Maternal and fetal outcomes associated with CFTR modulator use during pregnancy: a scoping review.

Abstract

With major therapeutic advances driven by cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm), increasing numbers of women with cystic fibrosis (CF) are living into adulthood and pursuing pregnancy. Women with CF may face pregnancy-related challenges that influence maternal and fetal outcomes. However, long-term data regarding the safety and effectiveness of CFTRm use during pregnancy remain limited.This scoping review aimed to evaluate the existing literature on the effects of CFTRm use in women with CF during pregnancy and the postpartum period, as well as the potential impact on the developing fetus. We analysed clinical studies, registry data and related literature published between 2003 and 2025 to assess reported differences in lung function, birth weight, pregnancy and neonatal complications, mode of delivery and screening biomarkers among pregnancies in women with CF treated with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor or elexacaftor/tezacaftor/ivacaftor, compared with pregnancies not exposed to CFTRm.Available evidence suggests that elexacaftor/tezacaftor/ivacaftor may improve maternal health through better lung function and nutritional status, while inadvertent fetal drug exposure has not been clearly associated with serious adverse outcomes. Reported fetal and neonatal outcomes following maternal CFTRm therapy have generally been reassuring. However, long-term effects in exposed children remain uncertain. There is also insufficient evidence to establish the safety of infant exposure or prolonged maternal CFTRm use during lactation. This review highlights the need for future studies evaluating dose optimisation, long-term follow-up of infants and children, and integration of registry data to better define the safety and effectiveness of CFTRm use during pregnancy.