Thyroid volume is the key predictor of hyperthyroidism remission after radioactive iodine therapy in pediatric patients.

Graves' disease (GD) is the leading cause of hyperthyroidism in pediatric patients. Radioactive iodine therapy (RAIT) is widely used to treat GD. However, it is still unclear exactly what determines the efficacy of RAIT in childhood and adolescence. The objective of our study was to reveal the most significant predictors of the efficacy of RAIT in pediatric GD patients. A single-center prospective observational exploratory study enrolled 144 pediatric patients (124 females and 20 males) between 8 and 18 years of age who underwent dosimetry-guided RAIT for GD for the first time. The estimated parameters included sex, age, thyroid volume, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone receptor antibodies (TRABs) at baseline and 12 months after RAIT, 10- to 20-min 99mTc thyroid uptake (%), maximum thyroid 131I uptake (%), specific 131I uptake (MBq/g), and therapeutic activity of 131I (MBq), which was limited to 1100 MBq. The Fisher's exact test, Mann-Whitney U-test, Wilcoxon signed-rank test, ROC analysis, and the Youden index were used for statistical analysis. Twelve months after RAIT, 119 patients (83%) successfully achieved remission, 6 patients (4%) had euthyroidism, and hyperthyroidism persisted in 19 patients (13%). Thyroid volume decreased from 17.6 [14.6; 24.1] to 9.3 [7.6; 13.3] mL 12 months after the treatment (p < 0.001). The main predictor that showed a statistically significant difference between the groups of patients who achieved and did not achieve remission of GD hyperthyroidism after RAIT was the initial thyroid volume. Using the Youden index, the optimal cut-off point for the initial thyroid volume at 45.4 mL was determined.     Conclusion: The dosimetry-guided RAIT in pediatric GD patients was 83% effective at 12 months after the treatment, and the initial thyroid volume of less than 45.4 mL was the most important predictor of RAIT success. Other predictors identified in our work included FT4 levels, TRABs levels, 99mTc-pertechnetate uptake, and specific 131I uptake. What is Known: •Radioiodine therapy is a common, effective, and safe treatment for pediatric patients with Graves' disease. What is New: •The initial thyroid volume in pediatric GD patients is an important predictor of achieving hypothyroidism following radioiodine therapy. If the thyroid volume is less than 45.4 ml, radioiodine therapy limited to 1100 MBq will be effective definitive treatment.

One-year recombinant growth hormone therapy does not improve hemoglobin state and morphology of erythrocytes in growth hormone deficient children.

An increase in growth rates of children suffering from growth hormone deficiency (GHD) subjected to recombinant growth hormone treatment (rGHT) was shown to be accompanied by acceleration of metabolic processes that may stimulate oxygen consumption in various organs and tissues. Therefore, oxygen-transporting properties of RBC should undergo considerable changes during the rGHT. The aim of this study was to examine the effects of rGHT on erythrocyte shape and hemoglobin state in GHD children. The level of oxyhemoglobin (Oxy-Hb) in RBC was analyzed by Raman spectroscopy. The RBC count, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and other parameters were calculated. The blood of eleven treatment-naive prepubertal children with GHD (aged 3-9, median 5.7 years) was examined and compared with control group (aged 5-7; median 6.0 years) at three time points: 0, 3 and 12 months of rGHT. Before rGHT, the MI in GHD children was higher (median 0.48 vs 0.14 p=0.0018) and the RBC count was lower (median 4.20 vs 4.96 1012 cells/L p=0.0022) than in control group. After the treatment, cell count in GHD patients did not differ significantly from the control group, but Oxy-Hb level became higher (median 0.64 vs 0.41 p=0.0075). During rGHT, MCV decreased (median 80.3 vs 83.2µm3 p=0.0231). Morphological and functional characteristics of erythrocytes in GHD children were shown to differ significantly from the healthy control group. A twelve-month rGHT partially improved some of the studied parameters but Oxy-Hb level and echinocyte count remained high.

