NutriBrain: protocol for a randomised, double-blind, controlled trial to evaluate the effects of a nutritional product on brain integrity in preterm infants.

BACKGROUND: The gut microbiota and the brain are connected through different mechanisms. Bacterial colonisation of the gut plays a substantial role in normal brain development, providing opportunities for nutritional neuroprotective interventions that target the gut microbiome. Preterm infants are at risk for brain injury, especially white matter injury, mediated by inflammation and infection. Probiotics, prebiotics and L-glutamine are nutritional components that have individually already demonstrated beneficial effects in preterm infants, mostly by reducing infections or modulating the inflammatory response. The NutriBrain study aims to evaluate the benefits of a combination of probiotics, prebiotics and L-glutamine on white matter microstructure integrity (i.e., development of white matter tracts) at term equivalent age in very and extremely preterm born infants. METHODS: This study is a double-blind, randomised, controlled, parallel-group, single-center study. Eighty-eight infants born between 24 + 0 and < 30 + 0 weeks gestational age and less than 72 h old will be randomised after parental informed consent to receive either active study product or placebo. Active study product consists of a combination of Bifidobacterium breve M-16V, short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides and L-glutamine and will be given enterally in addition to regular infant feeding from 48 to 72 h after birth until 36 weeks postmenstrual age. The primary study outcome of white matter microstructure integrity will be measured as fractional anisotropy, assessed using magnetic resonance diffusion tensor imaging at term equivalent age and analysed using Tract-Based Spatial Statistics. Secondary outcomes are white matter injury, brain tissue volumes and cortical morphology, serious neonatal infections, serum inflammatory markers and neurodevelopmental outcome. DISCUSSION: This study will be the first to evaluate the effect of a combination of probiotics, prebiotics and L-glutamine on brain development in preterm infants. It may give new insights in the development and function of the gut microbiota and immune system in relation to brain development and provide a new, safe treatment possibility to improve brain development in the care for preterm infants. TRIAL REGISTRATION: ISRCTN, ISRCTN96620855 . Date assigned: 10/10/2017.

25-Hydroxyvitamin D concentrations, asthma and eczema in childhood: The generation R study.

BACKGROUND & AIMS: A role of vitamin D in the development of respiratory and allergic disease in children remains unclear. It may be likely that vitamin D has an effect on airway inflammation, but only few studies examined the effect in children. We aimed to examine whether serum 25-hydroxyvitamin D (25(OH) vitamin D) concentrations are associated with the fraction of exhaled nitric oxide (FeNO), airway interrupter resistance (Rint), physician diagnosed asthma ever, wheezing and eczema in a population-based cohort study in 6 year old children. METHODS: Serum 25(OH) vitamin D concentration was assessed in 3815 children. 25(OH) vitamin D concentrations ≥75 nmol/L were considered as sufficient, between 50 and 75 nmol/L as insufficient, and <50 nmol/L as deficient. FeNO and Rint were measured at the research center. Data on physician diagnosed asthma, wheezing, and eczema were obtained by parent-reported questionnaires. RESULTS: In comparison with sufficient 25(OH) vitamin D concentration, deficient concentrations were associated with elevated FeNO of ≥25 ppb (OR: 2.54; 95% CI: 1.34-4.80). In addition, deficient and insufficient 25(OH) vitamin D concentrations were associated with a lower Rint (Z-score: -1.26; 95% CI: -1.66 to -0.85) (ß: -0.75; 95% CI: -1.08 to -0.42), and increased risks of eczema (OR: 1.65; 95% CI: 1.13-2.41) (OR: 1.44; 95% CI: 1.06-1.95). Insufficient 25(OH) vitamin D concentration were associated with a decreased risk of physician diagnosed asthma ever (OR: 0.59; 95% CI: 0.38-0.94). CONCLUSIONS: Our results indicate that lower 25(OH) vitamin D levels are associated with elevated FeNO levels, but lower Rint values. Lower 25(OH) vitamin D levels are also associated with a decreased risk for asthma diagnoses but an increased risk for eczema.

