The rehabilitation of children and adolescents with severe or medically complicated obesity: an ISPED expert opinion document.

Severe/medically complicated obesity in childhood, and particularly in adolescence, is a real disability that requires an intensive and continuous approach which should follow the procedures and schedule of rehabilitation medicine. Given the lack of a specific document focusing on children and adolescents, the Childhood Obesity Study Group set out to explore the available evidence for the treatment of severe or medically complicated obesity and to set standards tailored to the specific context of the Italian Health Service. Through a series of meetings and electronic communications, the writing committee (selected from members of the Study Group) selected the key issues, explored the literature and produced a draft document which was submitted to the other experts until the final synthesis was approved by the group. In brief, the following issues were involved: (1) definition and epidemiology; (2) identification of common goals designed to regain functional competence and limit the progression of metabolic and psychological complications; (3) a multi-professional team approach; (4) the care setting. This paper is an expert opinion document on the rehabilitation of severe and medically complicated obesity in children and adolescents produced by experts belonging to the Childhood Obesity Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED).

Cross-sectional exploration of maternal reports of food neophobia and pickiness in preschooler-mother dyads.

OBJECTIVE: To investigate cross-sectional associations of food neophobia and pickiness in preschoolers and in their mothers with regard also to food consumption, proposal of new foods, feeding, and weaning modes. DESIGN: Matched child and maternal data collected by means of self-report questionnaires administered to mothers. SETTING: Kindergartens of the City of Rome Municipality, Italy. SUBJECTS: One hundred twenty-seven mother-child pairs. Children were aged from 2 to 6 years. All participants were normal weight or obese. MEASURES OF OUTCOME: Mothers' and children's food neophobia and pickiness. RESULTS: Pickiness and neophobia were related within both children's (r(o) = 0.528, p = 0.001) and mothers' (r(o) = 0.186, p = 0.037) samples. Mothers' and children's neophobia and pickiness were significantly although modestly associated (neophobia r(o) = 0.223, p = 0.012; pickiness r(o) = 0.311, p = 0.001). Overweight and obese children were significantly more neophobic (18.8 ± 6.4 vs 15.7 ± 7.6; p = 0.03) and picky (6.87 ± 2.2 vs 5.72 ± 2.7; p = 0.03) than normal-weight children. CONCLUSIONS: Preschoolers' food neophobia and pickiness were correlated. Mothers and children displayed similarities in food neophobia, pickiness, and dietary habits. Genetics and environmental cues jointly contribute to shape preschoolers' attitudes toward familiar and unfamiliar foods. Hence, future longitudinal studies of larger samples are necessary to better define the role of genetics, parental feeding practices, and environmental characteristics in the development of food neophobia and pickiness.

Childhood Obesity and COVID-19 Lockdown: Remarks on Eating Habits of Patients Enrolled in a Food-Education Program.

Childhood obesity is a worldwide health emergency. In many cases, it is directly linked to inappropriate eating habits and a sedentary lifestyle. During lockdown aimed at containing the coronavirus disease (COVID-19) spread, children have been forced to stay at home. The present study aimed at investigating the lifestyles of outpatients (aged 5-17 years) with complicated obesity enrolled in the day-hospital food education program at the Children's Hospital Bambino Gesù in Rome. A survey was performed based on a structured questionnaire, investigating dietary habits and lifestyles. The questionnaire answers were rated as "yes/no/sometimes" or "often/never/sometimes". Eighty-eight families correctly completed the questionnaire between March and May 2020. The results highlighted that 85.2% (N = 75) of the patients ate breakfast regularly, and 64.3% (N = 72) consumed fruit as an afternoon snack. However, 21.6% (N = 19) did just "often" home workouts, and 50.0% (N = 44) reported an increase of feeling hungry with "sometimes" frequency. There is a significant relationship of feeling hungry with gender (p < 0.0001) and age (p = 0.048) and, also, between gender with having breakfast (p = 0.020) and cooking (p = 0.006). Living a healthy lifestyle during lockdown was difficult for the outpatients, mainly due to the increase in a sedentary lifestyle and the increase in feeling hungry, but some healthy eating habits were maintained, as advised during the food education program provided before lockdown.

