"Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)-Part-1".

PURPOSE: Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available. METHODS: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system. RESULTS: A literature search of articles in English for the term "varicoceles", "gynecomastia", "fertility preservation", "macroorchidism", "precocious puberty" and "pubertal delay" has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders. CONCLUSIONS: These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.

High 1-h glucose in youths with obesity as marker of prediabetes and cardiovascular risk.

PURPOSE: Testing 1-h glucose (1HG) concentration during oral glucose tolerance test is cost-effective to identify individuals at risk of incident type 2 diabetes. Aim of the study was to define 1HG cutoffs diagnostic of incident impaired glucose tolerance (IGT) in youths with obesity, and to evaluate prevalence and association of cutoffs identified in the cohort and from the literature (133 and 155 mg/dl) to cardiovascular disease (CVD) in a population of youths with obesity. METHODS: This is a longitudinal study of 154 youths to identify 1HG cutoffs, and cross-sectional study of 2295 youths to estimate prevalence of high 1HG and association to CVD. Receiver-operating characteristic curves (ROC) were used to establish 1HG cutoffs, and univariate regression analyses to test association of 1HG to blood pressure, lipids and aminotransferases. RESULTS: ROC analysis identified the 1HG cutoff of 159 mg/dl as having diagnostic accuracy of IGT with area under the ROC 0.82 (95% CI 0.66-0.98), sensitivity 0.86% and specificity 0.79%. In the cross-sectional population, prevalence of high 1HG was 36% and 15% for 133 and 155 mg/dl cutoffs, respectively, and 17% for the 159 mg/dl value. All the examined cutoffs were significantly associated with worse lipid profile, liver function test, reduced insulin sensitivity, secretion and disposition index. CONCLUSION: High 1HG is marker of persistent IGT and increased risk of metabolic abnormalities in youths. The 155 mg/dl cutoff is a convenient estimate in young people but longitudinal studies with retinopathy and overt diabetes as end points are advised to verify the 1HG cutoff with the best diagnostic accuracy.

Comparison of two advanced hybrid closed loop in a pediatric population with type 1 diabetes: a real-life observational study.

OBJECTIVE: The Advanced Hybrid Closed Loop (AHCL) systems have provided the potential to ameliorate glucose control in children with Type 1 Diabetes. The aim of the present work was to compare metabolic control obtained with 2 AHCL systems (Medtronic 780G system and Tandem Control IQ system) in a pediatric real-life clinical context. RESEARCH DESIGN AND METHODS: It is an observational, real-life, monocentric study; thirty one children and adolescents (M:F = 15:16, age range 7.6-18 years, mean age 13.05 ± 2.4 years, Diabetes duration > 1 year) with T1D, previously treated with Predictive Low Glucose Suspend (PLGS) systems and then upgraded to AHCL have been enrolled. CGM data of the last four weeks of "PLGS system" (PRE period) with the first four weeks of AHCL system (POST period) have been compared. RESULTS: For both AHCL systems, Medtronic 780G and Tandem Control IQ, respectively TIR at 4 weeks significantly increased, from 65.7 to 70.5% (p < 0.01) and from 64.8 to 70.1% (p < 0.01). (p < 0.01). The comparison between CGM metrics of the 2 evaluated systems doesn't show difference at baseline (last four weeks of PLGS system) and after four weeks of AHCL use. CONCLUSIONS: To our knowledge, this study is the first real-life one comparing 2 AHCL systems in a pediatric population with T1D. It shows an improvement in glucose control when upgrading to AHCL. The comparison between the two AHCL systems did not show significant differences in the analyzed CGM metrics, meaning that the algorithms currently available are equally effective in promoting glucose control.

Prevalence of copy number variants (CNVs) and rhGH treatment efficacy in an Italian cohort of children born small for gestational age (SGA) with persistent short stature associated with a complex clinical phenotype.

