Atherosclerotic Risk Factors in Children with Celiac Disease.

RESULTS: We found significantly lower concentrations of total cholesterol, lipoprotein LDL-C, apolipoproteins A1 and B, as well as hCRP in all children with CD. We showed decreased level (<5 ng/mL) of folic acid among 46% of children treated for >5 years. Moreover, we showed significant decrease of folic acid level already after 1 year of a GFD (12 vs. 5.6 ng/mL; p < 0.001). We also found significant negative correlation of z-score body mass index (BMI) with HDL and APOA1 level (r = -0.33; p = 0.015 and r = -0.28; p = 0.038, respectively) and modest positive correlation of z-score BMI with atherogenic factor of total cholesterol-HDL ratio and LDL-HDL ratio (r = 0.40; p = 0.002 and r = 0.36; p = 0.006, respectively). Analysis of physical activity showed an increase in the insulin levels with inactivity (r = 0.36; p = 0.0025). We also found positive correlation of the sleep duration with the adiponectin level (r = 0.41; p = 0.011). CONCLUSIONS: In children with CD treated with a GFD, decreased level of folic acid together with increased BMI, sedentary behavior, and an improper lipid profile may predispose them to atherosclerosis in the long run. This data suggests the need of further studies to determine the need for metabolic cardiovascular risk screening in children with CD.

Micronutrient intake adequacy in children from birth to 8 years. Data from the Childhood Obesity Project.

BACKGROUND: In European countries, suboptimal intake has been reported for several micronutrients (as calcium, iron, zinc, vitamin B12, D and folate) in both adulthood and childhood. No studies to date have prospectively compiled nutrient intake from healthy children in different European countries using the same methodology. AIM: To describe the adequacy of micronutrient intake during the first eight years of life in children from 5 European countries. METHODS: Prospective observational trial analyzing data from the EU Childhood Obesity Project. Infants were enrolled within the first two months of life and were followed regularly to age 8 years. Dietary intake was collected periodically with 3-day food records. Nutrient intake adequacy was estimated for calcium, phosphorus, iron, zinc, magnesium, iodine, folate and vitamins B12, A and D, following the American Institute of Medicine (IOM) guidelines at group (prevalence of adequacy >80%) and individual (high probability of adequate intake >80% of the children) level; the assessment was based on the Estimated Average Requirements of nutrients of the FAO, WHO and United Nations University (FAO/WHO/UNU) or the IOM if FAO/WHO/UNU data were not available. RESULTS: Intake data were available for a decreasing number of children, from 904 at 3 months to 396 at 8 years. Iron, iodine, folate and vitamin D were inadequately consumed when assessing adequacy at group level; at individual-level less than 80% of the children showed high probability of adequate intake for iron, iodine, folate and zinc at all ages, and calcium from 12 months onwards. CONCLUSIONS: Accurate dietary intake and adequacy assessment methodology in this prospective cohort of European children found iron, calcium, vitamin D, folate, iodine and zinc to be inadequately consumed in childhood, as described previously by epidemiologic studies. Further studies are needed to elucidate health consequences of these deficiencies. CHOP trial was registered at clinicaltrials.gov as NCT00338689.

Serum Concentrations of Insulin, Ghrelin, Adiponectin, Leptin, Leptin Receptor and Lipocalin-2 in Children with Celiac Disease Who Do and Do Not Adhere to a Gluten-Free Diet.

BACKGROUND/AIMS: The roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence). METHODS: Prepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD). RESULTS: Insulin levels in prepubertal (9.01±4.43 µIU/mL), pubertal (10.3±3.62 µIU/mL), and adolescent (10.8±4.73 µIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 µIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2. CONCLUSIONS: Adherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia.

Combination Testing Using a Single MSH5 Variant alongside HLA Haplotypes Improves the Sensitivity of Predicting Coeliac Disease Risk in the Polish Population.

Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing.

Coeliac disease not responding to a gluten-free diet in children: case studies and literature review.

