A framework to start the debate on neonatal screening policies in the EU: an Expert Opinion Document.

The European Union (EU) Council Recommendation on rare diseases urged the member states to implement national and EU collaborative actions to improve the health care of rare disease patients. Following this recommendation, the European Commission launched a tender on newborn screening (NBS) to report on current practices of laboratory testing, form a network of experts and provide guidance on how to further implement NBS screening in a responsible way, the latter of which was provided in an Expert Opinion document. After consultation of experts from EU member states, (potential) candidate member states and European Free Trade Association countries, in a consensus meeting in June 2011, 70 expert opinions were finalized. They included the need to develop case definitions for all disorders screened for to facilitate assessment and international outcome studies. Decision whether a screening program should be performed can be based on screening criteria updated from the traditional Wilson and Jungner (1968) criteria, relating to disease, treatment, test and cost. The interest of the child should be central in the assessment of pros and cons. A European NBS body should assess evidence on (new) screening candidate disorders. For rare conditions, best level evidence should be used. The health system should ensure treatment to cases diagnosed by screening, controlled and revised by follow-up outcome studies. Screening methodology should aim to avoid unintended findings, such as mild forms and carrier status information, as much as possible. Activities to improve NBS in Europe, such as training and scientific evaluation, could benefit from collaboration at EU level and beyond.

Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2. From screening laboratory results to treatment, follow-up and quality assurance.

In a survey conducted in 2010/2011 data from the 28 EU member states, four EU candidate states (Croatia, FYROM, Iceland, Turkey), three potential EU candidate states (Bosnia Herzegovina, Montenegro, Serbia), and two EFTA states (Norway and Switzerland) were collected. The status and function of newborn screening (NBS) programmes were investigated from the information to prospective parents and the public via confirmation of a positive screening result up to decisions on treatment. This article summarises the results from screening laboratory findings to start of treatment. In addition we asked about the existence of feedback loops reporting the conclusions of confirmation of screening results to the screening laboratory and communication of long-term outcome to diagnostic units and possibly existing central registries. Parallel to the description of actual practices of where, how and by whom the different steps of the programmes are executed, we also asked for the existence of guidelines or directives regulating the screening programmes, material to support information of parents about diagnoses and treatment and training facilities for professionals involved in the programmes. This survey gives a first comprehensive overview of the steps following a positive screening result in European NBS programmes. The 37 data sets reveal substantial variation of national screening panels, but also a lot of similarities. Analysis across all countries revealed that actual practice is often organised but not regulated by guidelines. Material to inform patients is available more often for explaining treatment (69 %) than explaining the necessity of confirmatory diagnostics (41 %). Training of professionals is rarely regulated by a guideline (2 %), but is offered for paediatricians (40 %) and dieticians (29 %) and only rarely for other professions (e.g. geneticists, clinical nurse specialists, psychologists). Registry-based evaluation of long-term outcome is as yet almost nonexistent (3 %).

Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1. From blood spot to screening result.

In many European countries neonatal screening has been introduced over the last 50 years as an important public health programme. Depending on health care structure, available funds, local politics, input from professional groups, parent groups, and the general public this introduction has led to different approaches in the way the screening programmes have been set up, financed and governed. To get some insight about the current situation, in 2009 the European Union, via its EAHC agency, put out a call for a tender that was acquired by our project group. An online survey was compiled in which the whole screening programme was covered by a questionnaire. This survey covered the EU member states, (potential) candidate member states and EFTA countries, in total 40 countries. Results showed little consensus concerning 1. information of parents including informed consent; 2. which conditions are screened for, ranging from 1 to around 30 conditions; 3. sampling time post partum; 4. screening methodology including cut-offs values even between screening laboratories within countries.; 5. storage of residual specimens, varying from 3 months to 1000 years. In addition, confirmatory diagnostics and follow-up also show large discrepancies (Burgard et al. http://www.iss.it/cnmr/prog/cont.php?id=1621&lang=1&tipo=64 2011). In addition to the current practices report an expert opinion document has been produced with recommendations to the EU Commission for future improvements, e.g. in parallel to the way the USA has harmonized its practices based on recommendations by the American College of Medical Genetics (Watson et al., Pediatrics 117: S296-S307, 2006).

Computational methods for metabolomic data analysis of ion mobility spectrometry data-reviewing the state of the art.

Ion mobility spectrometry combined with multi-capillary columns (MCC/IMS) is a well known technology for detecting volatile organic compounds (VOCs). We may utilize MCC/IMS for scanning human exhaled air, bacterial colonies or cell lines, for example. Thereby we gain information about the human health status or infection threats. We may further study the metabolic response of living cells to external perturbations. The instrument is comparably cheap, robust and easy to use in every day practice. However, the potential of the MCC/IMS methodology depends on the successful application of computational approaches for analyzing the huge amount of emerging data sets. Here, we will review the state of the art and highlight existing challenges. First, we address methods for raw data handling, data storage and visualization. Afterwards we will introduce de-noising, peak picking and other pre-processing approaches. We will discuss statistical methods for analyzing correlations between peaks and diseases or medical treatment. Finally, we study up-to-date machine learning techniques for identifying robust biomarker molecules that allow classifying patients into healthy and diseased groups. We conclude that MCC/IMS coupled with sophisticated computational methods has the potential to successfully address a broad range of biomedical questions. While we can solve most of the data pre-processing steps satisfactorily, some computational challenges with statistical learning and model validation remain.