Anne-Sophie Bonnel, Tiphaine Bihouée, Mélanie Ribault, Marine Driessen, David Grèvent, Frantz Foissac, Ngoc Hoa Truong, Myriam Benhamida, Baptiste Arnouat, Roxana Borghese, Frédérique Chedevergne, Laure Couderc-Kohen, Jennifer da Silva, Dominique Grenet, Véronique Houdouin, Anais Le, Sarah Marchal, Eric Deneuville, Delphine Pouradier, Véronique Rousseau, Jean-Marc Treluyer, Arnaud Francart, Julie Steffann, Philippe Reix, Sihem Benaboud, Marie France Mamzer, Yves Ville, Clémence Martin, Pierre-Régis Burgel, Isabelle Sermet-Gaudelus
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引用次数: 0
Abstract
Background: We aimed to build a cohort of Maternal-Cystic Fibrosis (CF) fetal dyads treated in utero with Variant Specific Therapy (VST), to assess the efficacy on Meconium Ileus (MI) and potential adverse effects of treatment.
Methods: Dyads were included if the foetus had a genetic diagnosis of CF and carried at least one variant responsive to VST. Standardized assessment included pre-VST Magnetic Resonance Imaging (MRI), repeated ultrasound (US), and VST drug concentrations in cord blood, maternal and infant plasma.
Results: We enrolled 13 dyads. One withdrew from the study. VST therapies (Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor(IVA) (ETI) n = 11, ivacaftor (IVA) n = 1) were administered to the pregnant women between 19 and 36 weeks' of gestation for a median[IQR] of 35[55] days, either as a curative indication of MI (n = 8) or as a tertiary prevention of fetal CF-related intestinal symptoms (n = 4). One foetus experienced increased bowel dilatation after ETI introduction. MRI revealed intestinal atresia. One dyad received only 2 doses. In the other 6 cases, resolution of MI was observed within 14[10] days of ETI. Fetal development and neonatal tolerance were excellent. Fecal elastase at birth was always below 200 ng/g even in the ETI breast-fed infant. Cord-to-maternal concentration yielded median ratios of 0.40 for ELX, 0.54 for IVA and 1.59 for TEZ.
Conclusion: ETI administration from the third trimester of pregnancy enables MI resolution. Trans-placental transfer is high. Fetal tolerance at ETI initiation needs to be monitored by a standardized assessment.
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.