Determinants of and interventions for Proton Pump Inhibitor prescription behavior: A systematic scoping review.

BACKGROUND: Proton Pump Inhibitors (PPI) are frequently prescribed. Long-term use is associated with side-effects and patients often lack a valid indication. Inappropriate PPI prescribing thus needs to be addressed. This review aims to scope 1) what determinants are studied as reasons for PPI prescribing, 2) what strategies are used for changing PPI (de)prescribing, and 3) whether important determinants are addressed in these interventions. METHODS: We searched eight databases for papers on determinants of physician PPI prescribing. Studies were included if they were conducted in a Western country and focused on oral PPIs for an adult population. By following the Behaviour Change Wheel, we extracted information regarding PPI prescribing behavior, behavioral determinants and intervention strategies. FINDINGS: We included 74 papers. Most focused on the determinants knowledge and beliefs about consequences. The latter was consistently related to PPI prescribing. Results for knowledge were mixed. Most interventions used education or enablement (e.g., algorithms, quality check improvements, involvement of pharmacists) as strategies. Enablement consistently improved PPI prescribing, while results for education were mixed. INTERPRETATION: There is an overemphasis on reflective processes in studies on PPI prescribing. Future research should comprehensively identify behavioral determinants, focusing on reflective and impulsive processes, such that interventions can address the most important determinants.

The introduction of a data-driven population health management approach in the Netherlands since 2019: The Extramural LUMC Academic Network data infrastructure.

Improving population health and reducing inequalities through better integrated health and social care services is high up on the agenda of policymakers internationally. In recent years, regional cross-domain partnerships have emerged in several countries, which aim to achieve better population health, quality of care and a reduction in the per capita costs. These cross-domain partnerships aim to have a strong data foundation and are committed to continuous learning in which data plays an essential role. This paper describes our approach towards the development of the regional integrative population-based data infrastructure Extramural LUMC (Leiden University Medical Center) Academic Network (ELAN), in which we linked routinely collected medical, social and public health data at the patient level from the greater The Hague and Leiden area. Furthermore, we discuss the methodological issues of routine care data and the lessons learned about privacy, legislation and reciprocities. The initiative presented in this paper is relevant for international researchers and policy-makers because a unique data infrastructure has been set up that contains data across different domains, providing insights into societal issues and scientific questions that are important for data driven population health management approaches.

Defining vulnerability subgroups among pregnant women using pre-pregnancy information: a latent class analysis.

BACKGROUND: Early detection of vulnerability during or before pregnancy can contribute to optimizing the first 1000 days, a crucial period for children's development and health. We aimed to identify classes of vulnerability among pregnant women in the Netherlands using pre-pregnancy data on a wide range of social risk and protective factors, and validate these classes against the risk of adverse outcomes. METHODS: We conducted a latent class analysis based on 42 variables derived from nationwide observational data sources and self-reported data. Variables included individual, socioeconomic, lifestyle, psychosocial and household characteristics, self-reported health, healthcare utilization, life-events and living conditions. We compared classes in relation to adverse outcomes using logistic regression analyses. RESULTS: In the study population of 4172 women, we identified five latent classes. The largest 'healthy and socioeconomically stable'-class [n = 2040 (48.9%)] mostly shared protective factors, such as paid work and positively perceived health. The classes 'high care utilization' [n = 485 (11.6%)], 'socioeconomic vulnerability' [n = 395 (9.5%)] and 'psychosocial vulnerability' [n = 1005 (24.0%)] were characterized by risk factors limited to one specific domain and protective factors in others. Women classified into the 'multidimensional vulnerability'-class [n = 250 (6.0%)] shared multiple risk factors in different domains (psychosocial, medical and socioeconomic risk factors). Multidimensional vulnerability was associated with adverse outcomes, such as premature birth and caesarean section. CONCLUSIONS: Co-existence of multiple risk factors in various domains is associated with adverse outcomes for mother and child. Early detection of vulnerability and strategies to improve parental health and well-being might benefit from focussing on different domains and combining medical and social care and support.

Prevalence of and risk factors for extended-spectrum beta-lactamase genes carriership in a population-based cohort of middle-aged and elderly.

