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Summary Background & aims it has previously been described that dietary patterns established early in life tracked to late childhood. The aim of the present work was to analyse the association of dietary patterns that tracked from 2 to 8y with cardiometabolic markers at 8y of age. Methods The 3 identified patterns at 2y (that previous analyses showed to track to age 8y) were: “CoreDP”, loaded for vegetables, fruits, fish, olive oil, etc.; “FS and “ProteinDP”, mainly loaded by animal protein sources. Cardiometabolic markers at 8y were systolic blood pressure (SBP), insulin resistance (HOMA-IR), and triglycerides, and BMI z-score. To examine whether the association of diet with the outcomes was the result of a direct effect of diet at either two or 8y, or synergy between them, we used structural equation models. Results the associations between the patterns and the health outcomes were: CoreDP was inversely associated with SBP and HOMA-IR; ProteinDP was directly associated with HOMA-IR and SBP; and adherence to F&SDP was directly associated with triglycerides and SBP. The associations between the patterns and the health outcomes were independent of BMI and were the result of a direct effect of diet at 2y, an indirect effect of diet at 2y through diet at 8y or a combination between both pathways. Conclusion dietary patterns acquired in early life, persisting to later childhood, were associated with cardiometabolic markers at school age independently of BMI.

Purpose Neuroblastoma (NB) is the most common extracranial, solid tumor in childhood, with a peak incidence in children under 6 years of age. Due to its variable course of disease, which ranges from spontaneous regression to metastatic spread, NB still represents a significant therapeutic challenge. Strikingly, a certain number of NBs intraoperatively show vessel adhesion and/or infiltrative growth, which is often not visible in pre-operative imaging. We proposed the term unexpected vessel infiltration of NB (UVIN) to denote this phenomenon. UVIN represents a major surgical challenge. Methods In this study, we determined frequency and clinical relevance of UVIN in a cohort of 100 NB-patients with subsequent correlation to several unfavorable characteristics of disease. RNA expression levels of MYCN and its co-regulated antisense transcript MYCNOS to identify markers was measured by PCR. Results We found UVIN to be present in 34% of cases and significantly correlated with incomplete resection, MYCN amplification, complications, neoadjuvant therapy, tumor grade and MYCNOS expression levels. MYCN expression levels showed no significant results with UVIN. Conclusion Collectively, our data show that UVIN represents a frequent surgical problem associated with a poor outcome in NB patients. MYCN and MYCNOS seem to be no appropriate markers for UVIN. Type of study Prognosis study. Level of evidence Level III.

Bone mineralization can be influenced by genetic factors, hormonal status, nutrition, physical activity and body composition. The association of higher calcium (Ca) intake or Ca supplementation with better bone mineral density (BMD) remains controversial. Furthermore, it has been speculated that maintaining long-term adequate Ca intake rather than having a brief supplementation period is more effective. The aim of the study was to prospectively analyse the influence of adequate Ca intake on BMD at 7 years of age in European children.Data from the Childhood Obesity Project were analysed in a prospective longitudinal cohort trial. Dietary intake was recorded using 3-day food records at 4, 5 and 6 years of age. The probability of adequate intake (PA) of Ca was calculated following the American Institute of Medicine guidelines for individual assessments, with FAO, WHO and United Nations University joint expert consultation dietary recommendations. Children were categorised as having high Ca PA (PA95%) or not (PA95%). At 7 years, whole body (WB) and lumbar spine (LS) BMD were measured in the Spanish subsample by dual-energy x-ray absorptiometry. Internal BMD z-scores were calculated; BMD below -1 z-score were considered to indicate osteopenia, and BMD z-scores below -2, "low bone mineral density for age".BMD was measured in 179 children. Ca intake at 6 years was positively correlated with LS BMD at 7 years (R = 0.205, p = 0.030). A Ca increase of 100 mg/day explained 19.4% (p = 0.011) of the LS BMD z-score variation, modifying it by 0.089 (0.021, 0.157) units. Children with Ca PA95% at 5 and 6 or from 4 to 6 years of age showed higher BMD z-scores at the LS and WB levels than children with Ca PA95% (p 0.001 and p 0.05 for LS and WB BMD, respectively). Ca PA95% maintained over 2 years explained 26.3% of the LS BMD z-score variation (p 0.001), increasing it by 0.669 (0.202, 1.137). PA95% maintained over 3 years explained 24.9% of the LS BMD z-score variation, increasing it by 0.773 (0.282, 1.264). The effects of Ca adequacy on WB BMD were similar. Children with PA95% over 2 years had an Odds ratio of 13.84 and 12 for osteopenia at the LS and WB levels, respectively (p = 0.001).Long periods of adequate Ca intake in childhood increase BMD and reduce osteopenia risk. The Childhood Obesity Project clinical trial (CHOP) was registered at clinicaltrials.gov as NCT00338689.

Summary 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 .

