Retrospective Analysis of Clinical Characteristics and Disease Outcomes in Children and Adolescents Hospitalized Due to COVID-19 Infection in Tunisia.

Due to low susceptibility of coronavirus disease of 2019 (COVID-19) in children, limited studies are available regarding COVID-19 in the pediatric population in Tunisia. The current study evaluated the incidence, clinical characteristics, and outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection among children hospitalized at Béchir Hamza Children's Hospital. A retrospective cohort analysis was conducted using the hospital database between March 2020 and February 2022 with children aged ≤15 years with SARS-CoV-2 infection (confirmed by RT-PCR). A total of 327 COVID-19 hospitalized patients with a mean age of 3.3 years were included; the majority were male. Neurological disease (20%) was the most common comorbidity, while fever (95.3%) followed by cough (43.7%) and dyspnea (39.6%) were the most frequent symptoms reported. Severe disease with oxygen requirement occurred in 30% of the patients; 13% were admitted in the Intensive Care Unit. The overall incidence rate of COVID-19 hospitalization (in Tunis governorates) was 77.02 per 100,000 while the inpatient case fatality rate was 5% in the study population. The most prevalent circulating variant during our study period was Delta (48.8%), followed by Omicron (26%). More than 45% of the study population were <6 months and one-fourth (n = 25, 26.5%) had at least one comorbidity. Thus, the study findings highlight the high disease burden of COVID-19 in infants.

Unusual onset of Graves' disease associated with thymic hyperplasia in a 5-year-old girl with congenital bilateral clinical anophthalmia: diagnostic and therapeutic challenges.

OBJECTIVES: Graves' disease (GD) is a rare auto-immune disorder in pediatric population. The association between GD and thymic hyperplasia was rarely reported in children. Diagnosis and management of GD are challenging in children. CASE PRESENTATION: This report presents the case of a 5-year-old girl with a personal history of asthma and congenital bilateral isolated clinical anophthalmia who presented with acute congestive heart failure, sinus tachycardia and atypical signs of orbitopathy with edema and erythema of the lower right eyelid and excessive tearing. The diagnosis of GD was based on detecting a suppression of serum TSH level and the presence of high titers of TRAbs. Relapse occurred after 10 months of antithyroid drugs with chief complaints of palpitations, dyspnea and dysphagia. Computed tomography showed heterogeneous anterior mediastinal mass with no invasion into the surrounding tissue. The marked shrinkage of the mass after radioiodine therapy supported the diagnosis of thymic hyperplasia associated with GD. CONCLUSIONS: The presence of clinical anophthalmia may be a confusing factor for the diagnosis of Graves' ophthalmopathy. Recognition of the association between GD and thymic hyperplasia would avoid invasive diagnostic procedures and unnecessary surgical resection. Radioiodine therapy may be used in young children with repeated relapses of GD.

Case based self-directed learning tool versus clinical reasoning learning sessions.

INTRODUCTION: Clinical reasoning (CR) is a core skill taught by medical schools. Clinical reasoning learning sessions (CRL) during hospital internship of externals in pediatrics was recently introduced in Faculty of Medicine of Tunis. AIM: To compare a case based self-directed learning (CBSDL) tool with CRL sessions in two groups of the students assigned to pediatric internship. METHODS: We conducted a randomized trial with draw of two groups: CRL group (students who attended the CRL session) and SDL group (students who received the CBSDL tool). Main judgment criterion was the final score obtained by the student at the test of sequential management problem (SMP). A docimological analysis of SMP test was performed. RESULTS: The mean final score in CRL group and SDL group was 12.03±1.44 and 14.05±1.64, respectively (p <0.001). The scores obtained at the different steps of SMP test were significantly higher in SDL group. The difficulty p and discrimination D indices of the SPM test were 0.65 and 0.21, respectively. The agreement between the two correctors was very good since the intra-class correlation coefficient was 0.977. We analyzed the reliability of the test by measuring Cronbach's α coefficient which was 0.955. CONCLUSION: CBSDL tool has allowed students to learn hypothetico-deductive reasoning. However, this tool must be supplemented by direct supervision at hospital internship to support CR.

