Consensus document on the primary prevention of cow's milk protein allergy in infants aged less than 7 days.

INTRODUCTION: Cow's milk protein allergy (CMPA) is the most frequent food allergy in the first year of life. There is no clear consensus regarding its prevention. A recommendation to avoid CMP in the first week of life as a preventive measure in all infants, regardless of their atopic risk, has recently been published. The purpose of this document is to issue a recommendation on the use of extensively hydrolyzed CMP formulas in the first week of life for the primary prevention of CMPA. METHODS: A group of experts was formed with members proposed by the Spanish Association of Pediatrics (AEP), the Spanish Society of Clinical Immunology and Allergology and Pediatric Asthma (SEICAAP), the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) and the Spanish Society of Neonatology (SENEO). The group conducted a critical review of the evidence on the subject published in the last 10 years. RESULTS: The search yielded 72 studies, of which 66 were rejected for not meeting the inclusion criteria. The final review included 6 documents: 3 clinical trials and 3 systematic reviews, 2 of them with meta-analysis. There was no evidence of a statistically significant reduction in the incidence of CMPA in the infants who received hypoallergenic formulae or exclusive breastfeeding. CONCLUSION: Based on the current evidence, it is not possible to draw clear conclusions about the effect of avoiding CMP in the first week of life for prevention of CMPA. Although there are data that suggest a certain beneficial effect of avoiding CMPA in atopic risk infants, these results are not conclusive enough to extend the recommendation to the general population.

Documento de consenso en la prevención primaria de alergia a proteínas de leche de vaca en lactantes menores de 7 días de vida / Consensus document on the primary prevention of cow's milk protein allergy in infants aged less than 7days

Introducción: La alergia a las proteínas de la leche de vaca (APLV) es la alergia alimentaria más frecuente en el primer año de vida. No existe un consenso claro respecto a su prevención. Recientemente se ha publicado la recomendación de evitar estas proteínas en la primera semana de vida como medida de prevención en todos los niños, con independencia de su riesgo atópico. El objetivo de este documento es emitir una recomendación sobre el uso de fórmulas extensamente hidrolizadas de PLV en la primera semana de vida para la prevención primaria de la APLV. Métodos: Se constituyó un grupo de expertos propuestos por la Asociación Española de Pediatría (AEP), la Sociedad Española de Inmunología Clínica y Alergología y Asma Pediátrica (SEICAAP), la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) y la Sociedad Española de Neonatología (SENEO). Se realizó una revisión crítica de la evidencia publicada en los últimos 10 años sobre el tema. Resultados: Se seleccionaron 72 estudios, de los cuales 66 fueron rechazados por no cumplir los criterios de inclusión. Se incluyeron en la revisión 6 documentos: 3 ensayos clínicos y 3 revisiones sistemáticas, 2de ellas con metaanálisis. No se observó una reducción estadísticamente significativa en la incidencia de APLV en los grupos de lactantes que recibieron fórmulas hipoalergénicas ni lactancia materna exclusiva. Conclusión: Con base en las evidencias existentes en la actualidad, no se pueden establecer conclusiones claras acerca del efecto de evitar las PLV durante la primera semana de vida en la prevención de la APLV. A pesar de existir datos que pudieran orientar a un cierto efecto beneficioso de su evitación en niños con riesgo atópico, estos resultados no son concluyentes ni generalizables a lactantes sin dicho riesgo. (AU)

Introduction: Cow's milk protein allergy (CMPA) is the most frequent food allergy in the first year of life. There is no clear consensus regarding its prevention. A recommendation to avoid CMP in the first week of life as a preventive measure in all infants, regardless of their atopic risk, has recently been published. The purpose of this document is to issue a recommendation on the use of extensively hydrolyzed CMP formulas in the first week of life for the primary prevention of CMPA. Methods: A group of experts was formed with members proposed by the Spanish Association of Pediatrics (AEP), the Spanish Society of Clinical Immunology and Allergology and Pediatric Asthma (SEICAAP), the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) and the Spanish Society of Neonatology (SENEO). The group conducted a critical review of the evidence on the subject published in the last 10 years. Results: The search yielded 72 studies, of which 66 were rejected for not meeting the inclusion criteria. The final review included 6 documents: 3 clinical trials and 3 systematic reviews, 2 of them with meta-analysis. There was no evidence of a statistically significant reduction in the incidence of CMPA in the infants who received hypoallergenic formulae or exclusive breastfeeding. Conclusion: Based on the current evidence, it is not possible to draw clear conclusions about the effect of avoiding CMP in the first week of life for prevention of CMPA. Although there are data that suggest a certain beneficial effect of avoiding CMPA in atopic risk infants, these results are not conclusive enough to extend the recommendation to the general population. (AU)

Neurologic Complications in Pediatric Allogeneic Stem Cell Transplantation: Analysis of Risk Factors and Outcome.

