Background: Developments in screening technology and increased understanding of the natural history and treatment of inborn errors of metabolism (IEMs) have produced pressure to extend neonatal screening programmes. This review aims to assess the evidence for the appropriateness of such programmes.
Methods: A formal systematic literature review was conducted. Exclusion and inclusion criteria were used to select papers for critical appraisal by pairs of reviewers. Standard criteria were used to assess the appropriateness of neonatal screening for various IEMs. Site visits were conducted to assess new technologies for newborn screening.
Results: A total of 1866 papers were identified and 407 systematically selected for full critical appraisal. Published evidence confirmed that universal newborn screening for phenylketonuria (PKU) meets all of the screening criteria and justifies the expense and infrastructure necessary for the collection and testing of neonatal blood spots. There was insufficient evidence in the literature to assess the cost-effectiveness of screening for any other IEMs. There was reasonable evidence to support inclusion in extended neonatal screening of four other IEMs: biotinidase deficiency, congenital adrenal hyperplasia (CAH), medium-chain acyl CoA dehydrogenase (MCAD) deficiency and glutaric aciduria type 1 (GA1).
Conclusions: Large-scale trials of screening for biotinidase, CAH, MCAD and GA1 should be conducted, with careful evaluation to establish their clinical effectiveness and cost-effectiveness in practice. Screening for the latter two disorders would be dependent upon the use of tandem mass spectrometry (tandem MS). The application of tandem MS to newborn screening requires further evaluation. The extension of neonatal screening programmes to other IEMs is not currently justified.