Effect of an exercise intervention or combined exercise and diet intervention on health-related quality of life-physical functioning after kidney transplantation: the Active Care after Transplantation (ACT) multicentre randomised controlled trial.

BACKGROUND: Robust evidence for interventions to improve health-related quality of life (HRQoL) in people who receive a kidney transplant is scarce. We aimed to assess the effects of a lifestyle intervention in this context. METHODS: We conducted a multicentre, open-label, parallel-group, randomised controlled trial among people who have received a kidney transplant. Participants from six hospitals across the Netherlands were randomly assigned 1:1:1 by an independent company into: usual care, exercise, and exercise plus diet. The exercise intervention encompassed two phases, a 3-month supervised exercise programme (twice weekly) followed by 12 months of lifestyle coaching, with 15 months of additional dietary counselling (12 sessions) for the exercise plus diet group. The primary outcome was HRQoL-domain physical functioning, assessed using the 36-item Short Form Survey at 15 months. FINDINGS: From Oct 12, 2010 to Nov 18, 2016, 221 participants who had received a kidney transplant (138 [62%] male and 83 [38%] female, with a mean age of 52·5 [SD 13·5] years, who were a median of 5·5 [IQR 3·6-8·4] months post-transplant) were included and randomly assigned to usual care (n=74), exercise intervention (n=77), and exercise plus diet intervention (n=70). In the intention-to-treat analyses, at 15 months post-baseline, no significant differences in HRQoL-domain physical functioning were found for the exercise group (5·3 arbitrary units, 95% CI -4·2 to 14·9; p=0·27), and the exercise plus diet group (5·9 arbitrary units, -4·1 to 16·0; p=0·25) compared with control. Safety outcomes showed no safety concerns. After 3 months of supervised exercise intervention, HRQoL-domain physical functioning improved in the exercise group (7·3 arbitrary units, 95% CI 1·2 to 13·3; p=0·018) but not in the exercise plus diet group (5·8 arbitrary units, -0·5 to 12·1; p=0·072). INTERPRETATION: A lifestyle intervention is safe and feasible in people who have received kidney transplants, paving the way for lifestyle intervention studies in other multimorbid populations with polypharmacy. However, improving HRQoL for people who have received a kidney transplant is challenging. The lifestyle interventions in the current study did not show significant improvements in HRQoL at the end of the study at the total group level. FUNDING: Dutch Kidney Foundation, Innovation Fund of the Dutch Medical Insurance Companies, and University Medical Center Groningen.

Vitamin C deficiency after kidney transplantation: a cohort and cross-sectional study of the TransplantLines biobank.

PURPOSE: Vitamin C deficiency is associated with excess mortality in kidney transplant recipients (KTR). We aim to evaluate plasma vitamin C status at different post-transplantation moments and assess the main characteristics associated with vitamin C deficiency in KTR. METHODS: Plasma vitamin C was assessed in 598 KTR at 3-, 6-, 12-, 24-, and 60-months post-transplantation, 374 late KTR with a functioning graft ≥ 1 year, and 395 potential donors. Vitamin C deficiency was defined as plasma vitamin C ≤ 28 µmol/L. Diet was assessed by a 177-item food frequency questionnaire. Data on vitamin C-containing supplements use were extracted from patient records and verified with the patients. RESULTS: Vitamin C deficiency ranged from 46% (6-months post-transplantation) to 30% (≥ 1 year post-transplantation). At all time points, KTR had lower plasma vitamin C than potential donors (30-41 µmol/L vs 58 µmol/L). In cross-sectional analyses of the 953 KTR at their first visit ≥ 12 months after transplantation (55 ± 14 years, 62% male, eGFR 55 ± 19 mL/min/1.73 m2), the characteristics with the strongest association with vitamin C deficiency were diabetes and smoking (OR 2.67 [95% CI 1.84-3.87] and OR 1.84 [95% CI 1.16-2.91], respectively). Dietary vitamin C intake and vitamin C supplementation were associated with lower odds (OR per 100 mg/day 0.38, 95% CI 0.24-0.61 and OR 0.21, 95% CI 0.09-0.44, respectively). CONCLUSION: Vitamin C deficiency is frequent among KTR regardless of the time after transplantation, especially among those with diabetes and active smokers. The prevalence of vitamin C deficiency was lower among KTR with higher vitamin C intake, both dietary and supplemented. Further research is warranted to assess whether correcting this modifiable risk factor could improve survival in KTR.

