Gut microbiota is associated with metabolic health in children with obesity.

BACKGROUND AND AIMS: We aimed to describe and characterize the gut microbiota composition and diversity in children with obesity according to their metabolic health status. METHODS: Anthropometry, Triglycerides, HDL cholesterol, HOMA-IR, and systolic and diastolic blood pressure (SBP, DBP) were evaluated (and z-score calculated) and faecal samples were collected from 191 children with obesity aged from 8 to 14. All children were classified depending on their cardiometabolic status in either a "metabolically healthy" (MHO; n = 106) or "metabolically unhealthy" (MUO; n = 85) group. Differences in gut microbiota taxonomies and diversity between groups (MUO vs MHO) were analysed. Alpha diversity index was calculated as Chao1 and Simpson's index, and ß-diversity was calculated as Adonis Bray-Curtis index. Spearman's correlations and logistic regressions were performed to study the association between cardiometabolic health and the microbiota. RESULTS: Children in the MUO presented significantly lower alpha diversity and richness than those in the MHO group (Chao1 index p = 0.021, Simpson's index p = 0.045, respectively), whereas microbiota ß-diversity did not differ by the cardiometabolic health status (Adonis Bray-Curtis, R2 = 0.006; p = 0.155). The MUO group was characterized by lower relative abundances of the genera Christensenellaceae R7 group (MHO:1.42% [0.21-2.94]; MUO:0.47% [0.02-1.60], p < 0.004), and Akkermansia (MHO:0.26% [0.01-2.19]; MUO:0.01% [0.00-0.36], p < 0.001) and higher relative abundances of Bacteroides (MHO:10.6% [4.64-18.5]; MUO:17.0% [7.18-27.4], p = 0.012) genus. After the adjustment by sex, age, and BMI, higher Akkermansia (OR: 0.86, CI: 0.75-0.97; p = 0.033), Christensenellaceae R7 group (OR: 0.86, 95% CI: 075-0.98; p = 0.031) and Chao1 index (OR: 0.86, CI: 0.96-1.00; p = 0.023) represented a lower risk of the presence of one or more altered cardiovascular risk factors. CONCLUSION: Lower proportions of Christensenellaceae and Akkermansia and lower diversity and richness seem to be indicators of a metabolic unhealthy status in children with obesity.

Mental performance in 8-year-old children fed reduced protein content formula during the 1st year of life: safety analysis of a randomised clinical trial.

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

The Effect of Postpartum Depression and Current Mental Health Problems of the Mother on Child Behaviour at Eight Years.

Background Maternal postpartum depression (PPD) could affect children's emotional development, increasing later risk of child psychological problems. The aim of our study was to assess the association between child's emotional and behavioural problems and mother's PPD, considering maternal current mental health problems (CMP). Methods This is a secondary analysis from the EU-Childhood Obesity Project (NCT00338689). Women completed the Edinburgh Postnatal Depression Scale (EPDS) at, 2, 3 and 6 months after delivery and the General Health Questionnaire (GHQ-12) to assess CMP once the children reached the age of 8 years. EPDS scores > 10 were defined as PPD and GHQ-12 scores > 2 were defined as CMP. The psychological problems of the children at the age of eight were collected by mothers through the Child's Behaviour Checklist (CBCL). Results 473, 474 and 459 mothers filled in GHQ-12 and CBCL tests at 8 years and EPDS at 2, 3 and 6 months, respectively. Anxiety and depression was significantly increased by maternal EPDS. Children whose mothers had both PPD and CMP exhibited the highest levels of psychological problems, followed by those whose mothers who had only CMP and only PPD. PPD and CMP had a significant effect on child's total psychological problems (p = 0.033, p < 0.001, respectively). Children whose mothers had PPD did not differ from children whose mothers did not have any depression. Conclusions Maternal postpartum depression and current mental health problems, separately and synergistically, increase children's psychological problems at 8 years.

Factors associated with sugar intake and sugar sources in European children from 1 to 8 years of age.

