Evaluating newborn screening programmes based on dried blood spots: futurechallenges

A UK national programme to screen all newborn infants for phenylketonuria w as introduced in 1969, followed in 1981 by a similar programme for congenit al hypothyroidism. Decisions to start these national programmes were inform ed by evidence from observational studies rather than randomised controlled trials. Subsequently, outcome for affected children has been assessed thro ugh national disease registers, from which inferences about the effectivene ss of screening have been made. Both programmes are based on a single blood specimen, collected from each infant at the end of the first week of life, and stored as dried spots on a filter paper or 'Guthrie' card. This infras tructure has made it relatively easy for routine screening for other condit ions to be introduced at a district or regional level, resulting in inconsi stent policies and inequitable access to effective screening services. This variation in screening practices reflects uncertainty and the lack of a na tional framework to guide the introduction and evaluation of new screening initiatives, rather than geographical variations in disease prevalence or s everity. More recently developments in tandem mass spectrometry have made i t technically possible to screen for several inborn errors of metabolism in a single analytical step. However, for each of these conditions, evidence is required that the benefits of screening outweigh the harms. How should t hat evidence be obtained? Ideally policy decisions about new screening init iatives should be informed by evidence from randomised controlled trials bu t for most of the conditions for which newborn screening is proposed, large trials would be needed. Prioritising which conditions should be formally e valuated, and developing a framework to support their evaluation, poses an important challenge to the public health, clinical and scientific community . In this chapter, issues underlying the evaluation of newborn screening pr ogrammes will be discussed in relation to medium chain acyl CoA dehydrogena se deficiency, a recessively inherited disorder of fatty acid oxidation.