Response of pure red cell aplasia to cyclophosphamide after failure of mycofenolate mofetil in a patient with polyglandular syndrome type I.

A 26-year-old female with the classic major and minor components of autoimmune polyglandular syndrome type 1 was diagnosed as having pure red cell aplasia. Treatment with 1.5 g/d mycofenolate mofetil for 3 months failed to restore erythroid production. Treatment with cyclosporine A produced a good partial response but led to renal toxicity and was therefore substituted with cyclophosphamide, which had a good partial effect and lasted for 18 months. The relapse of anemia was not observed during the 6-month follow-up period after the cessation of treatment.

Treatment with insulin detemir or NPH insulin in children aged 2-5 yr with type 1 diabetes mellitus.

This randomised (1:1), multinational, open-labelled, parallel group trial compared insulin detemir (IDet) with neutral protamine Hagedorn (NPH) insulin, in combination with mealtime insulin aspart, over 1 yr in subjects aged 2-16 yr with type 1 diabetes mellitus. Of 348 randomised subjects, 82 (23.6%) were 2-5 yr (IDet: 42, NPH: 40). This article is a descriptive subgroup analysis of these young children. Baseline characteristics (IDet vs. NPH) were similar: mean age, 4.3 vs. 4.5 yr; diabetes duration, 2.2 vs. 2.1 yr; males, 42.9 vs. 52.5%. Mean haemoglobin A1c (HbA1c) was similar between groups at baseline (8.2 vs. 8.1%), and changed little over 1 yr (8.1 vs. 8.3%). Fasting plasma glucose (FPG) was similar at baseline (8.44 vs. 8.56 mmol/L) and decreased during the study (-1.0 vs. -0.45 mmol/L). A lower rate of hypoglycaemia was observed with IDet compared with NPH (24-h; 50.6 vs. 78.3 episodes per patient-year; nocturnal hypoglycaemia, 8.0 vs. 17.4 episodes per patient-year). No severe hypoglycaemic episodes occurred with IDet, while 3 subjects reported 6 episodes with NPH. Change in weight standard deviation score standardised by age and gender was -0.17 with IDet and +0.03 with NPH. A slightly lower proportion of subjects in this age group reported adverse events with IDet than with NPH (69.0 vs. 77.5%). Serious adverse events were few (5 with IDet, 7 with NPH). In conclusion, long-term treatment with IDet in children aged 2-5 yr suggested similar glycaemic control, greater reduction in FPG, lower rates of hypoglycaemia, no inappropriate weight gain, and fewer adverse events compared with NPH.

The carriage of the type 1 diabetes-associated R262W variant of human LNK correlates with increased proliferation of peripheral blood monocytes in diabetic patients.

OBJECTIVE: Lymphocyte adaptor protein (LNK) plays a pivotal role as a suppressor of T-cell receptor-mediated immune signaling and negative regulator of lymphopoiesis and early hematopoiesis. Recently, association between the R262W (c.784T>C) variant of the SH2B3 gene (rs3184504) encoding human LNK and type 1 diabetes (T1D) was found in several populations. In this study, we aimed to check whether this marker is associated with T1D in a Russian population. METHODS: Using a Taqman allele discrimination assay, we genotyped 1062 unrelated Russian individuals with diabetes at childhood and adolescence onset and 1020 healthy controls. T-cell proliferation assay based on the measurement of incorporation of bromo-2'-deoxyuridine incorporation into newly synthesized DNA was used to evaluate whether carriage of SH2B3 784T>C correlates with T-cell proliferation in patients' peripheral mononuclear blood cells (PMBCs) stimulated with anti-CD28 and anti-CD3 antibodies. RESULTS: The allele 784C of SH2B3 was related to a higher risk of T1D (odds ratio of 1.52, p = 1.2 × 10(-12)). A correlation between the carriage of the predisposing C/C variant of LNK and increased proliferation of T lymphocytes was shown in PMBCs of both diabetic [C/C vs. C/T vs.T/T = optical density at 450 nm (OD(450)) 6.3 ± 0.8 vs. 4.4 ± 0.7 vs. 2.7 ± 0.5, p = 0.0007] and non-diabetic (C/C vs. C/T vs.T/T = OD(450) 2.9 ± 0.6 vs. 2.2 ± 0.4 vs. 1.7 ± 0.4, p = 0.022) patients. CONCLUSIONS: The SH2B3 784T>C variant could contribute to the pathogenesis of T1D through impaired immune response that promotes activation and expansion of self-reactive lymphocytes in susceptible individuals.