Poor Health Related Quality of Life and Unhealthy Lifestyle Habits in Weight-Loss Treatment-Seeking Youth.

Obesity is associated with unhealthy lifestyle behaviors and poor Health Related Quality of Life (HRQOL). The cumulative effect of lifestyle behaviors on HRQOL has been demonstrated in chronically ill adolescents, but not in adolescents with obesity. The present study aimed to assess the association between HRQOL and adherence to the Mediterranean Diet (MD) and/or low levels of physical activity (PA) in a large sample of outpatient adolescents with overweight or obesity seeking weight loss treatment. Four-hundred-twenty participants were enrolled from 10 Italian outpatient clinics. The demographics and anthropometric features, KIDMED scores, and exercise levels of the participants were collected, together with parental features. The HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL™), Adolescents Version 4.0. PedsQL total score and functioning subscales were lower in adolescents who reported one or two unhealthy habits. Compared with the high/intermediate groups, the risk of low HRQOL was twice as high for each unit increase in BMI SDS, while the percentage was reduced by 12.2% for every unit increase in the KIDMED score and by 32.3% for each hour increase of exercise. The clustering of these two unhealthy behaviors conferred a 120% higher risk of low HRQOL. Similarly, adolescents displaying better diet quality and/or a physically more active lifestyle have better physical and psychological functioning. Further studies are needed to disclose whether these characteristics may be predictive of better adherence to weight loss treatment.

Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity.

BACKGROUND: Melanocortin-4-receptor (MC4R) mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype. METHODS: To perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index > or = 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese), obesity onset before the 10 years old, height > or = 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 +/- 3.1, mean BMI 30.8 +/- 5.4) and in 200 controls (mean age 8.1 +/- 2.8; mean BMI 14.2 +/- 2.5). RESULTS: Three mutations have been found in five obese children. The S127L (C380T), found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T) and the Y332H (T994C) mutations were found in two patients. Functional studies showed that only Q307X impaired protein function. CONCLUSION: The low prevalence of MC4R mutations (1.6%) in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.

Oral glucose effectiveness and metabolic risk in obese children and adolescents.

AIM: To investigate whether GE is affected in children/adolescents with obesity and abnormalities of the metabolic syndrome (MetS). METHODS: Cross-sectional study of oral GE (oGE), insulin sensitivity and secretion (calculated on 5 time-points oral glucose tolerance test) and metabolic abnormalities in 1012 patients with overweight/obesity (aged 6.0-17.9 years old). A MetS risk score was calculated on the basis of distribution of fasting glucose, triglycerides, HDL-cholesterol, total cholesterol, systolic and diastolic blood pressure. Non-alcoholic fatty liver disease (NAFLD) was suspected based on thresholds of alanine aminotransferases. RESULTS: Four-hundred and eighty patients (47.73%) had low-MetS risk score, 488 medium (48.22% with 1-2 risk factors) and 41 (4.05% with ≥ 3 factors) high risk. oGE was significantly lower in subjects with obesity [3.81 (1.46) mg/dl/min- 1] than in those with overweight [4.98 (1.66) mg/dl/min- 1; p value < 0.001]. oGE was negatively correlated with BMI (ρ = - 0.79; p < 0.001) and BMI z score (ρ = - 0.56; p < 0.001) and decreased significantly among MetS risk classes (p = 0.001). The median difference of oGE from low to medium risk was estimated to be as - 4.9%, from medium to high as - 13.38% and from low to high as - 17.62%. oGE was not statistically different between NAFLD+ and NAFLD- cases. CONCLUSIONS: In children and adolescents with obesity oGE decreases. Noteworthy, it decreases as the Met score increases. Therefore, reduced oGE may contribute to the higher risk of these individuals to develop type 2 diabetes.