PURPOSE: Multiple factors influence intrauterine growth and lead to low birth sizes. The impact of genetic alterations on both pre- and post-natal growth is still largely unknown. The aim of this study was to investigate the prevalence of CNVs in an Italian cohort of SGA children with persistent short stature and complex clinical phenotype. rhGH treatment efficacy was evaluated according to the different genotypes. SUBJECTS AND METHODS: Twenty-four SGA children (10F/14M) with persistent short stature associated with dysmorphic features and/or developmental delay underwent CNV evaluation. RESULTS: CNVs were present in 14/24 (58%) SGA children. Six patients had a microdeletion involving the following regions: 3q24q25.1, 8p21.2p12, 15q26, 19q13.11, 20q11.21q12, 22q11.2. In three females, the same microdeletion involving 17p13.3 region was identified. In two different patients, two microduplications involving 10q21.3 and Xp11.3 region were observed. A further female patient showed both an 11q12.1 and an Xq27.1 microduplication, inherited from her mother and from her father, respectively. In a boy, the presence of a 12p13.33 microdeletion and a 19q13.43 microduplication was found. GH treatment efficacy, expressed by height gain and height velocity in the first 12 months of therapy, was similar in subjects with and without CNVs. CONCLUSIONS: These results show that pathogenic CNVs are common in SGA children with short stature associated with additional clinical features. Interestingly, the involvement of 17p13.3 region occurs with a relative high frequency, suggesting that genes located in this region could play a key role in pre- and post-natal growth. rhGH therapy has similar efficacy in the short term whether CNVs are present or not.

Post-traumatic stress disorder (PTSD) in parents of children with type 1 diabetes during Covid-19 pandemic.

INTRODUCTION: The Post-traumatic Stress Disorder (PTSD) is a group of persistent psychological and physiological symptoms due to a traumatic, severe, event. Only few studies focused on the effects of Covid-19 on psychosocial outcomes in children with Type 1 Diabetes (T1D) and their parents. AIM OF THE STUDY: The aim of this study was to evaluate the presence PTSD in parents of children with T1D during COVID-19 pandemic lockdown. PATIENTS AND METHODS: In the period between March and May 2020 we submitted the "Impact of Event Scale - Revised" (IES-R) questionnaire to the parents of 34 children with Type 1 Diabetes, asking them to express their emotions about the ongoing Covid-19 pandemic. RESULTS: A total of thirty mothers (mean age 43.0 ± 4.2 years) and 25 fathers (mean age 45.6 ± 5.9 years) participated in the survey and completed the questionnaires. 29.1% of parents had a score that allows to define a clinically relevant level of PTSD; ten mothers and 6 fathers had a PTSD clinically relevant score, corresponding, respectively, to 28.4 and 24% of total mothers and fathers. Finally, mothers and fathers, both express PTSD symptoms mainly in the form of intrusion and hyperarousal. CONCLUSIONS: The present study confirms a high prevalence symptoms related to PTSD in mothers and fathers of children with Type 1 Diabetes. We believe that psychosocial outcomes of the COVID-19 pandemic should be taken into account in the planning of the next future assistance for children with T1D.

Pilot study on circulating miRNA signature in children with obesity born small for gestational age and appropriate for gestational age.

BACKGROUND: Children born small for gestational age (SGA) are at increased risk of metabolic dysfunction. Dysregulation of specific microRNAs (miRNAs) contributes to aberrant gene expression patterns underlying metabolic dysfunction. OBJECTIVE: We aimed to determine and compare circulating miRNA (c-miRNA) profile of SGA and appropriate for gestational age (AGA) children with obesity and with normal weight, in order to identify biomarkers for early detection of increased risk of developing metabolic dysfunction in SGA and AGA children with obesity. METHODS: Small non-coding RNAs from serum of 15 SGA children with obesity (OB-SGA), 10 SGA children with normal weight (NW-SGA), 17 AGA children with obesity (OB-AGA) and 12 AGA children with normal weight (NW-AGA) (mean age 11.2 ± 2.6) have been extracted and sequenced in order to detect and quantify miRNA expression profiles. RESULTS: RNA-seq analyses showed 28 miRNAs dysregulated in OB-SGA vs. NW-SGA and 19 miRNAs dysregulated in OB-AGA vs. NW-AGA. Among these, miR-92a-3p, miR-122-5p, miR-423-5p, miR-484, miR-486-3p and miR-532-5p were up regulated, and miR-181b-5p was down regulated in both OB-SGA and OB-AGA compared with normal weight counterparts. Pathway analysis and miRNA target prediction suggested that these miRNAs were particularly involved in insulin signalling, glucose transport, insulin resistance, cholesterol and lipid metabolism. CONCLUSION: We identified a specific profile of c-miRNAs in SGA and AGA children with obesity compared with SGA and AGA children with normal weight. These c-miRNAs could represent specific biomarkers for early detection of increased risk of developing metabolic dysfunction in SGA and AGA children with obesity.