BACKGROUD/PURPOSE: Hirschsprung-associated enterocolitis (HAEC) represents a cause for significant pre- and postoperative morbidity and mortality in Hirschsprung disease (HD). Although multiple studies on HAEC have been performed and several mechanisms have been presumed, the pathogenesis of this condition remains unclear. As changes in colonic mucosal defense are key factors suggested in both Crohn's disease (CD) and HAEC pathogenesis, the aim of the current study was to investigate genetic alterations in the most important susceptibility gene for Crohn's enterocolitis (NOD2) to see whether carriers of polymorphisms within the NOD2 gene are predisposed to the development of HAEC.Genotyping for the NOD2 variants in exon 4 (p.Arg702Trp [rs2066844]), exon 8 (p.Gly908Arg [rs2066845]), and exon 11 (p.1007fs [rs2066847]) was performed in 52 white children with HD (41 boys, 11 girls), 152 healthy controls, and 152 children with CD (onset of disease17 years; mean, 11.8 years). Seventeen patients with HD (32.7%) were carriers of a RET germline mutation, 35 children (67.3%) had short segment disease, and 17 (32.7%) had long segment disease.Ten children (19.2%) with HD were heterozygous carriers of at least one NOD2 variant vs 17 (11.2%) in the healthy control group and 69 (45.4%) in the CD cohort. Hirschsprung-associated enterocolitis was observed in 7 children (13.5%), with 4 having short segment HD and 3 with long segment HD; but none of them were carriers of NOD2 variants.Our study shows that NOD2 variants described to be causatively associated with CD do not predispose to the development of HAEC. As data on the molecular basis of HAEC are limited, the distinct mechanisms involved in the pathogenesis of this complication remain unclear.

Varicella is an acute febrile, highly infectious disease. We describe the incidence and types of neurologic complications in children up to 16 years old. Hospitalized varicella cases were prospectively captured by active nationwide surveillance through the German Pediatric Surveillance Unit for Rare Diseases from January 2003 to December 2004. Neurologic complications occurred in 232 (25.4%) of 918 hospitalized children with varicella, and were the most frequent reason for hospitalization. The median age was 4.2 years (interquartile range 2.5-5.9). The median duration of hospital stay was 6 days (interquartile range 3-11). Neurologic complications were more frequent (P=0.054) in immunocompetent (32%) than immunocompromised (4%) children. The most frequent diagnoses comprised acute cerebellar ataxia in 72 (31.0%), febrile convulsion in 69 (29.7%), meningoencephalitis in 52 (22.4%), cerebral convulsions in 21 (9.1%), syncope in 9 (3.9%), and cerebral vasculitis/infarction in 6 (2.6%) of all children with neurologic complications. Twenty-eight (12%) demonstrated sequelae (18 with ataxia, four with epilepsy, two with hemiparesis, three with cerebral nerve palsy, and one with dysesthesia). Three patients died. The yearly incidence of neurologic varicella-associated hospitalizations was estimated at 2.4 neurologic complications per 100,000 children, corresponding to about one neurologic complication in 2000 varicella cases.

Since the concept of lasting programming effects on disease risk in human adults by the action of hormones, metabolites, and neurotransmitters during sensitive periods of early development was proposed >3 decades ago, ample supporting evidence has evolved from epidemiologic and experimental studies and clinical trials. For example, numerous studies have reported programming effects of infant feeding choices on later obesity. Three meta-analyses of observational studies found that obesity risk at school age was reduced by 15-25% with early breastfeeding compared with formula feeding. We proposed that breastfeeding protects against later obesity by reducing the occurrence of high weight gain in infancy and that one causative factor is the lower protein content of human milk compared with most infant formula (the early protein hypothesis). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial that includes > 1000 infants in 5 countries (Belgium, Germany, Italy, Poland, and Spain). We randomly assigned healthy infants who were born at term to receive for the first year infant formula and follow-on formula with higher or lower protein contents, respectively. The follow-up data obtained at age 2 y indicate that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the new World Health Organization growth standard, which may furnish a significant long-term protection against later obesity. We conclude that infant feeding practice has a high potential for long-term health effects, and the results obtained should stimulate the review of recommendations and policies for infant formula composition. ©2009 American Society for Nutrition., SCOPUS: cp.j, info:eu-repo/semantics/published

Summary Vaccine effectiveness (VE) was determined with a case-cohort approach using Cox regression. Cases with confirmed systemic Hib infections in children born from 1 August 2000 to 31 December 2004 were ascertained through two independent nationwide active surveillance systems. A representative cohort of 1303 children born in the same time frame was randomly sampled in a nationwide immunisation survey. Thirty cases were eligible for VE calculation; 19 were unvaccinated and 11 vaccinated with hexavalent vaccines. VE was 68.4% (95% CI: 19.0–87.6) for incomplete primary series and 90.4% (95% CI: 70.6–96.8) for the full primary series. For full immunisation VE was 100.0% (95% CI: 52.7–100.0). Hexavalent vaccines show a high effectiveness against invasive Hib disease in Germany.