Prenatal Betamethasone Exposure and its Impact on Pediatric Type 1 Diabetes Mellitus: A Preliminary Study in a Spanish Cohort.

Background: Betamethasone, a glucocorticoid used to induce lung maturation when there is a risk of preterm delivery, can affect the immune system maturation and type 1 diabetes (T1D) incidence in the progeny. It has been described that prenatal betamethasone protects offspring from experimental T1D development. The main aim of this study was to evaluate the possible association between betamethasone prenatal exposure and T1D in humans. Research Design and Methods. A retrospective case-control study with a total of 945 children, including 471 patients with T1D and 474 healthy siblings, was performed. Participants were volunteers from the Germans Trias i Pujol Hospital and DiabetesCero Foundation. Parents of children enrolled in the study completed a questionnaire that included questions about weeks of gestation, preterm delivery risk, weight at birth, and prenatal betamethasone exposure of their children. Multiple logistic regression was used to detect the association between betamethasone exposure and T1D. Results: We compared T1D prevalence between subjects prenatally exposed or unexposed to betamethasone. The percent of children with T1D in the exposed group was 37.5% (21 of 56), and in the unexposed group was 49.52% (410 of 828) (p = 0.139). The percentage of betamethasone-treated subjects with T1D in the preterm group (18.05%, 13 of 72) was significantly higher than that found in the control group (12.5%, 9 of 72) (p = 0.003). The odds ratio for T1D associated with betamethasone in the univariate logistic regression was 0.59 (95% confidence interval, 0.33; 1.03 [p = 0.062]) and in the multivariate logistic regression was 0.83 (95% confidence interval, 0.45; 1.52 [p = 0.389]). Conclusions: The results demonstrate that the prenatal exposure to betamethasone does not increase T1D susceptibility, and may even be associated with a trend towards decreased risk of developing the disease. These preliminary findings require further prospective studies with clinical data to confirm betamethasone exposure effect on T1D risk.

Candidate Biomarkers for the Prediction and Monitoring of Partial Remission in Pediatric Type 1 Diabetes.

The partial remission (PR) phase, a period experienced by most patients with type 1 diabetes (T1D) soon after diagnosis, is characterized by low insulin requirements and improved glycemic control. Given the great potential of this phase as a therapeutic window for immunotherapies because of its association with immunoregulatory mechanisms and ß-cell protection, our objective was to find peripheral immunological biomarkers for its better characterization, monitoring, and prediction. The longitudinal follow-up of 17 pediatric patients with new-onset T1D over one year revealed that, during the PR phase, remitter patients show increased percentages of effector memory (EM) T lymphocytes, terminally differentiated EM T lymphocytes, and neutrophils in comparison to non-remitter patients. On the contrary, remitter patients showed lower percentages of naïve T lymphocytes, regulatory T cells (TREG), and dendritic cells (DCs). After a year of follow-up, these patients also presented increased levels of regulatory B cells and transitional T1 B lymphocytes. On the other hand, although none of the analyzed cytokines (IL-2, IL-6, TGF-ß1, IL-17A, and IL-10) could distinguish or predict remission, IL-17A was increased at T1D diagnosis in comparison to control subjects, and remitter patients tended to maintain lower levels of this cytokine than non-remitters. Therefore, these potential monitoring immunological biomarkers of PR support that this stage is governed by both metabolic and immunological factors and suggest immunoregulatory attempts during this phase. Furthermore, since the percentage of TREG, monocytes, and DCs, and the total daily insulin dose at diagnosis were found to be predictors of the PR phase, we next created an index-based predictive model comprising those immune cell percentages that could potentially predict remission at T1D onset. Although our preliminary study needs further validation, these candidate biomarkers could be useful for the immunological characterization of the PR phase, the stratification of patients with better disease prognosis, and a more personalized therapeutic management.

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity.

OBJECTIVES: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. METHODS: Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. RESULTS: Circulating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (ßstd = .42, P = .008) but not in children (ßstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. CONCLUSIONS: Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity.

