50 years of newborn screening

Abstract

Half a century ago Robert Guthrie published his seminal paper on newborn screening for phenylketonuria. Few of us will remember these early years and the difficulties encountered by Bob and his then few followers. The period was wonderfully summarized by him in the journal Screening in 1992 (volume 1, pages 5–15). From the 1960s to the end of the last century newborn screening progressed steadily with some technical advances and consolidated professional structures. Just before the turn of the century, highly sophisticated high-throughput multiple-analytes platforms (ELISAs, tandemMS, DNA, etc.) were developed and adapted for use in newborn screening. Particularly the applications of tandem mass spectrometry, paralleled by advances in molecular medicine, have now brought screening very much to center stage of scientific, medical and ethical issues. The Joint Meeting of the APHL Newborn Screening and Genetic Testing Symposium and the International Society for Neonatal Screening, held in Atlanta, Georgia, USA in May 2013, combined looking back and drawing from the experience of 50 years with a comprehensive coverage of today s hot topics. This issue of the journal draws on the material presented. The World Health Organisation and the European Community have both identified orphan diseases as a major future health challenge. Among these diseases, inborn errors of metabolism are especially important because of their high morbidity and mortality, high recurrence risk in affected families, and, most importantly, emerging therapeutic options, all leading to the need to identify asymptomatic newborns by newborn screening. The introduction of cost-effective programs is the main focus of developing and third-world countries, while in the developed countries an additional focus is on questions on acceptability, regulations, management, and suitability of individual diseases for newborn screening. The criteria for an acceptable screening program are hotly debated to date, with consolidated different results between most European countries, which in general only consider a limited number of disorders suitable for expanded MS/MS screening, and the USA with its basic recommendations of screening for 30+ conditions with an additional 25+ disorders some of which clearly do not meet the classical screening criteria. These discrepancies do not reflect major differences in genetic backgrounds of populations or estimated prevalences, but rather highlight different approaches to the estimation of risks and benefits for newborn screening, and just lack of evidence. We are still lacking detailed knowledge about the natural course ofmany diseases and their variants, information on middleand long-term outcome after early treatment initiation, and solid data on screening projects in non-Caucasian populations. In addition to the disease panel, the spectrum of metabolites analyzed, the organization of laboratories, analytical procedures, follow-up management, proficiency, and quality control all vary considerably among countries. In addition to state-run programs there is an increasing private, sometimes internationally operating sector with a hodgepodge of disorders and methods on sale. Conferences like that in Atlanta give us the opportunity to further develop international collaboration and to actively G. F. Hoffmann (*) :M. Lindner Department of General Pediatrics, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany e-mail: georg.hoffmann@med.uni-heidelberg.de