Socioeconomic inequalities in overweight and obesity among 6- to 9-year-old children in 24 countries from the World Health Organization European region.

Childhood overweight and obesity have significant short- and long-term negative impacts on children's health and well-being. These challenges are unequally distributed according to socioeconomic status (SES); however, previous studies have often lacked standardized and objectively measured data across national contexts to assess these differences. This study provides a cross-sectional picture of the association between SES and childhood overweight and obesity, based on data from 123,487 children aged 6-9 years in 24 countries in the World Health Organization (WHO) European region. Overall, associations were found between overweight/obesity and the three SES indicators used (parental education, parental employment status, and family-perceived wealth). Our results showed an inverse relationship between the prevalence of childhood overweight/obesity and parental education in high-income countries, whereas the opposite relationship was observed in most of the middle-income countries. The same applied to family-perceived wealth, although parental employment status appeared to be less associated with overweight and obesity or not associated at all. This paper highlights the need for close attention to context when designing interventions, as the association between SES and childhood overweight and obesity varies by country economic development. Population-based interventions have an important role to play, but policies that target specific SES groups are also needed to address inequalities.

Methodology and implementation of the WHO European Childhood Obesity Surveillance Initiative (COSI).

Establishment of the WHO European Childhood Obesity Surveillance Initiative (COSI) has resulted in a surveillance system which provides regular, reliable, timely, and accurate data on children's weight status-through standardized measurement of bodyweight and height-in the WHO European Region. Additional data on dietary intake, physical activity, sedentary behavior, family background, and school environments are collected in several countries. In total, 45 countries in the European Region have participated in COSI. The first five data collection rounds, between 2007 and 2021, yielded measured anthropometric data on over 1.3 million children. In COSI, data are collected according to a common protocol, using standardized instruments and procedures. The systematic collection and analysis of these data enables intercountry comparisons and reveals differences in the prevalence of childhood thinness, overweight, normal weight, and obesity between and within populations. Furthermore, it facilitates investigation of the relationship between overweight, obesity, and potential risk or protective factors and improves the understanding of the development of overweight and obesity in European primary-school children in order to support appropriate and effective policy responses.

Socioeconomic differences in food habits among 6- to 9-year-old children from 23 countries-WHO European Childhood Obesity Surveillance Initiative (COSI 2015/2017).

BACKGROUND: Socioeconomic differences in children's food habits are a key public health concern. In order to inform policy makers, cross-country surveillance studies of dietary patterns across socioeconomic groups are required. The purpose of this study was to examine associations between socioeconomic status (SES) and children's food habits. METHODS: The study was based on nationally representative data from children aged 6-9 years (n = 129,164) in 23 countries in the World Health Organization (WHO) European Region. Multivariate multilevel analyses were used to explore associations between children's food habits (consumption of fruit, vegetables, and sugar-containing soft drinks) and parental education, perceived family wealth and parental employment status. RESULTS: Overall, the present study suggests that unhealthy food habits are associated with lower SES, particularly as assessed by parental education and family perceived wealth, but not parental employment status. We found cross-national and regional variation in associations between SES and food habits and differences in the extent to which the respective indicators of SES were related to children's diet. CONCLUSION: Socioeconomic differences in children's food habits exist in the majority of European and Asian countries examined in this study. The results are of relevance when addressing strategies, policy actions, and interventions targeting social inequalities in children's diets.

Socioeconomic disparities in physical activity, sedentary behavior and sleep patterns among 6- to 9-year-old children from 24 countries in the WHO European region.

