Dietary habits, traveling and the living situation potentially influence the susceptibility to SARS-CoV-2 infection: results from healthcare workers participating in the RisCoin Study.

PURPOSE: To explore occupational and non-occupational risk and protective factors for the coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs). METHODS: Serum specimens and questionnaire data were obtained between October 7 and December 16, 2021 from COVID-19-vaccinated HCWs at a quaternary care hospital in Munich, Germany, and were analyzed in the RisCoin Study. RESULTS: Of 3,696 participants evaluated, 6.6% have had COVID-19 at least once. Multivariate logistic regression analysis identified working in patient care occupations (7.3% had COVID-19, 95% CI 6.4-8.3, Pr = 0.0002), especially as nurses, to be a potential occupation-related COVID-19 risk factor. Non-occupational factors significantly associated with high rates of the disease were contacts to COVID-19 cases in the community (12.8% had COVID-19, 95% CI 10.3-15.8, Pr < 0.0001), being obese (9.9% had COVID-19, 95% CI 7.1-13.5, Pr = 0.0014), and frequent traveling abroad (9.4% had COVID-19, 95% CI 7.1-12.3, Pr = 0.0088). On the contrary, receiving the basic COVID-19 immunization early during the pandemic (5.9% had COVID-19, 95% CI 5.1-6.8, Pr < 0.0001), regular smoking (3.6% had COVID-19, 95% CI 2.1-6.0, Pr = 0.0088), living with the elderly (3.0% had COVID-19, 95% CI 1.0-8.0, Pr = 0.0475), and frequent consumption of ready-to-eat meals (2.6% had COVID-19, 95% CI 1.1-5.4, Pr = 0.0045) were non-occupational factors potentially protecting study participants against COVID-19. CONCLUSION: The newly discovered associations between the living situation, traveling as well as dietary habits and altered COVID-19 risk can potentially help refine containment measures and, furthermore, contribute to new mechanistic insights that may aid the protection of risk groups and vulnerable individuals.

Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium.

BACKGROUND: Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism. METHODS: We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2-6 years, N = 579) and late (7̄-12 years, N = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model. We also performed sex-stratified meta-analyses. Follow-up analyses included pathway analysis and eQTM look-up. RESULTS: Infant animal protein intake was not associated with DNA methylation in early childhood, but was associated with late-childhood DNA methylation at cg21300373 (P = 4.27 × 10¯8, MARCHF1) and cg10633363 (P = 1.09 × 10¯7, HOXB9) after FDR correction. Infant plant protein intake was associated with early-childhood DNA methylation at cg25973293 (P = 2.26 × 10-7, C1orf159) and cg15407373 (P = 2.13 × 10-7, MBP) after FDR correction. There was no overlap between the findings from the animal and plant protein analyses. We did not find enriched functional pathways at either time point using CpGs associated with animal and plant protein. These CpGs were not previously associated with childhood gene expression. Sex-stratified meta-analyses showed sex-specific DNA methylation associations for both animal and plant protein intake. CONCLUSION: Infant animal protein intake was associated with DNA methylation at two CpGs in late childhood. Infant plant protein intake was associated with DNA methylation in early childhood at two CpGs. A potential mediating role of DNA methylation at these CpGs between infant protein intake and health outcomes requires further investigation.

Sleep duration in preschool age and later behavioral and cognitive outcomes: an individual participant data meta-analysis in five European cohorts.

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children's Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: - 1.27, 95% CI [- 2.22, - 0.32] / - 2.39, 95% CI [- 3.04, - 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: - 0.28, 95% CI [- 0.83, 0.27] / - 0.42, 95% CI [- 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children's later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude.

BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N). CONCLUSIONS: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.

Effects of infant feeding with goat milk formula or cow milk formula on atopic dermatitis: protocol of the randomised controlled Goat Infant Formula Feeding and Eczema (GIraFFE) trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin condition significantly affecting quality of life. A small randomised trial showed an approximately one-third lower incidence of AD in goat milk formula-fed compared with cow milk formula-fed infants. However, due to limited statistical power, AD incidence difference was not found to be significant. This study aims to explore a potential risk reduction of AD by feeding a formula based on whole goat milk (as a source of protein and fat) compared with a formula based on cow milk proteins and vegetable oils. METHODS AND ANALYSIS: This two-arm (1:1 allocation), parallel, randomised, double-blind, controlled nutritional trial shall enrol up to 2296 healthy term-born infants until 3 months of age, if parents choose to start formula feeding. Ten study centres in Spain and Poland are participating. Randomised infants receive investigational infant and follow-on formulas either based on whole goat milk or on cow milk until the age of 12 months. The goat milk formula has a whey:casein ratio of 20:80 and about 50% of the lipids are milk fat from whole goat milk, whereas the cow milk formula, used as control, has a whey:casein ratio of 60:40 and 100% of the lipids are from vegetable oils. The energy and nutrient levels in both goat and cow milk formulas are the same. The primary endpoint is the cumulative incidence of AD until the age of 12 months diagnosed by study personnel based on the UK Working Party Diagnostic Criteria. The secondary endpoints include reported AD diagnosis, measures of AD, blood and stool markers, child growth, sleep, nutrition and quality of life. Participating children are followed until the age of 5 years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethical committees of all participating institutions. TRIAL REGISTRATION NUMBER: NCT04599946.