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics.

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.

Percentiles of serum uric acid and cardiometabolic abnormalities in obese Italian children and adolescents.

BACKGROUND: To investigate the association of serum uric acid (SUA) with cardiometabolic abnormalities in Caucasian overweight/obese children (<10 years of age) versus adolescents (≥10 years of age) by drawing age and gender specific percentiles of uric acid. METHODS: Cross-sectional evaluation of 1364 Caucasian overweight/obese patients (age 4.1-17.9 years; 726 males, 53%; 560 children, 41%). RESULTS: SUA levels were significantly lower in children than in adolescents (4.74 ± 1.05 vs. 5.52 ± 1.49 mg/dl, p < 0.001) and peaked in 12-14 years-old boys and 10-12 years-old girls. In children with levels of SUA in the highest quartile (N = 75, 13%), OR for high triglycerides was 4.145, 95% CI 1.506-11.407 (p = 0.009). In adolescents with SUA in the highest quartile (N = 274, 34%), ORs for insulin resistance was 2.399 (95%CI 1.4-4.113; p < 0.001); for impaired fasting glucose 2.184 (95% CI 0.877-5.441; p = 0.07); for impaired glucose tolerance 2.390 (95% CI 1.405-4.063; p = 0.001); and for high triglycerides 1.8, (95%CI 0.950-3.420; p = 0.05). Multivariable random-effect linear regression models demonstrated that waist circumference and age (p < 0.0001 for both) are the variables most significantly predicting SUA levels, followed by triglycerides (p = 0.005) and 2 h glucose (p = 0.03) while HOMA-IR and BMI z-score did not predict SUA. CONCLUSIONS: High uric acid is associated with metabolic abnormalities and particularly with waist circumference very early in childhood.

Triglycerides-to-HDL cholesterol ratio as screening tool for impaired glucose tolerance in obese children and adolescents.

AIMS: To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (n = 148, age 5-10 years) and adolescents (n = 531, age 10-17.9 year). METHODS: Phenotypes were defined as follows: obesity by the 95th cut-points of the Center for Disease Control body mass index reference standards, impaired fasting glucose (fasting plasma glucose ≥100 mg/dl), high circulating triglycerides (TG), TG/HDL cholesterol ≥2.2, waist-to-height ratio (WTHR) >0.6, and combination of the latter with high TG or TG/HDL cholesterol ≥2.2. RESULTS: In the 148 obese children, TG/HDL-C ≥ 2.2 (OR 20.19; 95 % CI 2.50-163.28, p = 0.005) and the combination of TG/HDL-C ≥ 2.2 and WTHR > 0.60 (OR 14.97; 95 % CI 2.18-102.76, p = 0.006) were significantly associated with IGT. In the 531 adolescents, TG/HDL-C ≥ 2.2 (OR 1.991; 95 % CI 1.243-3.191, p = 0.004) and the combination with WTHR > 0.60 (OR 2.24; 95 % CI 1.29-3.87, p = 0.004) were associated with significantly increased risk of IGT. In the whole sample, having high TG levels according to the NIH National Heart, Lung and Blood Institute Expert Panel was not associated with an increased risk of presenting IGT. CONCLUSIONS: TG/HDL-C ratio can be useful, particularly in children, to identify obese young patients at risk of IGT. Its accuracy as screening tool in a general population needs to be verified. The combination of TG/HDL-C ratio and WTHR > 0.6 did not improve prediction. Having high TG according to the NIH definition was not associated with increased risk of developing IGT.

Reference ranges of HOMA-IR in normal-weight and obese young Caucasians.

