Substitution of pure fruit juice for fruit and sugar-sweetened beverages and cardiometabolic risk in European Prospective Investigation into Cancer and Nutrition (EPIC)-NL: a prospective cohort study.

OBJECTIVE: Dietary guidelines on pure fruit juice differ between countries regarding the question whether pure fruit juice (without added sugars) is an acceptable substitute for fruit or should be avoided because of its comparable sugar content with that of sugar-sweetened beverages (SSB). We modelled whether substituting pure fruit juice for fruit or SSB was associated with cardiometabolic risk. DESIGN: Prospective cohort study. SETTING: Based on a validated FFQ at baseline, we calculated the relative contribution of pure fruit juice to total consumption of fruit and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{fruit}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$) and to total consumption of SSB and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{SSBs}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$). In multivariate analyses (Cox regression), we assessed associations with incidence of type 2 diabetes, CVD, CHD and stroke after an average follow-up of 14·6 years. PARTICIPANTS: About 35 000 participants from the EPIC-NL study, aged 20-70 years at enrolment. RESULTS: Substitution of pure fruit juice for SSB was associated with lower risk of all endpoints. For type 2 diabetes and CHD, for example, drinking 75-100 % (as compared with 0-<25 %) of total SSB + pure fruit juice as pure fruit juice showed hazard ratio (95 % CI) of 0·74 (95 % CI 0·64, 0·85) and 0·85 (95 % CI 0·76, 0·96), respectively. Substitution of pure fruit juice for fruit was not associated with the risk of type 2 diabetes, CVD, CHD and stroke. CONCLUSIONS: Substituting pure fruit juice for SSB was associated with lower cardiometabolic risk, whereas substituting pure fruit juice for fruit was not associated with cardiometabolic risk.

Air pollution and IgE sensitization in 4 European birth cohorts-the MeDALL project.

BACKGROUND: Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. OBJECTIVE: Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years. METHODS: A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 µm, less than 10 µm, and between 2.5 and 10 µm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021). RESULTS: Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-µg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-µg/m3 increase in exposure). CONCLUSION: Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.

Early childhood infections and body mass index in adolescence.

BACKGROUND: The incidence of childhood overweight and obesity is rising. It is hypothesized that infections in early childhood are associated with being overweight. This study investigated the association between the number of symptomatic infections or antibiotic prescriptions in the first 3 years of life and body mass index (BMI) in adolescence. SUBJECTS: The current study is part of the Prevention and Incidence of Asthma and Mite Allergy population-based birth cohort study. Weight and height were measured by trained research staff at ages 12 and 16 years. The 3015 active participants at age 18 years were asked for informed consent for general practitioner (GP) data collection and 1519 gave written informed consent. Studied exposures include (1) GP-diagnosed infections, (2) antibiotic prescriptions, and (3) parent-reported infections in the first 3 years of life. Generalized estimating equation analysis was used to determine the association between each of these exposures and BMI z-score. RESULTS: Exposure data and BMI measurement in adolescence were available for 622 participants. The frequencies of GP-diagnosed infections and antibiotic prescriptions were not associated with BMI z-score in adolescence with estimates being 0.14 (95% CI -0.09-0.37) and 0.10 (95% CI -0.14-0.34) for the highest exposure categories, respectively. Having ≥6 parent-reported infections up to age 3 years was associated with a 0.23 (95% CI 0.01-0.44) higher BMI z-score compared to <2 parent-reported infections. CONCLUSIONS: For all infectious disease measures an increase in BMI z-score for the highest childhood exposure to infectious disease was observed, although only statistically significant for parent-reported infections. These results do not show an evident link with infection severity, but suggest a possible cumulative effect of repeated symptomatic infections on overweight development.

Mental Well-being and General Health in Adolescents with Asthma: The Prevention and Incidence of Asthma and Mite Allergy Birth Cohort Study.

OBJECTIVES: To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma. STUDY DESIGN: Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental well-being and perceived general health using generalized estimating equations. RESULTS: At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages. CONCLUSIONS: The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health.

Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis.

PURPOSE: It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. METHODS: We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. RESULTS: A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI - 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. CONCLUSION: In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.

Timing of secondhand smoke, pet, dampness or mould exposure and lung function in adolescence.