BACKGROUND/OBJECTIVES: The World Health Organization recommends to limit intake of free sugars to 5% of total energy per day because of the great impact of high sugar intake on body fat deposition, adiposity and dental caries. However, little data exist about total intake and sources of sugar in European children. Therefore, this paper aims to describe sugar intake and dietary sugar sources and associated factors. SUBJECTS/METHODS: Three-day weighed dietary records were obtained at eight time points from children 1 to 8 years of age (n=995) in five European countries. Food items were classified into subgroups according to food composition. Linear mixed models were used to examine associated factors. RESULTS: Total sugar intake increased from 65 g/day (30.0% of energy intake (E%)) at 12 months of age to 83 g/day (20.9 E%) at 96 months of age. Around 80% of children's sugar intake was derived from the following sources: milk and dairy products, fruits and fruit products, confectionary and sugar sweetened beverages (SSB). Total sugar intake and dietary sugar sources varied significantly by country of residence. Boys had a significantly (P=0.003) higher total sugar consumption than girls.SSB consumption was significantly higher in children from young mothers while sugar intake from fruit products was lower in children from mothers with lower educational status and those with higher birth order. CONCLUSIONS: Sugar intake in our population was lower than in other studies. Total sugar intake was associated with country of residence and gender, while dietary sugar sources varied by country of residence, maternal age, education and birth order.

Association of early protein intake and pre-peritoneal fat at five years of age: Follow-up of a randomized clinical trial.

BACKGROUND AND AIMS: The double-blind randomized European Childhood Obesity Project (CHOP) demonstrated that reduced protein content in infant formula leads to a lower body mass index (BMI) up to six years of age. Here we aimed at assessing pre-peritoneal fat, a marker of visceral fat, in children participating in the CHOP trial. METHODS AND RESULTS: Healthy term formula-fed infants in five European countries were randomized either to higher (n = 550) or lower (n = 540) protein formulas in the first year of life. Infants who were exclusively breastfed for at least three months (n = 588) were enrolled as an observational (non randomized) group. At age 5 years, subcutaneous fat (SC) and pre-peritoneal fat (PP) were measured by ultrasound in a subgroup of 275 children. The PP fat layer was thicker in the higher compared to the lower protein group (adjusted estimated difference: 0.058 cm, 95%CI 0.002; 0.115; p = 0.043), while SC fat was not different. Girls showed a thicker SC fat layer than boys. CONCLUSIONS: Higher protein intake in formula-fed infants appears to enhance pre-peritoneal fat tissue accumulation at the age of 5 years, but not of subcutaneous fat, which may trigger adverse metabolic and health consequences.

Fish consumption in mid-childhood and its relationship to neuropsychological outcomes measured in 7-9 year old children using a NUTRIMENTHE neuropsychological battery.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA), particularly n-3 LCPUFA, play a central role in neuronal growth and the development of the human brain. Fish is the main dietary source of n-3 LCPUFA. To assess the relation between fish consumption, estimated dietary n-3 LCPUFA intake and cognition and behaviour in childhood in a multi-centre European sample. METHODS: Children from 2 European studies, CHOP and NUHEAL, were assessed at 8 and 7.5 years of age, respectively. Different outcomes of neuropsychological development (assessed with the standardized NUTRIMENTHE Neuropsychological Battery (NNB) consisting of 15 subtests) were related with outcomes from a food-frequency questionnaire (FFQ) focussing on the consumption of fish. RESULTS: A total of 584 children completed the FFQ and the neuropsychological tests. We found no associations with calculated DHA or EPA intakes for any of the neuropsychological domains. Children who consumed 2 fish meals per week including one of fatty fish, showed no substantive differences in the cognitive domains from the children who did not. However negative associations with fatty fish consumption were found for social problems (p = 0.019), attention problems (p = 0.012), rule-breaking problems (p = 0.019) and aggressive behaviour problems (p = 0.032). No association was observed with internalizing problems. Higher levels of externalizing problems (p = 0.018) and total problems (p = 0.018) were associated with eating less fatty fish. CONCLUSIONS: Children who consumed 2 fish meals per week including one of fatty fish were less likely to show emotional and behavioural problems than those who did not.

Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial.

