Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States; little is known about pregnancy outcomes with modulator use. The aim of this retrospective study was to determine the impact of CFTR modulators on maternal outcomes. RESEARCH QUESTION: Does pregnancy differentially affect outcomes in female individuals with CF with and without CFTR modulator exposure? STUDY DESIGN AND METHODS: Data on pregnancies from 2010 to 2021 were collected from 11 US adult CF centers. Multivariable longitudinal regression analysis was performed to assess whether changes in percent predicted FEV1 (ppFEV1), BMI, pulmonary exacerbations (PEx), and Pseudomonas aeruginosa prevalence differed from prior to, during, and following pregnancy according to CFTR modulator use while adjusting for confounders. Infant outcomes are also described based on maternal modulator use. RESULTS: Among 307 pregnancies, mean age at conception was 28.5 years (range, 17-42 years), before pregnancy ppFEV1 was 74.2, and BMI was 22.3 kg/m2. A total of 114 pregnancies (37.1%) had CFTR modulator exposure during pregnancy (77 with highly effective modulator therapy [HEMT] and 37 with other modulators). The adjusted mean change in ppFEV1 from before pregnancy to during pregnancy was -2.36 (95% CI, -3.56 to -1.16) in the unexposed group and 2.60 (95% CI, 0.23 to 4.97) in the HEMT group, with no significant change from during pregnancy to 1 year after pregnancy. There was an overall decline in ppFEV1 from before pregnancy to after pregnancy in the no modulator group (-2.56; 95% CI, -3.62 to -1.49) that was not observed in the HEMT group (1.10; 95% CI, -1.13 to 3.34). PEx decreased from before pregnancy to after pregnancy in the HEMT group, and BMI increased from before pregnancy to during pregnancy in all groups but with no significant change after pregnancy. Missing infant outcomes data precluded firm conclusions. INTERPRETATION: We observed superior pregnancy and after pregnancy pulmonary outcomes in individuals who used HEMT, including a preservation of ppFEV1, compared with those unexposed to HEMT. CHEST 2025; 167(2):348-361