Front-of-pack (FOP) labelling systems to improve the quality of nutrition information to prevent obesity: NutrInform Battery vs Nutri-Score.

Many systems for classifying food products to adequately predict lower all-cause morbidity and mortality have been proposed as front-of-pack (FOP) nutritional labels. Although the efforts and advances that these systems represent for public health must be appreciated, as scientists involved in nutrition research and belonging to diverse Italian nutrition scientific societies, we would like to draw stakeholders' attention to the fact that some FOP labels risk being not correctly informative to consumers' awareness of nutritional food quality. The European Commission has explicitly called for such a nutrition information system to be part of the European "strategy on nutrition, overweight and obesity-related issues" to "facilitate consumer understanding of the contribution or importance of the food to the energy and nutrient content of a diet". Some European countries have adopted the popular French proposal Nutri-Score. However, many critical limits and inadequacies have been identified in this system. As an alternative, we endorse a new enriched informative label-the NutrInform Battery-promoted by the Italian Ministry of Health and deeply studied by the Center for Study and Research on Obesity, Milan University. Therefore, the present position paper limits comparing these two FOP nutritional labels, focusing on the evidence suggesting that the NutrInform Battery can help consumers better than the Nutri-Score system to understand nutritional information, potentially improving dietary choices. LEVEL OF EVIDENCE: II. Evidence was obtained from well-designed controlled trials without randomization.

Psychological wellbeing in parents of children with phenylketonuria and association with treatment adherence.

BACKGROUND: Phenylketonuria (PKU) is a rare metabolic disorder that leads to severe neurological abnormalities unless early treated with a strict phenylalanine (Phe)-restricted diet. The parents' involvement in PKU management is crucial and could lead to psychological distress; however, few studies have explored the parents' psychological wellbeing. The study aimed to: 1) evaluate the presence of psychological distress and impaired quality of life among parents of children with PKU, assessing the impact of the diagnosis and the impact of the treatment management; 2) explore the associations between parents' psychological outcomes and their children's blood-Phe levels. METHODS: One hundred thirty-eight parents of patients with PKU (who need a Phe-restricted diet) and with a mild form (mild hyperphenylalaninemia-MHP, with no diet indication) filled-out self-report psychological questionnaires; Phe-levels of children with PKU were retrieved. RESULTS: Parents of children with PKU did not report higher levels of psychological distress neither compared with the normative scores nor with parents of children with MHP. Optimal Phe-levels were associated with a higher number of parents' depressive complaints, with a lower tendency to express anger feelings, with a lower social functioning, and a higher mental health. CONCLUSIONS: Parents of children with PKU showed a good psychological adaptation to their children's disease and treatment. Findings highlighted associations between parents' psychological wellbeing and their children's adherence to diet. Interestingly, an optimal adherence to the diet of their children was associated with parental low social functioning, a higher tendency to control the anger expression, and greater somatic depressive symptoms.

Point of view of the Italians pediatric scientific societies about the pediatric care during the COVID-19 lockdown: what has changed and future prospects for restarting.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. METHODS: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. RESULTS: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. CONCLUSIONS: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.

Commercial complementary food use amongst European infants and children: results from the EU Childhood Obesity Project.

PURPOSE: The objective of this secondary analysis is to describe the types of commercial complementary foods (CCF) consumed by infants and young children enrolled in the European Childhood Obesity Project (CHOP), to describe the contribution of CCF to dietary energy intakes and to determine factors associated with CCF use over the first 2 years of life. METHODS: The CHOP trial is a multicenter intervention trial in Germany, Belgium, Italy, Poland and Spain that tested the effect of varying levels of protein in infant formula on the risk for childhood obesity. Infants were recruited from October 2002 to June 2004. Dietary data on CCF use for this secondary analysis were taken from weighted, 3-day dietary records from 1088 infants at 9 time points over the first 2 years of life. RESULTS: Reported energy intakes from CCF during infancy (4-9 months) was significantly higher (p ≤ 0.002) amongst formula-fed children compared to breastfed children. Sweetened CCF intakes were significantly higher (p ≤ 0.009) amongst formula-fed infants. Female infants were fed significantly less CCF and infant age was strongly associated with daily CCF intakes, peaking at 9 months of age. Infants from families with middle- and high-level of education were fed significantly less quantities of CCF compared to infants with parents with lower education. Sweetened CCF were very common in Spain, Italy and Poland, with over 95% of infants and children fed CCF at 9 and 12 months of age consuming at least one sweetened CCF. At 24 months of age, 68% of the CHOP cohort were still fed CCF. CONCLUSIONS: CCF comprised a substantial part of the diets of this cohort of European infants and young children. The proportion of infants being fed sweetened CCF is concerning. More studies on the quality of commercial complementary foods in Europe are warranted, including market surveys on the saturation of the Western European market with sweetened CCF products.