Neurologic complications following stem cell transplantation are of utmost importance owing to their high morbimortality. Although many studies have been performed in the adult population, reports in children are scarce. Our objective was to determine the most common neurologic complications in a pediatric population and to analyze possible risk factors for their development. We performed an exploratory retrospective study of neurologic complications in pediatric patients who had allogeneic stem cell transplantation over the last 18 years. We identified 66 neurologic complications in 178 allogeneic stem cell transplantations. The most frequent neurologic complications were those involving the peripheral nervous system and those related to drug toxicity. Survival decreased significantly in the presence of neurologic complications. Multivariate logistic regression analysis showed that independent risk factors for developing neurologic complications were development of chronic extensive graft-vs-host disease requiring treatment, cytomegalovirus reactivation, and central nervous system radiation. Prompt diagnosis and preemptive treatment, if possible, are necessary to avoid long-term sequelae or mortality.

Cryopreservation of unrelated donor hematopoietic stem cells: the right answer for transplantations during the COVID-19 pandemic?

Cryopreservation was recommended to ensure continuity of unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) during COVID-19 pandemic. However, its impact on clinical outcomes and feasibility was not well known. We compared 32 patients who underwent UD HSCT using cryopreserved peripheral blood stem cells (PBSC) during the COVID-19 pandemic with 32 patients who underwent UD HSCT using fresh PBSC in the previous period. Median neutrophil engraftment was 17.5 and 17.0 days with cryopreserved and fresh grafts, respectively. Non-significant delays were found in platelet recovery days (25.5 versus 19.0; P = 0.192) and full donor chimerism days (35.0 and 31.5; P = 0.872) using cryopreserved PBSC. The rate of acute graft-versus-host disease at 100 days was 41% (95% CI [21-55%]) in cryopreserved group versus 31% (95% CI [13-46%]) in fresh group (P = 0.380). One-hundred days progression-relapse free survival and overall survival did not differ significantly. During COVID-19 pandemic, six frozen UD donations were not transfused and logistical and clinical issues regarding cryopreservation procedure, packaging, and transporting appeared. In summary, UD HSCT with cryopreserved PBSC was safe during this challenging time. More efforts are needed to ensure that all frozen grafts are transplanted and cryopreservation requirements are harmonized.

The Spectrum of COVID-19 Disease in Adolescents / El espectro de la COVID-19 en adolescentes

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Risk factors and outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). CONCLUSIONS: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (µg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 µg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.

Energy Dense Salty Food Consumption Frequency Is Associated with Diastolic Hypertension in Spanish Children.

High blood pressure (BP) is a risk factor for cardiovascular disease and sodium consumption is related to high BP. Moreover, sugar-sweetened beverages (SSB) and the Dietary Approach to Stop Hypertension (DASH) influence BP. For this reason, we investigated whether: 1) children with risk of elevated BP had a higher consumption frequency (CF) of energy-dense salty foods (EDSF), high-sugary foods (HSF) and SSB or a low DASH score; and 2) children with a higher CF of EDSF showed a worse anthropometric and metabolic profile. Anthropometry, BP and general biochemical parameters were measured in 687 Spanish children (5-16 years) with normal or excess weight. A food frequency questionnaire was used to calculate EDSF, HSF and SSB consumption, and modified DASH score. Results showed that sex and pubertal stage influenced modified DASH score. Diastolic hypertension was associated to higher CF of EDSF in the whole sample and to higher CF of SSB in pubertal children, both independently of nutritional status. In addition, CF of EDSF was positively associated with CF of HSF and SSB and inversely associated with modified DASH score. Targeted policies and intervention programs, specific for different age ranges, should be established that aim to reduce salt consumption from snacks and processed foods, which could reduce HSF and SSB consumption as well.