NK Cell Subsets Changes in Partial Remission and Early Stages of Pediatric Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by the autoimmune destruction of ß-cells in the pancreatic islets. T1D is preceded by islet-specific inflammation led by several immune cells. Among them, natural killer (NK) cells are emerging as important players in T1D development. Human NK cells are characterized by CD56 and CD16 expression, which allows classifying NK cells into four subsets: 1) CD56dimCD16+ or effector NK cells (NKeff); 2) CD56brightCD16- or regulatory NK cells (NKreg); 3) intermediate CD56brightCD16+ NK cells; and 4) CD56dimCD16- NK cells, whose function is not well determined. Since many studies have shown that T1D progression is associated with changes in various immune cell types, we hypothesize that the kinetics of NK cell subsets in the blood could correlate with different stages of T1D. To that aim, pediatric patients newly diagnosed with T1D were recruited, and peripheral NK cell subsets were analyzed by flow cytometry at several disease checkpoints: disease onset, partial remission (PR), 8 months (for non-remitters), and 12 months of progression. Our results showed that total NK cells and their four subsets are altered at the early stages of T1D. A decrease in the counts and percentage of total NK cells and NKeff cells at the different disease stages was found when compared to controls. These results suggest the extravasation of these cells into the islets at disease onset, which is maintained throughout the follow-up. By contrast, NKreg cells increased during the early stages after T1D onset, and both intermediate NK cells and CD56dimCD16- NK cells diminished at the PR stage, which might reflect the immunoregulatory attempts and could be candidate biomarkers for this stage. Also, CD56dimCD16- NK cells increased during T1D progression. Finally, changes in CD16 expression were identified in the different T1D stages, highlighting a CD16 expression reduction in total NK cells and NKeff cells 1 year after diagnosis. That may reflect a state of exhaustion after multiple cell-to-cell interactions. Altogether, our preliminary data provide a longitudinal picture of peripheral NK cell subpopulations during the different T1D stages, which could be potential candidate biomarkers indicators of disease progression.

Impaired Phagocytosis in Dendritic Cells From Pediatric Patients With Type 1 Diabetes Does Not Hamper Their Tolerogenic Potential.

Type 1 diabetes (T1D) is prompted by defective immunological tolerance, an event in which dendritic cells (DCs) are crucial as immune response orchestrators. In fact, they contribute to maintaining tolerance to self-antigens, but they can also prompt an immunogenic response against them, leading to autoimmunity. Countless factors can potentially impact on the proper functionality of the DCs, which range from altered subset distribution, impaired phagocytic function to abnormal gene expression. Moreover, in T1D, metabolic dysregulation could impair DC functions as well. Indeed, since T1D clinical course is likely to be more aggressive in children and adolescents and entails severe dysglycemia, the aim of this study was to analyze circulating DCs subpopulations in pediatric T1D at different stages, as well as to characterize their phagocytosis ability and tolerance induction potential. Thus, pediatric patients newly diagnosed with T1D, with established disease and control subjects were recruited. Firstly, DCs subsets from peripheral blood were found quantitatively altered during the first year of disease, but recovered in the second year of progression. Secondly, to study the tolerogenic functionality of DCs, liposomes with phosphatidylserine (PS) were designed to mimic apoptotic beta cells, which are able to induce tolerance, as previously demonstrated by our group in DCs from adult patients with T1D. In this study, monocyte-derived DCs from pediatric patients with T1D and control subjects were assessed in terms of PS-liposomes capture kinetics, and transcriptional and phenotypic changes. DCs from pediatric patients with T1D were found to phagocyte PS-liposomes more slowly and less efficiently than DCs from control subjects, inversely correlating with disease evolution. Nonetheless, the transcription of PS receptors and immunoregulatory genes, cytokine profile, and membrane expression of immunological markers in DCs was consistent with tolerogenic potential after PS-liposomes phagocytosis. In conclusion, T1D progression in childhood entails altered peripheral blood DCs subsets, as well as impaired DCs phagocytosis, although tolerance induction could still function optimally. Therefore, this study provides useful data for patient follow-up and stratification in immunotherapy clinical trials.

Measurement Properties of the Online EuroQol-5D-Youth Instrument in Children and Adolescents With Type 1 Diabetes Mellitus: Questionnaire Study.