Caustic ingestion in Tunisian children: Endoscopic findings, complications and predictors of severe injuries in a cohort of 1059 patients.

BACKGROUND AND AIMS: The ingestion of caustic substances remains a serious medical problem in Tunisian children. This study was conducted to describe the epidemiological, clinical, and endoscopic findings of caustic ingestion in Tunisian children, and to indentify predictive factors of severe esophageal and gastric injuries. PATIENTS AND METHODS: A retrospective review of all children referred to a tertiary pediatric center for caustic ingestion who underwent esophago-gastro-duodenoscopy was conducted. Severe esophageal and gastric injuries were defined as Grade 2b, 3a, 3b, and 4 using the Zargar classification. We conducted multivariate logistic regression analysis to identify predictive factors for severe esophageal and gastric caustic injuries. RESULTS: We analyzed 1059 diagnostic procedures performed for caustic ingestion. The mean age was 41.4± 31.9 months. The most frequently ingested caustic substance was household bleach followed by caustic soda granules. Endoscopy showed severe esophageal and gastric lesions, respectively, in 122 (11.5%) and 56 (5.3%) cases. Predictive factors of severe esophageal injuries were: alkaline ingestion (p<0.001; OR: 17.9; 95% CI: 8.4-38.1) and the presence of symptoms after caustic ingestion (p=0.02; OR: 2.4; 95% CI: 1.1-5.4). The occurrence of complications was significantly associated with the presence of severe gastric lesions at the initial procedure (p=0.046; OR: 2.3;95% CI: 0.9- .3). CONCLUSION: Esophago-gastro-duodenoscopy should always be performed for symptomatic children, asymptomatic children who have ingested an alkaline product, and asymptomatic children under the age of 6 years.

Prevalence of metabolic syndrome in Tunisian overweight and obese children.

AIMS: To assess the prevalence of metabolic syndrome (MS) and its parameters in a cohort of overweight and obese Tunisian schoolchildren and to investigate the involvement of leptin, and insulin in MS development via obesity. METHODS: A total of 306 schoolchildren between 10- 12 years: obese (n=35), overweight (n=99) and normal weight (n=172) were included in the study. Height, weight, waist circumference were measured and body mass index (BMI) was calculated. A blood sample was collected from each subject to measure glycemia, triglycerides, HDL cholesterol, leptin and insulin. MS diagnosis was based on criteria of  the International Diabetes Federation. RESULTS: Prevalence of MS was 14.3% in obese children compared to 1% in overweight and 0% in controls (p0.001). Abdominal obesity and hypertension  were the most frequent parameters (88.6% and 25.7% respectively) in obese children. Leptin levels were significantly higher in children with MS (p0.001). In obese children, leptin was positively correlated to waist circumference (r=0.55; p=0.001) and insulin (r=0.52; p=0.002). After adjustment for BMI, leptin remained correlated with insulin (r=0.47; p0.001). CONCLUSION: MS is relatively common among Tunisian overweight and obese children. Obesity is an important risk factor for MS development. Early management of childhood obesity is necessary to avoid metabolic complications.

Vitamin D deficiency is associated with metabolic syndrome in Tunisian children with obesity.

BACKGROUND: A negative association between serum vitamin D levels and obesity has been reported by several studies. Data on vitamin D status in Tunisian obese children and its relationship with metabolic syndrome remain rare. AIM: We aimed to study the prevalence of vitamin D deficiency in Tunisian obese children and to examine the correlation between vitamin D levels and metabolic syndrome. METHODS: Thirty obese children matched to 30 non-overweight volunteer controls by age, gender and pubertal stage were included in a prospective study. Anthropometric parameters and blood pressure were measured.  Vitamin D level, fasting glucose and lipid profile were performed in all subjects. RESULTS: Vitamin D deficiency was more common in obese children (94% vs 80 %, p=0.002). Vitamin D level was negatively correlated with BMI (p= 0.001, r= -0.51). Six obese children were diagnosed with metabolic syndrome. Vitamin D levels were negatively correlated with waist circumference (p=0.019, r=-0.13), systolic Blood pressure (p=0.04, r=-0.26), triglyceride level (p=0.025, r= -0.3), insulin (p=0.01, r=-0.34) and HOMA-IR (p=0.035, r=-0.29). CONCLUSIONS: despite the sunny climate, the deficiency in vitalmine D is common in Tunisia. Vitamin D levels are inversely correlated with BMI and the risk of metabolic syndrome.

