Over the past half-century, the medical community has witnessed remarkable strides in the treatment of cystic fibrosis (CF), a complex genetic disorder primarily affecting the lungs and digestive system. Historically, patients with CF faced daunting health challenges and markedly reduced life expectancy. However, advancements in symptomatic care, antibiotic therapies, nutritional management, and respiratory support have progressively transformed the trajectory of this disease. Most recently, the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been hailed as a paradigm shift, revolutionizing CF treatment and offering the promise of improved quality of life and extended survival.
CFTR modulators specifically target the molecular defect underlying cystic fibrosis, namely mutations in the CFTR gene that cause dysfunction in ion transport across epithelial cells. By correcting or potentiating the function of the mutant CFTR protein, these agents improve chloride and bicarbonate transport, leading to enhanced mucociliary clearance and reduced pulmonary infections. The clinical benefits observed with these therapies include improved lung function, decreased pulmonary exacerbations, and better nutritional status. Such outcomes have had profound implications not just for individual health but also for reproductive health considerations, including pregnancy.
The widespread adoption of CFTR modulators has been associated with a noticeable rise in pregnancies among women with cystic fibrosis, which was previously a rare occurrence due to disease-related infertility and health risks. This surge underscores an urgent need for a thorough understanding of the safety and efficacy of CFTR modulators in the context of pregnancy. Unfortunately, pregnant women were systematically excluded from the pivotal clinical trials that established these drugs’ efficacy. Consequently, the body of evidence regarding maternal and fetal safety remains relatively sparse, leaving clinicians and patients with limited guidance on optimal management during pregnancy.
Maternal outcomes in cystic fibrosis pregnancies have historically correlated with disease severity; women with advanced lung disease or nutritional deficits face increased risks of adverse events, including preterm birth and maternal morbidity. As such, the question arises whether CFTR modulators, by potentially stabilizing or improving maternal health, can alter these risk profiles favorably. While initial observational reports suggest maternal benefits, comprehensive longitudinal data are necessary to validate these findings. Furthermore, the impact of these medications on the developing fetus necessitates careful scrutiny, given the dynamic biological milieu of pregnancy and delicate fetal developmental processes.
Data regarding teratogenicity – the potential of these drugs to cause birth defects – remain reassuringly limited but largely favorable. Animal studies have generally demonstrated a low incidence of malformations at therapeutic doses, providing some reassurance regarding congenital anomalies. However, reports of rare cases, such as congenital cataracts identified postnatally in infants exposed to CFTR modulators in utero, prompt cautious evaluation. The mechanistic basis for such ocular findings is not well understood, warranting further investigation into the pharmacodynamics and placental transfer characteristics of these agents.
One of the most compelling frontiers of CFTR modulator research in pregnancy is their potential influence on fetuses affected by cystic fibrosis. As these drugs cross the placenta, albeit to varying degrees depending on molecular properties, they might exert therapeutic effects antenatally. This raises the tantalizing possibility of in utero intervention, mitigating severe CF manifestations such as meconium ileus, a life-threatening intestinal obstruction present at birth in affected infants. Such prenatal treatment strategies could redefine neonatal outcomes and open new therapeutic horizons.
Nonetheless, significant gaps in knowledge remain regarding the long-term neurological development of children exposed to CFTR modulators during gestation. The developing central nervous system is exquisitely sensitive to pharmacological perturbations, and current data are insufficient to conclusively determine whether these drugs have any influence – detrimental or beneficial – on neurodevelopmental trajectories. Continued surveillance and dedicated developmental assessments are essential to address this critical aspect of fetal safety.
Moreover, animal models have documented instances of lung abnormalities following prenatal exposure to CFTR modulators, raising concerns about pulmonary morphogenesis. Although species differences limit direct translation to humans, these findings underscore the importance of cautious interpretation and the necessity of rigorous post-market surveillance. Understanding the precise timing, dosage, and duration that balances maternal benefits and fetal safety is a key challenge that must be approached through carefully designed observational studies and registries.
From a clinical perspective, the management of pregnant women with cystic fibrosis receiving CFTR modulators demands multidisciplinary collaboration. Obstetricians, pulmonologists, neonatologists, and pharmacists must coordinate to optimize maternal health while vigilantly monitoring fetal development. Individualized risk assessments, frequent fetal imaging, and maternal pulmonary evaluations constitute integral components of comprehensive prenatal care in this evolving therapeutic landscape.
In parallel, ethical considerations arise when deciding whether to continue or discontinue CFTR modulators during pregnancy. The risk-benefit balance is complex: discontinuation may precipitate maternal clinical deterioration, whereas continuation introduces theoretical risks to the fetus. Shared decision-making, informed by emerging evidence and patient preferences, remains paramount, as does the transparent communication of uncertainties and unknowns.
Beyond pregnancy, the impact of CFTR modulators extends into lactation, necessitating analysis of drug excretion into breast milk and potential exposure to neonates. Data remain scarce in this domain as well, further highlighting the need for robust pharmacokinetic studies to guide postpartum recommendations and support informed maternal choices about breastfeeding.
The therapeutic revolution mediated by CFTR modulators embodies a striking example of precision medicine transforming a once-devastating genetic disease. Their ripple effects are now tangible in realms previously unexplored, such as reproductive health and prenatal therapy. However, the path forward is marked by the dual imperative to maximize benefits while safeguarding the vulnerable fetus, demanding rigorous research, vigilance, and collaborative care frameworks.
Emerging registries and real-world evidence collections promise to enrich understanding of maternal and fetal outcomes associated with CFTR modulator exposure during pregnancy. These data sources will be instrumental in delineating safety profiles, optimal dosing regimens, and potential adverse events, as well as elucidating long-term developmental impacts on offspring. Such endeavors will inform evidence-based guidelines to support clinician and patient decision-making.
Furthermore, the prospect of fetal therapy using CFTR modulators heralds an exciting new chapter in the management of congenital genetic diseases. If antenatal intervention proves safe and efficacious, it may pave the way for similar approaches in other inherited disorders, fostering a new paradigm of prenatal precision therapeutics that intervenes before irreversible disease manifestations occur.
In summation, the introduction of CFTR modulators has precipitated a therapeutic revolution in cystic fibrosis management, generating profound implications for pregnancy and fetal health. Although initial data suggest low teratogenic risk and potential maternal benefits, critical knowledge gaps persist regarding neurodevelopmental outcomes, rare adverse effects, and the nuances of transplacental drug transfer. Addressing these questions will require sustained research efforts, multidisciplinary collaboration, and thoughtful clinical stewardship, aimed at harnessing the promise of these innovative agents while ensuring the safest possible outcomes for both mother and child.
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Subject of Research:
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their effects on pregnant women with cystic fibrosis and fetal outcomes.
Article Title:
A therapeutic revolution: CFTR modulators in cystic fibrosis and their impacts on pregnant women and the fetus.
Article References:
Denef, M., Mawet, M., Pirson, J. et al. A therapeutic revolution: CFTR modulators in cystic fibrosis and their impacts on pregnant women and the fetus. J Perinatol (2026). https://doi.org/10.1038/s41372-026-02594-0
Image Credits: AI Generated
DOI: 23 February 2026