BACKGROUND & AIMS: The sterile newborn digestive tract is rapidly colonized after birth and feeding type could influence this process. Infant formulas try to mimic the bifidogenic effect of human milk using prebiotic supplementation. The aim of this study was to demonstrate the efficacy, safety and tolerance of a 0.8 g/dL Orafti(®)Synergy1 (oligofructose-enriched inulin) supplemented infant formula during the first 4 months of life. METHODS: In a double-blind, randomized, placebo-controlled and parallel trial, formula fed healthy term newborns were randomized to receive a control (controls) or SYN1 supplemented infant formula (SYN1). Breastfed newborns (BF) were also followed for comparison. Anthropometry, water balance, blood parameters, adverse events, stool frequency and characteristics and faecal microbiota were assessed. RESULTS: A total of 252 formula fed infants were randomized at birth (n = 124 controls, n = 128 SYN1) and 131 BF infants were recruited; after 4 months 68 controls, 63 SYN1 and 57 BF completed the study. SYN1 infants showed a microbiota composition closer to that of BF infants, with a trend towards higher Bifidobacterium cell counts, softer stools and a higher deposition frequency compared to controls. There were no differences between formulas in anthropometry and relevant adverse events, water balance or blood parameters. CONCLUSION: A 0.8 g/dL SYN1-supplemented infant formula during the first 4 months of life is safe and effective, promoting a gut microbiota closer to that of breastfeeding. This clinical trial was registered at Clinicaltrials.gov as Study on Fermentable Carbohydrates in Healthy Infants (number NCT00808756).

Effect of protein intake and weight gain velocity on body fat mass at 6 months of age: the EU Childhood Obesity Programme.

INTRODUCTION: Higher protein intake during the first year of life is associated with increased weight gain velocity and body mass index (BMI). However, the relationship of protein intake and weight gain velocity with body composition is unclear. OBJECTIVE: To assess if the increases in weight gain velocity and BMI induced by protein intake early in life are related to an increase in fat or fat-free mass. MATERIALS AND METHODS: In all, 41 infants randomized at birth to a higher or lower protein content formula (HP=17 and LP=24, respectively) and 25 breastfed infants were included. Anthropometric measures were assessed at baseline, 6, 12 and 24 months, and fat-free mass (FFM) and fat mass (FM) were assessed by isotope dilution at 6 months. RESULTS: Weight gain velocity (g per month) during the first 6 months of life was significantly higher among HP infants (807.8 (±93.8) vs 724.2 (±110.0) (P=0.015)). Weight gain velocity strongly correlated with FM z-score (r=0.564, P<0.001) but showed no association with FFM z-scores. FFM showed no association with BMI. Nevertheless, FM strongly correlated with BMI at 6, 12 and 24 months (r=0.475, P<0.001; r=0.332, P=0.007 and r=0.247, P=0.051, respectively). FFM and FM z-scores did not differ significantly between HP and LP infants (0.32±1.75 vs -0.31±1.17 and 0.54±2.81 vs -0.02±1.65, respectively). CONCLUSION: Our findings support the hypothesis that higher protein intakes early in life are associated with faster weight gain and in turn to higher adiposity. This mechanism could be a determinant factor for later obesity risk.

[The efficiency (cost-effectiveness) of palivizumab as prophylaxis against respiratory syncytial virus infection in premature infants with a gestational age of 32-35 weeks in Spain]. / La eficiencia (coste-efectividad) de palivizumab como profilaxis para la infección por virus respiratorio sincitial en prematuros de 32-35 semanas en España.

OBJECTIVES: To evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe respiratory syncytial virus (RSV) infection in premature infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk factors (RF) in Spain. DESIGN: decision tree model using data from the scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants with GA 32-35 and two or more RF who received palivizumab) sponsored by the Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life years (QALY) gained. PERSPECTIVES: the national health service (NHS), which includes direct costs (administration of palivizumab and hospital admissions), and the societal perspective, which also includes indirect costs (the child's future lost productivity). Discount: 3 % annually for effectiveness and indirect costs. Sensitivity analysis: construction of 37 scenarios modifying variables related to effectiveness and costs. RESULTS: Prophylaxis with palivizumab in premature infants with GA 32-35 and two or more RF produced an incremental cost-effectiveness ratio (ICER) of 13,849 euro/QALY from the NHS perspective, and an ICER of 4,605 euro/QALY from the societal perspective. In the sensitivity analysis, from the NHS perspective the ICER ranged from 5,351 euro/QALY (most favorable scenario) to 23,276 euro/QALY (least favorable scenario). CONCLUSIONS: Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favorable scenarios, is lower than the threshold of 30,000 Euro/QALY considered socially acceptable in Spain.

