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
Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.
Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Center, Leiden, the Netherlands.
JAMA Netw Open. 2025 Jan 2;8(1):e2454330. doi: 10.1001/jamanetworkopen.2024.54330.
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.
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 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.
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.
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.
在预防与妊娠相关的同种免疫方面所做的努力已大幅降低了胎儿和新生儿溶血病（HDFN）的患病率。因此，开展国际研究对于更深入了解HDFN的产后管理及结局至关重要。鉴于存在众多治疗方案，各中心之间可能存在很大的实践差异。
评估国际各中心HDFN产后管理及结局的差异，并确定改善护理的机会。
设计、背景和参与者：在这项国际回顾性队列研究中，来自22个国家的31个专家中心检索了2006年1月1日至2021年7月1日期间接受管理的HDFN新生儿的数据。统计分析于2023年7月19日至2024年10月28日进行。
主要结局包括换血频率、静脉注射免疫球蛋白的使用、促红细胞生成素类药物的使用、红细胞输血情况，以及出生时的胎龄与换血频率的关联和新生儿不良结局的危险因素。
该研究纳入了1855例新生儿（出生时胎龄中位数为36.4周[四分位间距，35.0 - 37.3周]；1034例为男孩[55.7%]），其中1017例（54.8%）接受了任何形式的产前治疗。大多数新生儿（1447例[78.0%]）有抗-D抗体。436例新生儿（23.5%）接受了换血治疗，各中心的换血频率比例从0%到78%不等。1743例新生儿中有429例（24.6%）接受了静脉注射免疫球蛋白治疗，各中心的比例从0%到100%不等。出生时胎龄越大，接受宫内输血的新生儿换血频率越低，从34周时的约38.2%（34例中的13例）降至37周0天后 的16.8%（107例中的18例）。出生时胎龄每周增加，新生儿出现不良结局的可能性降低43.3%（95%置信区间，36.1% - 49.7%），接受换血治疗的新生儿出现不良结局的可能性是未接受换血治疗新生儿的1.55倍（95%置信区间，1.10 - 2.18）。
在这项对22个国家31个中心管理的HDFN新生儿的队列研究中，发现HDFN产后管理存在显著的实践差异，凸显了缺乏共识以及达成共识的必要性。该研究表明，对于HDFN新生儿，等待至37周0天后分娩与换血频率之间可能存在有益的临床关联。本研究提供了实施国际指南的框架。
