Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn
Derek de Winter, E. J. T. Verweij, Anne Debeer, Roland Devlieger, Liesbeth Lewi, Sarah Verbeeck, P Maurice, Jean‐Marie Jouannic, Marie-Gabrielle Guillemin, Agnès Mailloux, Maria Cristina Santos, Cynthia Amaral de Moura Sá Pacheco, Maria Elisabeth Lopes Moreira, Marcella Martins de Vasconcelos Vaena, Kajsa Bohlin, Eleonor Tiblad, E. Thorup, Olav Bjørn Petersen, Maria Sanchez-Holgado, Aurora Viejo Llorente, Borna Poljak, Asma Khalil, Kévin Le Duc, Louise Ghesquière, Jana Lozar Krivec, Aneta Soltirovska-Šalamon, Christof Dame, J Blank, Alexander Hohnecker, Matthew A. Saxonhouse, Ngina Connors, Annegret Geipel, Johanna Rath, Smriti Prasad, Lizelle van Wyk, L. Geerts, Rahel Schuler, Nina Thon, Leah Leibovitch, Stav Cohen, Arturo Alejandro Canul-Euan, Edmond N. Kelly, Kamini Raghuram, Francesco Cavigioli, Sofia Fatima Guiseppina Colombo, Ziju Elanjikal, Jessica Brayley, Daniel Pfurtscheller, Gerhard Pichler, Ángel Guillermo Alcázar Grisi, Edgar Juan José Chávez Navarro, Joana Nunes, Henrique Soares, Ming Zhou, María José Garcia Borau, Elisenda Moliner Calderón, María F Galletti, Gonzalo Mariani, David Mackin, Fergal D. Malone, Andrea Lampland, Wing Ting Tse, James Castleman, Johanna G. van der Bom, Masja de Haas, Enrico Lopriore, Iris Hellsing, Karin Sundberg, Frederik Banch Clausen, E. Antolín, N H Segura Méndez, Baptiste Teillet, Thameur Rakza, Erika Hrastar, Mihaela Rus, Stefan Verlohren, Beate Mayer, Kerry Rademan, A Wolter, Ivonne Bedei, R Axt-Fliedner, Yoav Yinon, Tzipora Strauss, Raigam Jafet Martine-Portilla, Jose A. Montoya-Martinez, Johannes Keunen, Greg Ryan, Francesca Castoldi, Chiara Nava, Philipp Klaritsch, Mabel Laura Cabrera, Alexandra Matias, Fangfang Tao, Jiang-Qin Liu, Leandro Daniel Burgos Pratx, Mark D. Kilby, Rob Negrine
Abstract
Importance: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist. Objectives: To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care. Design, Setting, and Participants: In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024. Main Outcomes and Measures: Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes. Results: The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes. Conclusions and Relevance: In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.