Serum Fetuin-A levels in obese children with biopsy proven nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Fetuin-A has been proposed as a marker of liver damage in adults with obesity-related NAFLD. The aim of this study was to test serum fetuin-A concentrations in obese children with NAFLD diagnosed either by ultrasonography or by liver biopsy and to determine its applicability as predictive tool in pediatric NAFLD. METHODS AND RESULTS: Metabolic parameters and fetuin-A levels were investigated in 81 obese children with NAFLD diagnosed by biopsy, 79 obese children with NAFLD defined by liver ultrasonography and 23 lean subjects. Serum fetuin-A correlated significantly with age, waist circumference, systolic blood pressure, fasting insulin and 2-h postload insulin during OGTT, HOMA-IR, ISI, CRP, and apo B levels. Obese children with NAFLD detected by ultrasonography had significantly higher fetuin-A levels compared to those with normal liver. In obese children who underwent liver biopsy, no significant differences were detected in fetuin-A levels between subject with nonalcoholic steatohepatitis and those with simple steatosis. Fetuin-A was not different between obese and lean children. CONCLUSION: Fetuin-A is not related with the degree of liver damage in obese children with NAFLD and its routine measurement as marker of liver disease severity is therefore not recommended.

Circulating levels of miR-122 and nonalcoholic fatty liver disease in pre-pubertal obese children.

OBJECTIVES: The liver-specific miR-122 was proposed as biomarker for NAFLD in adults. Here, we investigated the relationship between miR-122 levels, parameters of liver metabolism and NAFLD in pre-pubertal obese children. METHODS: Parameters of liver metabolism (ALT, AST and GGT) of three European cohorts were included (German cohort [n = 71; age: 11.53 ± 1.29 years; BMI z-score: 2.96 ± 0.64], Italian cohort [n = 45; age: 9.60 ± 2.11 years; BMI z-score: 3.57 ± 1.16], Slovenian cohort [n = 31; age: 7.53 ± 1.47 years; BMI z-score: 3.66 ± 0.88]). MiR-122 levels and CK18 concentrations were measured in fasting blood samples. In the German and Italian cohort, the diagnosis of NAFLD and grading of NAFLD was assessed by ultrasound. RESULTS: NAFLD was diagnosed in n = 50 patients of the German cohort (29.6%) and in n = 29 patients (72.5%) of the Italian cohort. In all three cohorts, miR-122 was positively correlated with ALT and AST as well as with CK18 concentrations. MiR-122 levels were higher in children with NAFLD compared with healthy controls. CONCLUSIONS: MiR-122 levels in pre-pubertal obese children could be a potential biomarker for paediatric NAFLD.

Predictors of blood pressure at 7-13 years: The "new millennium baby" study.

BACKGROUND AND AIMS: The purpose of this study is to evaluate the association between blood pressure (BP) at 7-13 years of age and body mass index (BMI), early feeding, lifestyle indicators, and parental characteristics. METHODS AND RESULTS: Retrospective plus cross-sectional cohort study was started in 1294 children born in 2000-2004, right from their birth in primary care settings. Early feeding was estimated by measuring breast-feeding (BF) duration, complementary feeding (CF) introduction time, and lifestyle indicators such as daily screen time and weekly extracurricular sports activity time. Parental education, smoking, and obesity-related diseases were also considered. Multivariable linear regression and mediation analysis were used. CF introduction at 5-6 months of age was a negative predictor of systolic and diastolic BP (mean systolic BP-standard deviation score (SDS) -0.38 [95% CI: -0.47, -0.29] (p < 0.001); mean diastolic BP-SDS -0.32 [95% CI: -0.40, -0.24]) (p < 0.001); BMI was a positive predictor of systolic and diastolic BP (p < 0.001); and parental hypertension was a positive predictor of diastolic BP (p < 0.05). Predictors of mean BMI-SDS at 7-13 years of age were birth weight, screen time, and parental obesity and smoking (p < 0.001). BF had no effect on BP or BMI. Mediation analysis showed virtually no indication of the effect of CF on BP mediated by BMI. CONCLUSIONS: CF introduction between 5 and 6 months of age could be associated with low BP at 7-13 years. The effect of CF on BP seems to be independent of BMI. Low screen time is associated with low BMI. CF time may play a role in the occurrence of surrogates of noncommunicable disorders in future.

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

Non-Alcoholic Fatty Liver Disease (NAFLD) in children and adolescents with Prader-Willi Syndrome (PWS).