BACKGROUND: The lack of continuity between health-related quality of life (HRQoL) instruments designed for children and adults hinders change analysis with a life course approach. To resolve this gap, EuroQol (EQ) developed the EQ-5D-Youth (EQ-5D-Y), derived from the EQ-5D for adults. Few studies have assessed the metric properties of EQ-5D-Y in children with specific chronic conditions, and none have done so for children with type I diabetes mellitus (T1DM). OBJECTIVE: This study aimed to evaluate the acceptability, validity, reliability, and responsiveness of the EQ-5D-Y in children and adolescents with T1DM, when administered online. METHODS: Participants with T1DM were consecutively recruited from July to December 2014, from a list of potential candidates aged 8-19 years, who attended outpatient pediatric endocrinology units. Before every quarterly routine visit, participants received an email/telephone reminder to complete the online version of two generic HRQoL questionnaires: EQ-5D-Y and KIDSCREEN-27. The EQ-5D-Y measures five dimensions, from which an equally weighted summary score was constructed (range: 0-100). Completion rate and distribution statistics were calculated. Construct validity was evaluated through known group comparisons based on general health, acute diabetic decompensations, mental health, family function, and a multitrait, multimethod matrix between EQ-5D-Y and KIDSCREEN by using Spearman correlations. Construct validity hypotheses were stated a priori. Reliability was assessed with the intraclass correlation coefficient and responsiveness by testing changes over time and calculating the effect size. Reliability and responsiveness were tested among the stable and improved subsamples defined by a KIDSCREEN-10 index change of <4.5 points or ≥4.5 points, respectively, from the first to the fourth visit. RESULTS: Of the 136 participants, 119 (87.5%) responded to the EQ-5D-Y at the last visit. The dimensions that showed higher percentages of participants with problems were "having pain/discomfort" (34.6%) and "worried/sad/unhappy" (28.7%). The mean (SD) of the EQ-5D-Y summary score was 8.5 (10.9), with ceiling and floor effects of 50.7% and 0%, respectively. Statistically significant HRQoL differences between groups defined by their general health (excellent/very good and good/regular/bad) and mental health (Strengths and Difficulties Questionnaire score ≤15 and >16, respectively) were found in three EQ-5D-Y dimensions ("doing usual activities," "having pain/discomfort," and "feeling worried/sad/unhappy"), summary score (effect size for general health and mental health groups=0.7 and 1.5, respectively), and KIDSCREEN-10 index (effect size for general health and mental health groups=0.6 and 0.9, respectively). Significant differences in the EQ-5D-Y dimensions were also found according to acute diabetic decompensations in "looking after myself" (P=.005) and according to family function in "having pain/discomfort" (P=.03). Results of the multitrait, multimethod matrix confirmed three of the four relationships hypothesized as substantial (0.21, 0.58, 0.50, and 0.46). The EQ-5D-Y summary score presented an intraclass correlation coefficient of 0.83. Statistically significant change between visits was observed in the improved subsample, with an effect size of 0.7 (P<.001). CONCLUSIONS: These results support the use of the EQ-5D-Y administered online as an acceptable, valid, reliable, and responsive instrument for evaluating HRQoL in children and adolescents with T1DM.

Partial remission and early stages of pediatric type 1 diabetes display immunoregulatory changes. A pilot study.

Type 1 diabetes (T1D) is a chronic metabolic disease of unknown etiology that results from ß-cell destruction. The onset of the disease, which arises after a long asymptomatic period of autoimmune attack, may be followed by a relapsing and remitting progression, a phenomenon that is most evident during the partial remission phase (PR). This stage lasts for a few months, shows minor requirements of exogenous insulin and could be explained by a recovery of immunological tolerance. This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n = 52) and age-related control subjects (n = 30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-ß levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found during T1D progression, probably reflecting an attempt to restore self-tolerance. By contrast, a reduction in monocyte levels was observed at the early stages of diabetes. The results reveal significant changes in immunological parameters during the different early stages of T1D in children, which could ultimately serve as potential biomarkers to characterize the progression of T1D.

