In Utero CFTR Modulator Therapy in Fetuses With Cystic Fibrosis

Small molecule therapies that restore function to the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein, referred to as CFTR modulators, have emerged as a key therapeutic approach for people with CF who carry responsive genetic variants. Their effects have been transformative to the lives of many of those living with CF. As the reach of CFTR modulators expands, new questions arise about their role beyond approved clinical indications for people with CF. One such area of growing interest is the use of CFTR modulator therapy during pregnancy to treat suspected meconium ileus, a particularly severe fetal and immediate postnatal manifestation of CF. In this review, we summarize the current data about use of CFTR modulator therapy during pregnancy, including reported effects in pregnant persons and their offspring. We describe the potential of this in utero therapy to prevent meconium ileus and to maintain exocrine pancreatic function in infants with CF. However, these potential benefits must be weighed carefully with the known and potential risks of CFTR modulator therapy. We address ethical implications and important knowledge gaps related to prenatal CFTR modulator use during pregnancy. Further evidence is needed to determine best practices for CFTR modulator use during pregnancy.