Los primeros 1000 días: una oportunidad para reducir la carga de las enfermedades no transmisibles / The first 1000 days: an opportunity to reduce the burden of noncommunicable diseases

El crecimiento y desarrollo de un individuo está determinado desde la etapa embrionaria por su genética y los factores ambientales con los que interactúa. Los riesgos para la salud infantil y adulta pueden programarse durante las etapas fetal-neonatal y esta programación metabólica precoz puede afectar al desarrollo posterior de enfermedades como la obesidad y otras enfermedades no transmisibles (ENT) asociadas. La vida temprana, por la gran plasticidad que la caracteriza, constituye el momento ideal para intervenir y prevenir el riesgo de ENT (ventana de oportunidad). Una nutrición óptima durante los primeros 1000 días, que comprende desde la concepción hasta los dos años, es clave para la salud a lo largo de la vida. El rápido crecimiento y desarrollo del organismo y sus funciones durante el embarazo, la lactancia y el niño de corta edad conlleva requisitos nutricionales específicos en cada una de estas etapas. La microbiota del tracto gastrointestinal desempeña una labor fundamental en la función y el desarrollo del sistema inmune. Las interacciones entre el hospedador y su microbiota intestinal se consideran factores potenciales en la programación temprana de las funciones intestinales, con una evidencia creciente de que las alteraciones de la colonización bacteriana en el neonato se asocian con un mayor riesgo de enfermedad, incluidas las enfermedades alérgicas. La evidencia científica acumulada muestra que los primeros 1000 días son cruciales para alcanzar el mejor desarrollo y salud a largo plazo, y constituyen un periodo estratégico en términos de prevención y salud pública

Growth and development are determined by genetic and environmental factors since the very early embryonic life. Long-term health risks, as obesity and other non-communicable diseases (NCD), could be programmed since these early stages. Early life, characterized by plasticity, is the ideal time to intervene and to prevent the risk of suffering a NCD (window of opportunity). Optimal nutrition during the first 1,000 days, since conception to the end of the second year of life, has a determinant role for long-term health. Pregnancy, infancy and toddler periods have specific nutritional requirements. Intestinal microbiota enhances maturation and functioning of the immune system. The interactions between host and intestinal microbiota are potential factors influencing early programming of the intestinal function. Alterations in intestinal colonization are associated to a higher risk of allergic diseases in childhood. Scientific evidence supports the fact that the first 1,000 days are crucial to achieve a better long-term health and represents a strategic period to intervene under the perspective of prevention and public health

Early cardiac abnormalities in obese children and their relationship with adiposity.

OBJECTIVES: Childhood obesity rates are increasing as well as chronic disease and cardiovascular risk factors for patients at young ages. In this study, we evaluate the correlation between cardiac parameters, body mass index (BMI), and other body composition indicators in children and adolescents. METHODS: In this cross-sectional study, we evaluated anthropometric measurements, bioelectrical impedance parameters, and echocardiographic measurements including the left ventricular mass (LVM), LVM index (LVMI), and left atrial diameter (LAD) in children and adolescents ages 7 to 15 y. We performed linear and multivariate regression analyses and analyzed the correlations between cardiac parameters, BMI, and other body composition parameters. RESULTS: We analyzed 96 children and adolescents and found 40.6% to be obese and 29.2% overweight. LVMI and LAD indexed to height were significantly higher in individuals who were obese. LVMI increased significantly with increasing BMI (r = 0.717; P < 0.001), waist circumference (r = 0.670; P < 0.001), waist-to-height ratio (r = 0.650; P < 0.001), and body surface (r = 0.570; P < 0.001). Only BMI was significant in the multivariate analysis. LVMI was directly and positively correlated with fat mass (FM) and percentage of visceral and abdominal FM and negatively correlated with percentage of lean body mass. LAD was significantly correlated with body surface (r = 0.728; P < 0.001), BMI (r = 0.611; P < 0.001), waist circumference (r = 0.614; P < 0.001), and waist-to-height ratio (r = 0.341; P < 0.01). When indexed to height, LAD was only correlated with BMI and waist-to-height ratio. CONCLUSIONS: Obesity is associated with cardiac disturbances at a very early age and these changes are closely related to the degree of adiposity. Cardiac structural parameters are significantly correlated with BMI and waist circumference in pediatric patients ages 7 to 15 y.