INTRODUCTION: Increasing resistance to beta-lactam antibiotics is an alarming development worldwide. Fecal carriership of TEM, SHV, CTX-M and CMY was studied in a community-dwelling population of middle-aged and elderly individuals. PATIENTS AND METHODS: Feces was obtained from individuals of the Rotterdam Study. Carriership of the TEM, SHV, CTX-M and CMY genes was determined using real-time polymerase chain reaction (qPCR). Possible associations were investigated between carriership of these genes and several risk factors, such as the use of antimicrobial drugs, diabetes mellitus, protein pump inhibitor (PPI) use, travelling, the composition of the gut microbiota, and intake of certain foods. RESULTS: The most prevalent gene was TEM (53.0%), followed by SHV (18.4%), CTX-M (5.4%) and CMY (3.6%). Use of penicillins with extended spectrum was associated with TEM carriership, whereas use of macrolides and lincosamides was associated with TEM and SHV carriership. Interestingly, use of PPIs was associated with a higher prevalence of carriership of TEM, SHV and CMY (TEM: odds ratio [OR] 1.34; 95% confidence interval [CI] 1.05-1.77; SHV: OR 2.17; 95%CI 1.55-2.87; CMY: OR 2.26; 95%CI 1.23-4.11). Furthermore, associations were found between the richness and composition of the gut microbiota and TEM and SHV carriership. CONCLUSIONS: The prevalence of carriership of TEM was substantial, but the prevalence of carriership of the extended-spectrum ß-lactamase gene, CTX-M and the AmpC ß-lactamase gene, CMY was relatively low in this community-dwelling, population-based cohort. The composition of the microbiota might play a role in the retention of resistance genes, but future studies are necessary to further elucidate this relationship.

The Obesity Paradox in Lung Cancer: Associations With Body Size Versus Body Shape.

BACKGROUND: The association between obesity and lung cancer (LC) remains poorly understood. However, other indices of obesity on the basis of body shape instead of body size have not been examined yet. The aim of this study was to evaluate the association between different indices of body size and body shape and the risk of LC. In particular, this study examined the association between A Body Shape Index, a more precise indicator of abdominal fat than traditional anthropometric measures, and the risk of LC. METHODS: In the prospective cohort the Rotterdam Study, we analysed data of 9,689 participants. LC diagnoses were based on medical records and anthropometric measurements were assessed at baseline. Cox-regression analyses with corresponding Hazard Ratios were used to examine the association between the anthropometric measurements and the risk of LC with adjustment for potential confounders. Potential non-linear associations were explored with cubic splines using the Likelihood ratio (LR) test. RESULTS: During follow-up, 319 participants developed LC. Body mass Index (BMI) was inversely associated with the risk of lung cancer (HR 0.94, 95% CI: 0.91-0.97) and persisted after excluding lung cancer cases during the first 10 years of follow-up. There was evidence for a non-linear association between BMI and the risk of lung cancer (0,04, df = 1), which indicated that the inverse association between BMI and lung cancer was mainly present in non-obese participants. Waist circumference (WC) (HR 1.03 95% CI: 1.01-1.05), Waist-to-Hip Ratio (WHR) (HR 1.23 95% CI: 1.09-1.38) and ABSI (A Body Shape Index) (HR 1.17 95% CI: 1.05-1.30) were positively and linearly associated with the risk of lung cancer. CONCLUSIONS: Body shape rather than body size may be an important risk indicator of LC. Future research should focus on the role of visceral fat and the risk of LC as well as the underlying mechanisms.

Long-term effects of antimicrobial drugs on the composition of the human gut microbiota.

INTRODUCTION: Antimicrobial drugs are known to have effects on the human gut microbiota. We studied the long-term temporal relationship between several antimicrobial drug groups and the composition of the human gut microbiota determined in feces samples. METHODS: Feces samples were obtained from a community-dwelling cohort of middle-aged and elderly individuals (Rotterdam Study). Bacterial DNA was isolated and sequenced using V3/V4 16 S ribosomal RNA sequencing (Illumina MiSeq). The time between the last prescription of several antimicrobial drug groups and the day of sampling was categorized into 0-12, 12-24, 24-48 and >48 months. The effects of the antimicrobial drug groups on the Shannon alpha-diversity (diversity), the Bray-Curtis beta-diversity (community structure), the Firmicutes/Bacteroidetes (F/B) ratio and individual genera were determined. RESULTS: We studied the gut microbiota of 1413 individuals (57.5% female, median age 62.6 years). The alpha-diversity was significantly lower up to 4 years after prescriptions of macrolides and lincosamides. It was also lower in the first year after the use of beta-lactams. The community structure (beta-diversity) of the microbiota was significantly different up to 4 years for macrolides and lincosamides, the first year for beta-lactams and at least the first year for quinolones. For the F/B ratio, drugs with a high anaerobic activity shifted the ratio toward Firmicutes in the first year whereas other antimicrobial drugs shifted the ratio toward Bacteroidetes. CONCLUSION: Use of antimicrobial drugs is associated with a shift in the composition of the gut microbiota.These effects differ in strength and duration, depending on the antimicrobial drug group used. These findings should be considered when prescribing antimicrobial drugs.