We presented the cases of three children with coeliac disease who despite good adherence to a glutenfree diet remained non-responsive to treatment. Two patients, one of them with IgA deficiency, were successfully treated by complete gluten exclusion with enteral nutrition. However the third child with a severe coeliac disease did not achieve clinical and histologic improvement, even on immunosuppressive treatment. If no hidden sources of gluten can be identified, other causes of persistent villous atrophy, dierent from coeliac disease, have to be considered. They include e.g. inflammatory, immune and endocrine diseases of the digestive tract. In severe cases of childhood coeliac disease not responding to a gluten free diet, autoimmune enteropathy and refractory coeliac disease must be taken into account.

Long term follow up of celiac disease-is atherosclerosis a problem?

Celiac disease (CD) is a lifelong condition and it often involves impaired nutrition, wide spectrum of symptoms and it requires constant dietetic treatment. The impact of the gluten-free diet on patients' nutritional status and on the other biochemical parameters is being widely investigated. In this article we looked into particular risk factors that might lead to increased prevalence of atherosclerosis in CD patients, including nutritional status, gluten-free diet, lipids profile and concomitant disease-type 1 diabetes mellitus. Here, we present the current data and research on these risk factors of atherosclerosis with respect to celiac disease.

Efficiency of pancreatic duct stenting therapy in children with chronic pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) is a rare disease in childhood. Although ERCP is commonly performed in children, the effect of pancreatic duct stenting therapy in children with CP is unknown. OBJECTIVE: To investigate the efficacy of pancreatic duct stenting in children with CP. DESIGN: Retrospective analysis. SETTING: National referral center. PATIENTS: A total of 208 children with CP hospitalized between 1988 and 2012. INTERVENTIONS: ERCP with pancreatic duct stenting. MAIN OUTCOME MEASUREMENTS: Results of endoscopic therapy and number of pancreatitis episodes per year before and after treatment. RESULTS: A total of 223 pancreatic duct stenting procedures were performed in 72 children. The median number of stent replacements was 3 (range 1-21). A statistically significant decrease in the number of pancreatitis episodes per year was observed: from 1.75 to 0.23 after endoscopic treatment (P < .05). Pancreatic duct stenting was performed more frequently in patients with hereditary pancreatitis (61.5%) and in children with CP and anatomic anomalies of the pancreatic duct (65%; P < .05). LIMITATIONS: Retrospective analysis with the assessment of adverse events based on medical history. CONCLUSION: Pancreatic duct stenting therapy is a safe and effective procedure in children with CP. This therapy should be recommended especially for children with hereditary pancreatitis and patients with anatomic anomalies of the pancreatic duct.

[Nutritional guidelines for healthy children aged 1-3 years - Polish Expert Group statement. Part I- energy and nutritional components demand]. / Normy zywienia zdrowych dzieci w 1-3. Rokuzycia . stanowisko polskiej grupy ekspertów.czesc i - zapotrzebowanie na energiei skladniki odzywcze.

Updating of the nutritional guidelines for the Polish population requires updates of the nutritional norms for children. We present the Polish Expert Group statement (2012) on intake of selected nutrients (protein, lipids, carbohydrates, vitamin D and E) essential in nutrition of children aged 1-3 years. For this purpose the Expert Group reviewed available scientific data: the recent guidelines, nutritional norms and recommendations, systematic reviews and expert opinions as well as original publications, in relation to the specific requirements of the Polish population.

Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study.

Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4 correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038). In short-term observation, successful LRLTx led to bone metabolism normalization triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone status coincided with disturbances in bone metabolism. Bone metabolism markers, especially P1NP and CTx, appeared to be good predictors of changes in bone status evaluated by DXA.

Early obesity prevention: Polish contribution to European projects.

Poland faces the same problem of obesity epidemics as other European countries. Polish contribution to the EU research projects concerning overweight and obesity is a direct consequence of recognition of this problem and scientific activity of Polish researchers. At present time early prevention seems to be the only effective approach to decrease obesity and obesity-related chronic diseases in adulthood. Three studies described here consider early prevention of obesity - by decreasing protein intake in infancy (CHOP and EARNEST study) or by behavioural approach in preschoolers (TOYBOX). The Children's Memorial Health Institute is participating in all these projects as a recruiting centre of the subjects studied and as a central laboratory for the CHOP and EARNEST studies. The CHOP study proved in a randomized trial that high protein intake in infancy increases the risk of obesity. The results of the CHOP studies have already indicated the need for protein reduction in infant formulas. This was reduced to 1.8 g/100kcal in the 2006 EU Directive. The results from the TOYBOX project which was started in 2010 have not yet been published.

