Outcomes of prenatal use of elexacaftor/tezacaftor/ivacaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis.

Abstract

As cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies including elexacaftor/tezacaftor/ivacaftor (ETI) have become widely used in eligible patients with cystic fibrosis (CF), the use of these medications in pregnant people has become a critical area of investigation. Since these medications appear generally safe to both mother and fetus when taken by pregnant people with CF, interest has pivoted to the use of ETI in CF carrier mothers to decrease morbidity and mortality from meconium ileus (MI) in fetuses with cystic fibrosis. Here we discuss three infants at our institution with ultrasound findings of MI who were exposed to prenatal ETI through CF carrier mothers for the purposes of treating MI and lowering risk of intestinal complications from this severe manifestation of CF. These cases differ in the timing of ETI initiation, severity of outcome, and accessibility of this off-label medication use to families depending on their insurance. All infants and mothers tolerated the medication well without significant side effects. One infant had complete MI resolution, one had persistent MI at birth with easy clearance with minimally invasive therapies, and one had persistent MI requiring jejunostomy. The infant with the most severe outcome had the shortest duration of ETI exposure and may have been able to receive this medication sooner had a referral to a CF center been made. These cases highlight the potentially life-altering effects of prenatal ETI use and the need for awareness of this clinical situation among fetal care providers.