A prospective analysis of physical activity and mental health in children: the GECKO Drenthe cohort.

BACKGROUND: Mental health problems in young people have become a global health burden. The positive effects of physical activity on mental health in adults are well known but still not clear in children. The aim of this study was to investigate to what extent physical activity in early childhood would affect mental health in middle childhood. METHODS: From the Dutch GECKO Drenthe birth cohort, 850 children (51.5% boys) were enrolled in this analysis. Physical activity and sedentary time were measured at age 5-6 using ActiGraph GT3X. Mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ) at age 5-6 and age 10-11. Multiple linear regression models were used to estimate the associations between physical activity, sedentary time and SDQ subscales, stratified by gender, adjusting for age, BMI, maternal education level, family size, accelerometer wear time and season, and additionally adjusting for SDQ scores at age 5-6 to take tracking of mental health over time into account. RESULTS: Greater physical activity volume at age 5-6 was associated with lower peer problems scores at age 10-11 in boys and girls. An increase in MVPA was associated with lower peer problems scores in boys (b = -0.445, -0.713 to -0.176) and girls (b = -0.354, -0.601 to -0.107), however, increased sedentary time was linked to higher peer problems scores in boys (b = 1.18, 0.455 to 1.906) and girls (b = 0.870, 0.191 to 1.550). For hyperactivity, higher levels of physical activity volume and MVPA were associated with higher hyperactivity scores in boys. Increased sedentary time was related to lower hyperactivity scores in boys. Further adjustment for SDQ scores at age 5-6 attenuated associations between physical activity and hyperactivity in boys but hardly changed the relationships with peer problems. No significant associations between physical activity and other SDQ subscales or total difficulties scores were observed, neither in boys nor in girls. CONCLUSIONS: Children who are more physically active at age 5-6 have fewer peer problems at age 10-11, and for boys, greater activity levels at age 5-6 could be an indicator of hyperactivity at age 10-11.

Lifestyle factors related to prevalent chronic disease multimorbidity: A population-based cross-sectional study.

BACKGROUND: Multimorbidity is associated with poor quality of life, polypharmacy, health care costs and mortality, with those affected potentially benefitting from a healthy lifestyle. We assessed a comprehensive set of lifestyle factors in relation to multimorbidity with major chronic diseases. METHODS: This cross-sectional study utilised baseline data for adults from the prospective Lifelines Cohort in the north of the Netherlands (N = 79,345). We defined multimorbidity as the co-existence of two or more chronic diseases (i.e. cardiovascular disease, cancer, respiratory disease, type 2 diabetes) and evaluated factors in six lifestyle domains (nutrition, physical (in)activity, substance abuse, sleep, stress, relationships) among groups by the number of chronic diseases (≥2, 1, 0). Multinomial logistic regression models were created, adjusted for appropriate confounders, and odds ratios (OR) with 95% confidence intervals (95%CI) were reported. RESULTS: 3,712 participants had multimorbidity (4.7%, age 53.5 ± 12.5 years), and this group tended to have less healthy lifestyles. Compared to those without chronic diseases, those with multimorbidity reported physical inactivity more often (OR, 1.15; 95%CI, 1.06-1.25; not significant for one condition), chronic stress (OR, 2.14; 95%CI, 1.92-2.38) and inadequate sleep (OR, 1.70; 95%CI, 1.41-2.06); as expected, they more often watched television (OR, 1.70; 95%CI, 1.42-2.04) and currently smoked (OR, 1.91; 95%CI, 1.73-2.11), but they also had lower alcohol intakes (OR, 0.66; 95%CI, 0.59-0.74). CONCLUSIONS: Chronic stress and poor sleep, in addition to physical inactivity and smoking, are lifestyle factors of great concern in patients with multimorbidity.

Differences in birth weight between immigrants' and natives' children in Europe and Australia: a LifeCycle comparative observational cohort study.

OBJECTIVE: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives? SETTING: Western Europe and Australia. PARTICIPANTS: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance-France (N=12 494), the Raine Study-Australia (N=2283), Born in Bradford-UK (N=4132), Amsterdam Born Children and their Development study-Netherlands (N=4030) and the Generation R study-Netherlands (N=4877). We include male and female babies born to immigrant and native parents. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad. RESULTS: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p<0.10) and Australia (+40 g, p<0.10) and lower birth weight among children of immigrants in the UK (-82 g, p<0.05) and the Netherlands (-80 g and -73 g, p<0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives. CONCLUSION: The immigrant health advantage is not universally transferred to children in the form of higher birth weight in all host countries. Further research should investigate whether this cross-national variation is due to differences in immigrant communities, social and healthcare contexts across host countries.

Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. METHODS AND FINDINGS: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. CONCLUSIONS: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

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.

Ultra-processed food and incident type 2 diabetes: studying the underlying consumption patterns to unravel the health effects of this heterogeneous food category in the prospective Lifelines cohort.

BACKGROUND: The overall consumption of ultra-processed food (UPF) has previously been associated with type 2 diabetes. However, due to the substantial heterogeneity of this food category, in terms of their nutritional composition and product type, it remains unclear whether previous results apply to all underlying consumption patterns of UPF. METHODS: Of 70,421 participants (35-70 years, 58.6% women) from the Lifelines cohort study, dietary intake was assessed with a food frequency questionnaire. UPF was identified according to the NOVA classification. Principal component analysis (PCA) was performed to derive UPF consumption patterns. The associations of UPF and adherence to UPF consumption patterns with incidence of type 2 diabetes were studied with logistic regression analyses adjusted for age, sex, diet quality, energy intake, alcohol intake, physical activity, TV watching time, smoking status, and educational level. RESULTS: During a median follow-up of 41 months, a 10% increment in UPF consumption was associated with a 25% higher risk of developing type 2 diabetes (1128 cases; OR 1.25 [95% CI 1.16, 1.34]). PCA revealed four habitual UPF consumption patterns. A pattern high in cold savory snacks (OR 1.16 [95% CI 1.09, 1.22]) and a pattern high in warm savory snacks (OR 1.15 [95% CI 1.08, 1.21]) were associated with an increased risk of incident type 2 diabetes; a pattern high in traditional Dutch cuisine was not associated with type 2 diabetes incidence (OR 1.05 [95% CI 0.97, 1.14]), while a pattern high in sweet snacks and pastries was inversely associated with type 2 diabetes incidence (OR 0.82 [95% CI 0.76, 0.89]). CONCLUSIONS: The heterogeneity of UPF as a general food category is reflected by the discrepancy in associations between four distinct UPF consumption patterns and incident type 2 diabetes. For better public health prevention, research is encouraged to further clarify how different UPF consumption patterns are related to type 2 diabetes.

Diet quality and incident chronic kidney disease in the general population: The Lifelines Cohort Study.

RATIONALE & AIMS: Healthy dietary patterns have been associated with a lower risk of chronic kidney disease (CKD). We aimed to investigate the association of a fully food-based diet quality score assessed by the Lifelines Diet Score (LLDS) with either incident CKD or eGFR decline in the general population. METHODS: For this study, data from a prospective general population-based Lifelines cohort in the Northern Netherlands was used. Diet was assessed with a 110-item food frequency questionnaire at baseline. The LLDS, based on international evidence for diet-disease relations at the food group level, was calculated to assess diet quality. For the analysis, the score was divided into tertiles. Logistic regression was performed to evaluate the association of the LLDS at baseline with either incident CKD (eGFR <60 mL/min/1.73 m2) or a ≥20% eGFR decline at the second study visit, adjusted for relevant confounders. RESULTS: A total of 78 346 participants free of CKD at baseline were included. During a mean (SD) follow-up of 3.6 ± 0.9 years, 2071 (2.6%) participants developed CKD and 7611 (9.7%) had a ≥20% eGFR decline. Participants in the highest tertile of LLDS had a lower risk of incident CKD (fully adjusted OR 0.83, [95% CI: 0.72-0.96]) and ≥20% eGFR decline (fully adjusted OR 0.80, [95% CI: 0.75-0.86]), compared with those in the lowest tertile. Similar dose-response associations were observed in continuous LLDS. CONCLUSIONS: Higher adherence to a high-quality diet was associated with a lower risk of incident CKD or ≥20% eGFR decline in the general population.

Physical activity and 4-year changes in body weight in 52,498 non-obese people: the Lifelines cohort.

