Mental performance in 8-year-old children fed reduced protein content formula during the 1st year of life: safety analysis of a randomised clinical trial.

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

The Effect of Postpartum Depression and Current Mental Health Problems of the Mother on Child Behaviour at Eight Years.

Background Maternal postpartum depression (PPD) could affect children's emotional development, increasing later risk of child psychological problems. The aim of our study was to assess the association between child's emotional and behavioural problems and mother's PPD, considering maternal current mental health problems (CMP). Methods This is a secondary analysis from the EU-Childhood Obesity Project (NCT00338689). Women completed the Edinburgh Postnatal Depression Scale (EPDS) at, 2, 3 and 6 months after delivery and the General Health Questionnaire (GHQ-12) to assess CMP once the children reached the age of 8 years. EPDS scores > 10 were defined as PPD and GHQ-12 scores > 2 were defined as CMP. The psychological problems of the children at the age of eight were collected by mothers through the Child's Behaviour Checklist (CBCL). Results 473, 474 and 459 mothers filled in GHQ-12 and CBCL tests at 8 years and EPDS at 2, 3 and 6 months, respectively. Anxiety and depression was significantly increased by maternal EPDS. Children whose mothers had both PPD and CMP exhibited the highest levels of psychological problems, followed by those whose mothers who had only CMP and only PPD. PPD and CMP had a significant effect on child's total psychological problems (p = 0.033, p < 0.001, respectively). Children whose mothers had PPD did not differ from children whose mothers did not have any depression. Conclusions Maternal postpartum depression and current mental health problems, separately and synergistically, increase children's psychological problems at 8 years.

Association of early protein intake and pre-peritoneal fat at five years of age: Follow-up of a randomized clinical trial.

BACKGROUND AND AIMS: The double-blind randomized European Childhood Obesity Project (CHOP) demonstrated that reduced protein content in infant formula leads to a lower body mass index (BMI) up to six years of age. Here we aimed at assessing pre-peritoneal fat, a marker of visceral fat, in children participating in the CHOP trial. METHODS AND RESULTS: Healthy term formula-fed infants in five European countries were randomized either to higher (n = 550) or lower (n = 540) protein formulas in the first year of life. Infants who were exclusively breastfed for at least three months (n = 588) were enrolled as an observational (non randomized) group. At age 5 years, subcutaneous fat (SC) and pre-peritoneal fat (PP) were measured by ultrasound in a subgroup of 275 children. The PP fat layer was thicker in the higher compared to the lower protein group (adjusted estimated difference: 0.058 cm, 95%CI 0.002; 0.115; p = 0.043), while SC fat was not different. Girls showed a thicker SC fat layer than boys. CONCLUSIONS: Higher protein intake in formula-fed infants appears to enhance pre-peritoneal fat tissue accumulation at the age of 5 years, but not of subcutaneous fat, which may trigger adverse metabolic and health consequences.

Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition.

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest.

Diagnostic performance of three serologic tests in childhood celiac disease.

BACKGROUND: IgA- and IgG-antibodies against deamidated gliadin peptides (DGP) specifically bind the disease-inducing antigen and might be superior to transglutaminase type 2 (TG2) IgA in monitoring patients on a gluten-free diet (GFD). The aim of this study was to compare the performance of DGP-IgG and DGP-IgA with TG2-IgA of four manufacturers in pediatric celiac patients at diagnosis and during follow-up under a GFD. PATIENTS AND METHODS: In total 411 sera of 91 IgA competent children with biopsy proven celiac disease were analyzed at diagnosis and during follow-up on a GFD. Ninety-eight children with normal duodenal histology served as controls. The tests (TheBindingSite, Euroimmun, Phadia, part of Thermo Fisher Scientific, INOVA) for detection of TG2-IgA, DGP-IgG and DGP-IgA were used according to the manufacturers' instructions. RESULTS: Sensitivity to diagnose CD was high for TG2-IgA (100 %) and DGP-IgG (90 - 100 %), but lower for DGP-IgA (67 - 86 %). Specificity was high for all tests (97 - 100 %). The frequency of TG2-IgA titers > 10â€Š× upper limit of normal at diagnosis ranged from 47 - 90 %. Under a GFD DGP-IgA became negative more rapidly than DGP-IgG and TG2-IgA. Non-adherence to GFD was best indicated by positive TG2-IgA. CONCLUSIONS: Combined testing for TG2-IgA and DGP-IgG does not increase the detection rate of CD in IgA competent children compared to TG2-IgA only. There are significant differences with respect to proportions of celiac children with titers > 10â€Š× ULN between the manufacturers. This calls for harmonization of tests. TG2-IgA showed the highest titer rise with non-adherence to the GFD, independent of the manufacturer.