A Founder Effect of c.257 + 2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients.

Chronic granulomatous disease (CGD) is the prototypic functional neutrophil disorder caused by genetic defects in one of the five genes encoding the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits of phagocytes. Mutations causing the most prevalent form of CGD in western populations are located in the X-linked-CYBB gene. The four remaining autosomal recessive (AR) forms collectively account for one-third of CGD cases. We investigated the clinical and molecular features of eleven patients with CGD from 6 consanguineous families, originating from contiguous regions in the west of Tunisia. The patients' clinical phenotype is characterized by a high incidence of mycobacterial infections. Five out of the eleven patients died despite treatment arguing in favor of a severe clinical form of CGD. These findings correlated with the absence of functional p67phox protein as well as the absence of residual reactive oxygen intermediates (ROI) production. Genetic analysis showed the presence, in all patients, of a unique mutation (c.257 + 2T > C) in NCF2 gene predicted to affect RNA splicing. Segregating analysis using nine polymorphic markers overlapping the NCF2 gene revealed a common haplotype spanning 4.1 Mb. The founder event responsible for this mutation was estimated to have arisen approximately 175 years ago. These findings will facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families.

Predictive score for positive upper endoscopies outcomes in children with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common pediatric emergency. Esophago-gastro-duodenoscopy (EGD) is the first line diagnostic procedure to identify the source of bleeding. However etiology of UGIB remains unknown in 20% of cases. Furthermore, emergency endoscopy is unavailable in many hospitals in our country. AIMS: Identify clinical predictors of positive upper endoscopy outcomes and develop a clinical prediction rule from these parameters. METHODS: Retrospective study of EGDs performed in children with first episode of UGIB, in the endoscopic unit of Children's Hospital of Tunis, during a period of six years. Statistical analysis used SPSS20. Univariate analysis was performed and multivariate logistic regression was then modelled to derive a clinical prediction rule. RESULTS: We collected 655 endoscopies (23.2% normal, 76.8% pathological). We found that time to EGD within 24 hours from the onset of bleeding (p=0.027; Adj OR: 3.30 [1.14 - 9.53]), rebleeding (p=0.009; Adj OR: 6.01 [1.57 - 23.02]), positive gastric lavage outcome (p=0.001; Adj OR: 4.79 [1.95 - 11.79]) and non steroidal anti-inflammatory drugs intake (p=0.035; Adj OR: 5.66 [1.13 - 28.31]) were predictors of positive upper endoscopy outcomes. By assigning each factor, the adjusted odds ratio (Adj OR), we developed a score with four items, ranging from 4 to 20. Using the receiver operating characteristic (ROC) curve the best cut off ≥ 9 was defined (sensitivity 88.2%, specificity 60.6%, positive predictive value 92.7% and negative predictive value 47.6%). The score discriminated well with a ROC curve area of 0.837 (95% confidence interval [0.769 - 0.905]). CONCLUSIONS: This clinical prediction rule is a simple measure that may identify children who needed emergency endoscopy. A prospective study is required to validate our results and evaluate other clinical features that were insufficient for this analysis.

Celiac disease in the Mediterranean area.

BACKGROUND: The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. METHODS: By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. RESULTS: The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. CONCLUSIONS: This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines.