OBJECTIVES: We investigated associations between leisure-time physical activity (LTPA) at different intensities (moderate and vigorous or moderate-to-vigorous) and prospective weight gain in non-obese people. We also examined whether these associations were independent of other lifestyle factors and changes in muscle mass and whether they were age-dependent and changed over a person's life course. METHODS: The data were extracted from the Lifelines cohort study (N = 52,498; 43.5% men) and excluded obese individuals (BMI > 30 kg/m2). We used the validated SQUASH questionnaire to estimate moderate-to-vigorous (MVPA; MET≥4), moderate (MPA; MET between 4 and 6.5) and vigorous PA (VPA; MET≥6.5). Body weight was objectively measured, and changes were standardized to a 4-year period. Separate analyses, adjusted for age, educational level, diet, smoking, alcohol consumption and changes in creatinine excretion (a marker of muscle mass), were performed for men and women. RESULTS: The average weight gain was + 0.45 ± 0.03 kg in women. Relative to each reference groups (No-MVPA, No-MPA and No-VPA), MVPA (Beta (95%CI): - 0.34 kg (- 0.56;-0.13)), MPA (- 0.32 kg (- 0.54;-0.10)) and VPA (- 0.30 kg (- 0.43;-0.18)) were associated with less gain in body weight in women after adjusting for potential confounders, described above. These associations were dose-dependent when physically active individuals were divided in tertiles. Beta-coefficients (95%CI) for the lowest, middle, and highest MVPA tertiles relative to the 'No-MVPA' were, respectively, - 0.24 (- 0.47;-0.02), - 0.31 (- 0.53;-0.08), and - 0.38 (- 0.61;-0.16) kg. The average weight gain in men was + 0.13 ± 0.03 kg, and only VPA, not MPA was associated with less body weight gain. Beta-coefficients (95%CI) for the VPA tertiles relative to the 'No-VPA' group were, respectively, - 0.25 (- 0.42;-0.09), - 0.19 (- 0.38;-0.01) and - 0.20 (- 0.38;-0.02) kg. However, after adjusting for potential confounders, the association was no longer significant in men. The potential benefits of leisure-time PA were age-stratified and mainly observed in younger adults (men < 35 years) or stronger with younger age (women < 55 years). CONCLUSION: Higher leisure-time MVPA, MPA, and VPA were associated with less weight gain in women < 55 years. In younger men (< 35 years), only VPA was associated with less weight gain.

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

The Role of Children's Dietary Pattern and Physical Activity in the Association Between Breastfeeding and BMI at Age 5: The GECKO Drenthe Cohort.

OBJECTIVES: Breastfeeding is protective against childhood obesity, but the role of childhood lifestyle in this association is unclear. We investigated whether physical activity and dietary pattern at age 5 differed between breastfed and non-breastfed children, and how they relate to Body Mass Index (BMI) Z-scores. METHODS: 1477 children of the Dutch GECKO Drenthe birth cohort were included. At one month, children were categorized as breastfed (receiving breast milk exclusively or in combination with formula milk) or non-breastfed (receiving formula milk exclusively). At age 5, height and weight were objectively measured, physical activity was measured by ActiGraph GT3x and dietary patterns were assessed with a parent-reported food pattern questionnaire, assessing the consumption frequency of selected food items at seven occasions over the day. RESULTS: Non-breastfed children had higher BMI Z-scores (0.36 ± 0.90 vs. 0.20 ± 0.80 SD, p = 0.002), more frequently consumed sugar-sweetened beverages (25.0 ± 10.5 vs. 22.5 ± 9.71 times per week, p < 0.001), and consumed relatively less whole-wheat or brown bread (p = 0.007). Differences in sugar-sweetened beverage consumption were most pronounced during main meals. Total fruit consumption, sedentary time and moderate-to-vigorous physical activity levels did not differ between the groups. Multivariable adjusted linear regression analyses showed that the differences in BMI-z score between non-breastfed and breastfed children were not explained by the differences in sugar-sweetened beverages or type of bread consumed. CONCLUSIONS: Infant breastfeeding itself is indicative of healthy dietary behaviors in early life, and is also more likely to be followed by a favorable dietary pattern at toddler age. However, the differences in dietary habits between breastfed and non-breastfed children did not explain the difference in BMI Z-score at the age of 5.

Early Determinants of Childhood Blood Pressure at the Age of 6 Years: The GECKO Drenthe and ABCD Study Birth Cohorts.