A priori and a posteriori derived dietary patterns in infancy and cardiometabolic health in childhood: The role of body composition.

BACKGROUND & AIMS: Cardiometabolic risk has its origins in early life. However, it is unclear whether diet during early childhood is associated with cardiometabolic health, and what the role is of obesity. We aimed to study whether overall diet during early childhood is associated with cardiometabolic health and to examine if difference in body composition explain this association. METHODS: We examined associations of different types of dietary patterns in infancy with cardiometabolic health at school age among 2026 Dutch children participating in a population-based cohort in the Netherlands. Food intake at the age of 1 year was assessed with a food-frequency questionnaire. Three dietary pattern approaches were used: 1) An a priori-defined diet quality score; 2) dietary patterns based on variation in food intake, derived from principal component analysis (PCA); and 3) dietary patterns based on variations in fat and fat-free mass index, derived with reduced-rank regression (RRR). At the children's age of 6 years, we measured their body composition, systolic and diastolic blood pressure, and serum concentrations of insulin, triglycerides, and HDL-cholesterol, which we combined in a cardiometabolic risk-factor score. RESULTS: We observed that, after adjustment for confounders, children with higher adherence to a 'Health-conscious' PCA-derived pattern had a lower cardiometabolic risk-factor score (-0.07 SD (95%CI -0.12; -0.02) per SD). This association did not change after adjustment for fat and fat-free mass index. The RRR-derived dietary patterns based on variations in body composition were not associated with the cardiometabolic risk-factor score. CONCLUSIONS: Our results suggest that diet in early childhood may affect cardiometabolic health independent of differences in body composition.

Plasma fatty acid patterns during pregnancy and child's growth, body composition, and cardiometabolic health: The Generation R Study.

BACKGROUND: Exposure to different concentrations of fatty acids during fetal life may affect growth and metabolism. However, most studies examined individual fatty acids, whereas concentrations highly correlate and may interact with each other. We aimed to evaluate patterns of plasma fatty acids during pregnancy and their associations with growth, body composition, and cardiometabolic health of the 6-year-old offspring. METHODS: This study was performed in 4830 mother-child pairs participating in a population-based cohort in the Netherlands. Around 20 weeks of gestation, we measured plasma phospholipid concentrations of 22 fatty acids, in which we identified three fatty acid patterns using principal component analysis: a 'high n-6 polyunsaturated fatty acid (PUFA)' pattern, a 'monounsaturated and saturated fatty acid (MUFA and SFA)' pattern, and a 'high n-3 PUFA' pattern. When the children were 6 years old, we measured their anthropometrics and detailed body composition (using dual-energy X-ray absorptiometry), and we calculated their body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI). At the same age, children's blood pressure, and serum insulin, HDL-cholesterol, and triacylglycerol were measured. RESULTS: After adjustment for confounders and the other patterns, a higher score for the 'high n-6 PUFA' pattern during pregnancy was associated with a higher height, BMI, and FFMI in the offspring at 6 years, but not independently with cardiometabolic outcomes. The 'MUFA and SFA' pattern was not consistently associated with child body composition or cardiometabolic health. A higher score for the 'high n-3 PUFA' pattern was associated with a lower FMI, higher FFMI, higher HDL-cholesterol, and lower triacylglycerol. CONCLUSIONS: Our results suggest that plasma fatty acid patterns during pregnancy may affect offspring's body composition and cardiometabolic health. Specifically, a pattern characterized by high n-3 PUFA levels was associated with a more favorable body composition and blood lipid profile.

25-hydroxyvitamin D concentrations during fetal life and bone health in children aged 6 years: a population-based prospective cohort study.

