenta could offer a new treatment approach for pregnancies affected by severe hemolytic disease of the fetus and newborn (HDFN), potentially reducing the need for intrauterine transfusions.

Scott Shainker, DO, MS, director of the New England Center for Placental Disorders at Beth Israel Deaconess Medical Center, highlighted findings from a phase 2 study of nipocalimab during Saturday’s “Hemolytic Disease of the Fetus and Newborn in 2026” session at the 2026 AABB Annual Meeting.

He explained that nipocalimab is a monoclonal antibody designed to block the neonatal Fc receptor (FcRn), which facilitates the transfer of maternal immunoglobulin G (IgG) antibodies across the placenta. By reducing the transfer of pathogenic maternal antibodies into fetal circulation, the therapy could help reduce the risk of severe fetal anemia associated with HDFN.

The open-label study, published in 2024, involved pregnant patients at high risk for severe HDFN based on outcomes in previous pregnancies. All participants treated with nipocalimab had live births, and approximately half delivered without requiring an intrauterine transfusion. In contrast, none of the participants' qualifying previous pregnancies had resulted in a live birth without an intrauterine transfusion.

The therapy remains investigational with additional research underway, including a phase 3 trial. Shainker expressed optimism about the potential for the treatment to improve outcomes in affected pregnancies.

“I think the data that's published thus far is pretty encouraging, and I do think there's a lot more to come there,” he told the audience.

Shainker noted that until new therapies become available, intrauterine transfusion remains an important intervention for pregnancies complicated by severe fetal anemia. He also discussed the potential role of intravenous immunoglobulin (IVIG) in particularly severe cases. Although IVIG has not been shown to replace intrauterine transfusion, studies suggest it may delay the need for the procedure in selected high-risk pregnancies. Shainker stated that its use in this setting is supported by expert opinion but has not been incorporated into national guidelines.

During the session, Emily Whitesel, MD, an attending neonatologist at Beth Israel Deaconess Medical Center, emphasized that HDFN remains a significant cause of neonatal morbidity and mortality and that preventing bilirubin-induced neurologic injury requires careful monitoring and coordinated care. She noted that intensive phototherapy can reduce the need for exchange transfusions, although hospitals must maintain the capacity to perform these procedures when necessary.

“Early and intensive phototherapy can really keep us from breaching that exchange transfusion as much as possible, but we still need to be able to keep that capacity and keep those protocols in place so that we can use it when we need to,” Whitesel said.