Understanding the pubertal, psychosocial, and cognitive developmental trajectories of stunted and non-stunted adolescents: protocol of a multi-site Indonesian cohort study.

Background: The prevalence of stunting among Indonesian children aged 5-12 years decreased from 30.7% in 2013 to 23.6% in 2018 but has remained among the highest rates worldwide. Furthermore, Indonesian children were shorter than the standard reported by the World Health Organization and experienced obesity. The Indonesian government has created many programs to reduce stunting in children under the age of 5 years. An early preventive strategy is necessary because stunting can manifest within the initial 1,000 days of life, including during pregnancy. Therefore, a newer perspective, such as that achieved by addressing stunting in adolescents, has been deemed useful, given that adolescents are in their pubertal stage and are undergoing lifestyle changes. This cohort study was designed to measure these factors comprehensively in stunted and non-stunted children as they pass through adolescence. Methods: For the prospective cohort, 560 individuals will be recruited from DKI Jakarta, DI Yogyakarta, and East Java. The participants will be categorized into stunted and non-stunted groups, then undergo annual examinations in which key objectives, such as weight, height, and body mass index ,will be assessed for the growth profile; waist circumference, middle-upper arm circumference, hand-grip strength, body fat percentage, and food intake will be evaluated in a nutritional assessment; psychosocial and mental issues will be evaluated according to behavioral problems, symptoms of depression, quality of life, sleep patterns, anxiety disorders, and parenting style through the use of specific questionnaires; and pubertal stage will be assessed using a self-report questionnaire. Some cross-sectional data, such as cognitive performance, hair zinc levels, vitamin D levels, bone mineral density, and bone age, will also be included. All the outcomes will be analyzed in accordance with the variable types. Discussion: This study provides a thorough dataset of Indonesian adolescents encompassing several elements, such as growth, nutrition, psychosocial wellbeing, mental health, and pubertal development, for both stunted and non-stunted individuals. The data acquired from this study can be used to formulate policies to prevent stunting through targeted interventions for adolescents. Finally, a better understanding of adolescent health could lead to improved strategies to decrease the number of stunted individuals in the next Indonesian generation.

Effect of high-calorie formula on weight, height increment, IGF-1 and TLC in growth faltering children: A quasi-experimental study.

High-calorie formulas have been used to promote catch-up growth in undernourished children. The level of insulin-like growth factor 1 (IGF-1) is closely related to weight and nutritional intake, whereas low a total lymphocyte count (TLC) is associated with impaired immune system function in undernourished children. This study was conducted to investigate the effect of high-calorie formula as an intervention on weight, height increment, IGF-1 and TLC in children with growth faltering or undernutrition. A quasi-experimental study with pre- and post-design was conducted in the outpatient clinic of a private hospital during October 2021-July 2022 on children with growth failure and underlying infection. For 90 days, subjects were given a high-calorie formula. An enzyme-linked immunosorbent assay was then conducted to measure IGF-1, followed by a complete blood count examination. Subjects were divided into two groups based on age: Group 1 (12-24 months) and Group 2 (>24-60 months). There was a significant increment in body weight and body length/height after intervention but no significant difference between the groups. The increment of body length/height after intervention was greater in Group 1 than Group 2 (p = 0.000) and reduced the incidence of stunted/severely stunted and wasted/severely wasted children (p > 0.05). IGF-1 increased after the intervention but with no significant difference (1.42 ± 8.31 ng/ml; p = 0.144). There was a significant reduction in TLC after the intervention (1194.34 + 4400.34 cells/mm3; p = 0.002) that was reduced in Group 1 and slightly increased in Group 2 (p = 0.003). Being underweight/severely underweight increased the risk of a low TLC by 27.658-fold but this risk was reduced by 25.904-fold after nutritional intervention. High-calorie formula intervention increases body weight and body length/height, reduces the incidence of underweight, stunted and wasted children and improves IGF-1 levels.

Beyond the Scale: Investigating Adiponectin, ICAM-1, and VCAM-1 as Metabolic Markers in Obese Adolescents with Metabolic Syndrome.