BACKGROUND: 25-hydroxyvitamin D (25[OH]D) concentrations during fetal life might have long-lasting effects on skeletal development, but results from previous studies are inconsistent. We investigated the associations of maternal and fetal 25(OH)D concentrations with childhood bone health. METHODS: In a prospective multiethnic population-based cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), pregnant women living in the study area with an expected delivery date between April 1, 2002, and Jan 1, 2006, were eligible for participation in the study at our research centre in the Erasmus MC-Sophia Children's Hospital. We measured maternal 25(OH)D concentrations during mid-pregnancy (at a median of 20·4 weeks gestation [IQR 19·9-21·1]) and fetal 25(OH)D concentrations at birth (at a median of 40·1 weeks gestation [39·3-41·0]). We measured total-body bone mineral density, bone mineral content (BMC), area-adjusted BMC, and bone area using dual-energy X-ray absorptiometry (DXA) in offspring at 6 years of age. We examined associations using multivariable linear regression models, adjusted for several sociodemographic and lifestyle variables, and for child's height. FINDINGS: We enrolled 9901 mother-and-child pairs and obtained both mid-pregnancy maternal 25(OH)D concentrations and offspring DXA scans at age 6 years in 4815 pairs. Severe maternal 25(OH)D deficiency (<25 nmol/L) during mid-pregnancy was associated with higher offspring BMC (4·71 g, 95% CI 1·09 to 8·33; p=0·011) and larger bone area (7·54 cm2, 2·99 to 12·11; p=0·001) at age 6 years, compared with maternal 25(OH)D sufficiency (≥50 nmol/L) during mid-pregnancy. However, in a subgroup of children with available data on 25(OH)D concentrations at 6 years (n=3034), such associations for BMC (4·67 g, -0·05 to 9·39; p=0·052) and bone area (5·25 cm2, -0·41 to 10·91; p=0·069) were no longer significant after adjustment for the child's own 25(OH)D concentrations. No associations were seen between maternal 25(OH)D concentrations in mid-pregnancy and offspring bone mineral density (1·07 mg/cm2, -1·84 to 3·99; p=0·47) or area-adjusted BMC (-1·58 g, -4·72 to 1·61; p=0·32), and the association with skeletal parameters at 6 years did not differ by maternal BMI, maternal calcium intake, child sex, or weight status. Similar associations were seen with fetal 25(OH)D concentrations at birth. INTERPRETATION: We found inverse associations between 25(OH)D concentrations during fetal life with BMC and bone area in childhood, but these associations were no longer significant after adjustment for childhood 25(OH)D status. Our data suggest that 25(OH)D concentrations during childhood might be more relevant for bone outcomes than than 25(OH)D concentrations during fetal life. FUNDING: Erasmus University Medical Center, Organization for Health Research and Development (ZonMw), Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport.

The Influence of Meteorological Factors and Atmospheric Pollutants on the Risk of Preterm Birth.

Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure.

Dietary Intake of Protein in Early Childhood Is Associated with Growth Trajectories between 1 and 9 Years of Age.

BACKGROUND: High protein intake in infancy might lead to a higher body mass index (BMI) in childhood. However, whether these associations differ between different sources of protein is unclear. OBJECTIVE: We investigated associations between the intake of total protein, protein from different sources, and individual amino acids in early childhood and repeatedly measured height, weight, and BMI up to the age of 9 y. METHODS: This study was performed in 3564 children participating in the Generation R Study, a population-based prospective cohort study in Rotterdam, Netherlands. Intakes of total protein, animal protein, vegetable protein, and individual amino acids (including methionine, arginine, lysine, threonine, valine, leucine, isoleucine, phenylalanine, tryptophan, histidine, cysteine, tyrosine, alanine, asparagine, glutamine, glycine, proline, and serine) at 1 y were assessed by using a food-frequency questionnaire. Height and weight were measured at the approximate ages of 14, 18, 24, 30, 36, and 45 mo and at 6 and 9 y, and BMI was calculated. RESULTS: After adjustment for confounders, linear mixed models showed that a 10-g higher total protein intake/d at 1 y was significantly associated with a 0.03-SD greater height (95% CI: 0.00, 0.06), a 0.06-SD higher weight (95% CI: 0.03, 0.09), and a 0.05-SD higher BMI (95% CI: 0.03, 0.08) up to the age of 9 y. Associations were stronger for animal than for vegetable protein intake but did not differ between dairy and nondairy animal protein or between specific amino acids. CONCLUSIONS: A higher intake of protein, especially animal protein, at 1 y of age was associated with a greater height, weight, and BMI in childhood up to 9 y of age. Future studies should explore the role of growth hormones and investigate whether protein intake in early childhood affects health later in life.

