Maternal, Infant, Reproductive and Child Health in Cystic Fibrosis (MATRIARCH_CF): a prospective, observational study to evaluate pregnancy and parenthood in females with cystic fibrosis and health of the offspring in the CFTR-modulator era.

introductionCystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm) have altered the landscape of pregnancy and parenthood in cystic fibrosis (CF). As pregnant and breastfeeding females with CF (FwCF) were excluded from pivotal CFTRm trials, evidence to guide management and counsel families on maternal and child outcomes is limited. While CFTRm are unlicensed for use in pregnancy, substantial clinical benefit means most continue therapy. Early studies indicate that CFTRm cross the placenta and are detectable in breastmilk; reported associations include infant liver dysfunction and cataracts but risks remain poorly characterised. We describe the protocol for the first UK-based prospective study evaluating pregnancy and parenthood in FwCF and health outcomes in their children in the CFTRm era. METHODS AND ANALYSIS: A single protocol underpins three linked prospective observational substudies in the MATRIARCH_CF research programme. The 'Mama' cohort recruits FwCF planning pregnancy or pregnant, with follow-up from preconception to 24 months postpartum, assessing physical and psychological health, lung function and CF-related complications. 'Mini' recruits children aged 0-24 months born to a parent with CF and compares offspring exposed and unexposed to CFTRm in utero and/or through breastfeeding; measures include birth outcomes, congenital anomalies, liver biochemistry, growth and neurodevelopment. 'Midi' recruits children aged 3-6 years from the same exposure groups and assesses neurodevelopment and lung function. Longitudinal data across cohorts will strengthen the evidence base, support risk-benefit discussions and inform clinical guidance. ETHICS AND DISSEMINATION: The protocol was approved by NHS ethics HSC REC A committee (25/NI/0027 19 March 2025). Assessments align with routine care where possible. Visit windows are flexible and participants may decline individual assessments. The research team does not influence CFTRm initiation, cessation or dose adjustment. People with CF contributed throughout study design to ensure acceptability. Findings will be disseminated through PhD theses, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT06797206.