BACKGROUND Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies. METHODS In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available. FINDINGS 2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres. INTERPRETATION We found considerable variation in antenatal management and outcomes in haemolytic disease of the fetus and newborn between sites in different countries. Our study shows the capacity of the field to gather valuable data on a rare disease and to optimise care. FUNDING None.

中文翻译：

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胎儿和新生儿溶血性疾病产前管理和结果的变化：一项国际、回顾性、观察性队列研究。


背景 胎儿和新生儿溶血性疾病的进步导致了多种治疗选择。我们报告了高危妊娠中胎儿和新生儿溶血性疾病的管理和结局的实践差异。方法 在这项国际回顾性观察性队列研究中，从 22 个国家的 31 个中心检索了胎儿和新生儿中度或重度溶血性疾病病例的数据。符合条件的参与者患有胎儿溶血性疾病，导致胎儿在 16 + 0 周或更晚死亡，产前接受宫内输血或静脉注射免疫球蛋白治疗的参与者，或未接受产前治疗的新生儿接受强化光疗、换血疗法或红细胞输注治疗。所有患者均已确诊母体同种抗体和与母体同种抗体不相容的抗原阳性胎儿。仅 ABO 血型不合的患者被排除在外。我们评估了血清学诊断和转诊、产前治疗和时机、并发症、分娩途径和出生胎龄。对所有有完整数据的合格参与者进行了结局分析。结果 2006 年 1 月 1 日至 2021 年 7 月 1 日期间治疗的 2443 例患有胎儿和新生儿溶血性疾病的妊娠由 2021 年 12 月 1 日至 2023 年 3 月 1 日期间由中心共享并进行了分析。由于信息缺失，排除了 23 例妊娠，我们纳入了 2420 例进行进一步分析。1764 例妊娠中有 72·9% （2420 例）受到 D 抗体的影响。2420 例妊娠中有 95 例 （3·9%） 导致胎儿死亡。在 2325 名活产新生儿中，1349 名 （58·1%） 接受了任何形式的产前治疗，976 名 （41·9%） 仅接受了产后治疗。 转诊时的中位胎龄为 20·4 周 （IQR 14·9-28·0），各中心之间中位胎龄在 10·0 至 26·3 周之间。在 1276 例妊娠中，有 185 例 （14·5%） 在首次宫内输血时出现严重水肿，中心间比例在 0% 到 42% 之间。每次妊娠进行两次宫内输血 （IQR 1-4） 的中位数。宫内输血使用的胎儿通路部位在不同中心之间差异很大。肝内入路宫内输血的非致死性并发症发生率 （2·0%， 95% CI 1·1-3·3） 低于胎盘放置 （6·9%， 5·8-8·0） 和游离袢 （13·3%， 8·9-18·9）。静脉注射免疫球蛋白给药的用途和适应症差异很大。宫内输血新生儿的中位胎龄为 35·6 周 （IQR 34·0-36·7），各中心之间的中位胎龄为 33·2 至 37·3 周，而未接受产前治疗的新生儿的中位胎龄为 37·3 （IQR 36·3-38·1），中位胎龄为 34·9 至 38·9 周。解释 我们发现不同国家不同地点的胎儿和新生儿溶血性疾病的产前管理和结局存在相当大的差异。我们的研究表明，该领域能够收集有关罕见病的宝贵数据并优化护理。资金 无。