Measured free 25-hydroxyvitamin D in healthy children and relationship to total 25-hydroxyvitamin D, calculated free 25-hydroxyvitamin D and vitamin D binding protein.

BACKGROUND: vitamin D deficiency in children is still a global health problem. Measuring free 25-hydroxyvitamin D concentrations could provide a better estimate of the vitamin D status than total 25-hydroxyvitamin D (25(OH)D) levels. OBJECTIVE: To assess the relationship between measured free vitamin D (m-f25(OH)D) and calculated free 25(OH)D (c-f25(OH)D), total 25(OH)D, intact parathyroid hormone (iPTH) and other markers of phosphocalcic metabolism. To establish serum m-f25(OH)D concentrations corresponding to a total 25(OH)D > 50 nmol/L which is accepted as vitamin D-sufficiency status in children. DESIGN: Prospective cohort study. SETTING: January and February 2017 in a Mediterranean population. PATIENTS: healthy children. MEASUREMENTS: m-f25(OH)D and vitamin D binding protein (VDBP) by ELISA. Free 25(OH)D was calculated using the formula described by Bikle. RESULTS: m-f25(OH)D directly correlated with total 25(OH)D (r:0.804,p < .001), serum calcium (r:0.26,p:0.035), and c-f25(OH)D (r:0.553,p:0.016); and inversely with iPTH (r:-0.374, p:0.002), alkaline phosphatase (r:-0.28, p:0.026), and age (r:-0.289, p:0.018). Total 25(OH)D correlated with the same parameters as m-f25(OH)D except for serum calcium. However, c-f25(OH)D correlated only with total 25(OH)D and VDBP, both included in the calculation formula. Multiple regression analysis showed that m-f25(OH)D variations were independently explained by calcium (ß:0.156, p:0.026) and total 25(OH)D (ß:0.043, p < .001). The optimal m-f25(OH)D cut-off for discriminating between insufficient and sufficient total 25(OH)D was >9.8 pmol/L (Area Under Curve (AUC): 0.897 (95% confidence interval (CI): (0.798-0.958); p < .001; sensitivity:72.7% (95%CI: 49.8-89.3); specificity: 95.5% (95%CI: 84.5-99.4)). CONCLUSIONS: Directly measured free vitamin D correlated better with markers of phosphocalcic metabolism than total 25(OH)D and c-f25(OH)D in a population of healthy children.

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers.

Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the ß-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of ß-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called "honeymoon phase," which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining ß-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to ß-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

Impact of monitoring health-related quality of life in clinical practice in children with type 1 diabetes mellitus.

PURPOSE: To test whether the systematic monitoring of health-related quality of life (HRQOL) in clinical practice in Spanish pediatric patients with T1DM helps improve their daily life in a multicenter longitudinal study. METHODS: One hundred thirty-six patients participated, recruited from five centers in Barcelona, Spain (72 girls, mean age 13.4 years). Complete data were collected for 119 patients (85%). Pediatricians were randomly assigned to the HRQOL intervention (n = 70), or control group (n = 49). The intervention group discussed the results of HRQOL face to face with the physician, quarterly over a year. The control group received care as usual. HRQOL was assessed using KIDSCREEN-27 collected online. Standardized mean differences (effect size, ES) and generalized estimating equation (GEE) were computed to compare group differences between baseline and follow-up, taking into account sociodemographic and clinical variables. RESULTS: Statistically significant higher scores were seen in the intervention group at follow-up for the dimensions of Psychological well-being (ES = 0.56), School environment (ES = 0.56), and the KIDSCREEN-10 index (ES = 0.63). No differences were found in the control group. GEE analysis showed an improvement in HRQOL at follow-up with statistically significant association of the intervention on Psychological well-being (B = 4.32; p 0.03 for the interaction of group by follow-up) and School environment (B = 4.64; p 0.02 for the same interaction term). CONCLUSIONS: Routine assessment and face-to-face patient-physician discussion of HRQOL results improved HRQOL scores after a year of follow-up, especially in Psychological well-being and school environment. The results support the routinary use of HRQOL assessment in clinical practice.