Physical activity, sedentary behavior, and sleep are important predictors of children's health. This paper aimed to investigate socioeconomic disparities in physical activity, sedentary behavior, and sleep across the WHO European region. This cross-sectional study used data on 124,700 children aged 6 to 9 years from 24 countries participating in the WHO European Childhood Obesity Surveillance Initiative between 2015 and 2017. Socioeconomic status (SES) was measured through parental education, parental employment status, and family perceived wealth. Overall, results showed different patterns in socioeconomic disparities in children's movement behaviors across countries. In general, high SES children were more likely to use motorized transportation. Low SES children were less likely to participate in sports clubs and more likely to have more than 2 h/day of screen time. Children with low parental education had a 2.24 [95% CI 1.94-2.58] times higher risk of practising sports for less than 2 h/week. In the pooled analysis, SES was not significantly related to active play. The relationship between SES and sleep varied by the SES indicator used. Importantly, results showed that low SES is not always associated with a higher prevalence of "less healthy" behaviors. There is a great diversity in SES patterns across countries which supports the need for country-specific, targeted public health interventions.

Thinness, overweight, and obesity in 6- to 9-year-old children from 36 countries: The World Health Organization European Childhood Obesity Surveillance Initiative-COSI 2015-2017.

In 2015-2017, the fourth round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was conducted in 36 countries. National representative samples of children aged 6-9 (203,323) were measured by trained staff, with similar equipment and using a standardized protocol. This paper assesses the children's body weight status and compares the burden of childhood overweight, obesity, and thinness in Northern, Eastern, and Southern Europe and Central Asia. The results show great geographic variability in height, weight, and body mass index. On average, the children of Northern Europe were the tallest, those of Southern Europe the heaviest, and the children living in Central Asia the lightest and the shortest. Overall, 28.7% of boys and 26.5% of girls were overweight (including obesity) and 2.5% and 1.9%, respectively, were thin according to the WHO definitions. The prevalence of obesity varied from 1.8% of boys and 1.1% of girls in Tajikistan to 21.5% and 19.2%, respectively, in Cyprus, and tended to be higher for boys than for girls. Levels of thinness, stunting, and underweight were relatively low, except in Eastern Europe (for thinness) and in Central Asia. Despite the efforts to halt it, unhealthy weight status is still an important problem in the WHO European Region.

Physical Activity, Screen Time, and Sleep Duration of Children Aged 6-9 Years in 25 Countries: An Analysis within the WHO European Childhood Obesity Surveillance Initiative (COSI) 2015-2017.

BACKGROUND: Children are becoming less physically active as opportunities for safe active play, recreational activities, and active transport decrease. At the same time, sedentary screen-based activities both during school and leisure time are increasing. OBJECTIVES: This study aimed to evaluate physical activity (PA), screen time, and sleep duration of girls and boys aged 6-9 years in Europe using data from the WHO European Childhood Obesity Surveillance Initiative (COSI). METHOD: The fourth COSI data collection round was conducted in 2015-2017, using a standardized protocol that included a family form completed by parents with specific questions about their children's PA, screen time, and sleep duration. RESULTS: Nationally representative data from 25 countries was included and information on the PA behaviour, screen time, and sleep duration of 150,651 children was analysed. Pooled analysis showed that: 79.4% were actively playing for >1 h each day, 53.9% were not members of a sport or dancing club, 50.0% walked or cycled to school each day, 60.2% engaged in screen time for <2 h/day, and 84.9% slept for 9-11 h/night. Country-specific analyses of these behaviours showed pronounced differences, with national prevalences in the range of 61.7-98.3% actively playing for >1 h/day, 8.2-85.6% were not members of a sport or dancing club, 17.7-94.0% walked or cycled to school each day, 32.3-80.0% engaged in screen time for <2 h/day, and 50.0-95.8% slept for 9-11 h/night. CONCLUSIONS: The prevalence of engagement in PA and the achievement of healthy screen time and sleep duration are heterogenous across the region. Policymakers and other stakeholders, including school administrators and parents, should increase opportunities for young people to participate in daily PA as well as explore solutions to address excessive screen time and short sleep duration to improve the overall physical and mental health and well-being of children.