Background: Adiponectin acts to prevent vascular dysfunction due to obesity by inhibiting ICAM-1 and VCAM-1 expressions. Objective: We investigate adiponectin ICAM-1, VCAM-1, and metabolic syndrome (MetS) in obese adolescents. Methods: A cross-sectional study with healthy obese adolescents aged 13 to 18 years was conducted from October 2019 to January 2020. Statistical analysis conducted was a test of normality and homogeneity tests, ANOVA/Kruskal-Wallis, independent sample T-test/Mann-Whitney U test, and Spearman correlation and determined as significant if p value <0.05. Results: 125 obese adolescents were recruited. 42 (33.6%) were obese with MetS (we grouped as MetS) and 83 (66.4%) subjects without MetS (non-MetS group). VCAM-1 was significantly higher on boys with MetS compared to girls with MetS, and even girls with MetS had lower levels of VCAM-1 than boys with non-MetS. ICAM-1 was significantly higher in boys with low-level HDL-c (p < 0.05) and correlated weakly with HDL-c, while adiponectin levels were significantly lower in girls with central obesity and hypertriglyceridemia. Path analysis showed that triglyceride had a direct effect on ICAM-1 but not VCAM-1 in both obese boys and girls. Adiponectin had a negative direct effect on ICAM-1 and VCAM-1 in girls. However, on boys, diastole blood pressure had a negative direct effect, which might be the role of sex hormones indirectly. Conclusion: VCAM-1 was significantly higher in boys than girls, which showed that boys had a higher risk of atherosclerosis. ICAM-1 showed no significant difference in both gender and metabolic states. Adiponectin showed a protective effect by lowering ICAM-1 and VCAM-1 directly on girls.

Sleep duration and insulin resistance in obese adolescents with metabolic syndrome: is there a correlation?

BACKGROUND AND AIM: Short sleep duration causes many changes in several hormones (leptin, ghrelin, insulin, cortisol, growth hormone) and increases sympathetic activity with elevated levels of catecholamines, which causes an energy imbalance and leads to overweight or obesity and insulin resistance. The present study aimed to analyze the relationship between sleep duration and insulin resistance in obese adolescents with metabolic syndrome. METHODS: An observational cross-sectional research design concluded 124 obese adolescents with metabolic syndrome (MetS) aged 13-18 years. Anthropometry, blood pressure, and blood tests were conducted to determine obesity according to CDC 2000. MetS determination based on International Diabetes Federation 2007. Insulin resistance was assessed using HOMA-IR. Sleep duration was determined based on direct interviews with the research subjects. The obtained data were analyzed using the Spearman correlation test, Chi-Square, Mann-Whitney, and T-test (significant at P <0.05). RESULTS: The subjects were dominated by male adolescents 67.5%. There was a strong relationship between age and sleep duration (p = 0.035). Subjects were divided into two age groups based on sleep duration: those with < 8 hours and > 8 hours of sleep. There was a significant difference in fasting insulin levels and HOMA IR value between the two groups, higher in the subjects with < 8 hours of sleep than the subjects with > 8 hours of sleep. Sleep duration and HOMA-IR values ​​as a marker of insulin resistance had a significant negative correlation (rs= -0.581; P <0.001) and insulin levels (rs=-0.565, P <0.001). CONCLUSIONS: Sleep duration has a robust negative correlation with the HOMA-IR value, which is a parameter of insulin resistance. (www.actabiomedica.it).

Value of waist-to-hip ratio as a predictor of metabolic syndrome in adolescents with obesity.

BACKGROUND AND AIM: Metabolic syndrome is present in 7% of adolescents and 19 to 35% in obese adolescents, and the cause of this condition has not been fully understood. Early identification of the risk involved could be an initial step in preventing a metabolic syndrome. Increased waist circumference, which is a parameter of central obesity, is also risk factor for this condition. This study aims to determine the possibility cut-off value of waist-to-hip (WHR) as a predictor of metabolic syndrome. METHODS: We studied 208 obese adolescents between the ages of 13 to 18 years from junior and senior high schools who living in rural dan urban areas in East Java. These obese adolescents were divided into two groups, namely with and without a metabolic syndrome. Anthropometric measurements, including waist-to-hip ratio (WHR), were carried out to analyze the cut-off values between the two groups. RESULTS: 208 obese adolescents (51.4% males and 48.6% females) without the metabolic syndrome and 104 obese adolescents with metabolic syndrome were evaluated. There was a significant relationship between WHR and metabolic syndrome in obese adolescents (r = 0.203, P = 0.003). Those adolescents with a high WHR value > 0.891 had twice risk to develop metabolic syndrome compared to those with lower (OR 2.033; 95% CI = 1.165-3.545). CONCLUSIONS: Increased waist-to-hip ratio > 0.89 in adolescents was associated with higher risk to develop metabolic syndrome and can be proposed as a predictor for metabolic syndrome in obese adolescents.

METS-IR vs. HOMA-AD and Metabolic Syndrome in Obese Adolescents.

