Study Design of the Global Prospective Hemolytic Disease of the Fetus and Newborn Registry (GERANIUM).

Abstract

Objective: Hemolytic disease of the fetus and newborn (HDFN) is a rare and serious immune-mediated condition that can result in poor fetal and neonatal outcomes. During pregnancy, monitoring with middle cerebral artery Doppler ultrasound and intrauterine transfusions (IUTs) are the current standard of care, although intravenous immunoglobulin (IVIg) has been adopted in some centers to attempt to delay the onset of fetal anemia. Significant gaps remain in understanding the safety and effectiveness of current HDFN management, both during pregnancy and in neonates and children. We present the design of the Global Prospective Hemolytic Disease of the Fetus and Newborn Registry (GERANIUM; ClinicalTrials.gov Identifier: NCT07194070), a study that will provide real-world, prospective, longitudinal data on management, clinical course, and outcomes of HDFN from the antenatal period up to 2 years after birth.

Study design: GERANIUM is a prospective, observational study enrolling alloimmunized pregnant individuals (aged ≥18 years) before 24 weeks of gestational age who are at high risk for HDFN based on previous obstetric history. This study will enroll approximately 175 participants across multiple global sites. Data collected during pregnancy include fetal loss, frequency and severity of HDFN, treatment patterns, as well as effectiveness and adverse outcomes of IUTs and other interventions. Following birth, infants will be followed for the first 2 years of life, with documentation of HDFN sequelae, including treatments, growth, and development. Impact on the parents and children will be assessed using validated participant- and observer-reported outcome measures.

Conclusion: The GERANIUM registry will provide prospective, contemporaneous data on current management of HDFN and associated outcomes.

Key points: · HDFN can result in fetal loss or poor long-term outcomes.. · IUT and IVIg can be associated with serious complications.. · Impacts of HDFN on patients' quality of life are unclear.. · GERANIUM will provide contemporaneous data on HDFN care.. · Prospective data for mothers/infants will be collected..