Psychological and psychosocial implications for parenting a child with phenylketonuria: a systematic review.

INTRODUCTION: Since phenylketonuria (PKU) appears to have specificities that might challenge the parents' adaptation and well-being, the present review aimed to evaluate the impact of parenting a child with PKU on parents' psychological and psychosocial functioning. EVIDENCE ACQUISITION: A systematic electronic search was conducted using PubMED, Scopus, Embase, PsychInfo, Google Scholar and Cochrane Database to identify studies exploring psychological and psychosocial issues of parents of PKU children. The search retrieved 427 articles to review against inclusion criteria; a total of 17 studies were included in the review. Results were summarized qualitatively. EVIDENCE SYNTHESIS: Findings revealed a complex pattern of interrelated factors both on parental psychological wellbeing and psychosocial functioning. In particular, crucial for parents' adjustment to child PKU are the diagnosis resolution and the perceived social support; parents showed good coping strategies and quality of life; while, with regard to mental health, the studies reviewed showed inconsistent results, thus pointed out a moderate level of distress. The review examines patterns of results across studies and discusses methodological heterogeneities and problems related to different or inconsistent findings. CONCLUSIONS: Parenting a child with PKU had direct implications on the diagnosis resolution, the parents mental health and the disease management. Findings could help healthcare professionals to identify situations at risk for psychological maladjustments both in parents and in children, as the unresolved diagnosis or a tendency toward the social isolation. Results highlighted the necessity of a multidisciplinary caring approach for the family, with a particular focus on critical moments such diagnosis or developmental transitions.

DNA-Methylation and Body Composition in Preschool Children: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study.

Adiposity and obesity result from the interaction of genetic variation and environmental factors from very early in life, possibly mediated by epigenetic processes. Few Epigenome-Wide-Association-Studies have identified DNA-methylation (DNAm) signatures associated with BMI and body composition in children. Body composition by Bio-Impedance-Analysis and genome-wide DNAm in whole blood were assessed in 374 pre-school children from four European countries. Associations were tested by linear regression adjusted for sex, age, centre, education, 6 WBC-proportions according to Houseman and 30 principal components derived from control probes. Specific DNAm variants were identified to be associated with BMI (212), fat-mass (230), fat-free-mass (120), fat-mass-index (24) and fat-free-mass-index (15). Probes in genes SNED1(IRE-BP1), KLHL6, WDR51A(POC1A), CYTH4-ELFN2, CFLAR, PRDM14, SOS1, ZNF643(ZFP69B), ST6GAL1, C3orf70, CILP2, MLLT4 and ncRNA LOC101929268 remained significantly associated after Bonferroni-correction of P-values. We provide novel evidence linking DNAm with (i) altered lipid and glucose metabolism, (ii) diabetes and (iii) body size and composition in children. Both common and specific epigenetic signatures among measures were also revealed. The causal direction with phenotypic measures and stability of DNAm variants throughout the life course remains unclear and longitudinal analysis in other populations is required. These findings give support for potential epigenetic programming of body composition and obesity.

Work activity and phenylalanine levels in a population of young adults with classic PKU.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism characterized by increased blood concentrations of phenylalanine (Phe). OBJECTIVES: The aim of the present study was to assess the association between the metabolic compliance of adult patients affected by classic PKU and the characteristics of their present and past occupations. METHODS: The study population consisted of working adults, affected by classic PKU, and following a dietary treatment. Univariate linear-mixed models and multivariate analysis were applied to assess the association between Phe blood levels and individual covariates: age, sex, time at diagnosis, educational level and work characteristics. RESULTS: A linear relationship was found with age (an average annual increase of 30.56 µMol/L (C.I. 95%: 7.53; 53.60) in the mean Phe blood levels). Full-time work appeared to be associated with a worse metabolic compliance when compared to part-time work (mean Phe blood levels >281.11 µMol/L). Shift work was related to a worse metabolic compliance, with mean Phe plasmatic levels >356.73 µMol/L. CONCLUSIONS: Our data suggests that work may influence the metabolic compliance in adults with PKU. In particular, a part-time employment could allow for a better metabolic compliance, while daily work should be preferred to shift work.