Intervenciones clínicas en sobrepeso y obesidad: revisión sistemática de la literatura 2009-2014 / Clinical interventions in overweight and obesity: a systematic literature review 2009-2014

OBJETIVO: Actualizar la revision bibliográfica sobre la efectividad de las intervenciones clínicas en obesidad infantil propuestas en una Guía de Práctica Clínica, excluyendo los tratamientos farmacológicos y quirúrgicos y el abordaje de la prevención. MÉTODO: Revisión sistemática de las bases de datos electrónicas Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE y SCOPUS replicando la búsqueda de la Guía de Práctica Clínica, desde el año 2010 a 2014. Se tuvieron en cuenta las Guías de Práctica Clínica del National Institute for Health and Care Excellence. Se priorizaron las revisiones sistemáticas. Se llevó a cabo un análisis de la calidad de los estudios. RESULTADOS: De 3.703 documentos identificados se incluyeron 48 en la revisión. Los estudios mostraron gran heterogeneidad en cuanto al tipo y duración de la intervención, y a la medida de los resultados. En general, la adherencia a los tratamientos ha sido baja. Las intervenciones multicomponentes que incluyen alimentación, actividad física, sedentarismo y cambios de conducta, que implican a la familia y comienzan en edades precoces, son las más efectivas en la reducción del índice de masa corporal. No existe consenso en los criterios de derivación a la atención especializada. CONCLUSIONES: Se recomienda implementar programas multicomponentes llevados a cabo por profesionales con formación previa, con participación de la familia, y que aborde aspectos conductuales, individuales y sociodemográficos. La falta de adherencia es uno de los motivos de fracaso de las intervenciones. Sería necesario mejorar y homogeneizar los criterios de diagnóstico, las medidas de resultados y los criterios de derivación

OBJECTIVE: To update the literature review on the effectiveness of clinical interventions on childhood obesity, proposed in Clinical Practice Guidelines, excluding prevention and pharmacological and surgical treatments. METHOD: A systematic review was carried out in electronic databases of the Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE, and SCOPUS, replicating the search for the Clinical Practice Guidelines, from 2009 to 2014. The Clinical Practice Guidelines of National Institute for Health and Care Excellence were taken as a reference. Systematic reviews were given priority, and the quality of the studies was assesse. RESULTS: Out of a total of 3,703 documents initially identified, 48 were finally included. Studies showed great heterogeneity in the type and duration of interventions, and in outcome measures. Adherence to treatment was, in general, low. Multi-component interventions including diet, physical activity, sedentary lifestyle, and behaviour changes, involving the family, and starting at early ages, were the most effective for reducing body mass index. There is no consensus on criteria for referral to specialised care. CONCLUSIONS: It is recommended to implement multi-component programs conducted by professionals with previous training, involving the family, and addressing behavioural, individual and socio-demographic aspects. Lack of adherence is one of the reasons for failure of interventions. Diagnostic and referral criteria, the outcome measures, and the type and duration of interventions need to be improved and standardised

Health-related quality of life (HRQOL) and its associated factors in children with Type 1 Diabetes Mellitus (T1DM).

BACKGROUND: The objective of the study was to describe the baseline health-related quality of life (HRQOL) in a cohort of children and adolescents with type 1 diabetes mellitus (T1DM), and analyze its associated clinical and sociodemographic factors, assessing HRQOL through internet. METHODS: This was a descriptive study of 136 patients with T1DM from 5 hospitals in Catalonia, Spain (72 girls, mean age 13.4 years (range 8-19). Inclusion criteria were more than 6 months from diagnosis, more than 8 years old and without cognitive problems. Sociodemographic (age, sex, family level of education, type of family and origin) and clinical variables (type of insulin therapy, duration of disease, adherence to treatment, body mass index and HbA1c) were collected. HRQOL was assessed using the EuroQol-5D (EQ-5D-Y) and KIDSCREEN, collected via web. Mental health status was assessed using the Strengths and Difficulties Questionnaire. Multiple linear regression models were adjusted. RESULTS: Physical-well-being mean scores were lower (worse) than the European average (<50) and especially in girls, older children (>11 years old), those from single-parent families, and those with low adherence. Older children and patients with poor metabolic control (HbA1c >7,5% [58 mmol/mol]) showed worse scores in the KIDSCREEN-10 index. Similar results were observed with the EQ-5D-Y. Multivariate models showed that age, single-parent families, adherence and mental health were the most influential factors. CONCLUSIONS: Diabetic patients report similar HRQOL than the population of the same age with slightly worse physical well-being. The study shows some factors to be taken into account to improve HRQOL, and also the feasibility of using web to collect information in clinical practice.

