Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn
Authors: de Winter Derek P. , Verweij E. J. T. (Joanne) , Debeer Anne , Devlieger Roland , Lewi Liesbeth , Verbeeck Sarah , Maurice Paul , Jouannic Jean-Marie , Guillemin Marie-Gabrielle , Mailloux Agnès , Pessoa dos Santos Maria Cristina , Amaral de Moura Sá Pacheco Cynthia , Lopes Moreira Maria Elisabeth , Martins de Vasconcelos Vaena Marcella , Bohlin Kajsa , Tiblad Eleonor , Thorup Emilie , Petersen Olav Bjørn , Sanchez-Holgado Maria , Viejo Llorente Aurora , Poljak Borna , Khalil Asma , Le Duc Kévin , Ghesquiere Louise , Lozar Krivec Jana , Soltirovska-Šalamon Aneta , Dame Christof , Blank Jessica D. , Hohnecker Alexander , Saxonhouse Matthew , Connors Ngina K. , Geipel Annegret , Rath Johanna , Prasad Smriti , van Wyk Lizelle , Geerts Lut , Schuler Rahel , Thon Nina , Leibovitch Leah , Cohen Stav , Canul-Euan Arturo Alejandro , Kelly Edmond , Raghuram Kamini , Cavigioli Francesco , Colombo Sofia Fatima Guiseppina , Elanjikal Ziju , Brayley Jessica , Pfurtscheller Daniel , Pichler Gerhard , Alcázar Grisi Ángel Guillermo , Chávez Navarro Edgar Juan José , Pereira-Nunes Joana , Soares Henrique , Zhou Ming , Garcia Borau María José , Moliner Calderón Elisenda , Galletti Maria Fernanda , Mariani Gonzalo Luis , Mackin David , Malone Fergal , Lampland Andrea , Tse Wing Ting , Castleman James , van der Bom Johanna G. , de Haas Masja , Lopriore Enrico ,   Worldwide Collaboration for Hemolytic Disease of the Fetus and Newborn (DIONYSUS) Investigators, Hellsing Iris , Sundberg Karin , Clausen Frederik B. , Antolin Eugenia , Mendez Nieves , Teillet Baptiste , Rakza Thameur , Hrastar Erika , Rus Mihael , Verlohren Stefan , Mayer Beate , Rademan Kerry , Wolter Aline , Bedei Ivonne , Axt-Fliedner Roland , Yinon Yoav , Strauss Tzipora , Martine-Portilla Raigam Jafet , Montoya-Martinez Jose A. , Keunen Johannes , Ryan Greg , Castoldi Francesca , Nava Chiara , Klaritsch Philipp , Cabrera Mabel Laura , Matias Alexandra , Tao Fangfang , Liu Jiangqin , Burgos Pratx Leandro Daniel , Kilby Mark , Negrine Rob 
Published: January 2025

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.