Parental Perceptions of Children's Weight Status in 22 Countries: The WHO European Childhood Obesity Surveillance Initiative: COSI 2015/2017.

INTRODUCTION: Parents can act as important agents of change and support for healthy childhood growth and development. Studies have found that parents may not be able to accurately perceive their child's weight status. The purpose of this study was to measure parental perceptions of their child's weight status and to identify predictors of potential parental misperceptions. METHODS: We used data from the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative and 22 countries. Parents were asked to identify their perceptions of their children's weight status as "underweight," "normal weight," "a little overweight," or "extremely overweight." We categorized children's (6-9 years; n = 124,296) body mass index (BMI) as BMI-for-age Z-scores based on the 2007 WHO-recommended growth references. For each country included in the analysis and pooled estimates (country level), we calculated the distribution of children according to the WHO weight status classification, distribution by parental perception of child's weight status, percentages of accurate, overestimating, or underestimating perceptions, misclassification levels, and predictors of parental misperceptions using a multilevel logistic regression analysis that included only children with overweight (including obesity). Statistical analyses were performed using Stata version 15 1. RESULTS: Overall, 64.1% of parents categorized their child's weight status accurately relative to the WHO growth charts. However, parents were more likely to underestimate their child's weight if the child had overweight (82.3%) or obesity (93.8%). Parents were more likely to underestimate their child's weight if the child was male (adjusted OR [adjOR]: 1.41; 95% confidence intervals [CI]: 1.28-1.55); the parent had a lower educational level (adjOR: 1.41; 95% CI: 1.26-1.57); the father was asked rather than the mother (adjOR: 1.14; 95% CI: 0.98-1.33); and the family lived in a rural area (adjOR: 1.10; 95% CI: 0.99-1.24). Overall, parents' BMI was not strongly associated with the underestimation of children's weight status, but there was a stronger association in some countries. DISCUSSION/CONCLUSION: Our study supplements the current literature on factors that influence parental perceptions of their child's weight status. Public health interventions aimed at promoting healthy childhood growth and development should consider parents' knowledge and perceptions, as well as the sociocultural contexts in which children and families live.

[The efficacy of outpatient monitoring of children and adolescents with type 1 diabetes with regular use of professional continuous glucose monitoring].

BACKGROUND: According to research, only 38% of patients reach glycated hemoglobin targets. It is possible to improve the effectiveness of medical care for children with T1D using modern technologies, including continuous glucose monitoring (CGM). AIMS: To evaluate the effectiveness of outpatient monitoring of children and adolescents with T1D with regular use of professional continuous glucose monitoring. METHODS: The inclusion criteria: age 8−12 years; T1D at least 1 year; insulin therapy by multiple injections of insulin; inadequate glycemic control of T1D: НbА1с level of 7.5% and higher and / or children and adolescents with frequent episodes of hypoglycemia (usually 4 times a week) or with a history of severe hypoglycemia; signed informed consent. All patients initially and 12 weeks after inclusion in the study conducted a study of the level of НbА1с, and also performed CGM for 6 days. Based on the results of CGM, glycemia indicators and daily doses of insulin were recorded, treatment was evaluated and corrected, and recommendations for self-monitoring were made. Glucose monitoring was carried 120−144 hours using the blind method iPro2 (Medtronic, USA). RESULTS: In all, 99 children aged 8−18 years were included in the study in all centers. The decrease in the level of НbА1с by the end of the study was 0.72%, while the proportion of patients who reached the target level of НbА1с (defined as <7.5%) was statistically significantly higher at the end of the study (15.5% and 2%, respectively; p<0.05). During the study, patients showed a trend towards a decrease in the average level and variability of glycemia by the end of the study, however, statistical significance was achieved only in relation to the average level of glycemia (p=0.04). Conducted insulin therapy, determined by the average daily doses of long-acting and short-acting insulin, did not statistically significantly change at the end of the study. The frequency of DKA episodes and severe hypoglycemia did not statistically significantly differ from the initial level. CONCLUSIONS: For children with poor glycemic control of T1D, the use of professional CGM is effective in terms of glycemic control and a safe method.

