Jannine Williams, Compound Development Team Leader at Johnson & Johnson, discusses key takeaways from studies on hemolytic disease of the fetus and newborn (HDFN) presented at ISUOG World Congress 2025.
HDFN is a rare condition characterized by the destruction of fetal red blood cells due to maternal-fetal blood group incompatibility. The condition typically involved the Rh or ABO blood types. Rh incompatibility usually affects subsequent pregnancies due to maternal sensitization that occurs in the first pregnancy. This leads to more severe complications such as intrauterine hydrops fetalis in later pregnancies. ABO incompatibility can impact the first pregnancy due to preexisting maternal antibodies. Symptoms of disease in newborns include lethargy, jaundice, hepatosplenomegaly, and signs of hydrops fetalis.
There are currently no approved therapies for the treatment of HDFN. Pregnancies affected by severe HDFN may need repeated intrauterine transfusions (IUTs), invasive and technically complex surgical procedures that may be associated with increased rate of fetal mortality and premature birth.
Outcomes of intrauterine transfusion for the treatment of Hemolytic Disease of the Fetus and Newborn
The objective of this study was to evaluate outcomes of IUT for the treatment of severe HDFN in antenatal, perinatal, and infancy periods in 120 pregnancies. On average, each pregnancy underwent 2.9 IUTs and the gestational age at first IUT was 28 weeks.
Maternal complications related to infection from IUTs were uncommon but in 13% Cesarean section was performed within one day of an IUT. Additionally, preterm premature rupture of membrane, preterm birth, and Cesarean section delivery were elevated compared to the general pregnant population. More than two in three infants required admission to the NICU and more than half required phototherapy or transfusion treatment in the first 30 days of life.
HDFN diagnoses and symptoms, cardiac disorder, infection diagnosis, and respiratory diagnosis were evaluated in infants with IUT and compared to those from the general pregnant population. HDFN diagnoses and symptoms as well as cardiac disorders were more common in infants with antenatal IUT. Infection and respiratory diagnoses were balanced in both cohorts.
Qualitative Patient Experiences of Hemolytic Disease of the Fetus and Newborn (HDFN): Psychosocial Impacts Reported During an Ongoing Patient Council
The objective of this analysis was to identify patient-directed themes to better understand the
experience and unmet needs of HDFN-affected pregnancies. Key takeaways from the study included the feeling of patients needing to self-advocate, leading to stress, anxiety, and trauma that impact quality of life. Patients also highly valued social support and personalized, responsive medical care.
Additionally, practical considerations of HDFN care place a substantial burden on patients’ lives and put pressure on family and personal relationships. This analysis also illustrated the unclear short- and long-term implications of alloimmunization/HDFN and the lack of comprehensive and coordinated care. This highlights the need for additional education in the recognition and management of HDFN needed by physicians outside of the maternal-fetal medicine speciality.
Lived Experiences with Pregnancies Affected by Severe Hemolytic Disease of the Fetus and Newborn (HDFN): An Interview Study
The objective of this study was to understand the treatment experiences and preferences of participants who have severe HDFN in pregnancy. 27 patients participated in an online survey and telephone interviews exploring preferences and treatment experiences, focusing on diagnosis, monitoring, birth, and post-partum.
Seven themes were identified in patients with severe HDFN; (1) diagnosis communication and information seeking, (2) emotional journey at diagnosis, (3) navigating the treatment regimen, (4) physical and emotional challenges during pregnancy, (5) impacts on social life, (6) experience at delivery, and (7) post-delivery adjustment and reflections.
These themes revealed the need for improved communication and support regarding HDFN and its treatment through comprehensive support models and standardized management and treatment guidelines.
Clinical Outcomes and Treatment Patterns in Hemolytic Disease of the Fetus and Newborn: Evidence from United States Claims Data
The objective of this study was to describe the disease burden, treatment patterns, clinical characteristics, and outcomes of severe HDFN among pregnant individuals in a large claims database in the US.
The prevalence of alloimmunized pregnancies was 5.3% of the 6,102,538 pregnancies analyzed during the study period, with 0.1% classified as severe HDFN. Severe HDFN pregnancies had higher utilization of maternal intravenous immunoglobulin, antibody screening, MCA Doppler ultrasound, and amniocentesis compared to controls. Additionally, severe HDFN pregnancies had higher rates of IUTs, fetal hydrops, polyhydramnios, fetal growth restriction, preterm birth, and thrombocytopenia compared to controls. However, there was no significant difference in occurrence of ruptured membranes between severe HDFN pregnancies and controls.
All-cause inpatient healthcare resource utilization and direct costs in children affected by hemolytic disease of the fetus and newborn in Sweden
The objective of this study was to quantify inpatient healthcare resource utilization (HCRU) and direct costs in children treated for HDFN in Sweden. Results showed that of 14,519 liveborn children, 50% were identified to have HDFN and 27% received HDFN treatment. IUTs were used as treatment in 8%, postnatal transfusion in 31%, and phototherapy in 90%. Of these patients with HDFN, greater HCRU and inpatient direct costs in the first year than those without HDFN were observed, especially those treated with IUT and transfusion. In patients who received postnatal transfusion and not IUT, greater yearly inpatient HCRU and costs persisted beyond the first year into preschool years.
To learn more about HDFN and other rare hematology conditions, visit https://checkrare.com/diseases/hematologic-disorders/
Reference:
Hall, V., Vadakekut, E. S., & Avulakunta, I. D. (2025, January 22). Hemolytic disease of the fetus and newborn. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK557423/