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.

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.

29th Congress of the Italian Society of Neonatology - Lombardy section | Bergamo, 29-30 January 2016.

This abstract book contains the abstracts presented at the 29th Congress of the Italian Society of Neonatology - Lombardy section | Bergamo, 29-30 January 2016.

Management of adult patients with phenylketonuria: survey results from 24 countries.

UNLABELLED: Phenylketonuria (PKU) is no longer considered merely a pediatric concern; current guidelines recommend life-long treatment. However, information on the adult PKU patient population is scarce. A survey was initiated on behalf of the European PKU Group (EPG) that focused specifically on early-treated adult patients diagnosed by neonatal screening. The online survey was sent via email to 204 healthcare professionals (HCPs) in 33 countries. Eighty-one HCPs from 24 countries responded. The main findings were that the majority of adult patients with PKU in active follow-up are under 30 years of age and are managed in centers that also treat children. Seventy-eight percent of adult PKU patients in follow-up receive treatment, mainly by diet (71 %), with BH4 treatment rarely used in adulthood. Only 26 % of responding HCPs perform routine neurocognitive testing in all their adult patients. There was little consensus regarding target blood phenylalanine (Phe) concentrations, although the majority of respondents reported that their patients achieved blood Phe concentrations below 1200 µmol/l. CONCLUSION: This survey highlights the need for blood Phe concentration target recommendations and consensus guidelines, more research into adult PKU patient management, and the need to identify those patients lost to follow-up to ensure PKU is managed for life.

Randomized controlled trial of a protein substitute with prolonged release on the protein status of children with phenylketonuria.

OBJECTIVE: To examine whether a phenylalanine-free protein substitute with prolonged release may be beneficial to the protein status of children with phenylketonuria (PKU) compared to conventional substitutes. METHODS: Sixty children with PKU, 7 to 16 years of age, were randomly allocated to receive either a prolonged-release (test) or the current conventional protein substitute for 30 days. Subjects were additionally sex and age matched with 60 subjects with mild hyperphenylalaninemia and 60 unaffected subjects. The protein status in children with PKU was assessed by albumin, transthyretin, and retinol-binding protein (RBP), and changes throughout the trial period were the primary outcome measures. RESULTS: Children with PKU did not differ in anthropometry from children with mild hyperphenylalaninemia or unaffected children but they ingested lower amounts of proteins (p < 0.01). No differences occurred throughout the trial between or within children with PKU who received the test or conventional substitute for macronutrient intake. Albumin and RBP concentrations were within the age-specific reference range for all children. The rate of protein insufficiency (transthyretin concentration less than 20 mg/dL) did not differ statistically between children receiving test or conventional substitute (recruitment 51.8% vs 53.6%; end of the trial 44.4% vs 50.0%) but mean transthyretin recovered over 20 mg/dL in children who received the test substitute, increasing from 19.1 to 20.7 mg/dL (mean change, 1.6 mg/dL; 95% confidence interval 0.4 to 2.8 mg/dL). In children receiving conventional substitute mean transthyretin changed from 19.0 to 19.2 mg/dL (0.2; -0.2 to 0.6) mg/dL. CONCLUSIONS: Protein substitutes with prolonged release might be beneficial to protein status in children with phenylketonuria.

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.

Omega-3 fatty acids and asthma in children.

The purpose of this study was to summarize and analyze the results of studies supporting the use of omega-3 fatty acids for their therapeutic and preventive value in childhood asthma in light of recent genetic evidence strongly suggesting a pathogenetic role in asthma and to discuss the implications of these findings for future research. Although a considerable number of observational studies have been conducted in children showing a beneficial effect of omega-3 dietary intake in asthma, a fully well-designed, rigorously conducted investigational study is still lacking. Additionally, the few interventional trials with omega-3 supplementation conducted in asthmatic children have often yielded conflicting results. The genetic polymorphism and the gene-nutritional interactions that accompany asthma can be the missing factors and may explain the inconsistent results found in these interventional trials. Therefore, the analyses of key genes variants should be included in future studies to thoroughly investigate the effects of long-chain polyunsaturated fatty acid on asthma. Although a definitive conclusion can not be made supporting a beneficial effect of dietary modification or supplementation with omega-3 for the prevention or modification of asthmatic disease in children, there is sufficient evidence to support this possibility. There is, therefore, a clear need for future research to investigate the feasibility of this dietetic approach to reduce the likely development of asthma and/or the successful treatment of asthmatic disease. From a public health perspective, if a dietetic approach is successfully documented, even if only in a cohort of susceptible individuals, it would offer a far better management tool than currently available, better tolerated, and, in the long run, more cost-effective.