A priori and a posteriori dietary patterns at the age of 1 year and body composition at the age of 6 years: the Generation R Study.

Dietary patterns have been linked to obesity in adults, however, not much is known about this association in early childhood. We examined associations of different types of dietary patterns in 1-year-old children with body composition at school age in 2026 children participating in a population-based cohort study. Dietary intake at the age of 1 year was assessed with a food-frequency questionnaire. At the children's age of 6 years we measured their body composition with dual-energy X-ray absorptiometry and we calculated body mass index, fat mass index (FMI), and fat-free mass index (FFMI). Three dietary pattern approaches were used: (1) An a priori-defined diet quality score; (2) dietary patterns based on variation in food intake, derived from principal-component-analysis (PCA); and (3) dietary patterns based on variations in FMI and FFMI, derived with reduced-rank-regression (RRR). Both the a priori-defined diet score and a 'Health-conscious' PCA-pattern were characterized by a high intake of fruit, vegetables, grains, and vegetable oils, and, after adjustment for confounders, children with higher adherence to these patterns had a higher FFMI at 6 years [0.19 SD (95 % CI 0.08;0.30) per SD increase in diet score], but had no different FMI. One of the two RRR-patterns was also positively associated with FFMI and was characterized by intake of whole grains, pasta and rice, and vegetable oils. Our results suggest that different a priori- and a posteriori-derived health-conscious dietary patterns in early childhood are associated with a higher fat-free mass, but not with fat mass, in later childhood.

Maternal weight status, diet, and supplement use as determinants of breastfeeding and complementary feeding: a systematic review and meta-analysis.

CONTEXT: Infant feeding practices are influenced by maternal factors. OBJECTIVE: The aim of this review is to examine the associations between maternal weight status or dietary characteristics and breastfeeding or complementary feeding. DATA SOURCES: A systematic literature search of the Embase, Cochrane Library, Google Scholar, MEDLINE, PubMed, and Web of Science databases was performed. STUDY SELECTION: Interventional and cohort studies in healthy mothers and infants that reported on maternal weight status, diet, or supplement use were selected. DATA EXTRACTION: Outcomes assessed included delayed onset of lactogenesis; initiation, exclusivity, duration, and cessation of breastfeeding; and timing of complementary feeding. DATA ANALYSIS: Eighty-one studies were included. Maternal underweight, diet, and supplement use were not associated with infant feeding practices. Obese women had a relative risk of failure to initiate breastfeeding (risk ratio [RR] = 1.23; 95%CI, 1.03-1.47) and a delayed onset of lactogenesis (RR  =  2.06; 95%CI, 1.18-3.61). The RR for breastfeeding cessation was 1.11 (95%CI, 1.07-1.15) per increase in category of body mass index. CONCLUSIONS: Prevention of obesity in women of reproductive age, as well as counseling of obese women after delivery, could be targeted to improve infant feeding practices.

Macronutrient Intakes in Infancy Are Associated with Sleep Duration in Toddlerhood.

