WS06.01Prenatal CFTR Modulator Exposure: a Review of the European and U.S. Experience

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.522

S. Szentpetery , J. Taylor-Cousar , C. Luna Parades , I. Sermet-Gaudelus , P. Aleksander , A. Kowalik , A. Morales-Tirado , S. Gartner-Tizzano , C. de Manuel-Gómez , B. Fabrizzi

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引用次数: 0

Abstract

Objectives

Evaluate clinical outcomes, ethical considerations, and emerging data from U.S. and European cases of prenatal elexacaftor-tezacaftor-ivacaftor (ETI) exposure in cystic fibrosis (CF) pregnancies, focusing on treatment timing, postnatal management, and access disparities.

Methods

Case data were gathered via standardized tools, including REDCap, from published and ongoing reports. Clinical outcomes, prenatal, postnatal findings, and complications were analyzed.

Results

In U.S. cases, 78% of CF infants were diagnosed via amniocentesis (mean 18 6/7 weeks). Abnormal prenatal ultrasounds occurred in 89% of cases - echogenic or dilated bowel loops. These resolved in all cases after a mean ETI treatment of 5 5/7 weeks. Postnatal complications included NICU admission (55%), transient feeding or meconium passage issues. Sweat chloride averaged 69 mmol/L, and 71% of breastmilk-fed infants were found to be pancreatic sufficient.

In European cases, 83% were diagnosed via amniocentesis and 82% had abnormal ultrasounds. Resolution of findings occurred in 63% after a mean ETI treatment duration of 6 2/7 weeks. Postnatal complications included unresolved meconium ileus in three infants, requiring enemas or bowel resection. Sweat chloride averaged 83 mmol/L, and pancreatic sufficiency was transient, in contrast to the reported U.S. cases. Fourteen French dyads who received prenatal treatment will also be reviewed.

Adverse maternal events were rare, with occasional rash or mild transaminase elevation. Neonatal complications included one case of hyperbilirubinemia. Long-term follow-up showed improved pancreatic function in infants transitioning to oral CFTR modulators.

Conclusion

Prenatal ETI exposure shows promise in improving outcomes for CF infants, resolving prenatal abnormalities, and supporting early pancreatic function. Standardized protocols, equitable access, and further study are needed to address unresolved cases and ensure long-term safety.

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产前CFTR调节剂暴露：欧洲和美国经验的回顾

目的：评估美国和欧洲的囊性纤维化（CF）妊娠中产前暴露ETI的临床结果、伦理考虑和新数据，重点关注治疗时机、产后管理和获取差异。方法通过标准化工具（包括REDCap）从已发表和正在进行的报告中收集病例数据。分析临床结果、产前、产后发现和并发症。结果在美国，78%的CF婴儿是通过羊膜穿刺术诊断的（平均18 6/7周）。产前超声异常发生在89%的病例中-回声或肠袢扩张。所有病例在平均ETI治疗5 5/7周后均消退。产后并发症包括新生儿重症监护病房入院（55%）、短暂喂养或胎便通过问题。汗液氯化物平均为69毫摩尔/升，71%的母乳喂养婴儿被发现是胰腺充足的。在欧洲病例中，83%通过羊膜穿刺术诊断，82%超声异常。平均ETI治疗时间为6 2/7周后，63%的患者的症状得到缓解。产后并发症包括3例未解决的胎便性肠梗阻，需要灌肠或肠切除术。汗液氯化物平均为83 mmol/L，胰腺充足率是短暂的，与美国报告的病例相反。接受产前治疗的14对法国夫妇也将接受审查。产妇不良事件罕见，偶有皮疹或轻度转氨酶升高。新生儿并发症包括1例高胆红素血症。长期随访显示，过渡到口服CFTR调节剂的婴儿胰腺功能得到改善。结论产前ETI暴露有望改善CF婴儿的预后，解决产前异常，并支持早期胰腺功能。需要标准化方案、公平获取和进一步研究来解决未解决的病例并确保长期安全。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.