Improvements of complex post-traumatic stress disorder symptoms during a multimodal psychodynamic inpatient rehabilitation treatment - results of an observational single-centre pilot study.

Background: Complex post-traumatic stress disorder (CPTSD) describes chronic disturbances in self-organization (i.e. affect dysregulation; negative self-concept; severe difficulties in relationships) which are frequently observed in survivors of prolonged, repeated or multiple traumatic stressors. So far, evidence of psychodynamic treatment approaches for CPTSD is scarce.Methods: In this single-centre observational pilot study, symptom change during a 6-week psychodynamic inpatient treatment in a multimodal psychosomatic rehabilitation centre was evaluated using repeated measures analyses of variance (ANOVAs). Patients completed questionnaires on PTSD and CPTSD symptoms (ITQ), anxiety, depression and somatization (BSI-18), functional impairment (WHODAS) and epistemic trust, mistrust and credulity (ETMCQ) before (T1) and at the end of treatment (T2). A hierarchical linear regression analysis was calculated to identify factors associated with improved CPTSD symptoms.Results: A total of n = 50 patients with CPTSD were included in the study, of whom n = 40 (80%) completed treatment. Patients reported a significant reduction of CPTSD symptoms during treatment with a large effect size (-3.9 points; p < .001; η2 = .36), as well as a significant reduction of psychological distress (p < .001; η2 = .55) and functional impairment (p < .001; η2 = .59). At the end of treatment, 41.0% of patients no longer fulfilled the diagnostic criteria for CPTSD. Changes in epistemic stance included improved epistemic trust (ß = -.34, p = .026) and decreased epistemic credulity (ß = .37, p = .017), which together with lower age (ß = .43, p = .012) and lower depression levels at baseline (ß = .35, p = .054) were significantly associated with baseline adjusted mean change of CPTSD symptoms during therapy and explained 48% of its variance.Discussion: In our study, patients reported a significant reduction of CPTSD symptoms and comorbid symptoms during a multimodal psychodynamic inpatient rehabilitation treatment. Improved epistemic trust may facilitate the establishment of a trusting therapeutic relationship, thus fostering an environment of openness for knowledge transfer (i.e. social learning) and the exploration of diverse viewpoints and perspectives in the therapeutic process.

Complex post-traumatic stress disorder (CPTSD) is a condition often found in individuals who have experienced severe trauma, such as childhood abuse or torture.A study involving 50 patients with CPTSD showed significant improvements in symptoms and overall quality of life after undergoing a 6-week integrative multimodal psychodynamic inpatient rehabilitation treatment.The study also highlighted that improvement in epistemic trust could be a potential mechanism of change contributing to the positive therapeutic outcomes.

Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct.

AIMS/HYPOTHESIS: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. METHODS: We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. RESULTS: In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. CONCLUSIONS/INTERPRETATION: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort.

BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.

Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans.

BACKGROUND: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. PATIENTS AND METHODS: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. RESULTS: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. CONCLUSIONS: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

Mediterranean diet and incidence of hip fractures in a European cohort.

UNLABELLED: Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

Positive Psychological Intervention Effects on Depression: Positive Emotion Does Not Mediate Intervention Impact in a Sample with Elevated Depressive Symptoms.