AIMS: Insulin resistance (IR) may develop very early in life being associated with occurrence of cardiometabolic risk factors (CMRFs). Aim of the present study was to identify in young Caucasians normative values of IR as estimated by the homeostasis model assessment (HOMA-IR) and cutoffs diagnostic of CMRFs. METHODS: Anthropometrics and biochemical parameters were assessed in 2753 Caucasians (age 2-17.8 years; 1204 F). Reference ranges of HOMA-IR were defined for the whole population and for samples of normal-weight and overweight/obese individuals. The receiver operator characteristic analysis was used to find cutoffs of HOMA-IR accurately identifying individuals with any CMRF among total cholesterol and/or triglycerides higher than the 95th percentile and/or HDL cholesterol lower than the 5th for age and sex, impaired glucose tolerance, and alanine aminotransferase levels ≥40 U/l. RESULTS: Overweight/obese individuals had higher HOMA-IR levels compared with normal-weight peers (p < 0.0001) at any age. HOMA-IR index rose progressively with age, plateaued between age 13 and 15 years and started decreasing afterward. HOMA-IR peaked at age 13 years in girls and at 15 years in boys. The 75th percentile of HOMA-IR in the whole population (3.02; AUROC = 0.73, 95 % CI = 0.70-0.75), in normal-weight (1.68; AUROC = 0.76, 95 % CI = 0.74-0.79), and obese (3.42; AUROC = 0.71, 95 % CI = 0.69-0.72) individuals identified the cutoffs best classifying individuals with any CMRF. CONCLUSIONS: Percentiles of HOMA-IR varied significantly in young Caucasians depending on sex, age, and BMI category. The 75th percentile may represent an accurate cutoff point to suspect the occurrence of one or more CMRFs among high total cholesterol and triglycerides, low HDL cholesterol, and ALT ≥ 40 UI/l.

NutricheQ Questionnaire assesses the risk of dietary imbalances in toddlers from 1 through 3 years of age.

BACKGROUND: Although a nutrient-poor diet may affect children's growth, especially early in life, few tools to assess dietary imbalances in 1- to 3-year-old children have been developed. OBJECTIVES: To investigate the accuracy and test-retest reliability of the NutricheQ Questionnaire in the identification of toddlers with the risk of inadequate intake of micro- and macronutrients in a sample of Italian toddlers. DESIGN: A 3-day weighed food record was performed, and results were compared with outcomes of the NutricheQ Questionnaire in 201 toddlers (training set: 1-3 years old). The accuracy of NutricheQ in the identification of categories of nutritional risk was evaluated using the receiver operating characteristic (ROC) curves. Test-retest of the tool was estimated using the intraclass correlation coefficient (ICC) and the Cronbach's alpha statistic, in a validation set of 50 toddlers. RESULTS: The NutricheQ Questionnaire is a valid tool for the identification of toddlers at risk for dietary imbalances. Significant differences in nutrient intake (p<0.005) were found among the three groups of risk identified by the questionnaire: toddlers included in the high-risk group had a lower intake of key nutrients such as iron, vitamin D and other vitamins, and fibre compared to those included in the low-risk group. NutricheQ is also reliable between administrations, as demonstrated by its test-retest reliability. ICC and Cronbach's alpha were 0.73 and 0.83, respectively, for Section 1 of NutricheQ, and 0.55 and 0.70 for Section 2. CONCLUSIONS: The NutricheQ Questionnaire is a reliable and consistent tool for the assessment of possible dietary risk factors in Italian toddlers. It consistently identifies toddlers with a high probability of having poor iron and vitamin D intake, and other dietary imbalances.

Biomarkers of Alzheimer disease, insulin resistance, and obesity in childhood.