Endoscopic diagnosis in a Tunisian pediatric population with upper gastrointestinal bleeding.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is currently considered the first line diagnostic procedure chosen for Upper Gastrointestinal Bleeding (UGIB) since 1970. However, studies are still limited in our country. AIM: Finding out the most common causes of UGIB in children and whether the causes differed according to age in developing and developed countries. METHODS: A retrospective review of the medical records of children referred to the Paediatric Gastroenterology Department of The Tunis Hospital of Children between January 1998 and December 2006 for upper gastrointestinal bleeding. The children were divided into three groups; G1: neonates; G2: infants; G 3: children and adolescents. RESULTS: The study involved 614 endoscopies. The aetiology was not ascertained in 20.68%of cases. G1 included 125 newborns: 24 with no identified causes, 97 mucosal lesions (isolated or associated); two ulcers and two tumours. G2 and G3 included respectively 205 infants and 289 children. Toxic drug intake was recorded in 140 out of 489 patients. Endoscopy was normal in 101 cases. Peptic oesophagitis was recorded in 57/205 (27.8%) of G2 infants versus 52/284 (10%) of G3 children (p=0.015). Gastritis was recorded in 164/284 (55.6%) of G2 infants versus 86/205 (41.9%) of G3 children (p≤0.001). Peptic ulcers were reported in ten boys. Mallory Weiss tears and Variceal lesions were found in respectively eleven and ten cases. CONCLUSION: Aetiologies of UGIB in children in Tunisia varied according to age and geographic areas.

Postnatal leptin promotes organ maturation and development in IUGR piglets.

Babies with intra-uterine growth restriction (IUGR) are at increased risk for experiencing negative neonatal outcomes due to their general developmental delay. The present study aimed to investigate the effects of a short postnatal leptin supply on the growth, structure, and functionality of several organs at weaning. IUGR piglets were injected from day 0 to day 5 with either 0.5 mg/kg/d leptin (IUGRLep) or saline (IUGRSal) and euthanized at day 21. Their organs were collected, weighed, and sampled for histological, biochemical, and immunohistochemical analyses. Leptin induced an increase in body weight and the relative weights of the liver, spleen, pancreas, kidneys, and small intestine without any changes in triglycerides, glucose and cholesterol levels. Notable structural and functional changes occurred in the ovaries, pancreas, and secondary lymphoid organs. The ovaries of IUGRLep piglets contained less oogonia but more oocytes enclosed in primordial and growing follicles than the ovaries of IUGRSal piglets, and FOXO3A staining grade was higher in the germ cells of IUGRLep piglets. Within the exocrine parenchyma of the pancreas, IUGRLep piglets presented a high rate of apoptotic cells associated with a higher trypsin activity. In the spleen and the Peyer's patches, B lymphocyte follicles were much larger in IUGRLep piglets than in IUGRSal piglets. Moreover, IUGRLep piglets showed numerous CD79(+) cells in well-differentiated follicle structures, suggesting a more mature immune system. This study highlights a new role for leptin in general developmental processes and may provide new insight into IUGR pathology.

Nodular gastritis: an endoscopic indicator of Helicobacter pylori infection in children.

BACKGROUND: Helicobacter pylori (Hp) infection is a common and universally distributed bacterial infection. It is predominantly acquired in childhood. AIM: To assess the relationship between endoscopic nodular gastritis and Hp infection. METHODS: A retrospective study was conducted in children who underwent upper gastrointestinal endoscopy for chronic abdominal pain. All children who had five gastric biopsies for histologic analysis, urease test and Hp culture were included in the study. The Sensitivity and sensibility of nodular gastritis were determined and different parameters were studied according the presence or not of nodular gastritis(age, gender, Hp status, gastritis score and lymphoid follicles). RESULTS: 49 children, mean age 6.9 ± 3 years (range 1-12 years) were eligible for the analysis. Hp Infection was diagnosed in 35 out of the 49 children (71.5 %). Nodular gastritis was recorded in 16 out of 49 children and in 14 infected children and 2 out of 14 non infected children (p=0.07), 40% sensitivity, 85.7% specificity, 87.5% positive predictive value, and 36,4% negative predictive value. The parameters associated significantly to the presence of nodular gastritis were older age: (p=0.04), Hp infection: (p=0.01), chronic gastritis: (p=0.05), active gastritis: (p=0.02), follicular gastritis: (p=0.005), higher gastritis score: (p=0.005). Completely normal gastric mucosal histology was never found in infected children with antral nodularity. Among all infected children, the gastritis score was significantly higher when there was a nodular gastritis and follicular gastritis was significantly associated to nodular gastritis. CONCLUSION: The endoscopic pattern of antral nodularity identifies children with Hp infection, and active chronic follicular gastritis.