Positive psychological interventions (PPIs), programs that specifically target positive emotions, cognitions, and behaviors, have been shown to reduce depression and improve other aspects of psychological well-being. However, potential pathways linking PPIs to better outcomes have been under-explored. In this paper, we report the results of a randomized trial of a self-guided online delivered PPI called MARIGOLD (Mobile Affect Regulation Intervention with the Goal of Lowering Depression). Participants with elevated depression were randomized to receive MARIGOLD (n = 539) or an emotion reporting control condition (n = 63). In addition to testing direct effects of the intervention on depressive symptoms, we explored whether positive or negative emotion-operationalized as past day, past week, reactivity, or flexibility-mediated the intervention impact on depression. Results demonstrated that participants in the MARIGOLD condition had reduced depressive symptoms compared to controls and, although the effect did not reach statistical significance, reductions in past day negative emotion appeared to mediate this effect. Contrary to hypotheses, the intervention did not increase positive emotion compared to the control condition. Discussion focuses on the need for future studies to continue investigating the mechanisms of action for PPIs with emphasis on theoretically-based measurement and operationalization of emotion and other potential mediators to maximize the ultimate impact of PPIs on psychological well-being. Clinical Trials registration #NCT02861755.

Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

Effect of protein intake and weight gain velocity on body fat mass at 6 months of age: the EU Childhood Obesity Programme.

INTRODUCTION: Higher protein intake during the first year of life is associated with increased weight gain velocity and body mass index (BMI). However, the relationship of protein intake and weight gain velocity with body composition is unclear. OBJECTIVE: To assess if the increases in weight gain velocity and BMI induced by protein intake early in life are related to an increase in fat or fat-free mass. MATERIALS AND METHODS: In all, 41 infants randomized at birth to a higher or lower protein content formula (HP=17 and LP=24, respectively) and 25 breastfed infants were included. Anthropometric measures were assessed at baseline, 6, 12 and 24 months, and fat-free mass (FFM) and fat mass (FM) were assessed by isotope dilution at 6 months. RESULTS: Weight gain velocity (g per month) during the first 6 months of life was significantly higher among HP infants (807.8 (±93.8) vs 724.2 (±110.0) (P=0.015)). Weight gain velocity strongly correlated with FM z-score (r=0.564, P<0.001) but showed no association with FFM z-scores. FFM showed no association with BMI. Nevertheless, FM strongly correlated with BMI at 6, 12 and 24 months (r=0.475, P<0.001; r=0.332, P=0.007 and r=0.247, P=0.051, respectively). FFM and FM z-scores did not differ significantly between HP and LP infants (0.32±1.75 vs -0.31±1.17 and 0.54±2.81 vs -0.02±1.65, respectively). CONCLUSION: Our findings support the hypothesis that higher protein intakes early in life are associated with faster weight gain and in turn to higher adiposity. This mechanism could be a determinant factor for later obesity risk.

Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

[Infant feeding practice and later obesity risk. Indications for early metabolic programming]. / Frühkindliche Ernährung und späteres Adipositasrisiko. Hinweise auf frühe metabolische Programmierung.

Metabolic factors acting during limited and sensitive time periods of pre- and postnatal development can induce lasting effects on health and disease risk in later life up to old age, including later obesity risk, which is referred to as early metabolic programming of long-term health. Three meta-analyses of observational studies found that obesity risk at school age was reduced with early breastfeeding compared to formula feeding. We assumed 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 to usual infant formulas (the "early protein hypothesis"). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial enrolling 1,678 infants in five countries (Belgium, Germany, Italy, Poland, Spain). We have randomized healthy infants 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 years indicates that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the current WHO 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. The results obtained should stimulate the review of recommendations and policies for infant formula composition.

[Risk factors for delayed or missed measles vaccination in young children]. / Risikofaktoren für eine verspätete oder nicht erfolgte Masernimpfung bei Kleinkindern.

