The evolution of blood-spot newborn screening

Abstract

Over 50 years after the introduction of a blood-spot newborn screening test using the bacterial-inhibition assay (BIA), blood-spot newborn screening has evolved into complex public service scientific programmes. For several decades, many patients with phenylketonuria (PKU), congenital hypothyroidism (CH), cystic fibrosis (CF) and hemoglobinopathy disorders have benefited from early intervention across the world. In the last 20 years, there have been great changes in laboratory techniques and high-throughput data handling meaning that a huge spectrum of disorders can be identified from an increasing population. This coupled with the fact that there are an increasing number of therapies for specific rare disorders mean that health services may become inundated with complex and expensive demands in the future. Some of these issues have been realised in the implementation of multiplex assay such as electrospray tandem mass spectrometry (MSMS) programmes but will be much more exaggerated if genomic sequencing screening becomes a reality. In this context, the core-principles for implementation of newborn screening tests remain as important today as they have in the past when new tests are considered as part of the blood-spot screening programme.

Keywords: Neonatal screening; congenital hypothyroidism (CH); cystic fibrosis (CF); massively parallel sequencing (MPS); phenylketonuria (PKU); tandem mass spectrometry (MSMS).

Figure 1

Agar plate indicating BIA for PKU. The top line indicates control samples with increasing phenylalanine concentrations. One affected individual with PKU is identified at the centre of this gel. PKU, phenylketonuria; BIA, bacterial inhibition assay.

Figure 2

MSMS spectrum of amino acids. (A) MSUD—indicating elevated total leucines at position 188; (B) Elevated phenylalanine at position 222. MSMS, tandem mass spectrometry.