[Web site of La Tunisie Medicale was created two years ago ...]. / Le site web de la Tunisie Médicale www.latunisiemedicale.com a été créé depuis deux ans

BACKGROUND: La Tunisie Médicale, official journal of Tunisian Society for Medical Sciences and Tunisian Medical Organization, born in 1903 with ISSN number 0041-4131and INIST code 4691 of French Pascal database, had since September 2009 its website : www.latunisiemedicale.com AIM: To assess the editorial policy of «La Tunisie Médicale¼ METHODS: A descriptive analysis was performed to evaluate different categories of articles and number of papers written with English language. mdweb society, which created the website site www.latunisiemedicale.com , planned to have instantaneously a descriptive analysis concerning the number of consultants per article. The site www.scopus.com helped us to have the number of articles citations which was useful to calculate Impact Factor (IF). National Center for Biotechnology Information (NCBI) of National Library of Medicine provided monthly number of hits. RESULTS: Number of published articles increased regularly to reach 250 and 300 between 2009 and 2011. Beside original articles, cases report, overviews, continuing medical education and editorials, we introduced systematic reviews of literature, letters to editors, historical notes, section reserved for images in clinical practice, point of view, technical novelty and section for « Pro & Cons¼ in which readers could present their opinions with reply of authors. Articles written in English have increased to reach the number of 60 between 2010 and 2011. Visitors number of «la Tunisie Médicale¼ website, from 195 countries, was 465 596 between January 1st 2011 and December 22nd 2011. Half of consultants (51.06%) came from several sources such as «Google/organic¼ and «ncbi.nlm.nih.gov/ referral¼. Number of visits from NCBI was about 3000 per month from June 2010 to December 2011. The ten first visited articles concerned sexual organ and tuberculosis. Articles citations of «laTunisie Médicale¼ are in constant progress and Impact Factor, increased from 0.054 in 2004 to 0.277 in 2011. CONCLUSION: We succeeded to increase the number of articles written in English. Results are interesting Impact Factor of 2011 is 0,277; however we should be modest because we still have a very long way, we should help authors to perform systematic reviews with a sound methodology.

C677t polymorphism of MTHFR and G80A polymorphism of RFC genes and their relation with homocysteine levels in obese Tunisian children.

AIMS: To investigate the frequencies of C677T polymorphism in MTHFR gene and G80A polymorphism in RFC gene in obese and no obese Tunisian children and to assess their relation with homocysteine (tHcy), folate and vitamin B12 levels. METHODS: We have studied 31 obese compared to 22 no obese children. tHcy was assessed by fluorescence-immunoassay ; folate and vitamin B12 by radioimmunoassay. C677T and G80A mutations were detected using pyrosequencing. RESULTS: There were no differences in tHcy levels between obese and no obese, (10,34 ± 4,86µmoll/l vs11,00 ± 4,26µmoll/l). We found no difference for the allelic frequencies of the C677T polymorphism (29.03 % vs 30.95 %) and of the G80A polymorphism (64.52 % vs 59.52 %). Mean levels of tHcy, folic acid and vitamin B12 were not significantly different according to MTHFR and RFC genotypes. CONCLUSION: We demonstrated no difference in tHcy, folates, vitamin B12 levels and allelic frequencies of C677T and G80A polymorphisms in MTHFR and RFC genes between obese and no obese Tunisian children. These two polymorphisms don't seem to have any impact on homocysteine, folate and vitamin B12 status in the two populations.

Prevalence and risk factors of overweight and obesity in elementary schoolchildren in the metropolitan region of Tunis, Tunisia.