Diet as a risk factor for antimicrobial resistance in community-acquired urinary tract infections in a middle-aged and elderly population: a case-control study.

OBJECTIVES: There is an ongoing debate as to what extent antimicrobial resistance (AMR) can be transmitted from animals to humans via the consumption of animal products. Because epidemiological data on the role of diet in AMR in humans are lacking, we investigated this association between diet and AMR for different antimicrobial drugs in Escherichia coli (E. coli) in urinary tract infections (UTIs). METHODS: Susceptibility of E. coli in urinary cultures and information on diet (with food frequency questionnaires) were obtained from participants of the Rotterdam study, a population-based prospective cohort study. The association between intake of several food groups (meat, seafood, eggs, dairy products, crops) and resistance of E. coli to several antimicrobial drugs (amoxicillin, amoxicillin-clavulanic acid, trimethoprim, sulfamethoxazole-trimethoprim, first-generation cephalosporins, cefotaxime, nitrofurantoin, norfloxacin) was studied. RESULTS: Urinary cultures with E. coli were obtained from 612 individuals, of whom 481 (78.6%) were women. Resistance rates varied from 246/611 (40.3%) for amoxicillin and 167/612 (27.3%) for trimethoprim to only 29/612 (4.7%) for nitrofurantoin and 16/462 (3.5%) for cefotaxime. A higher intake of chicken was associated with cefotaxime resistance (OR 2.18; 95% CI 1.05-4.51 per tertile increase); a higher intake of pork was associated with norfloxacin resistance (OR 1.42; 95% CI 1.04-1.95 per quartile increase). In contrast, a higher intake of cheese was associated with lower AMR to amoxicillin (OR 0.84; 95% CI 0.72-0.99 per quartile increase) and amoxicillin-clavulanic acid (OR 0.67; 95% CI 0.53-0.86 per quartile increase). CONCLUSIONS: These findings support the hypothesis that diet may play a role in the AMR of E. coli in UTIs.

Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study.

We studied the relation between a diet that is high in acid-forming nutrients (e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone structure. We showed a negative relation, which was more prominent if proteins were of animal rather than of vegetable origin and if intake of dietary fibre was high. INTRODUCTION: Studies on dietary acid load (DAL) and fractures have shown inconsistent results. Associations between DAL, bone mineral density (BMD) and trabecular bone integrity might play a role in these inconsistencies and might be influenced by renal function and dietary fibre intake. Therefore, our aim was to study (1) associations of DAL with BMD and with the trabecular bone score (TBS) and (2) the potential influence of renal function and dietary fibre in these associations. METHODS: Dutch individuals aged 45 years and over (n = 4672) participating in the prospective cohort of the Rotterdam study were included. Based on food frequency questionnaires, three indices of DAL were calculated: the net endogenous acid production (NEAP) and the ratios of vegetable or animal protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD were derived from dual-energy X-ray absorptiometry measurements. RESULTS: Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated with low TBS (standardized ß (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11, -0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non-linear and differently shaped. Unfavourable associations between NEAP, BMD and TBS were mainly present in subgroups with high fibre intake. CONCLUSIONS: High NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS were non-linear and differently shaped. No significant associations of DAL with BMD were observed, nor was there any significant interaction between DAL and renal function. Mainly in participants with high intake of dietary fibre, DAL might be detrimental to bone.

Alcoholic beverage preference and diabetes incidence across Europe: the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project.

BACKGROUND/OBJECTIVES: It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. SUBJECTS/METHODS: Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when ⩾70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. RESULTS: Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. CONCLUSIONS: This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

Protein intake in early childhood and body composition at the age of 6 years: The Generation R Study.