BACKGROUND: Dietary composition has been associated with sleep indexes. However, most of the evidence is based on cross-sectional data, and studies in young children are lacking. OBJECTIVE: The aim of this study was to explore the longitudinal associations of macronutrient composition of the diet with sleep duration and consolidation (number of awakenings) in infancy and early childhood. METHODS: The study was performed in 3465 children from the Generation R Study, a population-based cohort study in the Netherlands. Mothers reported their child's food intake at 13 mo of age by using a validated food-frequency questionnaire and their child's sleep patterns at 2 and 3 y of age. We used nutrient substitution models to assess the associations of relative macronutrient intakes with sleep indexes and adjusted the models for sociodemographic and lifestyle factors. RESULTS: Isocaloric substitution of fat intake by protein or carbohydrate in infancy was associated with longer total sleep duration at 2 but not 3 y of age. For each 5% increase in energy intake of either protein or carbohydrate at the expense of fat, sleep duration at 2 y of age was longer by 6 min (95% CI: 0.4, 12 min) and 4 min (95% CI: 2, 6 min), respectively. Further exploration of macronutrient subtypes indicated no consistent differences between saturated or unsaturated fat and that intake of plant compared with animal protein or Trp did not explain the association of higher total protein intake with longer sleep duration at 2 y of age. Replacing unsaturated with saturated fat was associated with 7 min (95% CI: -13, -1 min) shorter total sleep duration at 3 y of age. Macronutrient intakes were not associated with sleep consolidation. CONCLUSIONS: Our results suggest that the macronutrient composition of the diet is associated with sleep duration in young children. Future research should further study the causality of this association and explore the underlying mechanisms.

Associations of breast-feeding patterns and introduction of solid foods with childhood bone mass: The Generation R Study.

Breast-feeding has been associated with later bone health, but results from previous studies are inconsistent. We examined the associations of breast-feeding patterns and timing of introduction of solids with bone mass at the age of 6 years in a prospective cohort study among 4919 children. We collected information about duration and exclusiveness of breast-feeding and timing of introduction of any solids with postnatal questionnaires. A total body dual-energy X-ray absorptiometry scan was performed at 6 years of age, and bone mineral density (BMD), bone mineral content (BMC), area-adjusted BMC (aBMC) and bone area (BA) were analysed. Compared with children who were ever breast-fed, those never breast-fed had lower BMD (-4·62 mg/cm2; 95 % CI -8·28, -0·97), BMC (-8·08 g; 95 % CI -12·45, -3·71) and BA (-7·03 cm2; 95 % CI -12·55, -1·52) at 6 years of age. Among all breast-fed children, those who were breast-fed non-exclusively in the first 4 months had higher BMD (2·91 mg/cm2; 95 % CI 0·41, 5·41) and aBMC (3·97 g; 95 % CI 1·30, 6·64) and lower BA (-4·45 cm2; 95 % CI -8·28, -0·61) compared with children breast-fed exclusively for at least 4 months. Compared with introduction of solids between 4 and 5 months, introduction <4 months was associated with higher BMD and aBMC, whereas introduction between 5 and 6 months was associated with lower aBMC and higher BA. Additional adjustment for infant vitamin D supplementation did not change the results. In conclusion, results from the present study suggest that ever breast-feeding compared with never breast-feeding is associated with higher bone mass in 6-year-old children, but exclusive breast-feeding for 4 months or longer was not positively associated with bone outcomes.

Protein intake in early childhood and cardiometabolic health at school age: the Generation R Study.

PURPOSE: High protein intake in infancy has been linked to obesity. We aimed to examine the associations of protein intake in early childhood with cardiovascular and metabolic outcomes at school age. METHODS: This study was performed in 2965 children participating in a population-based prospective cohort study. Protein intake at 1 year was assessed with a food frequency questionnaire and was adjusted for energy intake. At the children's age of 6 years, we measured their body fat percentage (BF%), blood pressure (BP), and insulin, HDL cholesterol, and triglyceride serum levels. These measures were incorporated into a cardiometabolic risk factor score, using age- and sex-specific SD scores. RESULTS: In covariate-adjusted models, higher protein intake was associated with a higher BF%, lower diastolic BP, and lower triglyceride levels. We observed a significant interaction of protein intake with child sex on metabolic outcomes. Stratified analyses showed that protein intake was positively associated with BF% [0.07 SD (95 % CI 0.02; 0.13) per 10 g/day] and insulin levels in girls, but not in boys. In boys, but not in girls, higher protein intake was associated with lower triglyceride levels [-0.12 SD (95 % CI -0.20; -0.04) per 10 g/day] and a lower cardiometabolic risk factor score. Protein intake was not consistently associated with systolic BP or HDL cholesterol levels. CONCLUSION: Protein intake in early childhood was associated with a higher BF% and higher insulin levels at 6 years in girls and with lower triglyceride levels in boys. Further studies are needed to explore these sex differences and to investigate whether the observed changes persist into adulthood.