BACKGROUND: Local data about prevalence of obesity in emerging countries are rather scarce. Risk factors for obesity, well known in most industrialized countries, are poorly understood in Tunisia. AIMS: To assess prevalence of overweight and obesity and to investigate associations with possible risk factors in a group of 6-12 year- old schoolchildren in Tunis, Tunisia. METHODS: A descriptive transversal study including a sample of 1335 schoolchildren (6-12 years; mean: 9.7 ± 1.5 years) was conducted in Tunis. Personal and parental data were collected by questionnaires completed by parents. Height and weight were measured and body mass index was calculated. Prevalence of overweight and obesity was defined based on international agreed cut-off points. RESULTS: Prevalence of overweight and obesity was 19.7% and 5.7%, respectively. Risk factors associated with overweight were: high degree- educated mother and father: 17.3% vs 11.7% (p=.01) (OR (95%CI): 1.58; 1.09-2.29) and 26% vs 17.4% (p=.002) (OR: 1.66; 1.21-2.29), respectively; mother, father high in occupational hierarchy: 7.2% vs 3.6% (p=0.009) (OR: 2.1; 1.2-3.7) and 14% vs 9% (p=.014) (OR: 1.6; 1.1-2.48), respectively. Overweight children had a significantly higher consumption of bread (p=.044), of snack intake (p=0.046) and of soft drink consumption (p=.035). CONCLUSIONS: Prevalence of overweight and obesity in this cohort are 19.7% and 5.7%, respectively. Substantial differences in food choices in families with the highest socio-economic status are among risk factors contributing to obesity development.

[Interventional endoscopy in the gastrointestinal tract in children]. / Activité endoscopique digestive interventionnelle chez l'enfant.

BACKGROUND: Interventional endoscopic procedures involving the gastrointestinal (GI) tract in children are very common. Over the last several years the number of procedures in this area has steadily increased. AIM: To study indications and results of GI interventional endoscopies performed in a Pediatric GI unit. METHODS: Retrospective study over a period of 10 years (1999-2008). Data were collected from endoscopic files. All procedures were performed endoscopically under general anesthesia. RESULTS: 185 interventional endoscopic procedures were done during this period in 96 patients (58 boys) median age: 4.9±4.7 years (1 month-13 years). Indications were as follows: esophageal stenosis (n=46; 47.9%), rectal polyp resection (n=21; 19.8%), esophageal varices ligation (n=19; 19.7%), foreign body extractions (n=8; 8.3%) and percutaneous endoscopic gastrostomy (n=2; 2.1%). One hundred and thirteen esophageal dilations (61.1% of procedures) were performed in 46 patients: caustic stenosis (n=22; 22.9%), peptic stenosis (n=13; 13.5%) and anastomotic stenosis (n=11; 11.4%). CONCLUSION: The main indication of interventional GI endoscopy in this series was oesophageal stenosis followed by rectal polyp resection, esophageal varices ligation and foreign body extractions.

Serum leptin concentration in Tunisian non obese children.

Leptin, an adipocyte-derived peptide hormone, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, we investigated leptin levels in 348 non overweight, non obese children (147 boys, 201 girls, age: 6-12 years) and then correlated these levels with age, anthropometric data, pubertal stage and insulin. A blood sample was collected from each subject to measure leptin and insulin levels by radioimmunoassay. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. The results showed an increase in leptin levels in an age related way (r = 0.32, p < 0.0001 in girls; r = 0.21, p = 0.011 in boys) following a pattern that paralleled body weight (r = 0.6 in girls; r = 0.56 in boys; p < 0.0001) and BMI (r = 0.59 in girls; r = 0.6 in boys, p < 0.0001), suggesting that body fatness is a regulator of leptin levels in both girls and boys. A significant gender difference (3.39 +/- 2.79 ng/mL in girls vs 1.99 +/- 2.08 ng/mL in boys, p < 0.0001) with an increase during pubertal development in girls was also showed, while the levels remained constant in boys from Tanner stages T1 to T3. A correlation between leptin and insulinemia was noted in girls (r = 0.38, p < 0.0001) but not in boys, suggesting that insulinemia could be a stimulator of leptin synthesis in girls.