BACKGROUND: Previous studies suggest that high protein intake in infancy leads to a higher body mass index (BMI) in later childhood. We examined the associations of total, animal and vegetable protein intake in early childhood with detailed measures of body composition at the age of 6 years. METHODS: This study was performed in 2911 children participating in a population-based cohort study. Protein intake at the age of 1 year was assessed with a validated food-frequency questionnaire and was adjusted for total energy intake. At the children's age of 6 years, we measured their anthropometrics and body fat (with dual-energy X-ray absorptiometry). We calculated age- and sex-specific s.d. scores for BMI, fat mass index (FMI) and fat-free mass index (FFMI). RESULTS: After adjustment for confounders, a 10 g per day higher total protein intake at 1 year of age was associated with a 0.05 s.d. (95% confidence interval (CI) 0.00, 0.09) higher BMI at age 6. This association was fully driven by a higher FMI (0.06 s.d. (95%CI 0.01, 0.11)) and not FFMI (-0.01 s.d. (95%CI -0.06, 0.05)). The associations of protein intake with FMI at 6 years remained significant after adjustment for BMI at the age of 1 year. Additional analyses showed that the associations of protein intake with FMI were stronger in girls than in boys (P for interaction=0.03), stronger among children who had catch-up growth in the first year of life (P for interaction<0.01) and stronger for intake of animal protein (both dairy and non-dairy protein) than protein from vegetable sources. CONCLUSIONS: Our results suggest that high protein intake in early childhood is associated with higher body fat mass, but not fat-free mass. Future studies are needed to investigate whether these changes persist into adulthood and to examine the optimal range of protein intake for infants and young children.

The associations of alcohol, coffee and tobacco consumption with gait in a community-dwelling population.

BACKGROUND/OBJECTIVES: Gait is an important health indicator, relating strongly to the risk of falling, morbidity and mortality. In a community-dwelling population, we investigated associations of alcohol, coffee and tobacco consumption with gait. SUBJECTS/METHODS: Two thousand forty-six non-demented participants from the Rotterdam Study underwent gait assessment by electronic walkway. We measured gait velocity and Global Gait, which is the average of seven gait domains: Rhythm, Phases, Variability, Pace, Tandem, Turning and Base of Support. Alcohol, coffee and tobacco consumption was assessed by questionnaires. With analysis of covariance, we investigated associations of consumption of alcoholic beverages, coffee consumption and smoking with Global Gait, gait velocity and the seven individual gait domains. RESULTS: In all, 81.9% of participants drank alcohol, 92.4% drank coffee, 17.3% were current smokers and 50.9% were past smokers. Moderate alcohol consumption (1-3 glasses per day) associated with better gait, as measured by Global Gait (0.20 standard deviations (s.d.) (95% confidence interval: 0.10; 0.31)), gait velocity (2.65 cm/s (0.80; 4.50)), Rhythm and Variability. Consuming high amounts of coffee (>3 cups per day) associated with better Global Gait (0.18 s.d. (0.08; 0.28)), gait velocity (2.63 cm/s (0.80; 4.45)), Pace, Turning and Variability. Current smoking associated with worse Global Gait (-0.11 s.d. (-0.21; 0.00)), gait velocity (-3.47 cm/s (-5.33; -1.60)), Rhythm and Pace, compared with non-smokers. CONCLUSIONS: In a community-dwelling population, consuming >1 cup of coffee and 1-3 glasses of alcohol relate to better gait, whereas smoking is related to worse gait. Further studies are required to evaluate whether interventions targeting substance consumption may aid to prevent or reduce gait deterioration and thereby related health problems.

Adherence to the Dutch dietary guidelines is inversely associated with 20-year mortality in a large prospective cohort study.

BACKGROUND/OBJECTIVES: The Dutch guidelines for a healthy diet aim to reduce major chronic diseases. However, supporting evidence on their overall association with all-cause and cause-specific mortality is limited. Recently, the Dutch Healthy Diet-index (DHD-index) has been developed to assess adherence to these guidelines. The aim was to examine the association between the DHD-index and all-cause mortality and deaths from cardiovascular disease (CVD), coronary heart disease (CHD), stroke and cancer. SUBJECTS/METHODS: We followed 3593 men and women aged 55 years and older enrolled in the Rotterdam Study, a population-based prospective cohort study, from baseline in 1990-1993 to 2011. A validated 170-item food frequency questionnaire at baseline was used to calculate the DHD-index score (maximum 90 points). Cox proportional hazard models were used to estimate hazard ratios (HRs) adjusting for age, sex, total energy intake, smoking and educational level. RESULTS: During the 20-year follow-up, 1831 (51%) deaths were reported. Mean DHD-index score was 60.6 (s.d. 10.6). The score was inversely associated with all-cause mortality (highest vs lowest quartile HR 0.77; 95% confidence interval (CI) 0.67, 0.89). Inverse but non-significant associations were observed for mortality due to CVD (HR 0.74; 95% CI 0.55, 1.01), CHD (HR 0.60; 95% CI 0.34, 1.06) and stroke (HR 0.67; 95% CI 0.36, 1.22), whereas no association was observed with cancer mortality (HR 0.99; 95% CI 0.90, 1.11). CONCLUSIONS: A higher level of adherence to the Dutch dietary guidelines, as assessed with the DHD-index, was associated with a lower risk of all-cause mortality, probably due to an inverse association with cardiovascular causes of death.