Antibiotic therapy and fat digestion and absorption in cystic fibrosis.

Antibiotic therapy in the cystic fibrosis (CF) mouse model has been shown to result in reduced bacterial load of the intestine and significant body mass gain. The effect was suggested to be linked to the improvement of intestinal digestion and absorption. Therefore, we aimed to assess the influence of routinely applied antibiotic therapy in CF patients on fat assimilation. Twenty-four CF patients aged 6 to 30 years entered the study. Inclusion criteria comprised confirmed exocrine pancreatic insufficiency and bronchopulmonary exacerbation demanding antibiotic therapy. Exclusion criteria comprised: antibiotic therapy six weeks prior to the test, liver cirrhosis, diabetes mellitus, oxygen dependency, the use of systemic corticosteroids. In all enrolled CF subjects, (13)C-labelled mixed triglyceride breath test ((13)C MTG-BT) was performed to assess lipid digestion and absorption, before and after antibiotic therapy. Sixteen subjects were treated intravenously with ceftazidime and amikacin, eight patients orally with ciprofloxacin. Cumulative percentage dose recovery (CPDR) was considered to reflect digestion and absorption of lipids. The values are expressed as means (medians). The values of CPDR before and after antibiotic therapy did not differ in the whole studied group [4.6(3.3) % vs. 5.7(5.3) %, p = 0.100] as well as in the subgroup receiving them intravenously [4.6(3.2) % vs. 5.7(5.3) %, p = 0.327] or in that with oral drug administration [4.6(3.4) % vs. 5.7(5.4) %, p = 0.167]. In conclusion, antibiotic therapy applied routinely in the course of pulmonary exacerbation in CF patients does not seem to result in an improvement of fat digestion and absorption.

Vitamin D supplementation and status in infants: a prospective cohort observational study.

OBJECTIVE: Vitamin D status in infants depends on supplementation. We examined the vitamin D status in relation to supplementation dose and scheme in infants. PATIENTS AND METHODS: One hundred thirty-four infants age 6 months and 98 infants age 12 months (drop out 27%) were investigated. Vitamin D intake (diet, supplements), anthropometry, and 25-hydroxyvitamin D (25-OHD) serum concentration at the 6th and 12th months were assessed. RESULTS: Vitamin D intake of 1062 ± 694 IU at the 6th month was not different from that at the 12th month (937 ± 618 IU). Vitamin D intake expressed in international units per kilogram of body weight decreased from 141 ± 80 IU/kg at the 6th month to 93 ± 62 IU/kg at the 12th month (P < 0.0001), which was associated with a reduction in 25-OHD from 43 ± 20 ng/mL to 29 ± 12 ng/mL, respectively (P < 0.0001). In the subgroup of everyday supplemented infants (n = 43), vitamin D intake decreased from 143 ± 88 IU/kg at the 6th month to 118 ± 60 IU/kg at the 12th month (P < 0.05), which coincided with a reduction of 25-OHD from 40 ± 19 ng/mL to 32 ± 13 ng/mL (P < 0.01). In the subgroup with variable supplementation habits (n = 32), vitamin D intake decreased from 146 ± 79 IU/kg to 77 ± 56 IU/kg (P < 0.001), which was associated with a reduction of 25-OHD from 42 ± 21 ng/mL to 25 ± 8 ng/mL (P < 0.0001). 25-OHD concentration change between the 6th and the 12th months negatively correlated with the 25-OHD level assessed at the 6th month (r = -0.82; P < 0.0001). CONCLUSIONS: Vitamin D supplementation of infants should consider their rapid body weight increment. We postulate vitamin D daily dose close to 100 IU/kg body weight as favorable for infants up to age 12 months.

[Recommendations of prophylaxis of vitamin D deficiency in Poland (2009)]. / Zalecenia dotyczace profilaktyki niedoborów witaminy D w polsce (2009).