Dietary acid load in early life and bone health in childhood: the Generation R Study.

BACKGROUND: Dietary contribution to acid-base balance in early life may influence subsequent bone mineralization. Previous studies reported inconsistent results regarding the associations between dietary acid load and bone mass. OBJECTIVE: We examined the associations of dietary acid load in early life with bone health in childhood. DESIGN: In a prospective, multiethnic, population-based cohort study of 2850 children, we estimated dietary acid load as dietary potential renal acid load (dPRAL), based on dietary intakes of calcium, magnesium, phosphorus, potassium, and protein, and as a protein intake to potassium intake ratio (Pro:K) at 1 y of age and in a subgroup at 2 y of age : Bone mineral density, bone mineral content (BMC), area-adjusted BMC, and bone area were assessed by dual-energy X-ray absorptiometry at the median age of 6 y. Data were analyzed by using multivariable linear regression models. RESULTS: After adjusting for relevant maternal and child factors, dietary acid load estimated as either dPRAL or Pro:K ratio was not consistently associated with childhood bone health. Associations did not differ by sex, ethnicity, weight status, or vitamin D supplementation. Only in those children with high protein intake in our population (i.e., >42 g/d), a 1-unit increase in dPRAL (mEq/d) was inversely associated with BMC (difference: -0.32 g; 95% CI: -0.64, -0.01 g). CONCLUSIONS: Dietary acid load in early life was not consistently associated with bone health in childhood. Further research is needed to explore the extent to which dietary acid load in later childhood may affect current and future bone health.

Identification of a dietary pattern prospectively associated with bone mass in Australian young adults.

BACKGROUND: Relatively little is known about the relations between dietary patterns and bone health in adolescence, which is a period of substantial bone mass accrual. OBJECTIVES: We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein, calcium, and potassium contents and investigated their prospective associations with bone mineral density (BMD), bone area, and bone mineral content (BMC) in a cohort of young adults. DESIGN: The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort (Raine) Study. Dietary information was obtained from food-frequency questionnaires at 14 and 17 y of age. Dietary patterns were characterized according to protein, calcium, and potassium intakes with the use of reduced-rank regression. BMD, bone area, and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age. RESULTS: We identified 2 major dietary patterns. The first pattern was positively correlated with intakes of protein, calcium, and potassium and had high factor loadings for low-fat dairy products, whole grains, and vegetables. The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat, poultry, fish, and eggs. After adjustment for anthropometric, sociodemographic, and lifestyle factors, a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [differences: 8.6 mg/cm(2) (95% CI: 3.0, 14.1 mg/cm(2)) and 21.9 g (95% CI: 6.5, 37.3 g), respectively, per SD increase in z score]. The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age. The second pattern at 14 or 17 y of age was not associated with BMD, BMC, or bone area. CONCLUSIONS: A dietary pattern characterized by high intakes of protein, calcium, and potassium in midadolescence was associated with higher BMD and BMC at 20 y of age. Our results indicate that high consumption of low-fat dairy products, whole grains, and vegetables in adolescence are associated with beneficial effects on bone development.

Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians.

BACKGROUND: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. OBJECTIVE: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. DESIGN: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. RESULTS: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. CONCLUSION: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Dietary Intakes of Folic Acid and Methionine in Early Childhood Are Associated with Body Composition at School Age.

