El papel de la salud publica como clave del éxito del programa de cribado neonatal en el País Vasco

Neonatal Screening Programs (PCN) have widely demonstrated their benefits since Dr. Guthrie published his developments on Phenylketonuria (PKU) in 1961. This paper describes how a simple and effective organization, which incorporates all the fundamental actors under the responsibility of the Public Health Directorate (DSP), has managed to ensure that the PCN of the Basque Country meets all the objectives required for a population screening. The acceptance by Basque society of the PCN allowed it to exceed 95% coverage in its second year of operation. Likewise, the limited negative social impact of PCN is evidenced by its low number of false positives and incorrect samples. Excellent response times allow every newborn with a positive result to have an early diagnosis and optimal initiation of treatment. There are two relevant experiences that support the importance of the effective exercise of the responsibility of the DSP. Congenital adrenal hyperplasia (CAH) was incorporated into the PCN in 1991 meeting all technical and clinical criteria. At the request of the experts, the DSP ordered in 1993 to cease this activity showing that it did not provide the expected benefits. The problems of organically integrating the PCN into the healthcare system were also experienced. The need to compete for resources put public health activities, including the PCN, at risk and led to their return to direct dependence on the DSP. The availability of this structure, in addition to facilitating the incorporation of other screenings, allows facing the future challenges.Los Programas de Cribado Neonatal (PCN) han demostrado ampliamente sus beneficios desde que en 1961 el Dr. Guthrie publicó sus trabajos sobre Fenilcetonuria (PKU). En este trabajo se describe cómo una organización sencilla y eficaz, que incorpora a todos los actores fundamentales bajo la responsabilidad de la Dirección de Salud Pública (DSP), ha conseguido que el PCN del País Vasco cumpla con todos los objetivos exigibles a un cribado poblacional. La aceptación por la sociedad vasca del PCN permitió superar el 95% de cobertura en su segundo año de funcionamiento. Asimismo, el limitado impacto social negativo del PCN se evidencia por su reducido número de falsos positivos y de muestras incorrectas. Los excelentes tiempos de respuesta permiten que todo recién nacido con resultado positivo disponga de un diagnóstico temprano y de un inicio óptimo del tratamiento. Hay dos experiencias relevantes que avalan la importancia del ejercicio eficaz de la responsabilidad de la DSP. La hiperplasia adrenal congénita (HAC) se incorporó en 1991 al PCN, cumpliendo con todos los criterios técnicos y clínicos. A petición de los expertos, la DSP ordenó en 1993 cesar esta actividad al evidenciar que no aportaba los beneficios esperados. También se experimentaron los problemas de integrar orgánicamente el PCN en el sistema asistencial. La necesidad de competir por los recursos puso en riesgo las actividades de Salud Pública, incluyendo el PCN, lo que provocó su retorno a la dependencia directa de la DSP. La disponibilidad de esta estructura, además de facilitar la incorporación de otros cribados, permite afrontar los retos del futuro

Maternal circulating Vitamin D3 levels during pregnancy and behaviour across childhood

Vitamin D deficiency during critical periods of development could lead to persistent brain alterations. We aimed to assess the association between maternal vitamin D3, the major circulatory form of vitamin D, at pregnancy and neurodevelopmental outcomes during childhood, namely: behavioural problems, Attention Deficit and Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) symptoms, and social competence. This study included 2,107 mother-child pairs of a Spanish population-based birth cohort. Maternal plasma vitamin D3 was measured in pregnancy. The outcomes were measured through questionnaires at 5, 8, 14, and 18 years old. We ran multivariate regression models adjusted for potential confounding variables. We found that per each 10 ng/mL increment of maternal vitamin D3, children obtained higher social competence scores (coefficient = 0.77; 95% CI = 0.19, 1.35) at 5 years old. However, we observed null associations between maternal vitamin D3 and total behavioural problems and ADHD and ASD symptoms in children from 5 to 18 years old. Further studies carried out in countries where the population is exposed to lower vitamin D levels are needed.We thank all the investigators who have collected information and samples from the participants. Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2; PI061756; PS0901958; PI14/00677 incl. FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfermedades Neurodegenerativas de La Caixa, and EC Contract No. QLK4-CT-2000-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; CPII/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, Fundació La marató de TV3 (090430), EU Commission (261357). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Valencia: This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, and MSII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017. Asturias: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), FIS-PI042018, FIS-PI09/02311, FIS-PI13/02429, FIS-PI18/00909, CIBERESP, Obra Social Cajastur/Fundación Liberbank and UNIVERSIDAD DE OVIEDO. Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090 and FIS-PI13/02187), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain)

