[Beginnings, evolution and current situation of the Newborn Screening Programs in Spain.] / Inicio, evolución y situación actual de los Programas de Cribado Neonatal en España.

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

Los Programas de Cribado Neonatal (PCN) nacen en España en Granada en el año 1968. Posteriormente, y hasta los años 80, se fueron desarrollando en torno al llamado "Plan Nacional de Prevención de la Subnormalidad" con una cobertura cercana al 30% de los recién nacidos españoles. A partir de 1982, con el inicio de la gestión de la sanidad a las comunidades autónomas (CCAA), los PCN se expandieron y se comenzaron a sentar las bases para que éstos se convirtieran en una actividad organizada y multidisciplinar, integrados y coordinados desde el Sistema de Salud. A pesar de dicha expansión no es hasta el inicio de la década de los 90 cuando se consigue una cobertura próxima al 100% de los RN en España. Los PCN fueron creciendo de forma muy asimétrica en las diferentes CCAA y en los años 2005 y 2006 las Sociedades Científicas SEQC (Sociedad Española de Química Clínica) y AECNE (Asociación Española de Cribado Neonatal), con la coordinación del Área de Promoción de la Salud de la Dirección General de Salud Pública, recopilaron la información y elaboraron un informe, sobre los PCN en España para el Consejo Interterritorial del sistema Nacional de Salud (CISNS). En julio de 2013 este Consejo aprobó las siete enfermedades que debían formar parte del panel de detección de los PCN territoriales, primer paso hacia la armonización de estos programas. Actualmente, los PCN incluyen entre 8 y 29 enfermedades por lo que es necesario seguir trabajando para conseguir una mayor uniformidad.

Criterios de extracción de muestra en situaciones especiales del cribado neonatal. Revisión / Criteria for specimen collection in special situations of newborn screening. Review

La espectrometría de masas en tándem (MS-MS) ha permitido ampliar el alcance del cribado neonatal. Eso hace más complicado determinar el momento más adecuado para la toma de muestra, sobre todo en recién nacidos prematuros y/o bajo peso y/o ingresados en unidades neonatales. El objetivo del presente estudio ha sido revisar las normas de toma de muestra de los distintos programas en estas situaciones, a nivel nacional e internacional. Se obtienen los datos a través de páginas web de salud pública, de plataformas de búsqueda o por contacto con los centros. Existe gran disparidad de criterios para la toma de una nueva muestra, incluso dentro de un mismo país. La limitación de información disponible, hizo imposible obtener resultados de muchos países, en particular de África, Asia o Latinoamérica. A pesar de que cada vez más estados se acogen a las recomendaciones del Clinical and Laboratory Standards Institute u otros organismos internacionales, el aumento del coste que implica, hace muy difícil conseguir la estandarización

The most significant breakthrough in the newborn screening (NBS) programs was the introduction of the tandem mass spectrometry (MS-MS) to the laboratory, which makes it possible to detect multiple disorders. However, it is difficult to choose the ideal time for the specimen collection, particularly in preterm, low birth weight, and sick newborns. The aim of this study was to revise the protocols, in national and international programs for specimen collection in these newborns. Data were collected from web pages of public health, internet searches, and contact with the laboratories. The results showed a great disparity in criteria for a new specimen collection, as well as among different centres within a country. It has been difficult to obtain this information from many countries in Africa, Asia, and Latin America. Although an increasing number of laboratories follow the recommendations of the Clinical and Laboratory Standards Institute or other international guidelines, the increased cost involved makes standardisation difficult

Resultados del programa de screening neonatal de fibrosis quística en Andalucía tras 5 años de su implantación / Results of the Andalusian Cystic Fibrosis Neonatal Screening Program, 5 Years After Implementation