BACKGROUND: Deficiency of vitamin B-6, vitamin B-12, folate, folic acid, or methionine may lead to dysregulation of DNA methylation, which might lead to disturbed energy and lipid metabolism. OBJECTIVE: We aimed to explore whether intakes of vitamin B-6, vitamin B-12, folate, folic acid, and methionine at 1 y are associated with measures of growth and body composition at the age of 6 y. METHODS: This study was performed in 2922 children participating in The Generation R Study, a population-based prospective cohort study. Dietary intakes of vitamins B-6 and B-12, folate, folic acid, and methionine were assessed at a median age of 12.9 mo by using a validated food-frequency questionnaire. At the age of 6 y, height and weight were measured, and body mass index (BMI; in kg/m(2)) was calculated. Body fat was measured with dual-energy X-ray absorptiometry, and body fat percentage and the ratio of android fat mass to gynoid fat mass (android:gynoid) were calculated. RESULTS: In models adjusted for maternal and child characteristics, children with folic acid intakes in the highest tertile had a 0.16 SD score (SDS) lower weight (95% CI: -0.31, -0.02 SDS) and a 0.14 SDS lower BMI (95% CI: -0.26, -0.01 SDS) than children in the lowest tertile. Children with vitamin B-12 intakes in the highest tertile had a 0.13 SDS higher android:gynoid (95% CI: 0.00, 0.25 SDS) than children in the lowest tertile. In addition, children with intakes in the highest tertile of methionine had a 0.09 SDS higher BMI (95% CI: 0.01, 0.17) and a 0.12 SDS higher android:gynoid (95% CI: 0.02, 0.22) than children in the lowest tertile. Vitamin B-6 and folate intakes were not associated with any of the body composition outcomes measured. CONCLUSIONS: In this population of children, early high folic acid intakes were associated with a lower body weight and BMI at the age of 6 y. In contrast, early higher methionine intakes were associated with unfavorable body composition at the age of 6 y. Future studies should investigate long-term consequences of these outcomes on health.

Protein intake in infancy and kidney size and function at the age of 6 years: The Generation R Study.

BACKGROUND: High protein intake has been linked to kidney growth and function. Whether protein intake is related to kidney outcomes in healthy children is unclear. METHODS: We examined the associations between protein intake in infancy and kidney outcomes at age 6 years in 2968 children participating in a population-based cohort study. Protein intake at 1 year was assessed using a food-frequency questionnaire and was adjusted for energy intake. At age 6 years we measured the kidney volume and urinary albumin/creatinine ratio (ACR) of all participating children, and we estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C levels. RESULTS: In models adjusted for age, sex, body surface area, and sociodemographic factors, a higher protein intake was associated with a lower ACR and a higher eGFR but was not consistently associated with kidney volume. However, after further adjustment for additional dietary and lifestyle factors, such as sodium intake, diet quality, and television watching, higher protein intake was no longer associated with kidney function. No differences in associations were observed between animal and vegetable protein intake. CONCLUSIONS: Our findings show that protein intake in early childhood is not independently associated with kidney size or function at the age of 6 years. Further study is needed on other early life predictors of kidney size and function in later life.

Effects of polyunsaturated fatty acid intake and status during pregnancy, lactation, and early childhood on cardiometabolic health: A systematic review.

The importance of polyunsaturated fatty acid (PUFA) intake in fetal life and infancy has been widely studied in relation to child cognitive and visual development, but whether early life PUFA exposure is related to cardiometabolic risk factors is unclear. The focus of this systematic review was to evaluate the effects of PUFA dietary intake and blood levels during pregnancy, lactation, or early childhood (⩽5 y) on obesity, blood pressure, blood lipids, and insulin sensitivity. We identified 4302 abstracts in the databases Embase, Medline and Cochrane Central (April 2014), of which 56 articles, reporting on 45 unique studies, met all selection criteria. Many of the included studies focused on obesity as an outcome (33 studies), whereas studies on insulin sensitivity were relatively scarce (6 studies). Overall, results for obesity, blood pressure, and blood lipids were inconsistent, with a few studies reporting effects in opposite directions and other studies that did not observe any effects of PUFAs on these outcomes. Four studies suggested beneficial effects of PUFAs on insulin sensitivity. We conclude that there is insufficient evidence to support a beneficial effect of PUFAs in fetal life or early childhood on obesity, blood pressure, or blood lipids. More research is needed to investigate the potential favorable effects of PUFAs on insulin sensitivity, and to examine the role of specific fatty acids in early life on later cardiometabolic health.

