Academy

Closing the Anti-D divide: the 2nd International Alloimmune Conference on HDFN

Gaia Mori

Worldwide Initiative for Rh disease Eradication (WIRhE) Foundation, Amsterdam, The Netherlands

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Hemolytic disease of the fetus and newborn (HDFN) is a preventable condition that continues to cause avoidable fetal and neonatal morbidity and mortality worldwide. The introduction of anti-D immunoglobulin, antenatal screening programmes, and specialist fetal-neonatal medical care have dramatically reduced the burden of RhD-related HDFN in many high-income countries. However, global access to prevention, diagnosis, and treatment remains highly variable.

This gap was the focus of the 2nd International Alloimmune Conference on Hemolytic Disease of the Fetus and Newborn, held in Leiden, the Netherlands, on May 28-29, 2026. The meeting convened clinicians, laboratory specialists, transfusion medicine professionals, researchers, blood services, patient advocates, regulators, and policy stakeholders to address one central question: how can the international community move forward to prevent and treat HDFN?

The program [SSL1.1]was both a scientific meeting and a working conference. Formal presentations were combined with open discussion, workshops, and a pre-conference questionnaire that received responses from 140 participants across 42 countries. The meeting outcomes included new and ongoing collaborations, the development of research consortia, and a shared research agenda involving screening, diagnostics, antenatal management, and postnatal care.

Group Work Activity

Day 1: The global anti-D shortage

The first day focused on the global anti-D shortage and sustainable solutions. The opening sessions addressed the “anti-D divide”: the reality that access to anti-D prophylaxis and HDFN care varies dramatically between countries and regions. Presentations from Africa, India, and Latin America showed that HDFN remains a global issue, with challenges extending beyond the availability of anti-D alone.

Participants discussed how gaps in awareness, screening, referral pathways, diagnostic capacity, neonatal treatment, and blood availability all contribute to preventable harm. Discussions of patient and family perspectives reminded participants that HDFN is not only a technical or laboratory issue, but also involves patient empowerment, health-system responsiveness, and equity.

Sessions on polyclonal anti-D explored past and present approaches to plasma collection, donor recruitment, and national supply models. Experiences from different settings showed that sustainable anti-D supply requires not only identifying suitable donors, but also ethical donor engagement, regulatory clarity, quality systems, fractionation capacity, financing mechanisms, and long-term political commitment.

Conference Day 2 Discussions

Developing monoclonal anti-D was also discussed as a potential solution. Participants considered the scientific promise of monoclonal anti-D, as well as the regulatory, ethical, and access issues that must be addressed if such products are to contribute meaningfully to global HDFN prevention. A recurring theme was that innovation must not widen existing inequities; rather, new solutions should be developed with the needs of the most affected populations in mind.

Parallel workshops translated these discussions into practical next steps. Topics included advocacy and policy pathways, research ethics, plasma collection and donor recruitment, patient and public involvement, and standards regarding anti-D dosage. In workshops, participants identified barriers, including limited data, low awareness, procurement challenges, cost, supply chain fragility, and fragmented clinical guidelines. They also identified solutions, including stakeholder engagement, stronger guidelines, community involvement, patient advisory structures, improved data systems, and international collaboration.

One key outcome was the establishment of two research consortia: one focused on polyclonal anti-D and one on monoclonal anti-D. These consortia will support coordinated research, implementation planning, and evidence generation for sustainable anti-D production and utilization.

Day 2: Worldwide variation in clinical practice

The second day focused on current clinical practice, including international variation in HDFN screening, laboratory diagnostics, antenatal treatment, and postnatal management.

Keynote lectures provided international perspectives on which pregnant women should be screened for which red blood cell antibodies, how laboratories can identify high risk pregnancies, how antenatal treatment has evolved, and variations in postnatal management.

Questionnaire results and panel discussions highlighted substantial differences between countries. These included variations in: the timing of first antibody screening, repeat screening strategies, screening-cell composition, fetal genotyping using cell-free fetal DNA, referral thresholds, fetal anemia monitoring, intrauterine transfusion usage, postnatal IVIg use, bilirubin thresholds, and exchange transfusion practices.

Some of this variation reflects differences in resources, infrastructure, and national guidelines. However, these variations also revealed important opportunities for international learning. Participants considered where harmonization may be useful, where local adaptation is necessary, and where more evidence is needed before firm recommendations can be made.

Aw research agenda was developed covering four broad domains: screening, diagnostics, antenatal management, and postnatal management. Priorities included improving antibody screening technologies, understanding the role of low-frequency antigens, integrating blood group determination into non-invasive prenatal testing, distinguishing immune from passively-administered anti-D, and evaluating cost-effective screening strategies.

For diagnostics, participants highlighted the need for better tools to predict clinically-significant disease, including quantitative antibody testing, bioassays, fetal genotyping, and biomarkers of fetal anaemia. For antenatal management, priorities included evaluating treatment options (e.g., IVIg), improving severe disease prediction, comparing intrauterine transfusion techniques, and strengthening long-term follow-up. Postnatal care priorities included the timing of delivery, the role of IVIg, exchange transfusion practices, bilirubin-related outcomes, and registries for acute bilirubin encephalopathy and kernicterus spectrum disorder.

Full conference day 1

Moving from knowledge to action

The conference made clear that HDFN prevention and treatment cannot be advanced solely through isolated efforts. The anti-D divide is a global challenge requiring coordinated action involving transfusion medicine, obstetrics, neonatology, laboratory medicine, public health, regulation, patient advocacy, and policy.

Nonetheless, progress is possible. Existing knowledge, emerging technologies, patient experience, and international collaboration can be synergized to build practical solutions. The challenge is to translate the momentum of the conference into research, policy, and implementation.

The 2nd International Alloimmune Conference closed with a clear message: HDFN remains preventable, but prevention requires effective systems. Strengthening those systems (e.g., from increasing anti-D supply to improving screening, diagnosis, antenatal care, and postnatal treatment) is essential if HDFN is to become completely preventable.

References

1. Pegoraro V, Urbinati D, Visser GHA, Di Renzo GC, Zipursky A, Stotler BA, et al. Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children. PLoS One. 2020;15:e0235807.

2. Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M, Ebbesen F, et al. Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res. 2013;74 Suppl 1:86-100.

3. Desalew A, Mjema RN, Schonewille H, van der Schoot CE, de Winter DP, van den Akker T, et al. RhD alloimmunization in pregnancy and hemolytic disease of the fetus and newborn in Africa: A systematic review and meta-analysis. Best Pract Res Clin Obstet Gynaecol. 2026;104:102700.

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