Background There is still uncertainty about the nature and relative impact of early determinants on childhood blood pressure. This study explored determinants of blood pressure at the age of 6 years in 2 Dutch birth cohorts. Methods and Results Results of hierarchical multiple linear regression analyses in GECKO (Groningen Expert Center for Kids With Obesity) Drenthe study (n=1613) were replicated in ABCD (Amsterdam Born Children and Their Development) study (n=2052). All analyses were adjusted for child's age, sex, height, and body mass index (BMI), and maternal education and subsequently performed in the combined sample. No associations were found between maternal smoking during pregnancy and childhood blood pressure. In the total sample, maternal prepregnancy BMI was positively associated with systolic blood pressure (SBP) (ß [95% CI], 0.09 [0.02-0.16] mm Hg) and diastolic blood pressure (ß [95% CI], 0.11 [0.04-0.17] mm Hg). Children of women with hypertension had higher SBP (ß [95% CI], 0.98 [0.17-1.79] mm Hg). Birth weight standardized for gestational age was inversely associated with SBP (ß [95% CI], -6.93 [-9.25 to -4.61] mm Hg) and diastolic blood pressure (ß [95% CI], -3.65 [-5.70 to -1.61] mm Hg). Longer gestational age was associated with lower SBP (ß [95% CI] per week, -0.25 [-0.42 to -0.08] mm Hg). Breastfeeding for 1 to 3 months was associated with lower SBP (ß [95% CI], -0.96 [-1.82 to -0.09] mm Hg) compared with no or <1 month of breastfeeding. Early BMI gain from the age of 2 to 6 years was positively associated with SBP (ß [95% CI], 0.41 [0.08-0.74] mm Hg) and diastolic blood pressure (ß [95% CI], 0.37 [0.07-0.66] mm Hg), but no effect modification by birth weight was found. Conclusions Higher maternal prepregnancy BMI, maternal hypertension, a relatively lower birth weight for gestational age, shorter gestational age, limited duration of breastfeeding, and more rapid early BMI gain contribute to higher childhood blood pressure at the age of 6 years.

Young Children's Sugar-Sweetened Beverage Consumption and 5-Year Change in BMI: Lessons Learned from the Timing of Consumption.

Sugar-sweetened beverages (SSBs) are an already known risk factor for weight gain in childhood. To identify windows of opportunity for public health interventions, insight into the consumption behavior of SSBs is needed. We investigated whether total SSB consumption was related to body mass index (BMI) change and overweight and compared whether the timing of consumption over the day differed between low and high consumers. In the Dutch GECKO Drenthe birth cohort, a cohort embedded within the Groningen Expert Center for Kids with Obesity (GECKO), height and weight were measured by trained nurses at age 5/6 years (y) and 10/11 y (N = 1257). BMI was standardized for age and sex (BMI-z). In the food pattern questionnaire completed by parents at age 5/6 y, beverages were assessed for seven time segments (breakfast, morning, lunch at school, lunch at home, afternoon, dinner, and evening). Linear and logistic regression analyses were adjusted for potential confounders (sex, baseline BMI-z, parental BMI, parental education level, maternal age at birth, maternal smoking during pregnancy). The median daily SSB consumption frequency ranged from 1.9 times per day (1.5-2.0, 25th-75th percentile) in the lowest quartile to 4.9 times per day (4.6-5.5) in the highest quartile. In the highest compared to the lowest quartile of SSB consumption frequency, the confounder-adjusted odds ratio for overweight incidence was 3.12 (95% CI, 1.60-6.07). The difference in consumption between quartile 1 and quartile 4 occurred mainly during main meals and in the evening, e.g., at breakfast (31% vs. 98%, p < 0.001), lunch at home (32% vs. 98%, p < 0.001), and dinner (17% vs. 72%, p < 0.001). These drinking occasions characterizing high SSB consumers mostly occurred in the home environment, where parental influence on dietary behaviors is profound. Therefore, these results exposed a window of opportunity, leading to the advice for parents to offer their children sugar-free drinks to quench thirst with main meals.

Socio-economic disparities in the association of diet quality and type 2 diabetes incidence in the Dutch Lifelines cohort.

