(349) Impact of CFTR modulators for cystic fibrosis on perinatal outcomes

Objective: Pregnancy in individuals with cystic fibrosis (CF) has been associated with acute deterioration of pulmonary function, leading to higher perinatal morbidity and mortality. Combination cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to improve outcomes in non-pregnant patients, but data on their use in pregnancy are limited. Here, we examine the CFTR modulator, Trikafta (Elexacaftor/Tezacaftor/Ivacaftor), and its impact on perinatal outcomes.

Study Design: In a retrospective cohort study, we identified individuals with CF and singleton, non-anomalous pregnancies within a multi-institution health system obstetric outcomes database between 2011-2023. We compared maternal and neonatal outcomes by perinatal Trikafta exposure using the Wilcoxon rank-sum test and Fisher’s exact test as indicated.

Results: 31 individuals with CF were identified, including 10 with Trikafta exposure in pregnancy. Baseline characteristics were similar between the two groups. There was no difference in the development of pregnancy complications such as diabetes or hypertensive disorders of pregnancy. Although there was no identified difference in acute pulmonary exacerbations, there was a trend toward improved FEV (Forced Expiratory Volume) during the third trimester in the Trikafta-exposed group. The Trikafta-exposed had a 5% improvement in FEV from their pre-pregnancy baseline to the third trimester, while the non-exposed had a 2% decline in FEV during the same time interval (p=0.10). Trikafta-exposed had a higher third trimester weight (75 kg vs. 64 kg, p=0.03) and experienced increased weight gain from pre-pregnancy to the third trimester than the non-exposed (13 kg vs. 9 kg, p=0.06). These results suggest that Trikafta may improve pulmonary function and nutritional status in pregnancy. There was no significant difference in gestational age at birth, birth weight, or NICU admission between groups.

Conclusion: The use of Trikafta in pregnancy tends to improve respiratory function and maternal weight gain without clearly increasing maternal or neonatal complications.