First-trimester maternal protein intake and childhood kidney outcomes: the Generation R Study.

BACKGROUND: Nutritional exposures during in utero development may have long-lasting consequences for postnatal renal health. Animal studies suggest that specifically maternal dietary protein intake during pregnancy influences childhood kidney function. OBJECTIVE: We examined the associations of total, animal, and vegetable maternal protein intake during pregnancy with kidney volume and function in school-aged children. DESIGN: This study was conducted in 3650 pregnant women and their children who were participating in a population-based cohort study from early life onward. First-trimester energy-adjusted maternal protein intake was assessed with a food-frequency questionnaire. At the child's age of 6 y, we assessed kidney volume, estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C concentrations, and microalbuminuria using urine albumin:creatinine ratios. RESULTS: First-trimester maternal total protein intake was associated with a higher childhood creatinine-based eGFR (difference: 0.06 mL × min(-1) × 1.73 m(-2); 95% CI: 0.01, 0.12 mL · min(-1) · 1.73 m(-2) per gram of protein intake). This association was mainly driven by vegetable protein intake (0.22 mL × min(-1) × 1.73 m(-2); 95% CI: 0.10, 0.35 mL · min(-1) · 1.73 m(-2) per gram of vegetable protein intake). These associations were not explained by protein intake in early childhood. First-trimester maternal protein intake was not significantly associated with childhood kidney volume, cystatin C-based eGFR, or the risk of microalbuminuria. CONCLUSIONS: Our findings suggest that higher total and vegetable, but not animal, maternal protein intake during the first trimester of pregnancy is associated with a higher eGFR in childhood. Further follow-up studies are needed to investigate whether maternal protein intake in early pregnancy also affects the risk of kidney diseases in later life.

Vitamin D deficiency in school-age children is associated with sociodemographic and lifestyle factors.

BACKGROUND: There is concern about a reemergence of vitamin D deficiency in children in developed countries. OBJECTIVES: The aims of this study were to describe vitamin D status in the Generation R study, a large multiethnic cohort of 6-y-old children in The Netherlands, and to examine sociodemographic, lifestyle, and dietary determinants of vitamin D deficiency. METHODS: We measured serum 25-hydroxyvitamin D [25(OH)D] concentrations in 4167 children aged 6 y and defined deficiency following recommended cutoffs. We examined the associations between subject characteristics and vitamin D deficiency with the use of multivariable logistic regression analyses. RESULTS: Serum 25(OH)D concentrations ranged from 4 to 211 nmol/L (median: 64 nmol/L), with 6.2% of the children having severely deficient (<25 nmol/L), 23.6% deficient (25 to <50 nmol/L), 36.5% sufficient (50 to <75 nmol/L), and 33.7% optimal (≥75 nmol/L) 25(OH)D concentrations. The prevalence of vitamin D deficiency [25(OH)D <50 nmol/L] was higher in winter (51.3%) than in summer (10.3%); and higher in African, Asian, Turkish, and Moroccan children (54.5%) than in those with a Dutch or other Western ethnic background (17.6%). In multivariable models, several factors were associated with vitamin D deficiency, including household income (OR: 1.74; 95% CI: 1.34, 2.27 for low vs. high income), child age (OR: 1.39; 95% CI: 1.20, 1.62 per year), child television watching (OR: 1.32; 95% CI: 1.06, 1.64 for ≥2 vs. <2 h/d), and playing outside (OR: 0.71; 95% CI: 0.57, 0.89 for ≥1 vs. <1 h/d). In a subgroup with dietary data (n = 1915), vitamin D deficiency was associated with a lower diet quality, but not with vitamin D intake or supplement use in early childhood. CONCLUSIONS: Suboptimal vitamin D status is common among 6-y-old children in The Netherlands, especially among non-Western children and in winter and spring. Important modifiable factors associated with vitamin D deficiency were overall diet quality, sedentary behavior, and playing outside.