Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Abstract

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders (“conditions”) then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40–50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.

Current Status of Newborn Screening in Southeastern Europe

“…The only European countries without screening for PKU (Montenegro) and screening for CH (Moldova) are a part of SE Europe. NBS in some form is now present in every European country, except in Albania, Kosovo and Tajikistan (20).…”

“…While several SE European countries reported plans for implementing CF in NBS, it was only available as a part of selective screening in some hospitals in North Macedonia at the time of our study (Table 2). Some regions in Italy and the Netherlands started screening for LSD, but they are not a regular part of other NBS programs in Europe (20). Screening for multiple LSD using MS/MS was considered economically justifiable in Hungary in 2012 due to cumulative frequency of LSD similar to acylcarnitine and amino acid IEMs (27).…”

“…Modern technologies, such as NGS, were already implemented for CF screening and as a second-tier test in Norway, while the UK conducted a trial of its use as a part of screening algorithm for CF (20,28,29). Croatia reported plans for introducing the method as a second-tier as well and Slovenia used it in the pilot study before expanding the NBS in 2018 (5,20).…”

“…Modern technologies, such as NGS, were already implemented for CF screening and as a second-tier test in Norway, while the UK conducted a trial of its use as a part of screening algorithm for CF (20,28,29). Croatia reported plans for introducing the method as a second-tier as well and Slovenia used it in the pilot study before expanding the NBS in 2018 (5,20). A survey conducted in 2017 in Bulgaria on potential use of whole-genome sequencing (WGS) in conjunction with the traditional NBS showed that Bulgarian pediatricians and geneticists believed that selective WGS could strengthen their current NBS programs while non-selective WGS for all newborns was not perceived as feasible at that time (30).…”

Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: High Incidence of Detected Patients With Expanded Newborn Screening Program

“…MCADD is the most common inborn error of fatty acid metabolism, with an incidence estimated at 1 in 15,000 live births (Orphanet, 2020: Mediumchain acyl CoA dehydrogenase deficiency; Grosse et al, 2006;Lindner et al, 2010), and our results are in agreement with that. In Southeastern Europe there is currently no NBS for VLCADD in a majority of the countries with exception of Slovenia and Croatia (Groselj et al, 2014a(Groselj et al, ,b, Šmon et al, 2015Bilandžija et al, 2018;Smon et al, 2018;Lampret et al, 2020;Loeber et al, 2021), which would detect more patients than are diagnosed clinically. To the best of our knowledge, only two adult patients with VLCADD were described so far in Southeastern Europe (Fatehi et al, 2020).…”