Blood lipids profile in hyperlipidemic children undergoing different dietary long chain polyunsaturated supplementations: a preliminary clinical trial.

The aim of this preliminary study was to explore the effect size of different dietary long chain polyunsaturated supplementations on blood lipid profile in children with primary hyperlipidemia. Thirty-six children (8-13 years) were recruited. After an 8-week stabilization period on the Step I diet, they were randomized to additionally receive for a 16-week period one capsule (500 mg) daily of docosahexaenoic acid (DHA) alone or a DHA plus eicosapentaenoic acid (EPA) mixture (45.6% DHA; 41.6% EPA) or wheat germ oil (control). An effect size (as percentage change from baseline) of +8%, -12% and -16% for high-density lipoprotein cholesterol (HDL-C), total cholesterol/HDL-C ratio and triglycerides was observed in children supplemented with DHA, compared to +2%, -8% and -12%, respectively, in children supplemented with DHA plus EPA. This preliminary study suggests powered trials appear feasible and are warranted to evaluate efficacy of n-3 long-chain polyunsaturated fatty acid dietary supplementations on the blood lipid profile of children with primary hyperlipidemia.

The status of invasive pneumococcal disease among children younger than 5 years of age in north-west Lombardy, Italy.

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive infection in young children causing morbidity and mortality. Active surveillance systems of invasive pneumococcal disease (IPD) are recommended worldwide. The aim of this study was to estimate the current incidence of IPD and to describe the serotype distribution and the antimocrobial susceptibility of S. pneumoniae isolates in children aged less than 5 years residing in North-West Lombardy, Italy. METHODS: A twelve-month prospective active surveillance system recruited all children aged less than 5 years admitted for suspicion of IPD at emergency room of ten hospitals located in the monitored area. Blood samples were taken in all participants for confirmation of IPD based on isolation of S. pneumoniae from blood. Pneumococcal meningitis and sepsis were additionally confirmed by cerebrospinal fluid analysis. Serotyping and antimicrobial susceptibility testing were performed on isolates from blood. RESULTS: A total of 15 confirmed cases of IPD were detected among 135 recruited children, including pneumonia (n = 8), bacteremia (n = 4), sepsis (n = 2) and meningitis (n = 1). The annual IPD incidence rate was 50.0/100,000 (95%CI, 30.5-82.5/100,000). Incidence was 58.3/100,000 (28.8-120.1/100,000) among children aged less than 2 years and 44.4/100,000 (22.9-87.5/100,000) among children aged 2-4 years. Thirteen isolates were typified. The most common serotype was 19A (23.1%) that together with serotypes 1, 7F and 19F accounted for 69.2% of typified isolates. Serotypes 14, 23F, 12B and 15C were also identified. The 7- and 13-valent pneumococcal conjugate vaccines covered respectively 30.8% and 84.6% of typified IPD cases. One isolate (serotype 15C) was penicillin-resistant and caused meningitis. CONCLUSIONS: The inclusion of the 13-valent pneumococcal conjugate vaccine in immunization programs of young children might be considered to reduce incidence and morbidity of invasive pneumococcal disease in this surveilled population.

Erythrocyte Galactose-1-phosphate measurement by GC-MS in the monitoring of classical galactosemia.

BACKGROUND: Classical galactosemia is a rare but very severe disease characterized by a deficiency of the galactose-1-phosphate uridyltransferase enzyme. The confirmed galactosemic patients are treated with a galactose-restricted diet. Nevertheless, metabolites such as galactose-1-phosphate can accumulate in red blood cells of treated patients and its measurement is a standard practice for their monitoring. At present, no commercial methods for measuring galactose-1-phosphate in erythrocytes are available. METHODS: In this study, we will describe the optimization and laboratory validation of a previously published quantitative gas chromatographic-mass spectrometric method and its clinical validation on normal donors and galactosemic patients both at the diagnosis and during the follow-up. RESULTS: The method was technically optimized and validated for its clinical use on normal donors and galactosemic newborns, children and adults. The method was suitable for the monitoring of dietary compliance. Galactose-1-phosphate levels were found to be well correlated with the clinical signs in the galactosemic patients at the follow-up. CONCLUSIONS: This paper provides information on the measurement of Galactose-1-phosphate levels that can be very useful for the management of classical galactosemia.

Attitudes and practices of family paediatricians in Italy regarding infant feeding.