PURPOSE: Obesity is associated with chronic low-grade inflammation in which is the key in the pathogenesis Insulin Resistance (IR) and Metabolic Syndrome (MetS). Homeostasis model assessment of insulin resistance (HOMA-IR) has been validated as a surrogate measure of IR. The combination of HOMA and adiponectin, known as HOMA-AD was proposed to measure IR in adults. However, study on these indicators in obese adolescents is still limited. This study aims to analyse METS-IR and HOMA-AD to determine MetS and IR in obese adolescents. METHODS: A cross-sectional study was conducted on obese adolescents who looked healthy from secondary schools in Surabaya and Sidoarjo, East Java, aged 12-18 years. Subjects were selected randomly and grouped into 2, namely MetS and non-MetS based on IDF 2000. Anthropometric examination and blood measurements, such as fasting blood glucose levels, lipid profiles, insulin, and adiponectin level were carried out according to standards. HOMA-IR, HOMA-AD, AND METS-IR were calculated using formula. Spearman's Rho correlation were conducted between assessment tools (METS-IR and HOMA-AD) to identify the correlation with MetS component (lipid profile, FBG, and blood pressures). A receiving operation curve (ROC) performed to find area under curve (AUC) and cut-off points based on the biggest Youden index. RESULT: A total of 250 subjects were enrolled the study, and found 103 subjects had MetS. METS-IR correlates with all lipid profile and blood pressures (p?

PLA2G6-Associated Neurodegeneration: A Rare Case Report of Neurodegeneration with Brain Iron Accumulation in Children.

This report aimed to describe and review the clinical features, neuroimaging findings, and PLA2G6 mutations identified in a 34-month-old girl with regression of developmental milestones. A 34 months old girl came to Dr.Soetomo Hospital's outpatient clinic, Surabaya, with a developmental regression for six months, and got worse until she could not do any activity and was followed by recurrent seizures. She had a sibling who had similar problems and symptoms and then died at five years of age. The head MRI revealed brain atrophy, the possibility of an early sign of metabolic disorder, and a white matter lesion at the globuspallidus bilateral that supports the encephalopathy metabolic view. The genetic test revealed a positive homozygous such as a pathogenic variant in the PLA2G6 gene, which confirmed the diagnosis. PLA2G6-Associated with Neurodegeneration (PLAN) should be considered as a diagnosis in children with developmental regression.

Effect of lactoferrin in oral nutrition supplement (ONS) towards IL-6 and IL-10 in failure to thrive children with infection.

Background: Growth failure due to infection in children is a major health problem throughout the world. It provokes a systemic immune response, with increased interleukin (IL)-6 and reduced IL-10. Lactoferrin (Lf) is a multifunctional iron-binding protein that can be found in whey protein inside formula milk such as oral nutrition supplement (ONS), which is able to upregulate anti-inflammatory cytokines (IL-10) and modulate pro-inflammatory cytokines. We conducted this study to investigate the effect of Lf supplementation in ONS on IL-6 and IL-10 levels in children with failure to thrive and infection. Methods: We performed a quasi-experimental pre- and post-study in children aged 12-60 months old with failure to thrive due to infectious illness. The subjects received 400 ml of oral nutritional supplements (ONS, 1 ml equivalent to 1 kcal) each day for 90 days, and their parents received dietary advice and medication based on the underlying illness. Blood was drawn to measure IL-6 and IL-10 before and after the intervention. Results: There were 75 subjects recruited and divided into group-1 and group-2 based on age. The incidence of undernutrition was 37.33%. Lf in ONS intervention improved body weight and body length. Lf also reduced IL-6, although there was not a significant difference before and after the intervention. However, the IL-6 reduction was significantly higher in subjects with undernutrition compared with subjects with weight faltering. Pre-intervention IL-6 levels were higher in children with stunting than in children with normal stature. There was a greater change in IL-6 in children with severe stunting than in children with normal stature or stunting. IL-10 was significantly reduced after the intervention. Conclusions: In addition to improving body weight and length, Lf supplementation in ONS improved immune response homeostasis by balancing IL-6 and IL-10 levels and by improving the IL-6/IL-10 ratio.ClinicalTrials.gov number ID: NCT05289674, dated May 3 rd 2022.

Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia.

OBJECTIVE: To investigate the use of glutamine administered orally during Methotrexate chemotherapy to prevent oral mucositis and reduce hospital costs in children with acute lymphoblastic leukemia (ALL). METHODS: Twenty-four children received oral glutamine (400 mg/kg body weight per day) and twenty four received placebo on days of chemotherapy administration and for at least 14 additional days. Oral mucositis  was graded daily at each day of treatment till completion of therapy. The study groups were compared for the oral mucositis development using the WHO scale. RESULTS: Oral mucositis occurred in 4.2 % of the glutamine group and 62.5% in the placebo group. The use of glutamine was directly associated with prevention of oral mucositis than placebo (OR 0,026; 95% CI: 0,003-0,228). The duration of length hospital stay was lower in the glutamine group than in the placebo group ((8 vs 12 days); p = 0,005). Hospital cost per day for glutamine group was 40 USD per day while placebo group was 48 USD per day. CONCLUSIONS: There was significant difference in the prevention of oral mucositis by oral glutamine vs placebo. The hospital cost for glutamine supplementation was lower than control group.

Impact of Intravenous Omega-3-Enriched Lipid Emulsion on Liver Enzyme and Triglyceride Serum Levels of Children Undergoing Gastrointestinal Surgery.