We tested the hypothesis that patients with Prader-Willi syndrome (PWS) may be at lower risk of developing non-alcoholic fatty liver disease (NAFLD) because of a higher insulin sensitivity. Twenty-one PWS patients and 42 control subjects closely similar for age, gender, pubertal stage and body mass index (CNT), were studied. Metabolic profile and body composition were assessed. NAFLD was established by a validated method of US grading (range from G0 to G3). PWS patients showed a significantly better metabolic profile (lower waist circumference, fasting glucose levels, HOMA-IR, cholesterol, transaminase levels and trunk fat mass/fat mass ratio). Furthermore, NAFLD G1stage was significantly more frequent in PWS subjects (P < 0.05), whereas G2 stage was significantly more frequent in control patients (P < 0.05). NAFLD grading seems to correlate with body composition in PWS, also after adjustment for sex and GH treatment. To our knowledge, this is the first report suggesting a reduced risk of NAFLD in PWS children.

Early retesting by GHRH + arginine test shows normal GH response in most children with idiopathic GH deficiency.

PURPOSE: Most children with idiopathic isolated GH deficiency (IGHD) normalize GH response to stimulation tests when retested at the completion of growth. The objective of this study was to test the effectiveness of early retesting in challenging the diagnosis of idiopathic IGHD and critically review the diagnostic workup leading to this diagnosis in children with short stature. METHODS: We cross-sectionally retested 38 children with idiopathic IGHD and still on GH treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH responses to two stimulation tests and normal brain imaging or minor/nonspecific findings at magnetic resonance. The GH response normalization at retesting was considered as the main outcome measure. Clinical features of children who were falsely classified as idiopathic IGHD based on first GH testing were retrospectively analyzed. RESULTS: GH secretion was normal in 36/38 children (95%). Two children showed slightly reduced peak GH responses and normal IGF-I levels. Fourteen children underwent GH retesting before puberty, 24 children during puberty. CONCLUSION: The diagnostic process should be improved to minimize the rate of false positive at GH testing and, in case of unsatisfactory response to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged with early retesting.

Preterm infants with severe extrauterine growth retardation (EUGR) are at high risk of growth impairment during childhood.

UNLABELLED: Extrauterine growth retardation (EUGR) seriously affects premature newborns and is related to the impairment of growth during childhood. There are very limited data available concerning the growth outcome of EUGR children. Our aim was to assess the growth outcome in a cohort of children born before 34 weeks of gestation with severe EUGR. This was a retrospective multicenter study, performed in outpatient endocrinology clinic. A total of 103 premature children with weight and/or length below -2 standard deviation score (SDS) of "intrauterine" growth expectation at the time of discharge from hospital (within 42 weeks of postmenstrual age) were included in the study. The study participants underwent a thorough anthropometric assessment at a mean age of 3.9 years ± 1.7 SD. Of the EUGR children, 12.6 % showed a height below -2 SDS and 7.7 % even below -2.5 SDS. Growth impairment was more common in males than in females (17 vs. 8 %). The prevalence of subnormal weight (below -2 SDS) was 13.6 %, being higher in males than in females (17 vs. 10 %). BMI values below -2 SDS were found in 18.4 % of our study population (22.7 % in males and 12 % in females). The 19.6 % of EUGR children did not catch up in head circumference during early childhood. Length at term was the major predictor of height in childhood (P < 0.001). CONCLUSION: A significant proportion of children born prematurely with severe EUGR show growth retardation in childhood thus suggesting the need for a close clinical follow-up to determine their growth potential and implement effective intervention strategies.

Personalized approach to growth hormone treatment: clinical use of growth prediction models.

The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.

The potential role of fatty liver in paediatric metabolic syndrome: a distinct phenotype with high metabolic risk?

BACKGROUND: The prevalence of obesity and its metabolic consequences has dramatically increased in the last two decades urging physicians to find a reliable definition for early detection, treatment and possibly prevention of metabolic syndrome (MS). MS could be diagnosed in adult patients in the presence of a large waist circumference and ≥2 of the following features: high serum triglycerides, low serum high-density lipoprotein cholesterol, high blood pressure and high fasting glucose. The definition of MS in children is more problematic, and the potential role of its single components on metabolic risk remains largely undefined. Recent evidence strongly suggests not only a relationship between non-alcoholic fatty liver disease (NAFLD) and MS in obese children, adolescents and adults, but also the key role exerted by liver fat deposition in the pathogenesis of MS. CONCLUSION: We propose that NAFLD should be routinely checked in obese subjects because early lifestyle changes may be effective in reducing the overall risk of MS.