BACKGROUND: It is unknown whether a socio-economic difference exists in the association of diet quality with type 2 diabetes incidence, nor how diet influences the socioeconomic inequality in diabetes burden. METHODS: In 91,025 participants of the population-based Lifelines Cohort (aged ≥30, no diabetes or cardiovascular diseases at baseline), type 2 diabetes incidence was based on self-report, fasting glucose ≥ 7·0 mmol/l and/or HbA1c ≥ 6·5%. The evidence-based Lifelines Diet Score was calculated with data of a 110-item food frequency questionnaire. Socio-economic status (SES) was defined by educational level. Cox proportional hazards models were adjusted for age, gender, smoking, energy intake, alcohol intake and physical activity. FINDINGS: In 279,796 person-years of follow-up, 1045 diabetes cases were identified. Incidence rate was 5·7, 3·2 and 2·4 cases/1000 person-years in low, middle and high SES, respectively. Diet was associated with greater diabetes risk (HR(95%CI) in Q1 (poor diet quality) vs. Q5 (high diet quality) = 2·11 (1·70-2·62)). SES was a moderator of the association(pINTERACTION = 0·038). HRs for Q1 vs. Q5 were 1·66 (1·22-2·.27) in low, 2·76 (1·86-4·08) in middle and 2·46 (1·53-3·97) in high SES. With population attributable fractions of 14·8%, 40·1% and 37·3%, the expected number of cases/1000 person-years preventable by diet quality improvement was 0·85 in low, 1·28 in middle and 0·90 in high SES. INTERPRETATION: Diet quality improvement can potentially prevent one in three cases of type 2 diabetes, but because of a smaller impact in low SES, it will not narrow the socioeconomic health gap in diabetes burden. FUNDING: None.

Relation Between Leisure Time, Commuting, and Occupational Physical Activity With Blood Pressure in 125 402 Adults: The Lifelines Cohort.

Background Whether all domains of daily-life moderate-to-vigorous physical activity (MVPA) are associated with lower blood pressure (BP) and how this association depends on age and body mass index remains unclear. Methods and Results In the population-based Lifelines cohort (N=125 402), MVPA was assessed by the Short Questionnaire to Assess Health-Enhancing Physical Activity, a validated questionnaire in different domains such as commuting, leisure-time, and occupational PA. BP was assessed using the last 3 of 10 measurements after 10 minutes' rest in the supine position. Hypertension was defined as systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or use of antihypertensives. In regression analysis, higher commuting and leisure-time but not occupational MVPA related to lower BP and lower hypertension risk. Commuting-and-leisure-time MVPA was associated with BP in a dose-dependent manner. ß Coefficients (95% CI) from linear regression analyses were -1.64 (-2.03 to -1.24), -2.29 (-2.68 to -1.90), and finally -2.90 (-3.29 to -2.50) mm Hg systolic BP for the low, middle, and highest tertile of MVPA compared with "No MVPA" as the reference group after adjusting for age, sex, education, smoking and alcohol use. Further adjustment for body mass index attenuated the associations by 30% to 50%, but more MVPA remained significantly associated with lower BP and lower risk of hypertension. This association was age dependent. ß Coefficients (95% CI) for the highest tertiles of commuting-and-leisure-time MVPA were -1.67 (-2.20 to -1.15), -3.39 (-3.94 to -2.82) and -4.64 (-6.15 to -3.14) mm Hg systolic BP in adults <40, 40 to 60, and >60 years, respectively. Conclusions Higher commuting and leisure-time but not occupational MVPA were significantly associated with lower BP and lower hypertension risk at all ages, but these associations were stronger in older adults.

Comparison of health behaviours between cancer survivors and the general population: a cross-sectional analysis of the Lifelines cohort.

PURPOSE: To compare the differences in lifestyle behaviours between cancer survivors (CSs) and cancer-free participants in a large and representative population-based cohort. METHODS: We included 115,257 adults from the Lifelines cohort. Cancer status was self-reported, and health behaviours were measured (e.g. body mass index [BMI]) or assessed by questionnaire (e.g. physical activity, smoking, alcohol consumption, sedentary behaviour and diet). The data were then categorised for logistic regression analysis, stratified and adjusted by sex and age (< 55 vs ≥ 55 years). RESULTS: CSs (5473; 4.7%) were diagnosed 9 ± 8.5 years before data collection, were older (mean age 55.4 vs 44.4 years) and more often female (66.6% vs 33.4%) than the cancer-free participants. They were also more likely to be physically active and to have a better diet, and also less likely to be alcohol drinkers; but, were more likely to have a higher BMI, be former smokers and to be sedentary. After adjustment for sex and age, however, BMI was more likely to be normal, physical activity was more likely to be higher and smoking to be prevalent in CSs. Current smoking was also significantly higher among females and those aged < 55 years who were CSs than for those with no history of cancer. CONCLUSIONS: In this population-based cohort, CSs have health behaviour comparable to those without a cancer diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Smoking cessation strategies should target all CSs, but efforts could yield greatest benefit if they target females and those younger than 55 years.