Adequate vitamin D intake and its status as well outdoor physical activity are important not only for normal bone development and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. National Consultants and experts in this field established the Polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women based on current literature review. Taking into consideration pleyotropic vitamin D action and safety aspects serum 25-hydroxyvitamin D (25-OHD) level of 20-60 ng/ml (50-750 nmol/l) in children and 30-80 ng/ml (75-200 nmol/I) in adults is considered as optimal. Sunlight exposure inducing vitamin D production in the skin is main endogen source of vitamin D in the body but sunscreens may reduce skin synthesis by 90%. In Poland, skin synthesis is effective only from April to September so other sources of vitamin D such as diet and supplements play an important role. All newborns should be supplemented with 400 IU/d of vitamin D beginning from the first few days of life and continue during infancy. In formula fed infants vitamin D intake from the diet should be taken into account. In preterm infants higher total vitamin D intake (400-800 IU/day) is recommended till 40 weeks post conception. Total vitamin D intake in children and adolescents required from all sources (diet and/or supplements) should be 400 IU/d between October and March and throughout the whole year in case of inadequate vitamin D skin synthesis during the summer months. In overweight/obese children supplementation with higher dosage of vitamin D up to 800-1000 IU/d should be considered. Adults require 800-1000 IU/d of vitamin D. In pregnant and lactating women such supplementation is recommended in case of inadequate intake from diet and/or skin synthesis supplementation. Monitoring of serum 25-OHD level to define optimal dosage should be considered.

[Prophylaxis of vitamin D deficiency--Polish recommendations 2009]. / Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D--2009.

Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.

[Prophylaxis of vitamin D deficiency--Polish recommendation 2009]. / Stanowisko Zespolu Ekspertów. Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D - 2009.

Adequate vitamin D intake and its status are important not only for bone health and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. Basing on current literature review and opinions of National Consultants and experts in the field, polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women have been established.

Maternal postnatal depression and child growth: a European cohort study.

BACKGROUND: Previous studies have reported postpartum depression to be associated with both positive and negative effects on early infant growth. This study examined the hypothesis that maternal postnatal depression may be a risk factor for later child growth faltering or overweight. METHODS: A total of 929 women and their children participating in a European multicenter study were included at a median age of 14 days. Mothers completed the Edinburgh postnatal depression scale (EPDS) at 2, 3 and 6 months after delivery. EPDS scores of 13 and above at any time were defined as maternal depression. Weight, length, triceps and subscapular skinfold thicknesses were measured, and body mass index (BMI) were calculated when the children were two years old and converted to standard deviation scores based on the WHO Multicentre Growth Reference Study (MGRS). RESULTS: Z-scores for weight-for-length at inclusion of infants of mothers with high EPDS scores (-0.55, SD 0.74) were lower than of those with normal scores (-0.36, SD 0.74; p = 0.013). BMI at age 24 months did not differ in the high (16.3 kg/m2, SD 1.3) and in the normal EPDS groups (16.2 kg/m2, SD 1.3; p = 0.48). All other anthropometric indices also did not differ between groups, with no change by multivariate adjustment. CONCLUSIONS: We conclude that a high maternal postnatal depression score does not have any major effects on offspring growth in high income countries.

Infantile colic, prolonged crying and maternal postnatal depression.

AIM: To study if infant crying is associated with maternal postnatal depression. METHODS: Data from 1015 mothers and their children participating in a prospective European multicentre study were analysed. Infantile colic and prolonged crying were defined as excessive crying as reported by the mothers 2 and 6 months after delivery, and at the same time the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: In cross-sectional analyses, infant crying was associated with high EPDS scores both 2 (OR: 4.4; 95% CI: 2.4-8.2) and 6 months postpartum (OR: 10.8; 95% CI: 4.3-26.9). More than one-third of the others of infants with prolonged crying had high EPDS scores 6 months postpartum. Longitudinal analyses showed that mothers of infants with colic had increased odds of having high EPDS scores 6 months after delivery even if crying had resolved (OR: 3.7; 95% CI: 1.4-10.1). CONCLUSION: Both infantile colic and prolonged crying were associated with high maternal depression scores. Most noteworthy, infantile colic at 2 months of age was associated with high maternal depression scores 4 months later.

Recurrence of non-alcoholic steatohepatitis after liver transplantation in a 13-yr-old boy.

Nonalcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to highlight NASH as a rare but possible problem in children. We present a case of 13-yr-boy with a well-established diagnosis of liver cirrhosis secondary to NASH, who underwent orthotopic liver transplantation (OLT) at the age of 13 years. Six months after transplantation recurrence of NASH in the graft was diagnosed. In the treatment metformin was used with good effect.