Disease severity and quality of life in children with atopic dermatitis: PO-SCORAD in clinical practice.

BACKGORUND: Atopic dermatitis (AD) can significantly compromise the quality of life (QoL). The aim of our investigation was to evaluate whether QoL correlates with AD severity, evaluated through the physician and the patient perspective, in a sample of Italian children. METHODS: Forty children with AD were evaluated. Disease severity was assessed by the physician and the patients (or their parents) using the SCORAD and the patient-oriented SCORAD (PO-SCORAD) tools, respectively. Patients or their parents completed specific QoL questionnaires (IDQOL/CDLQI). Spearman's correlation coefficient and non-parametric analysis of covariance were used to analyze the data. RESULTS: SCORAD e PO-SCORAD were moderately but significantly correlated (ρ Spearman=0.55, P<0.01). QoL scores ranged from 1 to 23, with a median score of 4.0 (higher scores represent more impaired QoL). After adjustment for age and sex, children with SCORAD>40 had significantly higher QoL scores (more impaired QoL) than those with SCORAD≤40 (median QoL of 5 and 4, respectively, P=0.048). Even higher differences emerged when AD severity was self-assessed (median QoL of 6 and 3.5 for children with PO-SCORAD>40 and PO-SCORAD≤40, respectively, P=0.01). AD children with concomitant food allergy had a significantly more impaired QoL than those with AD only (P=0.040). No significant difference in QoL was observed according to sex or age. CONCLUSIONS: In our sample of AD children, QoL appeared slightly-moderately altered, and increasing disease severity was associated with greater impairment in QoL. SCORAD and PO-SCORAD were fairly correlated and the association of QoL was somewhat stronger with the PO-SCORAD than the SCORAD Index. This supports the usefulness of PO-SCORAD for the self-assessment of AD in children, and suggests the importance to integrate physician and patient perspectives in the management of AD.

Relative Abundance in Bacterial and Fungal Gut Microbes in Obese Children: A Case Control Study.

BACKGROUND: Differences in relative proportions of gut microbial communities in adults have been correlated with intestinal diseases and obesity. In this study we evaluated the gut microbiota biodiversity, both bacterial and fungal, in obese and normal-weight school-aged children. METHODS: We studied 28 obese (mean age 10.03 ± 0.68) and 33 age- and sex-matched normal-weight children. BMI z-scores were calculated, and the obesity condition was defined according to the WHO criteria. Fecal samples were analyzed by 16S rRNA amplification followed by denaturing gradient gel electrophoresis (DGGE) analysis and sequencing. Real-time polymerase chain reaction (PCR) was performed to quantify the most representative microbial species and genera. RESULTS: DGGE profiles showed high bacterial biodiversity without significant correlations with BMI z-score groups. Compared to bacterial profiles, we observed lower richness in yeast species. Sequence of the most representative bands gave back Eubacterium rectale, Saccharomyces cerevisiae, Candida albicans, and C. glabrata as present in all samples. Debaryomyces hansenii was present only in two obese children. Obese children revealed a significantly lower abundance in Akkermansia muciniphyla, Faecalibacterium prausnitzii, Bacteroides/Prevotella group, Candida spp., and Saccharomyces spp. (P = 0.031, P = 0.044, P = 0.003, P = 0.047, and P = 0.034, respectively). CONCLUSION: Taking into account the complexity of obesity, our data suggest that differences in relative abundance of some core microbial species, preexisting or diet driven, could actively be part of its etiology. This study improved our knowledge about the fungal population in the pediatric school-age population and highlighted the need to consider the influence of cross-kingdom relationships.

Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis.

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

Maternal Smoking during Pregnancy and DNA-Methylation in Children at Age 5.5 Years: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study.