AIM: The aim of this study was to examine attitudes and practices of family paediatricians in Italy towards infant feeding. METHODS: A questionnaire was sent to 850 paediatricians across Italy, asking about attitudes and practices towards infant feeding with focus on the World Health Organization's criteria. RESULTS: The response rate was 91.2%. Breastfeeding is recommended for 6-11 months (70.6%) or longer (29.4%). A 95% of paediatricians recommend introducing complementary foods throughout 4-5.9 months. Among paediatricians who give indications about the minimum acceptable diet (61.7%), recommendations agree with WHO in 71.3% and 83.3% of cases for infants aged 6-8 or 9-11 months, respectively. A 95.6% of paediatricians recommend consumption of meat for infants aged 6 months or more, and 98.4% use of formula milk for infants having breastfeeding stopped in the first year of life. Paediatricians reported own experience (73.4%) and reading (54.2%) as main sources of information. A 70% of paediatricians know the WHO/Infant and Young Child Feeding Practices criteria regarding breastfeeding but <5% the complementary feeding indicators. CONCLUSION: Family paediatricians in Italy have positive disposition towards infant feeding but their knowledge and practices are suboptimal with respect to the WHO criteria, especially regarding complementary feeding.

"The city of Hepar": rituals, gastronomy, and politics at the origins of the modern names for the liver.

Medical etymology sometimes provides unexpected information about health concepts and medical practice in different times and cultures. We conducted an etymological analysis of the terms used to indicate "liver" in Germanic and Romance languages. The Greek word "hèpar" was originally connected to the concept of "pleasure", showing that in antiquity the liver was considered to be the seat of soul and human feelings. In Romance languages, the Latin term "ficatum" was linked to the ancient practice of fattening geese with figs (ficus in Latin) to make their livers more delicious. This relationship between the liver, fat, and carbohydrates seems to indicate that ancient gourmets had clear knowledge of the nutritional mechanisms underlying "fatty liver" in animals. On the other hand, the Germanic term "lifere" was initially connected to "life", underscoring the relation of the liver to health and existence. In the Early Modern Age, the liver became a recurring image in political reflection, especially within the Elizabethan tradition of the body politic, where the king was frequently described as the "liver" of his country. Finally, the liver was used to indicate courage, or the lack of it: some modern French and English idiomatic expressions derive from the ancient belief that people who had no blood in their liver ("lily-livered") would thus be cowards or betrayers.

A specific prebiotic mixture added to starting infant formula has long-lasting bifidogenic effects.

There is some evidence that early colonization of the intestine affects the composition of the intestinal microbiota after weaning. In the present study, the effect of prebiotics administered from the first day of life on fecal counts of bifidobacteria and lactobacilli were studied during and after the administration of the prebiotics. In this double-blind, randomized, placebo-controlled, explorative study, 20 newborns of hepatitis C virus-infected mothers who decided not to breast feed due to their concerns regarding their plasma viral load were randomly assigned to either a formula with 8 g/L of a specific prebiotic mixture (short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides, ratio 9:1) or a formula containing the same amount of maltodextrin (placebo). Clinical examination including anthropometric measurements, microbiological analysis of fecal samples, and blood leukocyte population analysis were performed at birth and 3, 6, and 12 mo age. At the age of 12 mo, hepatitis B vaccine-specific IgG serum titers (Hepatitis B virus surface antibodies) were also measured. Prebiotic supplementation resulted in more fecal bifidobacteria (P < 0.0001) and lactobacilli (P = 0.0044) compared with the placebo group. These differences between the groups were maintained during the second half of the first year without any prebiotic supplementation. There was no influence of the different diets on anthropometric data or the measured immunological variables. The data from this small explorative study indicate that early colonization of the intestine might have long-lasting effects on the composition of the intestinal microbiota.

Probiotics and health: an evidence-based review.

The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.

Plasma long-chain fatty acids profile and metabolic outcomes in normolipidaemic obese children after one-year nutritional intervention.

AIM: To assess the association between changes in plasma long-chain polyunsaturated fatty acids (LCPUFAs) profile and metabolic outcomes after 1-year nutritional intervention in normolipidaemic obese children. METHODS: Fifty-seven normolipidaemic obese children, aged 8-13 years, were recruited in the study. Body mass index (BMI) z-scores were calculated. Fasting blood samples were analysed for insulin, glucose, lipid profile and fatty acid (FA) levels at baseline and after an 1-year nutritional-behaviour intervention. Insulin resistance was estimated by homeostatic model assessment (HOMA). RESULTS: Fifty-one obese children completed the study. At the end of the intervention, the children showed decreased BMI z-score (mean reduction 0.25; 95% confidence interval [CI], 0.18-0.31), HOMA index (1.6; 0.6-2.5), plasma-saturated FA (1.49; 0.67-2.31 mg/dL), C20:3n-9 (0.05; 0.02-0.07 mg/dL) and increased plasma levels of monounsaturated FA (mean increase 1.35; 0.63-2.07 mg/dL), n-6 PUFA (1.02; 0.08-1.97 mg/dL), n-3 PUFA (0.24; 0.07-0.40 mg/dL), C20:4n-6 (0.37; 0.11-0.63 mg/dL), C18:3n-3 (0.04; 0.01-0.07 mg/dL), C22:6n-3 (0.30; 0.17-0.42 mg/dL) and the C22:6n-3/C20:4n-6 ratio (0.02; 0.01-0.03 mg/dL) ratio. CONCLUSIONS: Nutritional interventions may improve plasma LCPUFA profile and metabolic outcomes of normolipidaemic obese children.

