Abstract Introduction Alpha-1 antitrypsin deficiency (AATD) is an inherited condition caused by a spectrum of SERPINA1 gene variants, resulting in insufficient levels of circulating alpha-1 antitrypsin (AAT) protein, conferring varying risks of emphysema and liver disease. AATD remains underdiagnosed, with lung-index(symptomatic) patients commonly exhibiting established, irreversible lung disease at diagnosis. Studies from our group have shown significant rates of obstruction even in our family-screened populations (56% with an FEV1/FVC 0.7, range (22-91%), highlighting a critical need for earlier detection. Awareness of a pre-existing genetic susceptibility will allow individuals to make informed lifestyle choices to minimise their lifetime risk of disease development.Newborn screening (NBS) has been recommended by the WHO, but uncertainty remains about the feasibility of implementing large-scale newborn screening programmes. We will examine newborn screening (NBS) studies in AATD carried out to date, and reconsider its validity in the modern AATD landscape. Aims To systematically identify and synthesise pilot and feasibility studies evaluating newborn screening for alpha-1 antitrypsin deficiency, with a focus on implementation barriers, benefits, and reported outcomes. Methods A systematic search of PubMed, Embase, Scopus, CINAHL and Cochrane databases was conducted from 1963 to 2025. Eligible studies included pilot, feasibility, or implementation projects assessing NBS for AATD, either at a local or population level. Two reviewers independently screened studies, extracted data, and appraised methodological quality. Owing to heterogeneity in study designs and outcomes, results were synthesised narratively. Results 13 papers were identified and critically analysed. 3 papers performed longitudinal follow-up of children with AATD identified via NBS and are included as a sub-analysis. Significantly lower rates of smoking, and consequently respiratory disease, were seen in longitudinal follow-up studies of NBS cohorts. Conclusions NBS for AATD provides an opportunity for disease-modifying lifestyle changes. Multiple studies found NBS to be an inexpensive strategy for AATD detection, with acceptable specificity and sensitivity.Arguments against NBS in AATD historically focused on the paucity of treatment, lack of knowledge of the natural history of the disease and familial psychological stress. The majority of these studies were conducted in the 1970s and 1980s.The intervening decades have seen huge advances in knowledge, genetic counselling, the introduction of augmentation therapy and exciting novel therapeutics, including gene editing, are presently being trialed. The WHO has recommended the introduction of NBS for AATD and this review will discuss the potential for such a programme in Ireland, particularly given the high prevalence of AATD in Ireland. This abstract is funded by: Alpha-1 Foundation
Farrell et al. (2026) studied this question.