Bidirectional associations between circulating vitamin D and cholesterol levels: The Rotterdam Study.

OBJECTIVES: Higher levels of vitamin D have been associated with lower rates of cardiovascular disease perhaps through improved lipid profiles. However, results are inconsistent and the direction of the association between vitamin D and lipid levels remains unknown. We examined bidirectional associations between serum 25-hydroxyvitamin D (25(OH)D) and cholesterol concentrations. STUDY DESIGN: We used data from 1165 participants aged 55 to 88 years from the Rotterdam Study, a population-based prospective cohort study. MAIN OUTCOME MEASURES: Serum concentrations of 25(OH)D, total cholesterol (TC) and HDL cholesterol (HDL-C) were measured at two time points with a median time difference of 6 years. Bidirectional associations between 25(OH)D and each of the blood lipids was examined with path analyses in cross-lagged models. All models were adjusted for baseline age, sex, BMI, smoking status, and diet quality. RESULTS: The best-fit model for 25(OH)D and TC indicated that higher baseline TC concentrations were associated with lower 25(OH)D concentrations (standardized regression coefficient -0.05 (SE 0.02)), but 25(OH)D at baseline did not predict TC. For HDL-C, the best-fit model suggested a bidirectional inverse association between HDL-C and 25(OH)D (standardized regression coefficients of -0.03 (SE 0.02)) for both directions. CONCLUSIONS: Our results from path analyses on repeatedly measured 25(OH)D and lipid levels suggest that total cholesterol may be associated with decreased in 25(OH)D concentrations, but not the other way around, whereas the observed inverse association between HDL-C and 25(OH)D may be bidirectional.

Dietary vitamin A intake and bone health in the elderly: the Rotterdam Study.

BACKGROUND/OBJECTIVES: High vitamin A intake may be associated with a decreased bone mineral density (BMD) and increased risk of fractures. Our objectives were to study whether dietary intake of vitamin A (total, retinol or beta-carotene) is associated with BMD and fracture risk and if associations are modified by body mass index (BMI) and vitamin D. SUBJECTS/METHODS: Participants were aged 55 years and older (n=5288) from the Rotterdam Study, a population-based prospective cohort. Baseline vitamin A and D intake was measured by a food frequency questionnaire. BMD was measured by dual-energy X-ray absorptiometry at four visits between baseline (1989-1993) and 2004. Serum vitamin D was assessed in a subgroup (n=3161). Fracture incidence data were derived from medical records with a mean follow-up time of 13.9 years. RESULTS: Median intake of vitamin A ranged from 684 retinol equivalents (REs)/day (quintile 1) to 2000 REs/day (quintile 5). After adjustment for confounders related to lifestyle and socioeconomic status, BMD was significantly higher in subjects in the highest quintile of total vitamin A (mean difference in BMD (95% confidence interval (CI))=11.53 (0.37-22.7) mg/cm(2)) and retinol intake (mean difference in BMD (95% CI)=12.57 (1.10-24.05) mg/cm(2)) than in the middle quintile. Additional adjustment for BMI diluted these associations. Fracture risk was reduced in these subjects. Significant interaction was present between intake of retinol and overweight (BMI >25 kg/m(2)) in relation to fractures (P for interaction =0.05), but not BMD. Stratified analysis showed that these favourable associations with fracture risk were only present in overweight subjects (BMI >25 kg/m(2)). No effect modification by vitamin D intake or serum levels was observed. CONCLUSIONS: Our results suggest a plausible favourable relation between high vitamin A intake from the diet and fracture risk in overweight subjects, whereas the association between vitamin A and BMD is mainly explained by BMI.