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.

Management of phenylketonuria in Europe: survey results from 19 countries.

To gain better insight in the most current diagnosis and treatment practices for phenylketonuria (PKU) from a broad group of experts, a European PKU survey was performed. The questionnaire, consisting of 33 questions, was sent to 243 PKU professionals in 165 PKU centers in 23 European countries. The responses were compiled and descriptive analyses were performed. One hundred and one questionnaires were returned by 93/165 centers (56%) from 19/23 European countries (83%). The majority of respondents (77%) managed patients of all age groups and more than 90% of PKU teams included physicians or dieticians/nutritionists. The greatest variability existed especially in the definition of PKU phenotypes, therapeutic blood phenylalanine (Phe) target concentrations, and follow-up practices for PKU patients. The tetrahydrobiopterin (BH4; sapropterin) loading test was performed by 54% of respondents, of which 61% applied a single dose test (20mg/kg over 24h). BH4 was reported as a treatment option by 34%. This survey documents differences in diagnostic and treatment practices for PKU patients in European centers. In particular, recommendations for the treatment decision varied greatly between different European countries. There is an urgent need to pool long-term data in PKU registries in order to generate an evidence-based international guideline.

Symposium overview: Do we all eat breakfast and is it important?

Besides genetic and environmental factors, the breakfast meal and the frequency in which it is eaten may influence appetite control, dietary intake and composition, and chronic disease risk. Breakfast skipping may lead to up-regulation of appetite, possibly leading to weight gain over time and deleterious changes in risk factors for diabetes and cardiovascular disease. Breakfast skipping has also been linked to poorer overall diet quality. Regular breakfast consumption, on the other hand, may reduce the risk of chronic diseases due to the potential impact on the composition of the overall diet, and is also associated with improved learning abilities and better school performance in children. Considering the trend to skip, or to have nutritionally inadequate breakfast, suggestions to promote and support breakfast in children and adolescents will be considered.

The relevance of breakfast: concluding remarks.

The disease preventive role of breakfast emerges from epidemiological surveys. Thus, to accustom children to a regular breakfast consumption, and to maintain such behavior throughout the life-span, may have a significant health impact. Strategies to implement this dietary habit should be developed, as well as knowledge of the metabolic impact of different breakfast types according to local traditions and genetic background.

Liver fat change in obese children after a 1-year nutrition-behavior intervention.

OBJECTIVES: To evaluate whether a 1-year nutrition-behavior intervention based on normocaloric balanced diet and physical exercise may reduce liver fat in obese children. PATIENTS AND METHODS: Twenty-six obese children (11 boys and 15 girls), aged 6 to 14 years, underwent anthropometric, nutritional, metabolic, and liver magnetic resonance imaging (MRI) examinations at baseline and after a 1-year nutrition-behavior intervention. Anthropometry included weight, height, waist and hip circumference, and total upper arm area. Body mass index z scores were calculated. Biochemistry included serum aminotransferases, lipid profile, glucose, and insulin. Liver steatosis was judged as hepatic fat fraction (FF) by MRI and was > or =9%. RESULTS: Prevalence of steatosis was 34.6% at baseline and declined to 7.7% after intervention (P < 0.0001). Mean (95% CI) reduction of liver FF was 8.0% (4.0%-12.0%). In 77.8% of children with liver steatosis at baseline, the FF declined lower than 9% at the end of intervention, going from a mean (SD) of 18.7% (9.1) to 1.3% (4.1), (P < 0.0001). At the end of the intervention, children showed a mean reduction in body mass index z score of 0.26 (0.11-0.41) and waist circumference of 1.46 (0.34-2.60) cm. Triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B, ApoA1/ApoB ratio, and gamma-glutamyltransferase plasma values in plasma decreased at the end of intervention (P < 0.05). CONCLUSIONS: The results suggest that in obese children nutritional-behavior interventions may reduce the liver fat.