Prenatal Elexacaftor/Tezacaftor/Ivacaftor Treatment Prevents Meconium Ileus, but Not Exocrine Pancreatic Insufficiency and Lung Disease in Infants With Cystic Fibrosis
Paulina E. Aleksander
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Contribution: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing
Search for more papers by this authorStephanie Thee
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Berlin Institute of Health (BIH) at Charité, Berlin, Germany
Contribution: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing
Search for more papers by this authorFelix Doellinger
Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
Contribution: Writing - original draft, Writing - review & editing, Formal analysis
Search for more papers by this authorStyliani Zagkla
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Contribution: Writing - original draft, Writing - review & editing
Search for more papers by this authorMarcus A. Mall
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Berlin Institute of Health (BIH) at Charité, Berlin, Germany
Contribution: Writing - review & editing, Supervision
Search for more papers by this authorCorresponding Author
Mirjam Stahl
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Berlin Institute of Health (BIH) at Charité, Berlin, Germany
Correspondence: Mirjam Stahl ([email protected])
Contribution: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing, Supervision
Search for more papers by this authorPaulina E. Aleksander
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Contribution: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing
Search for more papers by this authorStephanie Thee
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Berlin Institute of Health (BIH) at Charité, Berlin, Germany
Contribution: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing
Search for more papers by this authorFelix Doellinger
Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
Contribution: Writing - original draft, Writing - review & editing, Formal analysis
Search for more papers by this authorStyliani Zagkla
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Contribution: Writing - original draft, Writing - review & editing
Search for more papers by this authorMarcus A. Mall
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Berlin Institute of Health (BIH) at Charité, Berlin, Germany
Contribution: Writing - review & editing, Supervision
Search for more papers by this authorCorresponding Author
Mirjam Stahl
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
German Center for Lung Research (DZL), Associated Partner Site Berlin, Berlin, Germany
Berlin Institute of Health (BIH) at Charité, Berlin, Germany
Correspondence: Mirjam Stahl ([email protected])
Contribution: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing, Supervision
Search for more papers by this author
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
All data analyzed are included in this published article.
References
- 1X. Sun, Y. Yi, Z. Yan, et al., “In Utero and Postnatal VX-770 Administration Rescues Multiorgan Disease in a Ferret Model of Cystic Fibrosis,” Science Translational Medicine 11, no. 485 (2019): eaau7531.
- 2I. A. Evans, X. Sun, B. Liang, et al., “In Utero and Postnatal Ivacaftor/Lumacaftor Therapy Rescues Multiorgan Disease in CFTR-F508del Ferrets,” JCI Insight 9, no. 8 (2024): e157229.
- 3C. N. Fortner, J. M. Seguin, and D. M. Kay, “Normal Pancreatic Function and False-Negative Cf Newborn Screen in a Child Born to a Mother Taking CFTR Modulator Therapy During Pregnancy,” Journal of Cystic Fibrosis 20, no. 5 (2021): 835–836.
- 4C. Fortner, “P006 False Negative Newborn Screen and Absent Clinical Features of Cystic Fibrosis After in Utero Modulator Exposure for An Infant With Two Cystic Fibrosis Causing Mutations,” Journal of Cystic Fibrosis 23, no. June 2024 (2024): S68.
- 5A. Kowalik, E. Roberts, A. H. Harris, et al., “Clinical Outcomes of Two Infants With Cystic Fibrosis, Including Presence of the Vas Deferens, Born to a Woman With Cystic Fibrosis Taking CFTR Modulators During Both Pregnancies,” Journal of Cystic Fibrosis 23, no. 5 (2024): 1027–1030.
- 6S. Szentpetery, K. Foil, S. Hendrix, et al., “A Case Report of CFTR Modulator Administration via Carrier Mother to Treat Meconium Ileus in a F508del Homozygous Fetus,” Journal of Cystic Fibrosis 21, no. 4 (2022): 721–724.
- 7E. Gómez-Montes, E. Salcedo Lobato, A. Galindo Izquierdo, et al., “Prenatal Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Promising Way to Change the Impact of Cystic Fibrosis,” Fetal Diagnosis and Therapy 50, no. 2 (2023): 136–142.
- 8Y. J. Blumenfeld, S. R. Hintz, N. Aziz, et al., “Treatment of Fetal Cystic Fibrosis With Cystic Fibrosis Transmembrane Conductance Regulator Modulation Therapy,” Annals of Internal Medicine 176, no. 7 (2023): 1015–1016.
- 9A. Metcalf, S. L. Martiniano, S. D. Sagel, M. V. Zaretsky, E. T. Zemanick, and J. E. Hoppe, “Outcomes of Prenatal Use of Elexacaftor/Tezacaftor/Ivacaftor in Carrier Mothers to Treat Meconium Ileus in Fetuses With Cystic Fibrosis,” Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society 24, no. 3 (2024): 466–468.
- 10M. Destoop, C. Brantner, E. B. Wilms, et al., “Cftr Modulator Therapy via Carrier Mother to Treat Meconium Ileus in a F508del Homozygous Fetus: Insights From an Unsuccessful Case,” Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society 24, no. 3 (2025): 476–478.
- 11A. S. Bonnel, T. Bihouee, M. Ribault, et al., “First Real-World Study of Fetal Therapy With CFTR Modulators in Cystic Fibrosis: Report From the MODUL-CF Study,” Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society 24, no. 3 (2025): 457–465.
- 12J. L. Goralski, J. E. Hoppe, M. A. Mall, et al., “Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2–5 Years With Cystic Fibrosis and at Least One F508del Allele,” American Journal of Respiratory and Critical Care Medicine 208, no. 1 (2023): 59–67.
- 13M. Stahl, J. Roehmel, M. Eichinger, et al., “Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial,” Annals of the American Thoracic Society 21, no. 11 (2024): 1550–1559.
- 14J. C. Davies, C. E. Wainwright, G. S. Sawicki, et al., “Ivacaftor in Infants Aged 4 to < 12 Months With Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial,” American Journal of Respiratory and Critical Care Medicine 203, no. 5 (2021): 585–593.
- 15P. McNally, A. Singh, S. A. McColley, et al., “Safety and Efficacy of Ivacaftor in Infants Aged 1 to Less Than 4 Months With Cystic Fibrosis,” Journal of Cystic Fibrosis 23, no. 3 (2024): 429–435.
- 16K. G. Stephenson, A. J. Lingle, K. A. Baumberger, et al., “Changes in Fecal Elastase-1 Following Initiation of CFTR Modulator Therapy in Pediatric Patients With Cystic Fibrosis,” Journal of Cystic Fibrosis 22, no. 6 (2023): 996–1001.
- 17M. Stahl, E. Steinke, S. Y. Graeber, et al., “Magnetic Resonance Imaging Detects Progression of Lung Disease and Impact of Newborn Screening in Preschool Children With Cystic Fibrosis,” American Journal of Respiratory and Critical Care Medicine 204, no. 8 (2021): 943–953.
- 18J. L. Taylor-Cousar and R. Jain, “Maternal and Fetal Outcomes Following Elexacaftor-Tezacaftor-Ivacaftor Use During Pregnancy and Lactation,” Journal of Cystic Fibrosis 20, no. 3 (2021): 402–406.
- 19R. Jain, A. Wolf, M. Molad, J. Taylor-Cousar, C. R. Esther, Jr., and M. Shteinberg, “Congenital Bilateral Cataracts in Newborns Exposed to Elexacaftor-Tezacaftor-Ivacaftor in Utero and While Breast Feeding,” Journal of Cystic Fibrosis 21, no. 6 (2022): 1074–1076.