OBJECTIVE: To answer the question of whether onset of insulin resistance (IR) early in life enhances the risk of developing dementia and Alzheimer disease (AD), serum levels of 2 molecules that are likely associated with development of AD, the amyloid ß-protein 42 (Aß42) and presenilin 1 (PSEN1), were estimated in 101 preschoolers and 309 adolescents of various BMI. METHODS: Participants (215 boys; 48.8%) were normal weight (n = 176; 40%), overweight (n = 135; 30.7%), and obese (n = 129; 29.3%). The HOmeostasis Model of IR (HOMA-IR), HOMA percent ß-cell function (HOMA-ß) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. RESULTS: Obese adolescents had values of Aß42 higher than overweight and normal-weight peers (190.2 ± 9.16 vs 125.9 ± 7.38 vs 129.5 ± 7.65 pg/mL; P < .0001) as well as higher levels of PSEN1 (2.34 ± 0.20 vs 1.95 ± 0.20 vs 1.65 ± 0.26 ng/mL; P < .0001). Concentrations of Aß42 were significantly correlated with BMI (ρ = 0.262; P < .0001), HOMA-IR (ρ = 0.261; P < .0001) and QUICKI (ρ = -0.220; P < .0001). PSEN1 levels were correlated with BMI (ρ = 0.248; P < .0001), HOMA-IR (ρ = 0.242; P < .0001), and QUICKI (ρ = -0.256; P < .0001). Western blot analysis confirmed that PSEN1 assays measured the full-length protein. CONCLUSION: Obese adolescents with IR present higher levels of circulating molecules that might be associated with increased risk of developing later in elderly cognitive impairment, dementia, and AD.

Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease.

OBJECTIVE: To investigate the association between plasma vitamin D (VD) levels and histological liver damage in children with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: In this cross-sectional study, carried out in a tertiary care center for obesity, 73 consecutive overweight and obese children with persistently elevated serum aminotransferase levels and diffusely hyperechogenic liver on ultrasonography were selected for liver biopsy. Nonalcoholic steatohepatitis (NASH) and fibrosis were histologically diagnosed using NAFLD Clinical Research Network (CRN) criteria. The plasma levels of 25-OH-VD were measured by HPLC. Bone mineral density (BMD) of lumbar spine was evaluated by dual-energy X-ray absorptiometry. Multiple linear regression analysis was used to evaluate the association between 25-OH-VD levels and the predictors of interest after correction for age, gender, waist circumference, BMI, and other potential confounders. RESULTS: The children (64% males) were aged 8-18 years, and their median BMI was 2.45 SDS. Both parathyroid hormone levels and BMD were within the normal range. All cases of fibrosis were detected in children with NASH. On multivariable linear regression with correction for age, gender, and BMI, 25-OH-VD levels were found to be 9 (95% CI 12-6) ng/ml lower in children with NASH than in those without NASH (P<0.001) and 9 (12-6) ng/ml lower in children with stage 1 fibrosis than in those with stage 0 fibrosis and 9 (13-6) ng/ml lower in children with stage 2 than in those with stage 0 fibrosis (P<0.001 for both). CONCLUSION: VD levels are inversely associated with NASH and fibrosis in children with NAFLD.

Insulin sensitivity from preschool to school age in patients with severe obesity.

BACKGROUND: Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age. RESEARCH DESIGN AND METHODS: Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI) ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI), Insulinogenic Index (IGI); ß-cell demand index (BCDI) and Insulin Secretion-Sensitivity Index 2 (ISSI-2) were longitudinally estimated during the oral glucose tolerance test. RESULTS: After a median follow-up of 2.23 (1-4.52) y, obese patients showed significant decrease in WBISI (p<0.0001), and increase in fasting (p = 0.005) and 2 h glucose (2HG, p = 0.001). One child in preschool age and 4 school age children presented with 2HG between 7.8-11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R(2) = 0.309; p = 0.002; ß = -0.556), ISSI-2 (R(2) = 0.465; p<0.0001; ß = -0.682), and BMI z-score (R(2) = 0.246; p = 0.008; 0.496), respectively. CONCLUSIONS: In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation.

Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth.

