Assessment of the effectiveness of newborn screening and impact of COVID-19 on the Cystic Fibrosis population in Ireland

Introduction: Newborn screening for Cystic Fibrosis (CF) was introduced in Ireland in July 2011. The aims of the thesis were: 1) To evaluate clinical outcomes in the screen-detected and clinically presenting CWCF up to the age of 12 years. 2) To evaluate the caregiver burden and challenges faced by parents of CWCF 3) To evaluate the impact of the COVID-19 pandemic on mental health, education, and healthcare of PWCF and CWCF and their families. Methods: A census-based historical cohort study (The Irish Comparative Outcome Study (ICOS)) was conducted across all six Irish hospitals with specialised CF paediatric services. Two CWCF cohorts were recruited: clinically diagnosed (born June 2008-June 2011 and those presenting 2011-2023) and screen-detected (born July 2011 to June 2023). Logistic and Cox regression and Generalised Additive Modelling were performed to assess associations between demographic/CF-related variables and key clinical outcomes in CWCF up to age 12. Parents of CWCF recruited to ICOS completed a newly validated “Challenge of Living with Cystic Fibrosis-Short Form” questionnaire. The chi-square test and linear regression were performed to determine associations between demographic/clinical factors and reported challenges or overall weighted challenge scores respectively. A cross-sectional study assessing the impact of COVID-19 pandemic on the lives of PWCF, CWCF and their families was conducted with Cystic Fibrosis Ireland. Multivariable logistic regression was used to determine independent factors associated with the deferral of hospital visits and mental health effects. Results: The ICOS study showed benefits of newborn screening including, improved growth parameters, reduced hospitalisations, delayed Pseudomonas aeruginosa infections and improved lung function. The screen detected cohort reported reduced hospital admissions due to pulmonary exacerbation (9.5% vs 30.7% at 60 months, p<0.001) or any other CF-related issues in the first 60 months, delayed acute (Adjusted hazards ratio (HR):1.78, 95%CI:0.72-1.62, p=0.72) or chronic Pa acquisition ( adjusted HR: 2.45, 95% CI: 0.92-6.48, p=0.07) and improved percent predicted forced expiratory volume in 1 second (ppFEV1) levels (unadjusted coefficient: 6.53, 95% CI: 4.57-8.49, p=0.003). Protective effects of the modulator on clinical parameters were found. Regarding caregiver burden, parents reported marginal to great difficulty in balancing daily lives with CF care (31%), managing extra expenses (46.8%) and establishment of the home CF care routine (76.5%). The majority of parents felt supported by pharmacy and CF care team. COVID-19 led to deferral of hospital visits; 57.4% of PWCF deferred by 3 months and 26% by 6 months, and 41.8% and CWCF consultations were deferred by 3 months. Online consultations were new to many; most found them helpful (PWCF = 87.8%; parents of CWCF = 81%). The key mental issues faced by children during the pandemic were increased anxiety (25.6%) and increased stress (33.3%). PWCF and parents of CWCF experienced nervousness and downheartedness. Conclusions: Important benefits of Newborn screening on clinical outcomes are documented; the introduction of CFTR modulators has further improved clinical outcomes. However, parents of children prescribed CFTR modulators reported higher levels of moodiness in older children. This study marks the first use of the “Challenge of Living with Cystic Fibrosis-Short Form” in a population setting. Multidisciplinary teams and the Irish government should consider the caregiving and financial burden, the associated financial burden and the psychological stress experienced by parents of CWCF. Age-adequate financial support and psychological support should be provided. During the COVID-19 pandemic, it was important to collaborate with charitable organisations and assist with research which could benefit the CF community, who were under considerable stress during the pandemic.