Determinants of self-reported smoking and misclassification during pregnancy, and analysis of optimal cut-off points for urinary cotinine: a cross-sectional study

10 p.Objectives: To estimate the prevalence and factors associated with smoking and misclassification in pregnant women from INMA (INfancia y Medio Ambiente, Environment and Childhood) project, Spain, and to assess the optimal cut-offs for urinary cotinine (UC) that best distinguish daily and occasional smokers with varying levels of second-hand smoke (SHS) exposure.-- Design: We used logistic regression models to study the relationship between sociodemographic variables and self-reported smoking and misclassification (self-reported non-smokers with UC >50 ng/ml). Receiver operating characteristic (ROC) curves were used to calculate the optimal cut-off point for discriminating smokers. The cut-offs were also calculated after stratification among non-smokers by the number of sources of SHS exposure. The cut-off points used to discriminate smoking status were the level of UC given by Youden's index and for 50 and 100 ng/ml for daily smokers, or 25 and 50 ng/ml for occasional smokers. -- Participants: At the third trimester of pregnancy, 2263 pregnant women of the INMA Project were interviewed between 2004 and 2008 and a urine sample was collected. -- Results: Prevalence of self-reported smokers at the third trimester of pregnancy was 18.5%, and another 3.9% misreported their smoking status. Variables associated with self-reported smoking and misreporting were similar, including born in Europe, educational level and exposure to SHS. The optimal cut-off was 82 ng/ml (95% CI 42 to 133), sensitivity 95.2% and specificity 96.6%. The area under the ROC curve was 0.986 (95% CI 0.982 to 0.990). The cut-offs varied according to the SHS exposure level being 42 (95% CI 27 to 57), 82 (95% CI 46 to 136) and 106 ng/ml (95% CI 58 to 227) for not being SHS exposed, exposed to one, and to two or more sources of SHS, respectively. The optimal cut-off for discriminating occasional smokers from non-smokers was 27 ng/ml (95% CI 11 to 43). -- Conclusions: Prevalence of smoking during pregnancy in Spain remains high. UC is a reliable biomarker for classifying pregnant women according to their smoking status. However, cut-offs would differ based on baseline exposure to SHS.The INMA project is funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041) and Fundación Roger Torné. The studies in the specific regions were funded by the Spanish Ministry of Health (FIS 03/1615, 04/1436, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/0867,06/1213, 07/0314, 08/1151, 09/02647, 04/2018, 09/02311), the Generalitat de Catalunya (CIRIT 1999SGR00241), the Diputación Foral de Gipuzkoa (DFG06/004), the Department of Health of the Basque Government (2005111093), the Regional Government of Andalucía (SAS 07/183), Obra social Cajastur, University of Oviedo and the Conselleria de Sanitat Generalitat Valenciana. http://www.proyectoinma.org/instituciones-participantes/en_entidades-colaboradoras/

Maternal circulating Vitamin D3 levels during pregnancy and behaviour across childhood

Vitamin D deficiency during critical periods of development could lead to persistent brain alterations. We aimed to assess the association between maternal vitamin D3, the major circulatory form of vitamin D, at pregnancy and neurodevelopmental outcomes during childhood, namely: behavioural problems, Attention Deficit and Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) symptoms, and social competence. This study included 2,107 mother-child pairs of a Spanish population-based birth cohort. Maternal plasma vitamin D3 was measured in pregnancy. The outcomes were measured through questionnaires at 5, 8, 14, and 18 years old. We ran multivariate regression models adjusted for potential confounding variables. We found that per each 10 ng/mL increment of maternal vitamin D3, children obtained higher social competence scores (coefficient = 0.77; 95% CI = 0.19, 1.35) at 5 years old. However, we observed null associations between maternal vitamin D3 and total behavioural problems and ADHD and ASD symptoms in children from 5 to 18 years old. Further studies carried out in countries where the population is exposed to lower vitamin D levels are needed.We thank all the investigators who have collected information and samples from the participants. Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2; PI061756; PS0901958; PI14/00677 incl. FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfermedades Neurodegenerativas de La Caixa, and EC Contract No. QLK4-CT-2000-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; CPII/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, Fundació La marató de TV3 (090430), EU Commission (261357). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Valencia: This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, and MSII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017. Asturias: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), FIS-PI042018, FIS-PI09/02311, FIS-PI13/02429, FIS-PI18/00909, CIBERESP, Obra Social Cajastur/Fundación Liberbank and UNIVERSIDAD DE OVIEDO. Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090 and FIS-PI13/02187), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain)

Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data

Context: Low maternal free T4 (FT4) has been associated with poor child neurodevelopment in some single-center studies. Evidence remains scarce for the potential adverse effects of high FT4 and whether associations differ in countries with different iodine status. Objective: To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status. Design, Setting, and Participants: Meta-analysis of individual participant data from 9036 mother–child pairs from three prospective population-based birth cohorts: INMA [Infancia y Medio Ambiente (Environment and Childhood project) (Spain)], Generation R (Netherlands), and ALSPAC (Avon Longitudinal Study of Parents and Children, United Kingdom). The exclusion criteria were multiple pregnancies, fertility treatments, thyroid-interfering medication usage, and known thyroid disease. Main Outcomes: Child nonverbal IQ at 5 to 8 years of age, verbal IQ at 1.5 to 8 years of age, and autistic traits within the clinical range at 5 to 8 years of age. Results: FT4 97.5th percentile was associated with a 1.9-fold (95% CI, 1.0 to 3.4) greater risk of autistic traits. No independent associations were found with TSH. Conclusions: Low maternal FT4 was consistently associated with a lower IQ across the cohorts. Further studies are needed to replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay.EUthyroid Project: European Union’s Horizon 2020 research and innovation programme (grant 634453). INMA, Spain: This study was funded by grants from the European Union (grants FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1) and Spain: Instituto de Salud Carlos III (grants Red INMA G03/176, CB06/02/0041, FIS-FEDER: PI041436, PI05/1079, PI06/0867, PI081151, FIS- and PS09/00090, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, and PI16/1288, Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051, MS13/00054), Generalitat Valenciana: FISABIO (grants UGP 15-230, UGP-15-244, and UGP-15-249), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La Marató de TV3 (grants 090430), Department of Health of the Basque Government (grants 2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (grants DFG06/004 and DFG08/001)

Métodos para la evaluación económica de programas de cribado neonatal

Newborn screening programs are a fundamental tool for secondary prevention or pre-symptomatic detection of certain conditions. The implementation of a newborn screening program requires an evaluation of effectiveness, safety, cost-effectiveness, feasibility and budget impact. Economic evaluation aims to contribute to the sustainability and solvency of health systems, especially when it comes to informing about financing health interventions with public funds. This funding must be justified on the basis of robust evidence of effectiveness, safety, cost-effectiveness, and acceptability. One of the most important limitations when evaluating the cost-effectiveness of a newborn screening program for hereditary disorders or congenital errors of metabolism is the scarcity of scientific evidence that limits the robustness of the economic analysis. Given the low availability of data, the use of expert opinion as a data source is unavoidable to complete the information. However, two main problems make it difficult to synthesize data obtained from various sources: biases and heterogeneity. Moreover, the measurement of quality-adjusted life years (QALYs) in pediatric populations poses serious methodological challenges. In Spain, although there is some heterogeneity in the supply of newborn screening programs between regions, guidelines are being established based on the best available scientific evidence to achieve the homogenization of newborn screening policies and programs at national level.Los programas de cribado neonatal son una herramienta fundamental para la prevención secundaria o detección presintomática de determinadas afecciones. La implantación de un programa de cribado neonatal requiere necesariamente de una evaluación de su efectividad, seguridad, coste-efectividad, factibilidad e impacto presupuestario. La evaluación económica pretende contribuir a la sostenibilidad y solvencia de los sistemas sanitarios, especialmente a la hora de informar sobre la posible financiación, con fondos públicos, de intervenciones sanitarias como el cribado poblacional. Esta financiación debe justificarse en base a pruebas robustas de efectividad, seguridad, coste-efectividad y aceptabilidad. Una de las limitaciones más importantes a la hora de evaluar el costeefectividad de un programa de cribado neonatal de trastornos hereditarios o de errores congénitos del metabolismo es la escasez de evidencia científica que limita la solidez y robustez del análisis de evaluación económica. Dada la baja disponibilidad de datos, el uso de la opinión de expertos como fuente de datos es inevitable para completar la información necesaria. Sin embargo, dos problemas principales dificultan la síntesis de datos obtenidos de varias fuentes: sesgos y heterogeneidad. Por otro lado, la medición de los años de vida ajustados por calidad (AVAC) en poblaciones pediátricas plantea serios desafíos metodológicos en un análisis de evaluación económica. En España, aunque existe cierta heterogeneidad en la oferta de programas de cribado neonatal entre CC.AA., se están estableciendo directrices basadas en la mejor evidencia científica disponible para conseguir la homogeneización de políticas y programas de cribado neonatal a nivel nacional