Infant dietary patterns and bone mass in childhood: the Generation R Study.

UNLABELLED: Early life nutrition affects peak bone mass attainment. In this prospective cohort study, children with high adherence to a "dairy and whole grains" pattern in infancy had higher bone mineral density at the age of 6 years. Although the observed effects are small, our study provides insight into mechanisms linking early nutrition to bone acquisition in childhood. INTRODUCTION: Nutrition in early life may affect peak bone mass attainment. Previous studies on childhood nutrition and skeletal health mainly focused on individual nutrients, which does not consider the cumulative effects of nutrients. We investigated the associations between dietary patterns in infancy and childhood bone health. METHODS: This study included 2850 children participating in a population-based prospective cohort study. Dietary information was obtained from a food frequency questionnaire at the age of 13 months. Using principal component analysis, three major dietary patterns were extracted, explaining in total 30% of the variation in dietary intake. At the age of 6 years, a total body dual-energy X-ray absorptiometry (DXA) scan was performed, and bone mineral density (BMD), bone mineral content (BMC), area-adjusted BMC (aBMC), and bone area (BA) were analyzed. RESULTS: Higher adherence score to a "dairy and whole grains" pattern was positively associated with BMD and aBMC, but not with BMC and BA. Accordingly, children in the highest quartile of the "dairy and whole grains" pattern had higher BMD (difference 3.98 mg/cm(2), 95% confidence interval (CI) 0.36 to 7.61) and aBMC (difference 4.96 g, 95% CI 1.27 to 8.64) than children in the lowest quartile. Stratification for vitamin D supplementation showed that the positive associations between the "dairy and whole grains" pattern and bone outcomes were only observed in children who did not receive vitamin D supplementation. A "potatoes, rice, and vegetables" and a "refined grains and confectionery" pattern were not consistently associated with bone outcomes. CONCLUSIONS: An infant dietary pattern characterized by high intakes of dairy and cheese, whole grains, and eggs is positively associated with bone development in childhood. Further research is needed to investigate the consequences for bone health in later life.

Sugar-containing beverage intake in toddlers and body composition up to age 6 years: the Generation R study.

BACKGROUND/OBJECTIVE: Intake of sugar-containing beverages (SCBs) has been associated with higher body mass index (BMI) in childhood. The potential effect of SCB intake during infancy is unclear. We examined the association of SCB intake at 13 months with BMI development until 6 years and body composition at age 6 years. SUBJECTS/METHODS: This study included 2371 Dutch children from a population-based prospective cohort study. SCB intake at 13 months was assessed using a Food Frequency Questionnaire with validation against 24-h recalls and was standardized for total energy. BMI was calculated from repeated weight and height measurements, and age- and sex-specific s.d. scores were calculated. Adiposity was measured using Dual-energy X-ray absorptiometry. RESULTS: In girls, higher SCB intake at 13 months was significantly associated with higher BMI at ages 2, 3, 4 and 6 years (at age 6 years BMI (s.d. score) increase 0.11 (95% confidence interval (CI) +0.00; 0.23), high versus low intake). We observed a tendency towards higher android/gynoid fat ratio in girls with high intake (s.d. increase 0.14 (95% CI -0.02; 0.29), versus low intake) but not with body fat percentage. In boys, there was no association with BMI or body composition, but boys with high SCB intake at 13 months were taller at age 6 years (s.d. increase 0.14 (95% CI +0.00; 0.27), versus low intake). CONCLUSIONS: Higher SCB intake at 13 months was associated with higher BMI up to age 6 years in girls but not in boys. Our results imply that the unfavorable effects of SCB intake start early in life and that dietary advice regarding limiting SCB intake should already be given early in life.

Vitamin D status and metabolic syndrome in the elderly: the Rotterdam Study.