Because of low measles vaccine coverage rates, measles outbreaks have been observed several times during recent years in Germany. The aim of this study is to identify parents' attitudes and beliefs towards immunisations and socio-economic factors which are associated with delayed or missed first measles vaccination in young children. We used data from a representative German-wide immunisation survey on 2116 children born between 1 January 2002 and December 2004 by collecting precise vaccination information from vaccination cards. The influence of socio-economic determinants and parental attitudes towards immunisations on the timing of the first measles dose was analysed by using multivariable Cox regression. Of these children 46.8% (95% CI: 44.5-49.1) received their first measles dose according to the recommendations of the standing committee on vaccination (STIKO) by month 15. In multivariable analysis, fathers aged 28-33 years and birth order as well as parents' belief in homeopathy and other parental attitudes indicating lack of knowledge about the importance of vaccinations significantly influenced an early immunisation. Not general opposition, but insufficient parental knowledge about the harmfulness of measles infection seemed to be responsible for the low measles vaccination rates.

Factors associated with sugar intake and sugar sources in European children from 1 to 8 years of age.

BACKGROUND/OBJECTIVES: The World Health Organization recommends to limit intake of free sugars to 5% of total energy per day because of the great impact of high sugar intake on body fat deposition, adiposity and dental caries. However, little data exist about total intake and sources of sugar in European children. Therefore, this paper aims to describe sugar intake and dietary sugar sources and associated factors. SUBJECTS/METHODS: Three-day weighed dietary records were obtained at eight time points from children 1 to 8 years of age (n=995) in five European countries. Food items were classified into subgroups according to food composition. Linear mixed models were used to examine associated factors. RESULTS: Total sugar intake increased from 65 g/day (30.0% of energy intake (E%)) at 12 months of age to 83 g/day (20.9 E%) at 96 months of age. Around 80% of children's sugar intake was derived from the following sources: milk and dairy products, fruits and fruit products, confectionary and sugar sweetened beverages (SSB). Total sugar intake and dietary sugar sources varied significantly by country of residence. Boys had a significantly (P=0.003) higher total sugar consumption than girls.SSB consumption was significantly higher in children from young mothers while sugar intake from fruit products was lower in children from mothers with lower educational status and those with higher birth order. CONCLUSIONS: Sugar intake in our population was lower than in other studies. Total sugar intake was associated with country of residence and gender, while dietary sugar sources varied by country of residence, maternal age, education and birth order.

Breast milk composition and infant nutrient intakes during the first 12 months of life.

BACKGROUND/OBJECTIVES: The objective of this study was to quantify human milk supply and intake of breastfed infants up to age 12 months. In addition, human milk composition was quantified per energetic macronutrient and fatty-acid composition in a subsample of lactating mothers. SUBJECTS/METHODS: One hundred and seventy-four Italian breastfed children were followed using test-weighing and 3-day food protocols from birth to age 12 months. From a subsample of 30 mothers breast milk samples were collected at child ages one (T1), two (T2), three (T3) and six (T6) months, and were analyzed for the amount of protein, digestible carbohydrates, total lipids and fatty-acid composition. RESULTS: One hundred and forty-two (82%) filled in at least one 3-day food protocol within the first 12 months of life and complied with test-weighing of all milk feeds. The number of valid food protocols declined from 126 infants at 1 month to 77 at 12 months of age. Only galactose, non-protein nitrogen and protein decreased significantly from age 1 to age 6 months of lactation. Maternal body mass index and age affected fatty-acid levels in human milk. Median human milk intake decreased from 625 ml at T1, over 724 ml at T3 to 477 ml/day at T6. Average energy and %energy from protein intake per day increased from 419 kcal (s.d. 99) and 8.4% (1.0) at T1, respectively, to 860 kcal (145) and 16.1% (2.6) at T12. CONCLUSIONS: These data provide a reference range of nutrient intakes in breastfed infants and may provide guidance for defining optimal nutrient intakes for infants that cannot be fully breastfed.