[Assessment of autoantibodies against 21-hydroxylase in the diagnosis of primary autoimmune adrenal insufficiency].

Primary adrenal insufficiency is manifested by a deficiency of adrenal cortex hormones and can lead to a life-threatening condition. Early diagnosis is key to patient survival. Auto-antibodies to one of the adrenal steroidogenesis enzymes, 21-hydroxylase, are an immunological marker of autoimmune adrenal insufficiency. On the one hand, the study of antibodies to 21-hydroxylase is a method that helps establish the etiology of the disease – the autoimmune genesis of adrenal gland damage. On the other hand, the determination of autoantibodies to 21-hydroxylase is the only prognostic factor of the risk of adrenal insufficiency, which makes it possible to prevent the development of acute adrenal crisis. The article provides a brief literature review on autoantibodies to 21-hydroxylase and the pathogenesis of autoimmune adrenal insufficiency, and a series of clinical cases that illustrates the significant role of autoantibodies to 21-hydroxylase in diagnosis of adrenal insufficiency.

[Remote monitoring and treatment of children and adolescents with type 1 diabetes].

RATIONALE: Continuous subcutaneous insulin infusion (CSII) is an effective method for optimizing glycemic control in children with type 1 diabetes mellitus (DM1). However, the use of CSII does not always result in adequate glycemic control. Telehealth can be applied as one of the methods to improve the effectiveness of treatment. AIMS: To evaluate the use of remote medical support of children and adolescents with DM1 and its influence on glycemic control, quality of life, and incidence of acute complications of DM1. MATERIALS AND METHODS: We conducted a 24-week multi-institutional prospective open-label controlled clinical trial. 180 children and adolescents were included in this study and divided into the following categories: 1) age 8-18 years; 2) DM1 at least 1 year; 3) pump insulin therapy Medtronic Paradigm (Medtronic MiniMed, USA) at least 6 months; 4) self-monitoring of glycemia at least 4 times a day and replacement of the insulin pump infusion system at least once every 3 days; 5) inadequate glycemic control of DM1: the level of glycated hemoglobin (HbA1c) 7.5% or higher. Patients were assigned to a remote consultation group (RC; n=100) or a traditional control group (TC; n=80). All patients were trained on the basic principles of DM1 and CSII, and we measured initial HbA1c, then after 12 and 24 weeks, also registered and analyzed glycemic indicators and daily doses of insulin, evaluated and corrected the treatment. Patients or their parents in the RC group sent pump data via the Internet to the pump insulin therapy center at least once every 2 weeks at home and received treatment recommendations in response. RESULTS: The total number of patients included in the study in all institutions was 180 children at 8-18 years. Patients in both groups did not differ in age, gender, duration of DM1 and CSII, and HbA1c level. The total amount of remote consultations for all institutions was 949. The decrease in the level of HbA1c by the end of the study against the initial one was statistically significantly greater in the RC group: 1.17% compared to 0.59% in the TC group (p<0.05). The proportion of patients who reached the target level of HbA1c (<7.5%) was significantly higher in the RC group (32%) compared to the TC group (12.5%, p<0.05). During the study, the incidence of DKA and severe hypoglycemia in the RC group was statistically significantly lower. CONCLUSIONS: Remote monitoring in children with DM1 resulted in significant improvements in glycemic control (HbA1c, glycemic variability, and hypoglycemic frequency). The accumulation of evidence on the effectiveness and safety of telehealth in DM should contribute to implementing this approach in practical health care.

A Snapshot of European Children's Eating Habits: Results from the Fourth Round of the WHO European Childhood Obesity Surveillance Initiative (COSI).