OBJECTIVE: The effects of vitamin D in the elderly are inconsistent. The aim of this study was to evaluate the association between vitamin D status and the metabolic syndrome (MetS) in the elderly, as well as between vitamin D status and the components of MetS (i.e. serum glucose, triglycerides (TG), HDL cholesterol (HDL-C), waist circumference (WC), and blood pressure (BP)). METHODS: The study was embedded in the Rotterdam Study, a population-based cohort of middle-aged and elderly adults. We analyzed data from 3240 people (median age 71.2 years) who did not have type 2 diabetes mellitus at baseline. RESULTS: We found higher 25-hydroxyvitamin D (25(OH)D) concentrations associated with lower prevalence of MetS (odds ratio (OR); 95% CI: 0.61; 0.49, 0.77 for adequate levels (≥75  nmol/l) vs deficiency (<50  nmol/l). In addition, in analysis of the individual components, the ORs for adequate vs deficient vitamin D levels were: 0.66 (95% CI 0.53, 0.83) for elevated WC, 0.67 (95% CI 0.52, 0.86) for reduced HDL-C, 0.69 (95% CI 0.54, 0.88) for elevated TG, and 0.80 (95% CI 0.65, 0.99) for elevated fasting glucose. Vitamin D was not associated with elevated blood pressure, and ORs for adequacy vs deficiency were 0.82 (95% CI 0.65, 1.03). CONCLUSION: Higher 25(OH)D concentrations in the elderly are associated with lower prevalence of MetS and, in particular, with more beneficial HDL-C, TG, WC, and serum glucose. Since the prevalence of vitamin D deficiency is common worldwide and its risk increases with age, if causality is proven, benefits of improving vitamin D status among the elderly may be great.

Genetic taste blindness to bitter and body composition in childhood: a Mendelian randomization design.

BACKGROUND: The ability to taste 6-n-propylthiouracil (PROP) may be associated with body composition, but previous findings from observational studies are conflicting and cannot be interpreted causally. The aim of this study was to estimate the causal association between PROP taster status and body composition in a population-based cohort study. METHODS: The study was embedded in a population-based prospective birth cohort study. The TAS2R38 genotype (rs713598) was used as an instrumental variable (IV) to obtain unbiased effect estimates of the relation between PROP taster status and body weight (n=3778). Adiposity measures included body mass index (BMI) and fat mass measured by dual- energy X-ray absorptiometry scan at the child's age of 6 years. Associations were investigated using both ordinary linear regression (OLS) and two-stage least squares regression (2SLS). RESULTS: Non-taster girls had higher BMI standard deviation scores (SDS) and higher body fat as compared with taster girls (results from linear regression BMI SDS: -0.09, P=0.023, body fat mass (%): -0.49, P=0.028). The TAS2R38 genotype predicted PROP phenotype (F=240), indicating a strong IV. The 2SLS effect estimates were imprecise but similar to the observational estimates (-0.08 for BMI SDS and -0.46 for body fat mass %) and were not significantly different from the OLS results (Hausman test: P>0.10). For boys there were no differences observed between tasters and non-tasters. CONCLUSIONS: Our findings suggest a causal relation between PROP taster status and body weight among 6-year-old girls; Mendelian randomization was consistent with conventional estimates. In contrast, body weight among boys appeared to be independent of the PROP taster status. Further research should focus on possible underlying pathways, such as dietary behavior.

Neonatal folate, homocysteine, vitamin B12 levels and methylenetetrahydrofolate reductase variants in childhood asthma and eczema.

OBJECTIVES: To assess the associations of folate, homocysteine and vitamin B12 levels of children at birth and their methylenetetrahydrofolate reductase (MTHFR) variants with asthma and eczema in childhood. METHODS: This study was embedded in a population-based prospective cohort study (n = 2,001). Neonatal cord blood folate, homocysteine and vitamin B12 levels were measured, and MTHFR C677T and A1298C genotyped. Wheezing and physician-diagnosed eczema were annually obtained by questionnaire until 4 years. At 6 years, we collected information on physician-diagnosed asthma ever and self-reported eczema ever, measured fractional exhaled nitric oxide (FeNO), and interrupter resistance (Rint). Data were analysed with generalized estimating equations or logistic regression: continuous outcomes with linear regression models. RESULTS: Folate, homocysteine and vitamin B12 levels of children at birth were not associated with wheezing or eczema until 4 years, asthma and eczema ever, or FeNO or Rint at 6 years. In children carrying C677T mutations in MTHFR, higher folate levels were associated with an increased risk of eczema (repeated eczema until 4 years: OR 1.40 (95% CI 1.09-1.80) (SD change) P-interaction = 0.003, eczema ever at 6 years: OR 1.41 (0.97-2.03) P-interaction = 0.011). No interactions between MTHFR and child folate and homocysteine levels were observed for wheezing and asthma. CONCLUSIONS: Folate, homocysteine and vitamin B12 levels of children at birth did not affect asthma- and eczema-related outcomes up to the age of 6 years. Further studies are warranted to establish the role of MTHFR variants in these associations.