# Exposure to CFTR Modulators During Pregnancy in Cystic Fibrosis: Four Cases to Highlight Neonatal Diagnostic Challenges and Outcomes

## TL;DR

This paper discusses four cases of newborns with cystic fibrosis (CF) whose mothers used CFTR modulators during pregnancy, highlighting challenges in diagnosing CF in these infants.

## Contribution

The study provides real-world cases to better understand neonatal outcomes and diagnostic challenges when CFTR modulators are used during pregnancy.

## Key findings

- Three CF newborns exposed to ETI had false-negative newborn screening results.
- Two of the ETI-exposed newborns were pancreatic sufficient at birth.
- A newborn exposed to TI alone had elevated IRT and severe pancreatic insufficiency.

## Abstract

CFTR modulators have transformed the clinical evolution of patients with CF. The number of pregnancies is increasing in women with CF, most of whom are now treated with CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) or Tezacaftor/Ivacaftor. This raises some questions as we still lack data on foetal and maternal safety. The preliminary data seem to support the continuation of modulators. Some of these mothers may also give birth to newborns with CF and this raises more questions. We report here four cases of CF newborns whose mothers were treated with CFTR modulators throughout pregnancy to help refine potential foetal outcomes of in utero administration of CF modulators. No maternal or foetal complications could be attributed to CFTR modulators. Three CF newborns were exposed to ETI and were false negative of the newborn screening. Two of them were pancreatic sufficient at birth. The remaining patient, exposed to Tezacaftor/Ivacaftor (TI) alone, showed elevated immunoreactive trypsin (IRT) and severe pancreatic insufficiency at birth. These cases highlight that in utero administration of ETI could potentially improve neonatal outcomes of CF newborns and cause newborn screening false negative.