Mounting evidence links prenatal exposure to maternal tobacco smoking with disruption of DNA methylation (DNAm) profile in the blood of infants. However, data on the postnatal stability of such DNAm signatures in childhood, as assessed by Epigenome Wide Association Studies (EWAS), are scarce. Objectives of this study were to investigate DNAm signatures associated with in utero tobacco smoke exposure beyond the 12th week of gestation in whole blood of children at age 5.5 years, to replicate previous findings in young European and American children and to assess their biological role by exploring databases and enrichment analysis. DNA methylation was measured in blood of 366 children of the multicentre European Childhood Obesity Project Study using the Illumina Infinium HM450 Beadchip (HM450K). An EWAS was conducted using linear regression of methylation values at each CpG site against in utero smoke exposure, adjusted for study characteristics, biological and technical effects. Methylation levels at five HM450K probes in MYO1G (cg12803068, cg22132788, cg19089201), CNTNAP2 (cg25949550), and FRMD4A (cg11813497) showed differential methylation that reached epigenome-wide significance according to the false-discovery-rate (FDR) criteria (q-value<0.05). Whereas cg25949550 showed decreased methylation (-2% DNAm ß-value), increased methylation was observed for the other probes (9%: cg12803068; 5%: cg22132788; 4%: cg19089201 and 4%: cg11813497) in exposed relative to non-exposed subjects. This study thus replicates previous findings in children ages 3 to 5, 7 and 17 and confirms the postnatal stability of MYO1G, CNTNAP2 and FRMD4A differential methylation. The role of this differential methylation in mediating childhood phenotypes, previously associated with maternal smoking, requires further investigation.

Endocrine and Metabolic Biomarkers Predicting Early Childhood Obesity Risk.

There is growing evidence of long-term effects of early dietary intervention in infancy on later obesity risk. Many studies showed reduced risk of obesity with breastfeeding in infancy, which could be related to the reduced protein intake with human milk compared to infant formula. In a randomized controlled trial (Childhood Obesity Project), we were able to show that infant formula with reduced protein content results in lower BMI both at 2 and 6 years. These effects seem to be mediated mainly by branched-chain amino acids which stimulate the insulin-like growth factor (IGF)-1 axis and insulin release. In this trial, we also showed an influence of high-protein diet on larger kidney size, which seems to be partly explained by a significant effect of free IGF-1 on kidney volume. The IGF-1 axis was shown to regulate early growth, adipose tissue differentiation and early adipogenesis in animals and in humans. Leptin and adiponectin can also be regarded as important endocrine regulators of obesity. These markers were tested in observational studies. Leptin seems to be closely correlated with BMI but changes in adiponectin require further exploration. Still, there is a lack of good data or some results are contradictory to indicate the role of either leptin or adiponectin in infancy for determining later obesity risk.

Leptin and Adiponectin Serum Levels from Infancy to School Age: Factors Influencing Tracking.

BACKGROUND: Early adiponectin and leptin in children correlate with those measured at a later age. Prenatal and early life factors may influence the pattern of leptin and adiponectin longitudinal changes. We aimed to identify subgroups of children with distinct trajectories of leptin and adiponectin over the first eight years of life, and to explore determinants predisposing an individual to be included in a specific trajectory class. METHODS: The analysis was based on data obtained from the EU Childhood Obesity Project (CHOP) cohort. The current study involved 459 children with adiponectin and leptin measured at 6 months, 5½ and 8 years of age. RESULTS: Three groups of leptin trajectories were identified: low-decreasing, medium-stable, and high-increasing, and two trajectory groups for adiponectin: lower and higher. The risk to be classified in the high-increasing group was higher than in the low-decreasing group for female gender (OR 10.67; 95% CI 4.94-23.05; p < 0.001); formula feeding (OR 3.34; 95% CI 1.11-10.09; p < 0.05); maternal overweight (OR 4.43; 95% CI 2.20-8.94; p < 0.001); and smoking in pregnancy (OR 4.14; 95% CI 2.07-8.29; p < 0.001). No predictors for being in the higher vs. lower adiponectin group were discovered. CONCLUSIONS: Mothers' smoking during pregnancy, maternal overweight, and formula feeding distinguished different courses of leptin trajectories; but the effect may be associated with changes in adiposity.

Atopic dermatitis: recent insight on pathogenesis and novel therapeutic target.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It affects infancy, but it is also highly prevalent in adults and it is one of the disease burdens for the patients and their families. Nowadays, AD is recognized as a heterogenous disease with different subtypes with variable clinical manifestations which is affected by the impairments of the skin barrier. The severity of AD dictates the level of treatment. Current AD treatment focuses on restoration of the barrier function, mainly through the use of moisturizers and corticosteroids to control the inflammation, topical calcineurin inhibitors, and immunosuppresive drugs in the most severe cases. However, targeted disease-modifying therapies are under investigation. The most recent findings on the skin microbial dysbiosis is a promising future direction for the development of new treatments. We need to improve the understanding of the complex microbiome-host interactions, the role of autoimmunity, the comparative effectiveness of therapies and the ways to appropriately implement the educational strategies.