[Clinical interventions in overweight and obesity: a systematic literature review 2009-2014]. / Intervenciones clínicas en sobrepeso y obesidad: revisión sistemática de la literatura 2009-2014.

OBJECTIVE: To update the literature review on the effectiveness of clinical interventions on childhood obesity, proposed in Clinical Practice Guidelines, excluding prevention and pharmacological and surgical treatments. METHOD: A systematic review was carried out in electronic databases of the Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE, and SCOPUS, replicating the search for the Clinical Practice Guidelines, from 2009 to 2014. The Clinical Practice Guidelines of National Institute for Health and Care Excellence were taken as a reference. Systematic reviews were given priority, and the quality of the studies was assessed. RESULTS: Out of a total of 3,703 documents initially identified, 48 were finally included. Studies showed great heterogeneity in the type and duration of interventions, and in outcome measures. Adherence to treatment was, in general, low. Multi-component interventions including diet, physical activity, sedentary lifestyle, and behaviour changes, involving the family, and starting at early ages, were the most effective for reducing body mass index. There is no consensus on criteria for referral to specialised care. CONCLUSIONS: It is recommended to implement multi-component programs conducted by professionals with previous training, involving the family, and addressing behavioural, individual and socio-demographic aspects. Lack of adherence is one of the reasons for failure of interventions. Diagnostic and referral criteria, the outcome measures, and the type and duration of interventions need to be improved and standardised.

Variability in adherence to rhGH treatment: Socioeconomic causes and effect on children's growth.

BACKGROUND: In children with growth disorders, mean final height is associated to poor adherence to Growth Hormone therapy. The primary goal of this study is to identify patients who do not adhere to GH therapy and determine the influence of adherence in response to the treatment. The role of serum IGF-I and influence of socio-economic factors on the therapeutic adherence will also be evaluated. METHODS: 158 children under treatment with rhGH were included in the study. Age, gender, etiology, Tanner stage, duration of treatment, growth rate, IGF-I serum values, daily dose, and annual rhGH dose data were collected. Adherence to therapy was defined as moderate-to-poor when the patient had taken less than 92% of the prescribed medication. A subgroup of 106 patients completed a questionnaire to assess social and environmental effects. RESULTS: Moderate-to-poor adherence to rhGH treatment was determined in 33.5% of study patients. A decrease in adherence was associated to treatment duration (p=0.001). A significant correlation was determined between adherence and height velocity (p=0.002) and IGF-I (p<0.0001) levels. Adherence rates were associated to the mother's educational level (p=0.007). CONCLUSION: Poor adherence to GH therapy was observed in one-third of study patients, resulting in suboptimal growth. IGF-I levels can be helpful to identify patients with poor adherence to GH medication. Physicians should pay special attention to certain characteristics of the patient and their environment, and encourage desirable therapeutic compliance.

Avances en el diagnóstico y tratamiento de la talla baja en la infancia / Advances in the diagnosis and treatment of short stature in chilhood