Consuming a healthy diet in childhood helps to protect against malnutrition and noncommunicable diseases (NCDs). This cross-sectional study described the diets of 132,489 children aged six to nine years from 23 countries participating in round four (2015-2017) of the WHO European Childhood Obesity Surveillance Initiative (COSI). Children's parents or caregivers were asked to complete a questionnaire that contained indicators of energy-balance-related behaviors (including diet). For each country, we calculated the percentage of children who consumed breakfast, fruit, vegetables, sweet snacks or soft drinks "every day", "most days (four to six days per week)", "some days (one to three days per week)", or "never or less than once a week". We reported these results stratified by country, sex, and region. On a daily basis, most children (78.5%) consumed breakfast, fewer than half (42.5%) consumed fruit, fewer than a quarter (22.6%) consumed fresh vegetables, and around one in ten consumed sweet snacks or soft drinks (10.3% and 9.4%, respectively); however, there were large between-country differences. This paper highlights an urgent need to create healthier food and drink environments, reinforce health systems to promote healthy diets, and continue to support child nutrition and obesity surveillance.

Association between Characteristics at Birth, Breastfeeding and Obesity in 22 Countries: The WHO European Childhood Obesity Surveillance Initiative - COSI 2015/2017.

BACKGROUND: In Europe, although the prevalence of childhood obesity seems to be plateauing in some countries, progress on tackling this important public health issue remains slow and inconsistent. Breastfeeding has been described as a protective factor, and the more exclusively and the longer children are breastfed, the greater their protection from obesity. Birth weight has been shown to have a positive association with later risk for obesity. OBJECTIVES: It was the aim of this paper to investigate the association of early-life factors, namely breastfeeding, exclusive breastfeeding and birth weight, with obesity among children. METHOD: Data from 22 participating countries in the WHO European COSI study (round 4: 2015/2017) were collected using cross-sectional, nationally representative samples of 6- to 9-year-olds (n = 100,583). The children's standardized weight and height measurements followed a common WHO protocol. Information on the children's birth weight and breastfeeding practice and duration was collected through a family record form. A multivariate multilevel logistic regression analysis regarding breastfeeding practice (both general and exclusive) and characteristics at birth was performed. RESULTS: The highest prevalence rates of obesity were observed in Spain (17.7%), Malta (17.2%) and Italy (16.8%). A wide between-country disparity in breastfeeding prevalence was found. Tajikistan had the highest percentage of children that were breastfed for ≥6 months (94.4%) and exclusively breastfed for ≥6 months (73.3%). In France, Ireland and Malta, only around 1 in 4 children was breastfed for ≥6 months. Italy and Malta showed the highest prevalence of obesity among children who have never been breastfed (21.2%), followed by Spain (21.0%). The pooled analysis showed that, compared to children who were breastfed for at least 6 months, the odds of being obese were higher among children never breastfed or breastfed for a shorter period, both in case of general (adjusted odds ratio [adjOR] [95% CI] 1.22 [1.16-1.28] and 1.12 [1.07-1.16], respectively) and exclusive breastfeeding (adjOR [95% CI] 1.25 [1.17-1.36] and 1.05 [0.99-1.12], respectively). Higher birth weight was associated with a higher risk of being overweight, which was reported in 11 out of the 22 countries. Bulgaria, Croatia, France, Italy, Poland and Romania showed that children who were preterm at birth had higher odds of being obese, compared to children who were full-term babies. CONCLUSION: The present work confirms the beneficial effect of breastfeeding against obesity, which was highly increased if children had never been breastfed or had been breastfed for a shorter period. Nevertheless, adoption of exclusive breastfeeding is below global recommendations and far from the target endorsed by the WHO Member States at the World Health Assembly Global Targets for Nutrition of increasing the prevalence of exclusive breastfeeding in the first 6 months up to at least 50% by 2025.

A familial insulin-like growth factor-I receptor mutant leads to short stature: clinical and biochemical characterization.