Effect of Protein Intake Early in Life on Kidney Volume and Blood Pressure at 11 Years of Age.

High protein intake has been associated with kidney hypertrophy, which is usually reversible; however, when it occurs early in life, it could lead to cell programming with a long-lasting effect. This study aimed to assess whether higher protein ingestion early in life has a persistent effect on kidney volume at 11 years of age, as well as its influence on blood pressure. This is a secondary analysis of a randomized control trial that compared the growth of infants fed with a higher-protein formula versus those fed with a lower-protein formula, with a control group of breastfed infants. Renal ultrasound and anthropometric measurements were assessed at 6 months and 11 years of age. At 11 years, urinary protein, albumin and creatinine, and blood pressure were measured in 232 children. Feeding with a higher-protein formula was associated with a larger kidney volume (ß = 8.71, 95%CI 0.09-17.33, p = 0.048) and higher systolic blood pressure (ß = 3.43, 95%CI 0.78-6.08, p = 0.011) at 11 years of age. Microalbuminuria was detected in 7% of the patients, with no differences among groups (p = 0.56). The effect of increased protein ingestion early in life may condition kidney volume and blood pressure in later childhood.

Eating Frequency in European Children from 1 to 96 Months of Age: Results of the Childhood Obesity Project Study.

We aimed to investigate the eating frequency (EF) in children over age, and examined the influence of country, sex, feeding mode and weight status on EF. We used the dietary data of the Childhood Obesity Project, which comprised European children from five countries. Dietary data of 3-days weighed and estimated records were available monthly from 1 to 9 and at 12-, 24-, 36-, 48-, 60-, 72- and 96-months old. Generalized additive mixed effects models were used to estimate EF trajectories with EF as outcome and applying age splines. Additionally, the models were further adjusted for country, feeding mode, sex or weight status. Data from 1244 children were analysed. EF was highest at 1 month with on average 7.3 ± 1.9 feeds per day, and fell to 5.1 ± 1.1 eating occasions at the age 96 months. Night feeding was similarly often than day feeding at 1 month but declined thereafter. Significant differences in EF were observed between countries (p < 0.05), with the highest EF in Poland, and between infant feeding modes, with a higher EF in breastfed than non-breastfed infants (p < 0.05). Sex and body weight were not associated with EF. Despite the importance of EF towards total energy intake, no association with weight status was found.

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.

BACKGROUND: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. METHODS: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. RESULTS: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. CONCLUSION: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Distribution of energy and macronutrient intakes across eating occasions in European children from 3 to 8 years of age: The EU Childhood Obesity Project Study.

PURPOSE: We aimed to characterize the distribution of energy and macronutrient intakes across eating occasions (EO) in European children from preschool to school age. METHODS: Data from 3-day weighed food records were collected from children at ages 3, 4, 5, 6 and 8 years from Belgium, Germany, Italy, Poland and Spain. Food intakes were assigned to EO based on country-specific daytimes for breakfast, lunch, supper and snacks (morning, afternoon). The average energy and nutrient intakes were expressed as percentage of total energy intake (%E). Nutrients were additionally expressed as percentage per EO (%EEO). Foods were assigned to food groups; variation in intake was calculated via coefficient of variation (CV). We analyzed age trends in diurnal intake using mixed-effects beta regression. RESULTS: The 740 healthy children included in the analysis consumed the largest proportion of daily energy at lunch (31%E ± 8, M ± SD) and supper (26%E ± 8), followed by breakfast (19%E ± 7) and snacks [afternoon (16%E ± 8); morning (8%E ± 7)], with the most variable intake at morning snack (CV = 0.9). The nutrient composition at lunch and supper was highest for fat (36 ± 9%ELunch; 39 ± 11%ESupper) and protein (18 ± 5%ELunch; 18 ± 6%ESupper) and at breakfast and snacks for carbohydrates (54 ± 12%EBreakfast; 62 ± 12%ESnacks). High-sugar content foods were consumed in relatively large proportions at breakfast and snacks. Food intakes varied significantly with age, with lower snack intakes at later ages (p < 0.001). CONCLUSION: Possibly unhealthy EOs with high-fat intakes and high-sugar-content foods were observed. Changes in nutrient composition of EOs may be beneficial for health. TRIAL REGISTRY: ClinicalTrials.gov: NCT00338689; 19/June/2006.