Serum insulin-like growth factor-I (IGF-I) reference ranges for chemiluminescence assay in childhood and adolescence. Data from a population of in- and out-patients.

BACKGROUND: Insulin-like growth factor I (IGF-I) measurement is widely used for the diagnosis of disorders of GH secretion and sensitivity, and for monitoring of both GH and IGF-I replacement therapies. However, the lack of appropriate reference values obtained from large and representative samples undermines its practical utility. OBJECTIVE: To establish IGF-I reference values for a commonly used enzyme-labeled chemiluminescent immunometric assay in a large population of children aged 0 to 18 years. DESIGN: Cross-sectional analysis of serum IGF-I levels from samples collected in the two major Italian Children's Hospitals. SUBJECTS AND METHODS: IGF-I was measured using a solid-phase, enzyme-labeled chemiluminescent immunometric assay in 24403 children (50.6% girls) aged 0 to 18 years. Quantile regression coupled to multivariable fractional polynomials was used to produce age- and sex-specific reference values. MAIN OUTCOME MEASURE: Age- and sex-specific IGF-I reference values. RESULTS AND CONCLUSION: Reference values for immunometric assay of IGF-I were produced in a large sample of children and adolescents. Prediction equations were provided to automatize their calculations.

Effect of intrauterine growth retardation on liver and long-term metabolic risk.

Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction.

Responses to GHRH plus arginine test are more concordant with IGF-I circulating levels than responses to arginine and clonidine provocative tests.

BACKGROUND/OBJECTIVE: Although pharmacological GH stimulation tests are still considered the gold standard for GH deficiency (GHD) diagnosis, they are burdened by poor specificity. The majority of children diagnosed as having GHD show normal GH responses when re-tested at the end of growth, thus questioning the initial diagnosis. We evaluated the concordance between IGF-I levels and GH responses to provocative tests. METHODS: We analyzed 105 GHRH plus arginine tests, 79 arginine tests, and 124 clonidine tests performed in 192 short children. IGF-I levels ≤-2SD score (SDS) were considered suggestive for high likelihood of GHD. The percentage of positive and negative results for each test was determined and compared with IGF-I levels, clinical follow-up and response to therapy. RESULTS: In children with IGF-I>-2SDS the arginine test showed a concordance rate of 6.9%, the clonidine test of 28.6%, and GHRH plus arginine test of 70%. In children with IGF-I≤-2SDS the concordance was 96.1%, 85.7%, and 46.4%, respectively. The overall concordance was 66.7% for GHRH plus arginine, 42.7% for clonidine, and 27.8% for arginine tests. CONCLUSION: Our results suggest that GHRH plus arginine test provides the best concordance with the assessment of IGF-I levels thus suggesting that the combination of the two procedures may significantly reduce the need of a second provocative test.

Retinol-binding protein 4 in neonates born small for gestational age.

BACKGROUND: Retinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance and Type 2 diabetes. The relationship of RBP4 with insulin resistance and metabolic risk in human beings has been the subject of several studies. Subjects born small for gestational age (SGA) are at risk of insulin resistance and Type 2 diabetes. Though RBP4 could represent an early marker of insulin resistance, to date, none have determined RBP4 in SGA children. AIM: Our aim was to measure RBP4 concentrations in cord blood of SGA newborns compared with those in children born with a birth weight appropriate for gestational age (AGA) and to determine whether serum RBP4 levels at birth correlate with insulin sensitivity markers. SUBJECTS AND METHODS: Sixty-four newborns, 17 born SGA (mean gestational age: 36.4+/-2.1 weeks), and 47 born AGA (mean gestational age: 37.0+/-3.6 weeks) were studied. The main outcome measures included anthropometry, lipid profile, insulin, homeostasis model assessment, quantitative insulin-sensitivity check index, adiponectin, and RBP4. RESULTS: RBP4 concentrations were significantly reduced in SGA newborns (p<0.002). No relationship was found between RBP4 and insulin sensitivity parameters. Stepwise regression analysis revealed that birth weight was the major predictor of RBP4 serum concentrations (p<0.001). CONCLUSION: RBP4 is reduced in SGA newborns, birth weight representing the major determinant of RBP4 concentrations, and is not related to insulin sensitivity. No significant difference in adiponectin levels and insulin sensitivity markers was found between SGA and AGA neonates.