Introducción: Andalucía dispone de screening neonatal de fibrosis quística (SNFQ) desde mayo 2011, basado en doble determinación de tripsinógeno inmunorreactivo ([TIR] [TIR1/TIR2]). Si el screening es positivo realizamos un test del sudor y si es positivo o dudoso solicitamos genética. Objetivo: Analizar el SNFQ, basado en los resultados de los primeros 4,5 años. Material y método: Estudio descriptivo prospectivo de los neonatos sometidos a SNFQ. Se recogen los niveles de TIR, cloruro en sudor, mutaciones. Mediante SPSS12.0 se realizó análisis estadístico. Resultados: Desde mayo 2011 a diciembre 2016, 474.953 neonatos fueron sometidos a SNFQ. Mil ochenta y siete (0,23%) presentaron TIR2 elevado. Desde la implantación del SNFQ se diagnosticaron 73 casos con fibrosis quística; 60 de ellos fueron diagnosticados mediante un SNFQ positivo, mientras que 13 no. Concretamente un paciente comenzó con clínica clásica de fibrosis quística y se comprobó que no se había realizado el SNFQ por decisión paterna; los 12 restantes tuvieron un SNFQ negativo (falsos negativos). De estos, un paciente fue diagnosticado presintomáticamente al tener su hermano gemelo con SNFQ positivo; otro con cloruro en el límite alto de la normalidad se diagnosticó presintomáticamente mediante genética; 10 pacientes comenzaron clínicamente. Excluyendo los pacientes con íleo meconial, la sensibilidad y especificidad del programa de SNFQ asciende al 85,71 y 99,78% respectivamente. La incidencia de la enfermedad en Andalucía es de 1/6.506 recién nacidos vivos. Conclusión: Los presentes resultados nos permiten reflexionar sobre posibles áreas de mejoras adicionales del algoritmo del SNFQ, que debe pasar por la introducción de estudios genéticos para así aumentar la sensibilidad y disminuir los falsos positivos

Introduction: Cystic fibrosis neonatal screening (CFNS), based on double determination of immunoreactive trypsinogen ([IRT] [IRT1/IRT2]), has been available in Andalusia since May 2011. If screening is positive, a sweat test is performed, and if that is positive or inconclusive, genetic testing is requested. Objective: To analyze CFNS, based on results from the first 4.5 years of the program. Materials and methods: Prospective descriptive study of neonates undergoing CFNS. IRT levels, sweat chloride, and mutations were recorded. Statistical analysis was performed using SPSS 12.0. Results: Between May 2011 and December 2016, 474,953 neonates underwent CFNS. Of these, 1,087 (0.23%) had elevated IRT2. Since CFNS was introduced, 73 cases of cystic fibrosis were diagnosed; 60 were diagnosed by positive CFNS, and 13 were diagnosed by other means. In one case, the patient developed a typical clinical picture of cystic fibrosis, but had not undergone CFNS at the decision of the parents; the remaining 12 had a negative CFNS (false negatives). Of these, one patient was diagnosed before symptoms developed, as his twin brother had a positive CFNS result; another had chloride at the upper limit of normal, and was subsequently diagnosed with genetic testing before symptoms appeared; and 10 patients developed clinical signs and symptoms. Excluding patients with meconium ileus, sensitivity and specificity of the CFNS program were 85.71% and 99.78%, respectively. The incidence of the disease in Andalusia is 1/6,506 live births. Conclusion: These results are a basis for reflection on possible areas for improvement of the CFNS algorithm, and thought may be given to the introduction of genetic studies to increase sensitivity and reduce false positives

Results of the Andalusian Cystic Fibrosis Neonatal Screening Program, 5 Years After Implementation. / Resultados del programa de screening neonatal de fibrosis quística en Andalucía tras 5 años de su implantación.

INTRODUCTION: Cystic fibrosis neonatal screening (CFNS), based on double determination of immunoreactive trypsinogen ([IRT] [IRT1/IRT2]), has been available in Andalusia since May 2011. If screening is positive, a sweat test is performed, and if that is positive or inconclusive, genetic testing is requested. OBJECTIVE: To analyze CFNS, based on results from the first 4.5 years of the program. MATERIALS AND METHODS: Prospective descriptive study of neonates undergoing CFNS. IRT levels, sweat chloride, and mutations were recorded. Statistical analysis was performed using SPSS 12.0. RESULTS: Between May 2011 and December 2016, 474,953 neonates underwent CFNS. Of these, 1,087 (0.23%) had elevated IRT2. Since CFNS was introduced, 73 cases of cystic fibrosis were diagnosed; 60 were diagnosed by positive CFNS, and 13 were diagnosed by other means. In one case, the patient developed a typical clinical picture of cystic fibrosis, but had not undergone CFNS at the decision of the parents; the remaining 12 had a negative CFNS (false negatives). Of these, one patient was diagnosed before symptoms developed, as his twin brother had a positive CFNS result; another had chloride at the upper limit of normal, and was subsequently diagnosed with genetic testing before symptoms appeared; and 10 patients developed clinical signs and symptoms. Excluding patients with meconium ileus, sensitivity and specificity of the CFNS program were 85.71% and 99.78%, respectively. The incidence of the disease in Andalusia is 1/6,506 live births. CONCLUSION: These results are a basis for reflection on possible areas for improvement of the CFNS algorithm, and thought may be given to the introduction of genetic studies to increase sensitivity and reduce false positives.