Development of the food-based Lifelines Diet Score (LLDS) and its application in 129,369 Lifelines participants.

BACKGROUND/OBJECTIVES: Many diet quality scores exist, but fully food-based scores based on contemporary evidence are scarce. Our aim was to develop a food-based diet score based on international literature and examine its discriminative capacity and socio-demographic determinants. SUBJECTS/METHODS: Between 2006 and 2013, dietary intake of 129,369 participants of the Lifelines Cohort (42% male, 45 ± 13 years (range 18-93)) was assessed with a 110-item food frequency questionnaire. Based on the 2015 Dutch Dietary Guidelines and underlying literature, nine food groups with positive (vegetables, fruit, whole grain products, legumes&nuts, fish, oils&soft margarines, unsweetened dairy, coffee and tea) and three food groups with negative health effects (red&processed meat, butter&hard margarines and sugar-sweetened beverages) were identified. Per food group, the intake in grams per 1000 kcal was categorized into quintiles, awarded 0 to 4 points (negative groups scored inversely) and summed. Food groups with neutral, unknown or inconclusive evidence are described but not included. RESULTS: The Lifelines Diet Score (LLDS) discriminated well between high and low consumers of included food groups. This is illustrated by e.g. a 2-fold higher vegetable intake in the highest, compared to the lowest LLDS quintile. Differences were 5.5-fold for fruit, 3.5-fold for fish, 3-fold for dairy and 8-fold for sugar-sweetened beverages. The LLDS was higher in females and positively associated with age and educational level. CONCLUSIONS: The LLDS is based on the latest international evidence for diet-disease relations at the food group level and has high capacity to discriminate people with widely different intakes. Together with the population-based quintile approach, this makes the LLDS a flexible, widely applicable tool for diet quality assessment.

Dietary patterns and physical activity in the metabolically (un)healthy obese: the Dutch Lifelines cohort study.

BACKGROUND: Diversity in the reported prevalence of metabolically healthy obesity (MHO), suggests that modifiable factors may be at play. We evaluated differences in dietary patterns and physical activity between MHO and metabolically unhealthy obesity (MUO). METHODS: Cross-sectional data of 9270 obese individuals (30-69 years) of the Lifelines Cohort Study was used. MHO was defined as obesity and no metabolic syndrome risk factors and no cardiovascular disease history. MUO was defined as obesity and ≥2 metabolic syndrome risk factors. Sex-specific associations of dietary patterns (identified by principal component analysis) and physical activity with MHO were assessed by multivariable logistic regression (reference group: MUO). Analyses were adjusted for multiple covariates. RESULTS: Among 3442 men and 5828 women, 10.2% and 24.4% had MHO and 56.9% and 35.3% MUO, respectively. We generated four obesity-specific dietary patterns. Two were related to MHO, and in women only. In the highest quartile (Q) of 'bread, potatoes and sweet snacks' pattern, odds ratio (OR) (95% CI) for MHO was 0.52 (0.39-0.70). For the healthier pattern 'fruit, vegetables and fish', an OR of 1.36 (1.09-1.71) in Q3 and 1.55 (1.21-1.97) in Q4 was found for MHO. For physical activity, there was a positive association between moderate physical activity and vigorous physical activity in the highest tertile and MHO in women and men, respectively (OR 1.19 (1.01-1.41) and OR 2.02 (1.50-2.71)). CONCLUSION: The healthier diet -characterized by 'fruit, vegetables and fish'- and moderate physical activity in women, and vigorous physical activity in men may be related to MHO. The (refined) carbohydrate-rich 'bread, potatoes and sweet snacks' dietary pattern was found to counteract MHO in women.

Maternal alcohol consumption and offspring DNA methylation: findings from six general population-based birth cohorts.

AIM: Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero. MATERIALS & METHODS: We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium. RESULTS: We found no strong evidence of association at either individual CpGs or across larger regions of the genome. CONCLUSION: Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association.