1 CF transmembrane conductance regulator (CFTR) modulators, a class of drugs that addresses the basic 2 defect in cystic fibrosis (CF), have led to large increases in the health and life expectancy of people with CF. In 3 turn, a large majority are now considering parenthood. The United States (US) CF Foundation Patient Registry 4 report (CFFPR) demonstrated a near-doubling of pregnancies in people with CF from 310 in 2019 to 619 in 2020. 5 Greater understanding of the health impacts of parenthood is critical to inform reproductive decisions and provide 6 effective interventions for those with CF who decide to become parents. 7 This co-funded application with the National Institutes of Health and the CF Foundation (CFF) will seek 8 to determine the health impact of parenthood on men and women with CF in the era of CFTR modulators. To 9 provide relatively immediate evidence on parenthood’s effect on pulmonary health and the influence of the intro- 10 duction and use of all available CFTR modulators, in Aim 1 we will assess changes in pre- vs. intra-parenthood 11 percent predicted forced expiratory volume in 1 second (ppFEV1) in a retrospective longitudinal cohort study 12 linking CFFPR data with cross-sectional surveys collected from 249 new parents attending participating US CF 13 centers between 2011-2020. We will identify predictors and timing of lung function loss using 747 non-parents 14 from participating centers as a comparison group and examine the impact of CFTR modulators on parental 15 health. In Aim 2, we will prospectively collect physical and mental health data to comprehensively evaluate the 16 impact of parenthood in CF with widespread highly effective CFTR modulator use. We will follow 146 new parents 17 of children <5 years of age over 5 years to assess the primary outcome of ppFEV1 change. To model potential 18 confounding/effect modification on the association between parenthood and outcomes, we will combine objective 19 physical health data and survey assessments of mental health, parental responsibility/stress, quality of life, and 20 adherence. We will conduct dyadic interviews with a subset of parents and their key supports to explore the 21 parenthood experience and identify future interventions. This study of the CF population would be the first, large- 22 scale epidemiologic data collection of how becoming a parent interplays with having a chronic disease. 23 Dr. Kazmerski, the principal investigator, is a pulmonologist and health services researcher with exper- 24 tise in sexual and reproductive healthcare for people with pediatric-onset chronic disease. The results of this 25 long-term, observational study will determine whether parenthood adversely impacts the health of people with 26 CF and the ability of CFTR modulators to mitigate such effects. Healthcare providers can use the data to pro- 27 vide evidence-based guidance to help those with CF make informed parenthood decisions. Future interven- 28 tions tar...