1078 History and evolution of newborn screening for cystic fibrosis in the United Kingdom. (17th August 2022)

• Record Type: Journal Article
• Authors: Pillai, Anjay; Southern, Kevin W
• Is Part Of: Archives of disease in childhood. Volume 107(2022)Supplement 2
• Page Start: A266
• Page End: A267
• Publication Date: 2022-08-17
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2022-rcpch.431
• Languages: English
• ISSNs: 0003-9888

Abstract

Abstract : Aims: To describe a) the history and evolution of newborn bloodspot screening (NBS) tests for cystic fibrosis (CF) in the United Kingdom (UK) and b) the developments which led to this being adopted as part of a national UK programme. Methods: The history and evolution of the newborn screening programme for cystic fibrosis was reviewed and summarised from relevant review articles, textbooks and monographs and also by direct interaction and interviews with some of the pioneers in this field. Key developments and overarching themes are highlighted. Results: Initial attempts to screen newborns for CF were undertaken in 1970s based on measurement of albumin content in meconium but the test was not reliable. Subsequent observation of elevated immunoreactive trypsinogen (IRT) in infants with CF raised the possibility of adding this condition to established dried blood spot (DBS) programmes. Following promising reports from Auckland, this technique was adopted by scientists based at Caen (France) and Peterborough (United Kingdom) for NBS for CF. As IRT levels can be transiently high even in healthy infants, a two stage (IRT-IRT) strategy was adopted, and persistently positive infants referred to paediatricians. 1 This generated interest, and two pilot regional schemes were established in East Anglia and Trent regions. Improvements in the performance of sweat testing provided a confirmatory diagnostic test for those identified by screening. Northern Ireland started a successful regional screening programme in 1984. Identification of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene in 1989 led to evolution of NBS protocols to incorporate analysis for common CFTR gene variants. In 1996, following a clinical trial, a NBS programme was established in Wales. At this time, the UK CF Trust (a national charity) began campaigning actively for a national programme. A clinical trial from Wisconsin provided some evidence of nutritional benefit. The UK government announced the decision to include CF screening in the existing national newborn screening program in 2001, but this was not fully implemented until 2007. The UK protocol has a number of unique features, including a 'safety net' whereby infants with persistently very high IRT are referred for evaluation even if no CFTR variants are identified. Conclusion: NBS for cystic fibrosis has been an important development in the history of paediatrics and reflects the cumulative work of many professionals starting from the 1970s. The long term benefits of early identification (and subsequent early intervention) is now better established and such benefits can only continue to improve, with the introduction of variant specific therapy for the CFTR gene. 2 References: Travert G, Heeley M, Heeley A. (2020). History of Newborn Screening for Cystic Fibrosis—The Early Years. International Journal of Neonatal Screening . 6(1):8. C astellani, C., Massie, J., Sontag, M., & Southern, K. W. (2016). Newborn screening for cystic fibrosis. The Lancet Respiratory Medicine, 4(8), 653-661.