Different protein intake in the first year and its effects on adiposity rebound and obesity throughout childhood: 11 years follow-up of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Infant feeding affects child growth and later obesity risk. We examined whether protein supply in infancy affects the adiposity rebound, body mass index (BMI) and overweight and obesity up to 11 years of age. METHODS: We enrolled healthy term infants from five European countries in a double blind randomized trial, with anticipated 16 examinations within 11 years follow-up. Formula-fed infants (n = 1090) were randomized to isoenergetic formula with higher or lower protein content within the range stipulated by EU legislation in 2001. A breastfed reference group (n = 588) was included. Adiposity rebound and BMI trajectories were estimated by generalized additive mixed models in 917 children, with 712 participating in the 11 year follow-up. RESULTS: BMI trajectories were elevated in the higher compared to the lower protein group, with significantly different BMI at adiposity rebound (0.24 kg/m2, 0.01-0.47, p = 0.040), and an increased risk for overweight at 11 years (adjusted Odds Ratio 1.70; 1.06-2.73; p = 0.027) but no significant difference for obesity (adjusted Odds Ratio 1.47; 0.66-3.27). The two formula groups did not differ in the timing of adiposity rebound, but all children with obesity at 11 years had an early adiposity rebound before four years. CONCLUSIONS: Compared to conventional high protein formula, feeding lower protein formula in infancy lowers BMI trajectories up to 11 years and achieves similar BMI values at adiposity rebound as observed in breastfed infants.

Time of Dietary Energy and Nutrient Intake and Body Mass Index in Children: Compositional Data Analysis from the Childhood Obesity Project (CHOP) Trial.

Meal timing is suggested to influence the obesity risk in children. Our aim was to analyse the effect of energy and nutrient distributions at eating occasions (EO), including breakfast, lunch, supper, and snacks, on the BMI z-score (zBMI) during childhood in 729 healthy children. BMI and three-day dietary protocols were obtained at 3, 4, 5, 6, and 8 years of age, and dietary data were analysed as the percentage of the mean total energy intake (TEI; %E). Intakes at EOs were transformed via an isometric log-ratio transformation and added as exposure variables to linear mixed-effects models. Stratified analyses by country and recategorization of EOs by adding intake from snacks to respective meals for further analyses were performed. The exclusion of subjects with less than three observations and the exclusion of subjects who skipped one EO or consumed 5% energy or less at one EO were examined in sensitivity analyses. Around 23% of the children were overweight at a given time point. Overweight and normal-weight children showed different distributions of dietary intakes over the day; overweight children consumed higher intakes at lunch and lower intakes of snacks. However, no significant effects of timing of EOs on zBMI were found in regression analyses.

Effect of maternal smoking during pregnancy on child blood pressure in a European cohort.

Hypertension is a public health issue that can have its origin in the early phases of development. Maternal smoking during pregnancy (MSDP) could play a role in offspring's cardio-metabolic programming. To assess the relationship between MSDP and later blood pressure (BP) in children we conducted a secondary analysis of a randomized dietary intervention trial (EU-Childhood Obesity Project). Healthy term infants with normal birth weight were recruited during the first 8 weeks of life in 5 European countries and followed until 11 years of age. Data on MSDP was collected at recruitment. BP and anthropometry were assessed at 11 years of age. Children were classified according to AAP guidelines as normal BP: BP < 90th percentile; high BP: ≥ 90th percentile with the subset of children having BP > 95th percentile categorized as hypertensive. Out of 572 children, 20% were exposed to MSDP. At 11 years, 26.8% had BP over the 90th centile. MSDP beyond 12 weeks of gestation was associated with higher systolic BP percentile (adjusted B 6.935; 95% CI 0.454, 13.429; p = 0.036) and over twofold increase likelihood of hypertension (OR 2.195; 95% CI 1.089, 4.423; p = 0.028) in children at 11 years. MSDP was significantly associated with later BP in children.

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood.

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis.

BACKGROUND: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. METHODS: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4-13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. RESULTS: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10-8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10-8, n = 577) and sleep onset latency (p = 8.8 × 10-9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716-2539). CONCLUSION: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

BACKGROUND: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. METHODS: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). RESULTS: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. CONCLUSIONS: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.

Parental Perception of Body Weight Status of Their 8-year-old Children: Findings from the European CHOP Study.