La eficiencia (coste-efectividad) de palivizumab como profilaxis para la infección por virus respiratorio sincitial en prematuros de 32-35 semanas en España / The efficiency (cost-effectiveness) of palivizumab as prophylaxis against respiratory syncytial virus infection in premature infants with a gestational age of 32-35 weeks in Spain

Objetivos Evaluar la eficiencia (coste-efectividad) de palivizumab para prevenir la infección grave por virus respiratorio sincitial (VRS) en prematuros de edad gestacional de 32 a 35 semanas (EG 32-35) y dos o más factores de riesgo (FR) en España. Métodos Diseño: modelo de decisión alimentado con datos de la literatura científica y de los estudios FLIP I y FLIP II (cohorte de 326 niños con EG 32-35 y dos o más FR que recibieron palivizumab) promovidos por la Sociedad Española de Neonatología. Medida de efectividad principal: años de vida ajustados por calidad (AVAC) ganados. Perspectivas: la del Sistema Nacional de Salud (SNS), que incluye los costes directos (administración de palivizumab e ingresos hospitalarios), y la perspectiva social, que incluye además los costes indirectos (futura productividad perdida del niño). Descuento: 3 % anual para la efectividad y costes indirectos. Análisis de sensibilidad: construcción de 37 escenarios modificando variables relacionadas con la efectividad y los costes. Resultados La profilaxis con palivizumab en prematuros de EG 32-35 y dos o más FR produce una relación de coste-efectividad incremental (CEI) de 13.849 euros/AVAC con la perspectiva del SNS, y de 4.605 euros/AVAC con la perspectiva social. En el análisis de sensibilidad, con la perspectiva del SNS, el CEI osciló de 5.351 euros/AVAC (escenario más favorable) a 23.276 euros/AVAC (escenario menos favorable). Conclusiones Palivizumab es una terapia coste-efectiva como profilaxis frente a VRS en niños de EG 32-35 y dos o más FR. Su uso es eficiente desde la perspectiva del SNS, al conseguir un AVAC, incluso en los escenarios menos favorables, por debajo del umbral de 30.000 euros/AVAC, considerado en España como socialmente aceptable

Objectives To evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe respiratory syncytial virus (RSV) infection in premature infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk factors (RF) in Spain. Methods Design: decision tree model using data from the scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants with GA 32-35 and two or more RF who received palivizumab) sponsored by the Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life years (QALY) gained. Perspectives: the national health service (NHS), which includes direct costs (administration of palivizumab and hospital admissions), and the societal perspective, which also includes indirect costs (the child's future lost productivity). Discount: 3 % annually for effectiveness and indirect costs. Sensitivity analysis: construction of 37 scenarios modifying variables related to effectiveness and costs. Results Prophylaxis with palivizumab in premature infants with GA 32-35 and two or more RF produced an incremental cost-effectiveness ratio (ICER) of 13,849 euros/QALY from the NHS perspective, and an ICER of 4,605 euros/QALY from the societal perspective. In the sensitivity analysis, from the NHS perspective the ICER ranged from 5,351euros/QALY (most favorable scenario) to 23,276 euros/QALY (least favorable scenario). Conclusions Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favorable scenarios, is lower than the threshold of 30,000 euros/QALY considered socially acceptable in Spain

La densidad horaria de pacientes acumulados como indicador de saturación en urgencias / The hourly accumulated patient density as an indicator of Emergency Clinic saturation

Objetivo: Definir y estudiar el comportamiento de un indicador sensible a la acumulación de pacientes en Urgencias, la densidad horaria de pacientes acumulados (DHPA), que indica el número de pacientes que en una hora determinada están pendientes de alta. Método: Con la hora de admisión y de alta, se ha cuantificando la contribución a la (DHPA) de todos los pacientes pediátricos que transitaron por urgencias en el último cuatrimestre del 2002. Se ha realizado un estudio descriptivo retrospectivo, diferenciando entre septiembre-octubre, período con demanda considerada habitual, y noviembre-diciembre con demanda epidémica. Resultados: En el periodo no epidémico no se llegó ningún día a la cifra de referencia de 80 visitas, mientras que en el periodo epidémico se superó esta cifra el 18% de los días. La DHPA a la llegada de un paciente fue superior en los que decidieron marcharse sin ser visitados (mediana 12). Con el criterio de una DHPA 12, se detectaron 10 días (16,4%) con saturaciones del período no epidémico y, 39 días (63,9%) del epidémico. Conclusiones: Este indicador detecta periodos puntuales de acumulación no evidenciados por el análisis del número de urgencias y puede ayudar en la mejora de la asignación de recursos y la mejora de la calidad (AU)

