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Evaluating newborn screening programmes based on dried blood spots: future challenges
1Department of Epidemiology and Public Health, Institute of Child Health, London, UK.
Insights
Newborn screening programmes for phenylketonuria and congenital hypothyroidism in the UK were based on observational data. Evaluating new screening tests requires robust evidence, ideally from randomized controlled trials, to ensure benefits outweigh harms.
Area of Science:
- Public Health
- Genetics
- Neonatal Medicine
Background:
- UK national screening programmes for phenylketonuria (1969) and congenital hypothyroidism (1981) were established without randomized controlled trials.
- Screening effectiveness has been inferred from national disease registers, leading to inconsistent policies and inequitable access for other conditions.
- Advances in tandem mass spectrometry enable screening for multiple inborn errors of metabolism, necessitating evidence-based evaluation frameworks.
Purpose of the Study:
- To discuss the challenges in evaluating newborn screening programmes.
- To explore the evidence required to justify the expansion of newborn screening.
- To examine the evaluation of medium chain acyl CoA dehydrogenase deficiency screening as a case study.
Main Methods:
- Review of historical UK newborn screening programmes.
- Discussion of evidence-based policy making for screening initiatives.
- Analysis of challenges in conducting randomized controlled trials for rare diseases.
Main Results:
- Historical screening decisions relied on observational data, not randomized controlled trials.
- Current infrastructure allows for expanded screening but lacks a national framework for evaluation.
- Significant challenges exist in generating robust evidence for new screening tests.
Conclusions:
- A national framework is needed to guide the introduction and evaluation of new newborn screening programmes.
- Randomized controlled trials are ideal for evaluating screening benefits versus harms, but often impractical for rare conditions.
- Prioritizing and developing methods for evaluating new screening initiatives is crucial for public health.
Abstract:
A UK national programme to screen all newborn infants for phenylketonuria was introduced in 1969, followed in 1981 by a similar programme for congenital hypothyroidism. Decisions to start these national programmes were informed by evidence from observational studies rather than randomised controlled trials. Subsequently, outcome for affected children has been assessed through national disease registers, from which inferences about the effectiveness 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 infrastructure has made it relatively easy for routine screening for other conditions to be introduced at a district or regional level, resulting in inconsistent policies and inequitable access to effective screening services. This variation in screening practices reflects uncertainty and the lack of a national framework to guide the introduction and evaluation of new screening initiatives, rather than geographical variations in disease prevalence or severity. More recently, developments in tandem mass spectrometry have made it 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 that evidence be obtained? Ideally policy decisions about new screening initiatives should be informed by evidence from randomised controlled trials but for most of the conditions for which newborn screening is proposed, large trials would be needed. Prioritising which conditions should be formally evaluated, 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 programmes will be discussed in relation to medium chain acyl CoA dehydrogenase deficiency, a recessively inherited disorder of fatty acid oxidation.