BACKGROUND: Maternal perception of child weight status in children with overweight or obesity has received a lot of attention but data on paternal perception of children from presumably healthy cohorts are lacking. OBJECTIVE: We aimed to investigate paternal and maternal perception of child weight status at the age of 8 years in a cohort of 591 children from 5 European countries. MATERIAL AND METHODS: Included were 8-year-old children and their parents participating in the European Childhood Obesity Project (EU CHOP). Weight and height of children and parents were measured and Body Mass Index (BMI, kg/m2) was calculated. Both parents were asked to assess their perception of child weight status using Eckstein scales and their concern about child overweight. The agreement between mother and father perceptions was assessed by Cohen kappa coefficient and their relationship was analyzed by linear mixed effects models based on ordinal logistic regression, accounting for country, child gender and BMI, parental BMI, level of education, concern and type of feeding during first year of life. RESULTS: Data from children and both parents were available for 432 girls and boys. Mean BMI was comparable in boys and girls (16.7 ± 2.31 vs. 16.9 ± 2.87 kg/m2, P = 0.55). In total, 172 children (29.3%) were overweight or obese. There was a high degree of agreement between mother and father perceptions of their child's weight status (Cohen kappa 0.77). Multivariate modelling showed that perception levels significantly increased with child BMI but were globally lower than assessed. They differed between countries, gender and types of feeding during first year of life, were influenced by education level of the father but were not related to parental BMI and concern about childhood overweight. CONCLUSIONS: The study showed no overall differences between mothers and fathers in rating their child's weight status but both parents had a propensity to underestimate their child's actual weight, particularly in boys. The EU CHOP trial registered at clinicaltrials.gov as NCT00338689.

Usefulness of the waist-to-height ratio for predicting cardiometabolic risk in children and its suggested boundary values.

BACKGROUND & AIMS: Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages. METHODS: We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile. RESULTS: The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively). CONCLUSION: A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population.

Sleep duration and problem behaviour in 8-year-old children in the Childhood Obesity Project.

There is growing evidence that insufficient sleep has negative effects on the mental health of children. The aim of this study is to examine the associations between device-measured sleep duration and internalizing and externalizing problems in 8-year-old children. The study is a secondary analysis of data from the Childhood Obesity Project conducted in five European countries. Nocturnal sleep duration was measured with the SenseWear™ Armband 2. Parents rated their child's internalizing and externalizing problems on the Child Behaviour Checklist. Behaviour scores were dichotomized at the 90th percentile based on sex- and country-specific z-scores. Logistic regression models were applied to test the associations between sleep duration and behaviour. Data were available for 406 8-year-old children. The average sleep duration was 9.25 h per night (SD: 0.67) with 1464 nights measured in total. The sleep duration recommendation of the American Academy of Sleep Medicine for school-aged children (9-12 h) was met by 66.7% of children. One hour of additional sleep per night significantly reduced the risk of having internalizing problems (adjusted OR = 0.51; 95% CI 0.29-0.91). Children who adhered to the sleep duration recommendation had a lower risk for internalizing problems (adjusted OR = 0.45; 95% CI 0.21-0.99). Sleep duration and externalizing problems showed no significant association. Longer sleep duration was associated with a reduced risk of having internalizing problems but not externalizing problems. Results highlight that it is important to ensure adequate sleep duration throughout primary-school years for the optimal emotional health of children. Trial registration number: NCT00338689. Registered: June 19, 2006.

Zinc and iron adequacy and relative importance of zinc/iron storage and intakes among breastfed infants.

Neonatal nutrient storage and supplies from breast milk contribute to nutrient status and growth of infants during their early life. This study investigated the adequacy of zinc and iron intakes among breastfed infants during the first 4 months and determined the relative importance of zinc/iron storage versus nutrient intakes with infant's biochemical status and growth. A longitudinal study followed lactating women and their breastfed infants from birth to 4 months postpartum. Cord zinc and ferritin concentrations, as indicators of nutrient storages, were determined. Zinc and iron intakes from breast milk were determined by measurement of breast milk volume together with milk zinc and iron concentrations at 2 and 4 months postpartum. Inadequacy of nutrient intakes was determined using average requirement (AR) which were 1.6 and 0.24 mg/day for zinc and iron respectively. Infant's serum zinc and ferritin were determined at 4 months of age. The data were collected from 64 and 56 participants at 2 months and 4 months postpartum. Inadequate zinc intake was found in 14.5 and 40% of infants at 2 and 4 months old, respectively. The prevalence of biochemical zinc and iron deficiency in infants were 76 and 11%, respectively. Iron endowment was significantly associated with serum ferritin at 4 months. The cumulative zinc intake was positively associated with weight gain and weight-for-length Z-score, but not length. This study provides quantitative data on zinc and iron intakes, and demonstrates the relative importance of nutrient storage versus intakes on biochemical status and growth of breastfed infants.