Fundamento. La talla baja es un motivo de consulta frecuente en la consulta del pediatra y en determinados momentos puede generar dudas de seguimiento. Objetivo. Mostrar unos criterios diagnósticos claros de la talla baja y definir cuales son los motivos de derivación al especialista, así como explicar los avances en su tratamiento. Método. Trabajo de revisión a partir de la literatura actualizada. Avenços en el diagnòstic i el tractament de la talla baixa a la infància Marta Murillo, Joan Bel Unitat d’Endocrinologia Pediàtrica. Servei de Pediatria. Hospital Universitari Germans Trias i Pujol. Badalona (Barcelona) Resultados. Se define talla baja como una talla por debajo de -2 desviaciones estándares según la edad y el sexo del paciente. Hay que diferenciar las tallas bajas según la época de la vida en la que se diagnostican (período neonatal, infancia o pubertad), ya que pueden influir diferentes aspectos en cada una de ellas. Es muy importante comparar con los estándares de referencia adecuados según cada población, así como realizar una historia clínica y una exploración física esmeradas para descartar patologías existentes. Si es necesario se realizarán pruebas complementarias específicas para buscar alteraciones en el eje somatotropo. Además del déficit de hormona de crecimiento (GH) existen otras cinco indicaciones de tratamiento con GH, una de ellas es la nueva indicación para alteraciones en el gen SHOX. Últimamente ha surgido una nueva medicación, el factor de crecimiento insulínico tipo I (IGF-I) recombinante, para los casos de déficit del mismo. Conclusiones. Para el seguimiento de los pacientes con una patología tan frecuente como la talla baja hay que comparar los datos con estándares adecuados como son en nuestro caso las nuevas curvas de crecimiento. Destacar las novedades en indicación de tratamiento con GH y la nueva medicación para el déficit de IGF-I(AU)

Background. Short stature is a frequent reason for consulting a paediatrician, and at times it may raise questions about following up. Objective. To show clear diagnostic criteria of short stature in childhood and to define the reasons for referring a patient to a specialist, as well as to explain advances in treatment. Method. A review project based on up-to-date literature. Results. Short stature is defined as a size of less than - 2 standard deviations according to the age and sex of the patient. Short stature must be differentiated according to the period of life in which it is diagnosed (neonatal period, childhood, or puberty), as in each phase different aspects may have an influence. It is very important to compare with appropriate standards of reference according to each population, as well as taking a clinical history and making a careful physical examination, in order to discard existing pathologies. If it is necessary, specific supplementary tests will be made to search for alterations in the somatotropic axis. Besides a shortage of growth hormone (GH) there are about five other indications for treatment with GH, one is the new indication for alterations in the SHOX gene. Lately a new medication has arisen, the type I (IGF-I) recombinant insulin-like growth factor, for cases of a shortage of it. Conclusions. To follow patients with such a frequent pathology as short stature, one must compare the data with appropriate standards, like the new growth curves in our case. The new information in the indication for treatment with GH and the new medication for the lack of IGF-I stand out(AU)

Bombes d’insulina / No disponible

No disponible

Seudohermafroditismo masculinopor déficit de 17 Beta-hidroxiesteroidedes hidrogenasa / Male pseudohermaphroditism due to 17 Beta-hydroxysteroid dehydrogenase deficiency

No disponible

Hiperclaritat pulmonar / Lung hyperlucency

No disponible

[Growth retardation and nutritional status in foster children]. / Retraso de crecimiento y estado nutricional en niños ingresados en una institución de acogida.

BACKGROUND: Our main objective was to determine growth retardation in children entering a foster home and catch-up growth at the end of the stay. We also analyzed the nutritional status and its relationship with growth retardation. SUBJECTS AND METHOD: Height and weight were determined in 118 children, aged between one month and fifteen years; they were examined at admission and at the time of leaving the center. In another group of 31 prepubertal children, we analized their nutritional status determining the body mass index, prealbumin, retinol binding protein, GHBP, IGF-1, IGFBP-3 and leptin at admission. RESULTS: 31 (26.2%) out of the of the 118 children group had a height deficit (height < 2 SDS) at admission. 32 (27.1%) of the overall group of children showed significant catch-up growth after their stay at the foster home, and 15 (46.8%) of them showed a catch-up growth > 0.5 SDS. Children below two years of age showed the most important growth deficit. The nutritional status study showed normal results in all parameters in the 31 children group. Significant correlations were observed between IGF-I and weight/height, IGFBP-3 and weight/height, GHBP and body mass index, and leptin and body mass index. CONCLUSIONS: An important proportion of children showed significant growth retardation at entering a foster home, although a significant catch-up growth was observed at the end of their stay. Growth failure in this population does not appear to be related to the nutritional status.