Current Status of Newborn Screening in Southeastern Europe

Abstract

Significant part of Southeastern Europe (with a population of 76 million) has newborn screening (NBS) programs non-harmonized with developed European countries. Initial survey was conducted in 2013/2014 among 11 countries from the region (Albania, Bulgaria, Bosnia and Herzegovina (BIH), Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, and Slovenia) to assess the main characteristics of their NBS programs and their future plans. Their cumulative population at that time was ~52,5 million. At that time, none of the countries had an expanded NBS program, while phenylketonuria screening was not introduced in four and congenital hypothyroidism in three of 11 countries. We repeated the survey in 2020 inviting the same 11 countries, adding Cyprus, Greece, Hungary, and Malta (due to their geographical position in the wider region). The aims were to assess the current state, to evaluate the change in the period, and to identify the main obstacles impacting the implementation of expanded NBS and/or reaching a wider population. Responses were collected from 12 countries (BIH—Federation of BIH, BIH—Republic of Srpska, Bulgaria, Croatia, Greece, Hungary, Kosovo, North Macedonia, Malta, Montenegro, Romania, Serbia, Slovenia) with a population of 68.5 million. The results of the survey showed that the regional situation regarding NBS only modestly improved in this period. All of the surveyed countries except Kosovo screened for at least congenital hypothyroidism, while phenylketonuria was not screened in four of 12 countries. Croatia and Slovenia implemented an expanded NBS program using tandem mass spectrometry from the time of last survey. In conclusion, the current status of NBS programs in Southeastern Europe is very variable and is still underdeveloped (or even non-existent) in some of the countries. We suggest establishing an international task-force to assist with implementation and harmonization of basic NBS services where needed.

Optimizing the Phenylalanine Cut-Off Value in a Newborn Screening Program

“…Different methods now exist for NBS for PKU worldwide, from enzymatic and bacterial inhibition assays to fluorimetric methods and methods using tandem mass spectrometry (MS/MS) [ 21 ]. Slovenia started the NBS program for PKU in 1979 and used the fluorimetric method since 1992, which is still in use in some Southeastern European countries [ 12 ]. Many NBS globally have Phe cut-off levels set higher than 120 µmol/L—e.g., 38.5% of 65 Latin American laboratories use 180 µmol/L or higher (up to 240 µmol/L) [ 11 ].…”

“…This Phe cut-off value has been in use for almost thirty years and has never been revised. Cut-offs vary significantly among countries [ 6 ]; Slovenia’s is relatively low in comparison to others [ 11 , 12 ], with a high rate of sample recall.…”

Newborn Screening of Primary Carnitine Deficiency: An Overview of Worldwide Practices and Pitfalls to Define an Algorithm before Expansion of Newborn Screening in France

“…Consequently, to minimize false negatives on NBS and to ensure diagnosis of all PCD patients, a nationwide second screening performed at two months of age had been introduced [ 40 ]. In addition, all Scandinavian countries have included PCD to NBS, and few other countries have conducted pilot studies or have already began to screen PCD, such as Portugal or Italy [ 21 , 41 ]. It is to be noted that the UK does not screen PCD, to date, even though in 2009, England had conducted a pilot study of amino acid and acylcarnitines analysis on cord blood samples to identify inborn errors of metabolism [ 42 ].…”

“…Regarding the incidence, the knowledge of this disease’s natural history, and the availability of a safe and efficient treatment, PCD follows consolidated principles for newborn screening [ 16 ], especially as free carnitine (C 0 ) represents an easily measurable biomarker on dried blood spot (DBS) [ 17 ]. New South Wales (Australia) was the first state to evaluate PCD newborn screening in the late 1990s [ 18 ], and this was usually conducted by expanded newborn screening programs deployed since then [ 19 , 20 , 21 ]. Nevertheless, screening of primary carnitine deficiency is not simple, due to various secondary carnitine deficiencies that may generate false-positives (e.g., maternal carnitine deficiency, organic acidurias, pivalic acid-based antibiotherapy, pre-term birth, etc.)…”

Towards Achieving Equity and Innovation in Newborn Screening across Europe

“…Encouragingly, in the countries with existing NBS, the number of diseases screened and the proportion of newborns included has risen steadily. The main obstacles for programme expansion are the lack of financial resources, lack of organisation and staff [ 30 , 31 ]. The complex and diverse situation in this region illustrates the need for a greater collaboration within the NBS community to help improve the situation in some of the less-developed countries of Europe; this might include schemes for exchange of experiences, best-practices, and professionals (e.g., training opportunities).…”