CONTEXT: IGF-I/IGF-I receptor (IGF-IR) signaling pathways play important roles in longitudinal growth. A novel Arg481Glu (R481Q) mutation in IGF-IR was detected in a family with intrauterine and postnatal growth retardation. OBJECTIVE: The objective of the study was to explore the mechanism whereby the R481Q mutation may be causative in growth retardation. PATIENTS: A 13-yr-old girl with short stature was studied for functional analysis of the R481Q mutation in the IGF-IR. RESULTS: Two members of a family who showed intrauterine and postnatal growth retardation, with increased serum IGF-I levels, demonstrated a substitution of arginine for glutamine at 481 (R481Q) in the IGF-IR. This mutation results in the formation of an altered fibronectin type III domain within the alpha-subunit. NIH-3T3 fibroblasts that overexpress the human wild-type or R481Q mutant IGF-IR demonstrated normal cell surface ligand binding by 125I-IGF-I binding assay. However, the fold increase of IGF-I stimulated tyrosine phosphorylation of the IGF-IR beta-subunit as well as downstream activation of ERK1/2 and Akt was reduced in cells overexpressing the mutant receptor. Additionally, basal and IGF-I-stimulated levels of cell proliferation were also reduced in cells overexpressing the mutant receptor. CONCLUSION: Our results demonstrate that NIH-3T3 cells overexpressing a mutant form of the Igf1r gene, in which arginine at 481 is substituted by glutamine, lead to reduced levels of the fold increase of IGF-IR beta-subunit phosphorylation as well as ERK1/2 and Akt phosphorylation and was accompanied by decreased cell proliferation. These results are postulated to be the cause of intrauterine and postnatal growth retardation in the described patients.

A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency.

Valtropin is a recombinant human GH (rhGH) manufactured using a novel yeast expression system, classed as a 'biosimilar'. Valtropin was compared with Humatrope in children with GH deficiency (GHD). Treatment-naive, prepubertal children with GHD were randomized to Valtropin (n = 98) or Humatrope (n = 49) for 1 year. Standing height was measured 3-monthly and height velocity (HV) calculated. Serum IGF-I, IGFBP-3 and GH antibodies were determined centrally. HV at 1 year was 11.3 +/- 3.0 cm/year with Valtropin and 10.5 +/- 2.8 cm/year with Humatrope. Treatment difference was 0.09 cm/year with 95% confidence limits of -0.71, 0.90, within the preset non-inferiority limit of -2.0 cm/year. Height standard deviation (SD) scores were increased in both treatment arms with no acceleration of bone maturation. IGF-I and IGFBP-3 were increased comparably for both treatments. Adverse events showed no clinically relevant differences between treatment groups. Anti-GH antibodies were detected in 3 (3.1%) Valtropin and 1 (2.0%) Humatrope patients and the growth pattern was indistinguishable from the rest of the cohort. The 1-year efficacy and safety profile of Valtropin, a new biosimilar rhGH, are equivalent to the comparator rhGH, Humatrope. Valtropin can be used for the treatment of children with GHD and longer term data will fully establish its efficacy and safety profile.

A glucokinase gene mutation in a young boy with diabetes mellitus, hyperinsulinemia, and insulin resistance.

We report the case of a 12-year-old boy with a glucokinase (GCK) mutation, and diabetes with hyperinsulinemia and insulin resistance. For 4 years, the patient intermittently received insulin medications Actrapid HM and Protaphane HM (total dose 5 U/day), with glycated hemoglobin (HbA1c) levels of 6.6%-7.0%. After extensive screening the patient was found to carry a heterozygous mutation (p.E256K) in GCK (MIM #138079, reference sequence NM_000162.3). Insulin therapy was replaced by metformin at 1,700 mg/day. One year later, his HbA1c level was 6.9%, postprandial glycemia at 120 min of oral glucose tolerance test was 15.4 mmol/L, hyperinsulinemia had increased to 508.9 mU/L, homeostasis model assessment index was 114.2 and the Matsuda index was 0.15. Insulin resistance was confirmed by a hyperinsulinemic euglycemic clamp test - M-index was 2.85 mg/kg/min. This observation is a rare case of one of the clinical variants of diabetes, which should be taken into account by a vigilant endocrinologist due to the need for nonstandard diagnostic and therapeutic approaches.