BACKGROUND: To describe the morphology of glucose curve during the oral glucose tolerance test (OGTT) and any association with glucose tolerance, insulin action and secretion in obese youth. STUDY DESIGN: Cross-sectional. METHODS: OGTT data of 553 patients were analysed. Subjects were divided in groups based on the morphology (i.e. monophasic, biphasic, triphasic and upward monotonous) of glucose curve. Insulin action was estimated by the homeostasis model assessment of insulin resistance, the insulin sensitivity, the muscle insulin sensitivity and the hepatic insulin resistance indexes (HIRI), and the oral glucose insulin sensitivity (OGIS). Insulin secretion was estimated by the insulinogenic index (IGI). Disposition index, including the insulin secretion-sensitivity index-2, and areas under glucose (AUC(G)) and insulin (AUC(I)) curves were computed. RESULTS: In patients with normal glucose tolerance (n=522), prevalent morphology of the glucose curve was monophasic (n=285, 54%). Monophasic morphology was associated with the highest concentration of 1 h plasma glucose (P<0.0001) and AUC(G) (P<0.0001); biphasic morphology with better insulin sensitivity as estimated by OGIS (P<0.03) and lower AUC(I) (P<0.0001); triphasic morphology with the highest values of HIRI (P<0.02) and IGI (P<0.007). By combining morphologies of glucose and insulin curves or time of the glucose peak, a deeper characterisation of different phenotypes of glucose metabolism emerged. CONCLUSIONS: Morphologies of the glucose curve seem reflecting different metabolic phenotypes of insulin action and secretion, particularly when combined with morphologies of insulin curve or time of glucose peak. Such findings may deserve validation in cohort study, in which glucose metabolism would be estimated by using gold standard techniques.

Intima-media thickness and liver histology in obese children and adolescents with non-alcoholic fatty liver disease.

OBJECTIVE: To evaluate the relationship between biopsy-proven non-alcoholic fatty liver disease (NAFLD) and carotid artery intima-media thickness (CIMT) in children and adolescents. METHODS: A case-control study was performed. Cases were 31 mostly obese children and adolescents, with NAFLD detected at ultrasonography, and confirmed by liver biopsy. Controls were 49 mostly obese children matched for gender, age and BMI without NAFLD at ultrasonography and with normal levels of aminotransferases. Besides standard laboratory measurements, subjects underwent an oral glucose tolerance test to evaluate glucose tolerance and to estimate whole body insulin sensitivity (ISI). RESULTS: CIMT was similar in cases and controls on the right side but higher in cases on the left side. Although statistically significant, this difference is unlikely to be clinically relevant because of substantial overlap of CIMT values between cases and controls. Moreover, there was no association between CIMT and the severity of steatosis, ballooning, fibrosis, and the non-alcoholic steato-hepatitis score in cases. At multivariable analysis in the pooled sample (n=80), age and the z-score of BMI but not NAFLD, gender, blood pressure and triglycerides, were associated with CIMT. CONCLUSIONS: We found no association between CIMT and NAFLD in children and adolescents. More importantly, there was no association between histological severity and CIMT in children with NAFLD.

Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents, and it may progress to liver fibrosis and cirrhosis. Liver biopsy, which is the recognized gold standard for the diagnosis of hepatic fibrosis, is invasive. Thus, there has been increasing interest in the development of noninvasive markers. Hyaluronic acid (HA) has been shown to be a good marker of liver fibrosis in adults. In the current study, we evaluated the association of HA with liver fibrosis in 100 consecutive children with biopsy-proven NAFLD. In all, 65% of the children had liver fibrosis. Using proportional-odds ordinal logistic regression, we found that values of HA ≥ 1200 ng/mL made the absence of fibrosis (F0) unlikely (7%, 95% confidence interval [CI]: 1% to 14%), whereas values of HA ≥ 2100 ng/mL made F2, F3, or F4 fibrosis likely (89%, 95% CI: 75% to 100%). Our study shows that HA is a predictor of fibrosis in children with NAFLD followed at a tertiary care center. Additional studies are needed to test whether HA can be employed to predict liver fibrosis in pediatric populations with similar and lower prevalence of liver fibrosis.