[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.

Challenges in screening for congenital hypothyroidism: Optimization of thyrotropin cut-off values.

BACKGROUND-AIM: Different protocols exist for newborn screening of congenital hypothyroidism (CH) worldwide, with different thyrotropin cut-off values for repetition and confirmation tests. This study aimed to assess local protocol in terms of specificity and improve our screening process by optimizing thyrotropin cut-off values. Subsequently, the cut-off values obtained were retrospectively applied to evaluate the number of tests avoided. METHODS: Retrospective observational study between 2013 and 2019. All newborn children with a confirmation test for CH were considered for the study. ROC curve analysis was performed for thyrotropin cut-off value optimization in DBS which triggers a confirmatory test, and odds ratios were calculated. For individuals affected by the cut-off value modification, serum thyrotropin and free thyroxine in the confirmation test were analyzed for consideration of clinical outcomes. RESULTS: A total of 72,133 newborn children were screened for CH, and 208 individuals were included in the study. Incidence in our population was 1:2,000 live births. The area under the ROC curve was 0.819 (CI 95%: 0.748-0.897). While the current cut-off value (thyrotropin ≥ 10mIU/L) had a specificity of 31.8% [ORs: 3.5 (CI 95%: 1.4-8.8)], the optimal cut-off value (thyrotropin ≥ 15mIU/L) yielded a specificity of 92.4% for the detection of CH and transient hypothyroidism [ORs: 15.9 (CI 95%: 7.1-35.8)], with no loss of sensitivity. DISCUSSION: While keeping a maximum sensitivity, optimization of cut-off values may be of great use not only in management, but also in reducing family stress, which is of special relevance for the newborn.

Usefulness of Benedict's test for the screening of galactosemia.

BACKGROUND: Benedict's test for the screening of galactosemia presents a high false-positive rate, which puts into question its usefulness. METHODS: We evaluated the results of Benedict's test as screening strategy for galactosemia, and the patients' definite diagnosis in our hospital in the last 25 years. We also assessed the most prevalent clinical conditions among the false-positive cases. RESULTS: Apart from glycosuria, many non-galactosemic newborns with heart alterations, prematurity, icterus and sepsis usually lead to false-positive results using Benedict's. No false-negative case for Benedict's test was reported in our hospital. CONCLUSIONS: A better approach in terms of cost-effectiveness, sensitivity and specificity is needed for an effective screening of galactosemia.

Histamine intolerance as a cause of chronic digestive complaints in pediatric patients.

INTRODUCTION: histamine intolerance (HI) is a poorly described disease in gastroenterology that may present with predominant digestive complaints. The goals of this study include a report of two cases diagnosed in a pediatric gastroenterology clinic. MATERIAL AND METHODS: observational, retrospective study of patients diagnosed with HI from September 2010 to December 2011 at the pediatric gastroenterology clinic of a tertiary hospital.They were deemed to have a diagnosis of HI in the presence of 2 or more characteristic digestive complaints, decreased diamino oxidase (DAO) levels and/or response to a low histamine diet with negative IgE-mediated food allergy tests. RESULTS: sixteen patients were diagnosed. Males predominated versus females (11/5). Mean age at symptom onset was 4 years (6 months vs. 13 years and 6 months) and mean age at diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months), with an interval of 2 years and 1 month between symptom onset and diagnosis (5 months vs. 4 years). Predominant symptoms included diffuse abdominal pain (16/16), intermittent diarrhea (10/16), headache (5/16), intermittent vomiting (4/16), and skin rash (2/16). The diagnosis was established by measuring plasma diamino oxidase levels, which were below 10 kU/L (normal > 10 kU/L) in 14 cases, and symptom clearance on initiating a low histamine diet. In two patients DAO levels were above 10 kU/L but responded to diet. Treatment was based on a diet low in histamine-contaning food, and antihistamines H1 y H2 had to be added for two cases. CONCLUSIONS: histamine intolerance is a little known disease with a potentially relevant incidence. Predominant complaints include diffuse abdominal pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is based on clinical suspicion, plasma DAO measurement, and response to a low histamine diet. Management with the latter provides immediate improvement.

Intolerancia a la histamina como causa de síntomas digestivos crónicos en pacientes pediátricos / Histamine intolerance as a cause of chronic digestive complaints in pediatric patients

Introducción: la intolerancia a la histamina (IH) es una patología poco descrita en gastroenterología y que puede tener una sintomatología digestiva predominante. Los objetivos de este estudio son describir los casos diagnosticados en una consulta de gastroenterología pediátrica. Material y métodos: estudio observacional y retrospectivo analizando los pacientes diagnosticados de IH desde septiembre de 2010 a diciembre de 2011 en la consulta de gastroenterología pediátrica de un hospital terciario. Se consideraron con diagnóstico de IH al presentar 2 o más síntomas digestivos característicos, determinación de diaminooxidasa disminuida y/o respuesta a la dieta baja en histamina con pruebas de alergia IgE-mediada a alimentos negativos. Resultados: se han diagnosticado 16 pacientes. Hubo un predominio de niños (11/5) frente a las niñas. La edad media al inicio de los síntomas fue de 4 años (6 meses vs. 13 años y 6 meses) y la edad media al diagnóstico fue de 6 años y 6 meses (17 meses vs. 13 años y 11 meses). Los síntomas predominantes fueron dolor abdominal difuso (16/16), diarrea intermitente (10/16), cefalea (5/16) y vómitos intermitentes (4/16). Conclusiones: la intolerancia a la histamina es una patología poco conocida pero con una incidencia que puede ser relevante. Los síntomas predominantes son dolor abdominal difuso, diarrea, cefalea y vómitos de aparición crónica e intermitente. El diagnóstico se realiza por sospecha clínica, determinación de diaminooxidasa plasmática y respuesta a dieta baja en histamina. Con el tratamiento de dieta baja en histamina presentan una mejoría inmediata (AU)

Introduction: histamine intolerance (HI) is a poorly described disease in gastroenterology that may present with predominant digestive complaints. The goals of this study include a report of two cases diagnosed in a pediatric gastroenterology clinic. Material and methods: observational, retrospective study of patients diagnosed with HI from September 2010 to December 2011 at the pediatric gastroenterology clinic of a tertiary hospital. They were deemed to have a diagnosis of HI in the presence of 2 or more characteristic digestive complaints, decreased diamino oxidase (DAO) levels and/or response to a low histamine diet with negative IgE-mediated food allergy tests. Results: sixteen patients were diagnosed. Males predominated versus females (11/5). Mean age at symptom onset was 4 years (6 months vs. 13 years and 6 months) and mean age at diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months), with an interval of 2 years and 1 month between symptom onset and diagnosis (5 months vs. 4 years). Predominant symptoms included diffuse abdominal pain (16/16), intermittent diarrhea (10/16), headache (5/16), intermittent vomiting (4/16), and skin rash (2/16). The diagnosis was established by measuring plasma diamino oxidase levels, which were below 10 kU/L (normal > 10 kU/L) in 14 cases, and symptom clearance on initiating a low histamine diet. In two patients DAO levels were above 10 kU/L but responded to diet. Treatment was based on a diet low in histamine-contaning food, and antihistamines H1 y H2 had to be added for two cases. Conclusions: histamine intolerance is a little known disease with a potentially relevant incidence. Predominant complaints include diffuse abdominal pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is based on clinical suspicion, plasma DAO measurement, and response to a low histamine diet. Management with the latter provides immediate improvement (AU)