PURPOSE: To investigate the impact of omega-3-enriched lipid emulsion (LE) on liver enzyme (aspartate transaminase [AST] and alanine aminotransferase [ALT]) and triglyceride (TG) levels of children undergoing gastrointestinal surgery. METHODS: This experimental randomized controlled group pretest-posttest design study included 14 children who underwent gastrointestinal surgery due to duodenal atresia, jejunal atresia, esophageal atresia, and need for parenteral nutrition for a minimum of 3 days at RSUD Dr. Soetomo Surabaya between August 2018 and January 2019. These children were divided into two groups, those who received standard intravenous LE (medium-chain triglyceride [MCT]/long-chain triglyceride [LCT]) and those who received intravenous omega-3-enriched LE. Differences in AST, ALT, and TG levels were measured before surgery and 3 days after the administration of parenteral nutrition. RESULTS: Liver enzyme and TG levels in each group did not differ significantly before versus 3 days after surgery. However, TG levels were significantly lower in the omega-3-enriched intravenous LE group (p=0.041) at 3 days after surgery, and statistically significant difference in changes in TG levels was noted at 3 days after surgery between MCT/LCT intravenous LE group and the omega-3-enriched intravenous LE group (p=0.008). CONCLUSION: The intravenous omega-3-enriched LE had a better TG-lowering effect than the MCT/LCT intravenous LE in children undergoing gastrointestinal surgery.

Effects of a multispecies synbiotic on intestinal mucosa immune responses.

BACKGROUND AND OBJECTIVES: Probiotics and prebiotics are known to regulate immune responses. A synbiotic is a product that combines probiotics and prebiotics in a single dosage form. In this study, we attempt to present the effects of a multispecies synbiotic on intestinal mucosa immune responses after exposure to Escherichia coli O55:B5 lipopolysaccharide (LPS). MATERIALS AND METHODS: Totally 21 male Balb/c mice were randomly classified into two groups. The K-I group received LPS and a synbiotic, and the K-II group received LPS alone. The synbiotic was administered for 21 consecutive days, whereas LPS was administered once on the 15th day. Specifically, a synbiotic containing 1 × 109 colony forming units (CFUs) of the probiotic combination of Lactobacillus acidophilus PXN 35, L. casei subsp. casei PXN 37, L. rhamnosus PXN 54, L. bulgaricus PXN 39, Bifidobacterium breve PXN 25, B. infantis PXN 27 and Streptococcus thermophilus PXN 66 and the prebiotic fructo-oligosaccharide was administered through an orogastric tube. Immunohistochemistry was performed to measure immunoglobulin A (IgA) levels for humoral immune responses and CD4+ and CD8+ levels for cellular immune responses. RESULTS: An independent-samples t-test revealed significant increases of the numbers of IgA- (p = 0.027) and CD4-expressing cells (p = 0.009) but not the number of CD8-expressing cells in the K-I group compared with those in the K-II group. CONCLUSION: The multispecies synbiotic had immunoregulatory effects on IgA and CD4 expression in LPS-exposed mice.

Carotid intima-media thickness, hypertension, and dyslipidemia in obese adolescents.

INTRODUCTION: Obesity is a global health problem with growing prevalence in developing countries. Obesity causes chronic inflammation due to imbalances between pro- and anti-inflammatory cytokines. This causes metabolic complications such as dyslipidemia, hypertension, and cardiovascular disorder. Carotid intima-media thickness (CIMT) is a predictor of atherosclerosis which could be measured easily and non-invasively. Early detection of cardiovascular diseases in obese adolescents at risk is hoped to improve outcomes. METHODS: This is a cross-sectional study on obese adolescents aged 13-16 year old at Pediatric Clinic of Dr. Soetomo General Hospital. Obesity is defined as Body mass index higher than 95th percentiles according to CDC (2000). Dyslipidemia is diagnosed when either an increase in cholesterol, LDL, triglyceride or a decrease in HDL level is found, as recommended by NCPE and American Academy of Pediatrics. Hypertension is defined as an increase of blood pressure > P95 according to age and gender. The differences of CIMT based on dyslipidemia, hypertension, and gender were analyzed with Wilcoxon Mann Whitney with significant p value (p < 0,005). RESULTS: This study included 59 obese adolescents, consisting of 32 (54.2%) male adolescents and 35 (59.3%) female adolescents. Dyslipidemia was found on 38 (64.4%) adolescents and hypertension was found on 35 (59.3%) adolescents. No difference of CIMT was found between obese adolescents with and without dyslipidemia and with and without hypertension based on gender (p > 0.05). CONCLUSION: No difference of CIMT based on gender between adolescents aged below 18. The high number of dyslipidemia and hypertension in obese adolescents need an early detection of cardiovascular complication.