THAO-CHILD HEALTH PROGRAMME: COMMUNITY BASED INTERVENTION FOR HEALTHY LIFESTYLES PROMOTION TO CHILDREN AND FAMILIES: RESULTS OF A COHORT STUDY.

INTRODUCTION: childhood obesity is one of the main public health concerns. The multifactorial and multilevel causes require complex interventions such the community based interventions (CBI). Thao-Child Health Programme is a CBI implemented in Spain since 2007. GOAL: show the Thao methodology and the latest cross-sectional and longitudinal results. METHODS: longitudinal cohort study (4 years of follow- up) and cross sectional study. RESULTS: the longitudinal study found an increase of 1% in the overweight prevalence after a follow-up of 4 years of Thao-Programme implementation in 10 municipalities with 6 697 children involved. The cross-sectional study carried out with 20 636 children from 22 municipalities found a childhood overweight prevalence of 26.6%. DISCUSSION: currently a brake in the increase of childhood overweight prevalence is considered a success due to the high prevalence worldwide. More studies well methodologically performed are needed to know the efficacy of the CBI's in this field.

Introducción: la obesidad infantil es una de las principales preocupaciones de salud pública. La etiología multifactorial y multinivel requiere de intervenciones complejas como las intervenciones de base comunitaria (CBI). El Programa Thao-Salud Infantil es una CBI implementada en España desde 2007. Objetivo: mostrar la metodología Thao y los últimos resultados transversales y longitudinales. Métodos: estudio de cohortes longitudinal (4 años de seguimiento) y estudio transversal. Resultados: el estudio longitudinal encontró un incremento del 1% en la prevalencia de exceso de peso tras 4 años de implementación del Programa Thao en 10 municipios con 6.697 niños y niñas involucrados. El estudio transversal llevado a cabo con 20.636 niños y niñas de 22 municipios encontró una prevalencia de exceso de peso infantil del 26,6%. Discusión: actualmente un freno en el incremento de la prevalencia de exceso de peso infantil es considerado como un éxito debido a la alta prevalencia a nivel mundial. Son necesarios más estudios metodológicamente bien realizados para conocer la eficacia de las CBI en este campo.

Thao-Child Health Programme: community based intervention for healthy lifestyles promotion to children and families: results of a cohort study / Programa Thao-Salud Infantil: intervención de base comunitaria de promoción de estilos de vida saludables en la población infantil y las familias: resultados de un estudio de cohorte

Introduction: childhood obesity is one of the main public health concerns. The multifactorial and multilevel causes require complex interventions such the community based interventions (CBI). Thao-Child Health Programme is a CBI implemented in Spain since 2007. Goal: show the Thao methodology and the latest cross-sectional and longitudinal results. Methods: longitudinal cohort study (4 years of follow-up) and cross sectional study. Results: the longitudinal study found an increase of 1% in the overweight prevalence after a follow-up of 4 years of Thao-Programme implementation in 10 municipalities with 6 697 children involved. The cross-sectional study carried out with 20 636 children from 22 municipalities found a childhood overweight prevalence of 26.6%. Discussion: currently a brake in the increase of childhood overweight prevalence is considered a success due to the high prevalence worldwide. More studies well methodologically performed are needed to know the efficacy of the CBI’s in this field (AU)

Introducción: la obesidad infantil es una de las principales preocupaciones de salud pública. La etiología multifactorial y multinivel requiere de intervenciones complejas como las intervenciones de base comunitaria (CBI). El Programa Thao-Salud Infantil es una CBI implementada en España desde 2007. Objetivo: mostrar la metodología Thao y los últimos resultados transversales y longitudinales. Métodos: estudio de cohortes longitudinal (4 años de seguimiento) y estudio transversal. Resultados: el estudio longitudinal encontró un incremento del 1% en la prevalencia de exceso de peso tras 4 años de implementación del Programa Thao en 10 municipios con 6.697 niños y niñas involucrados. El estudio transversal llevado a cabo con 20.636 niños y niñas de 22 municipios encontró una prevalencia de exceso de peso infantil del 26,6%. Discusión: actualmente un freno en el incremento de la prevalencia de exceso de peso infantil es considerado como un éxito debido a la alta prevalencia a nivel mundial. Son necesarios más estudios metodológicamente bien realizados para conocer la eficacia de las CBI en este campo (AU)