Pregnancy in People With Cystic Fibrosis Treated With Highly Effective Modulator Therapy

We read with interest the article by Goralski et al1 in the January 2025 issue. The article sheds light on a crucial yet underexplored area of cystic fibrosis (CF) care. It offers a thorough exploration of the challenges and opportunities related to modulator therapy. As more patients with CF reach reproductive age and opt for these therapies, the article's insights into their use during pregnancy are essential in guiding patient care. We thoroughly appreciated the inclusion of case studies and the ongoing MAYFLOWERS study (Prospective Study of Pregnancy in Women With Cystic Fibrosis), which truly enriched the discussion, offering a glimpse into future clinical care models. Although the article highlights the limited data available on the long-term effects of modulator therapy in pregnancy, it could have emphasized more the critical need for longitudinal studies; one survey highlighted the necessity for systematic follow-up of children exposed to CF transmembrane conductance regulator (CFTR) modulators in utero to exclude delayed adverse effects.2 Another research article examined short-term health outcomes for parents with CF and called for prospective studies to investigate the broader implications of modulator therapy in the context of parenthood.3 Including these perspectives would provide a more comprehensive discussion and reinforce the importance of initiatives such as the MAYFLOWERS study, which aims to bridge these knowledge gaps. The article briefly mentions the risks to maternal health from discontinuing therapy, but this could have been explored further. Research shows that stopping modulator therapy during pregnancy can lead to CF symptom exacerbation, increased hospitalizations, and a decline in pulmonary function, which is linked to poorer maternal health outcomes.2 This can increase the risk of preterm birth, lower birth weight, and other pregnancy complications.2 Although individualized decision making is emphasized, the article could better highlight the importance of maintaining CFTR modulator therapy to optimize maternal health. Further research is needed to balance maternal benefits with potential fetal risks. Finally, the article addresses the potential effects of modulator therapy on newborn screening results, especially false-negative results, which could significantly complicate early diagnoses. A more detailed investigation into this issue would strengthen the understanding of how CFTR modulators may interfere with routine screening practices.