Lens opacities in glycogenoses type I and III.

OBJECTIVE: The glycogen storage diseases (GSD) or glycogenoses comprise several inherited diseases caused by abnormalities of the enzymes that regulate the synthesis or degradation of glycogen. This report presents lens opacities not previously described in patients with type I or III GSD. PARTICIPANTS: Eleven patients with type I and III GSD. METHODS: We examined a series of 11 consecutive patients (aged 13-40 years) with type I and III GSD by full ophthalmologic examination. RESULTS: We found changes of the lens on 7 of 11 patients (aged 23-40 years) with glycogenoses I and III. In 6 patients, the lens showed multiple, bilateral, punctate, and peripheral opacities; only 1 patient showed a posterior subcapsular opacity in both eyes. We did not observe changes in the cornea and the posterior pole correlated to the accumulation of glycogen and lipids. CONCLUSIONS: In this series, we found that 60% of patients with type I and III GSD show lens opacities. These opacities are bilateral, peripheral, multiple, and small; they do not give any visual disturbance. Considering that subjects with age ranging from 13 to 23 years had no lens opacities, we postulate that they could progressively develop over time because of exposure to recurrent attacks of hypoglycemia, which lead to a progressive depletion of hexokinase.

Effect of high-dose sublingual immunotherapy on respiratory infections in children allergic to house dust mite.

BACKGROUND: Allergic rhinitis is characterized by eosinophil inflammation. Allergic inflammation may induce susceptibility to respiratory infections (RI). House dust mite (HDM) sensitization is very frequent in childhood. Allergen immunotherapy may cure allergy as it restores a physiologic immune and clinical tolerance to allergen and exerts anti-inflammatory activity. OBJECTIVE: This study investigated whether six-month high-dose, such as 300 IR (index of reactivity), HDM-sublingual immunotherapy (SLIT) could affect RI in allergic children. METHODS: Globally, 40 HDM allergic children (18 males; mean age, 9.3 years) were subdivided in 2 groups: 20 treated by symptomatic drugs (group 1) and 20 by high-dose HDM-SLIT (group 2), since September 2012 to April 2013. The daily maintenance dose of HDM-SLIT was 4 pressures corresponding to 24, 4.8, and 60 µg, respectively of the major allergens Dermatophagoides pteronyssinus (Der p) 1, Der p 2, and Dermatophagoides farinae (Der f) 1. RI was diagnosed when at least 2 symptoms or signs, and fever were present for at least 48 hours. A family pediatrician provided diagnosis on a clinical ground. RESULTS: SLIT-treated children had significantly (p = 0.01) less RI episodes (3.5) than control group (5.45). About secondary outcomes, SLIT-treated children had less episodes of pharyngo-tonsillitis (p < 0.05) and bronchitis (p < 0.005), and snoring (p < 0.05) than control group. In addition, SLIT-treated children had less fever (p < 0.01) and took fewer medications, such as antibiotics (p < 0.05) and fever-reducers (p < 0.01), than control group. CONCLUSION: This preliminary study might suggest that also a short course (6 months) of high-dose SLIT, titrated in µg of major allergens, could reduce RI in allergic children.

Flavor, relative palatability and components of cow's milk hydrolysed formulas and amino acid-based formula.

BACKGROUND: Both extensively hydrolysed formulas (eHF) and amino acid-based formula (AAFs) have been demonstrated effective for the treatment of CMA. However, in clinical practice, parents complain that hydrolysates are rejected by children due to their bad taste. Flavor of hydrolysed formulas has been poorly investigated although it affects the acceptance of milk over all the other attributes. The aim of the present study was to understand the factors underlying the unpleasant flavor of hydrolysed 25 formulas and amino acid-based formula. SUBJECTS AND METHODS: One hundred and fifty trained panelists performed a randomized-double-blind test with different milks. The smell, texture, taste and aftertaste of each formula were evaluated on a scale ranging from -2 (worst) to 2 (best). RESULTS: Formulas showed significant difference, as compared to cow's milk, in smell, texture, taste and aftertaste. Overall, whey eHFs were judged of better palatability than casein eHF and the AAFs (p < 0.05). Whey eHF showed significant differences among them for sensory attributes, especially for taste and aftertaste. CONCLUSIONS: These results suggest that a broad range of flavor exists among the hydrolysed formulas. Further studies, adequately designed to investigate the relationship between milks' flavor and nutrient profile of hydrolysed formulas are warranted.

Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.

OBJECTIVE: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5(th) percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. METHODS: A one month old infant with failure to thrive, severe hypocholesterolemia and acanthocytosis was clinically and genetically characterized. Molecular characterization of the proband and her parents was performed by direct sequencing of the APOB gene and functional role of the identified mutations was assessed by the minigene methodology. RESULTS: The proband was found carrying two novel splicing mutations of the APOB gene (c.3696+1G > C and c.3697-1G > A). CHOK1H8 cells expressing minigenes harbouring the mutations showed that these two mutations were associated with the retention of intron 23 and skipping of exon 24, resulting in two truncated apoB fragments of approximate size of 26-28 % of ApoB-100 and the total absence of apoB. CONCLUSION: We describe the first case of Ho-FHBL due to two splicing mutations affecting both the donor and the acceptor splice sites of the same intron of the APOB gene occurring in the same patient. The clinical management of the proband is discussed and a review of the clinical and genetic features of the published Ho-FHBL cases is reported.

Protein intake in infancy and carotid intima media thickness at 5 years--a secondary analysis from a randomized trial.

BACKGROUND: Nutrition in childhood has an influence on the cardiovascular function later on in life. European Childhood Obesity Project is a multicenter, randomized clinical intervention trial examining the effect of early protein intake on later health outcomes, particularly adiposity and related disorders. The aim of the study was to examine the effect of nutritional intervention--different protein intake in infancy on carotid intima-media thickness (cIMT) at 5 years. The association of cardiovascular risk factors with cIMT was also assessed. METHODS: Healthy term formula-fed infants in five European countries were enrolled either to the higher (HP) or to the lower (LP) protein group. Observational group consisted of breastfed infants. Plasma insulin, glucose, lipid profile, IGF-1, apolipoprotein A1 and B were measured as well as anthropometric parameters of parents and a child, blood pressure and physical activity. RESULTS: No difference in cIMT between HP and LP group was observed. Insulin, HOMA-IR index and total IGF-1 were positively associated with cIMT but after adjustment for confounders only an inverse association between ApoA1 and positive between ApoB/ApoA1 and cIMT were significant. CONCLUSION: High versus low protein intake in infancy does not influence cIMT at 5 years. cIMT in healthy children at 5 years is associated with their apolipoprotein profile.

Prebiotic effect of an infant formula supplemented with galacto-oligosaccharides: randomized multicenter trial.

OBJECTIVE: The objective of the study was to investigate the effects of a galacto-oligosaccharides (GOS)-supplemented formula on the intestinal microbiota in healthy term infants, with a specific consideration for gastrointestinal symptoms as colic, stool frequency and consistency, regurgitation. METHODS: This was a randomized, double-blind, controlled, parallel-group clinical trial performed simultaneously by 6 centers in Italy. Three groups were considered: breastfed, formula-fed, and GOS-supplemented formula-fed infants. Formula-fed infants were randomized to receive either the control or the study formula and consume the assigned formula exclusively until the introduction of complementary feeding. The nutritional composition of the 2 formulas were identical, apart from the supplemented GOS (0.4 g/100 mL) in the study formula. Four different types of bacteria were evaluated in order to assess the efficacy of GOS-supplemented formula on infants: Bifidobacterium, Lactobacillus, and Clostridium, Escherichia coli. RESULTS: A total of 199 breastfed infants and 163 formula-fed infants were recruited. When considering stool frequency and consistency, GOS-supplemented formula presented normal and soft stools in the majority of episodes (89%). In the supplemented group the incidence of colic was lower with respect to the control group. A significantly lower count of Clostridium and a higher count of Bifidobacterium were found when comparing study formula and control formula in infants with colic. In children with colic the ratio between Clostridium count and Bifidobacterium and Lactobacillus count was in favor of the latter two when considering the GOS-supplemented formula group with respect to the control one. CONCLUSIONS: The prebiotic-supplemented formula mimicked the effect of human milk in promoting Bifidobacterium and Lactobacillus growth and in inhibiting Clostridium growth, resulting in a significantly lower presence of colic.