Aim: To define and study the behaviour of a sensitive indicator or patient accumulation in the Outpatient Emergency Clinic, the “hourly accumulated patient density” (HAPD), which indicates the number of patients who, within a given hour, are still pending discharge. Method: Considering the hour of admission and the hour of discharge, the contribution to the HAPD of all paediatric patients attending the Outpatient Emergency Clinic during the last four months in the year 2002 has been calculated. A retrospective descriptive study was carried out differentiating the september-october period, considered as a “normal demand” one, and the novemeber-december one, considered as an “epidemic demand” period. Results: The 80-visit level was nott achieved in any single day of the non-epidemic-demand period, but was exceeded in 18% of the days in the epidemic demand one. The HAPD on arrival of a patient was highest among those who decided to leave without consultation (median, 12). With the HAPD >= 12 criterion, ten days with saturations (16.4%) were detected in the non-epidemic-demand period, versus 39 days (63.9%) in the epidemic-demand one. Conclusions: This indicator detects discrete accumulation periods which are not evidenced by the “number of emergency attendances” analysis, and may help in the improvement of resources assignation and general quality improvement (AU)

Onset of puberty at eight years of age in girls determines a specific tempo of puberty but does not affect adult height.

AIMS: To analyse the effect of early puberty (onset between 7.5 and 8.5 y) on pubertal growth and adult height in girls, and the implications of this effect for the age limit for normal onset of puberty. METHODS: Longitudinal study in Reus (Spain) of 32 girls with early puberty until they reached adult height. Data from these girls were compared with longitudinal data from girls (116) from the same population with normal onset at 10 (n = 37), 11 (n = 47), 12 (n = 19) and 13 (n = 13)y. We analysed height, target height, adult height, pubertal height increase, duration of pubertal growth, age at menarche and time to menarche. RESULTS: The adult height of girls with early puberty (160.9 +/- 5.4cm) was similar to that of girls with onset at later ages (p = not significant). In these girls, puberty lasted 5.4 +/- 0.7 y and the mean growth during puberty was 31.1 +/- 3.5 cm. As the age of onset of puberty increases, the duration of puberty and mean growth during puberty progressively decreased (p < 0.001). Girls with early puberty reached menarche at a mean age of 10.9 +/- 1.0 y, 3.2 +/- 0.9 y after onset of puberty, and this time span was greater than in the other groups. CONCLUSION: Girls with onset of puberty at 8 y show all the compensatory phenomena related to height at onset, pubertal duration and height increase during puberty. These phenomena cause their adult height to be similar to that of girls who begin puberty at the age of 10 to 13 y.

Síndrome de Alagille asociado a seudohermafroditismo masculino / Alagille syndrome associated with male pseudohermaphroditism

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Definición. Epidemiología / No disponible

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Aturdimiento miocárdico / Myocardial stunning

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Hemangiomatosis neonatal / Neonatal hemangiomatosis

Los hemangiomas son los tumores más frecuentes en la infancia, y ocurren aproximadamente en el 1 por ciento de los nacimientos. Hay una completa resolución en más del 50 por ciento de los niños a la edad de 5 años y en más del 70 por ciento a la edad de 7 años. La mayoría son asintomáticos, pero el 10 por ciento pueden causar complicaciones que requieren tratamiento. La hemangiomatosis neonatal difusa es una raro proceso caracterizado por la aparición de hemangiomas en la piel, las membranas mucosas y los órganos internos. Los hemangiomas laríngeos son la manifestación vascular visceral más frecuente. Los hemangiomas hepáticos y gastrointestinales son raros, y excepcionales los intracraneales. A pesar del tratamiento con corticoides, la mortalidad puede ser alta. La RM es usada para evaluar la extensión de la afectación visceral y documentar la respuesta a la terapia con corticoides. Se expone el caso de una lactante de 2 meses de vida con estridor laríngeo de 4 días de evolución, que presentaba en la exploración física hemangiomas en palma y muñeca izquierda, labio inferior y zona preauricular, mandibular, mentoniana y laterocervical izquierda. La RM mostró un angioma mentoniano en ambas glándulas parotídeas de predominio en izquierda y angiomatosis a nivel subglótico. No se evidenciaron angiomas en otros órganos. Con el diagnóstico de hemangiomatosis neonatal difusa se inició tratamiento con corticoides con buena respuesta, aunque presentó algún brote de estridor con dosis decrecientes (AU)

Hiperglucemia en el recién nacido prematuro / Hyperglycemia in premature newborn infants

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