BACKGROUND: The relevance of timing of exposure in the associations of secondhand tobacco smoke (SHS), pets, and dampness or mould exposure with lung function is unclear. We investigated the relevance of timing of these exposures for lung function in adolescence. METHODS: We used data from participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort with spirometric measurements at ages 12 and 16 years (n=552). Data on residential exposure to SHS, pets, and dampness or mould were obtained by repeated parental questionnaires. We characterised timing of exposure through longitudinal patterns using latent class growth modelling and assessed associations of these patterns with FEV1 and FVC at ages 12 and 16 and FEV1 and FVC growth between ages 12 and 16 using linear regression models. RESULTS: Childhood SHS exposure was associated with reduced FEV1 growth/year (95% CI) (-0.34% (-0.64% to -0.04%)). Late childhood and early life pet exposure was associated with increased FEV1 growth (0.41% (0.14% to 0.67%)) and reduced FVC growth (-0.28% (-0.53% to -0.03%)), respectively, compared with very low exposure. Early life dampness or mould exposure was associated with reduced lung function growth. All time windows of SHS exposure tended to be associated with lower attained lung function and pet exposure tended to be associated with higher FEV1. CONCLUSION: SHS exposure during childhood could lead to reduced lung function growth and lower attained lung function in adolescence. While pet exposure in late childhood may not adversely affect lung function, early childhood pet exposure may slow down FVC growth in adolescence.

Air pollution and the development of asthma from birth until young adulthood.

BACKGROUND: Air pollution is associated with asthma development in children and adults, but the impact on asthma development during the transition from adolescence to adulthood is unclear. Adult studies lack historical exposures and consequently cannot assess the relevance of exposure during different periods of life. We assessed the relevance of early-life and more recent air pollution exposure for asthma development from birth until early adulthood. METHODS: We used data of 3687 participants of the prospective Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort and linked asthma incidence until age 20 years to estimated concentrations of nitrogen dioxide (NO2), particulate matter with a diameter <2.5 µm (PM2.5), <10 µm (PM10), and 2.5-10 µm, and PM2.5 absorbance ("soot") at the residential address. We assessed overall and age-specific associations with air pollution exposure with discrete time-hazard models, adjusting for potential confounders. RESULTS: Overall, we found higher incidence of asthma until the age of 20 years with higher exposure to all pollutants at the birth address (adjusted odds ratio (95% CI) ranging from 1.09 (1.01-1.18) for PM10 to 1.20 (1.10-1.32) for NO2) per interquartile range increase) that were rather persistent with age. Similar associations were observed with more recent exposure defined as exposure at the current home address. In two-pollutant models with particulate matter, associations with NO2 persisted. CONCLUSIONS: Exposure to air pollution, especially from motorised traffic, early in life may have long-term consequences for asthma development, as it is associated with an increased risk of developing asthma through childhood and adolescence into early adulthood.

House dust endotoxin, asthma and allergic sensitization through childhood into adolescence.

BACKGROUND: House dust endotoxin may have beneficial effects on allergic sensitization and asthma in children. Evidence is scarce for adolescents and most studies so far have been cross-sectional and limited to a single exposure measurement. OBJECTIVE: We assessed associations of house dust endotoxin with asthma and allergic sensitization from birth to age 17 years longitudinally taking into account exposure early in life and at primary school age. METHODS: We used data of 854 participants of the prospective Dutch PIAMA birth cohort study with house dust endotoxin measurements at 3 months and/or 5-6 years and data on asthma and/or allergic sensitization from at least one of 11 follow-ups until age 17. We assessed overall and age-specific associations of the prevalence of asthma and sensitization with mattress and living room floor dust concentrations (per gram of dust) and loads (per m2 of sampling surface). RESULTS: Higher living room floor dust endotoxin concentrations at 3 months were associated with lower odds of asthma until age 4 [odds ratio (95% confidence interval) ranging from 0.70 (0.51-0.97) at age 1 to 0.76 (0.57-1.00) at age 3 per interquartile range increase], but not thereafter in children of allergic mothers. Higher living room floor dust endotoxin at 5-6 years was associated with higher odds of sensitization at 8-16 years [eg odds ratio (95% confidence interval) 1.70 (1.17-2.47) per interquartile range increase in endotoxin load]. CONCLUSIONS AND CLINICAL RELEVANCE: House dust endotoxin may have beneficial effects on asthma in preschool children of allergic mothers, which do not persist into adolescence. Beneficial associations with allergic sensitization could not be confirmed.

Pure Fruit Juice and Fruit Consumption Are Not Associated with Incidence of Type 2 Diabetes after Adjustment for Overall Dietary Quality in the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) Study.

BACKGROUND: Dietary guidelines on pure fruit juice consumption vary from country to country regarding the inclusion of pure fruit juice in the recommendations as an acceptable alternative for fruit. Current epidemiological evidence on the association between pure fruit juice consumption and diabetes risk is scarce. OBJECTIVE: We studied the association of both pure fruit juice and fruit consumption with diabetes risk and investigated the differences between low and high fruit consumers in the association of pure fruit juice consumption with diabetes risk. METHODS: This prospective cohort study included 36,147 participants in the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) Study aged 20-69 y at baseline. Fruit juice and fruit consumption were assessed using a validated food-frequency questionnaire; amounts of consumption were divided into 5 categories and quintiles, respectively. Incident type 2 diabetes cases were mainly self-reported and verified against medical records. Cox regression was used to estimate adjusted HRs and 95% CIs. RESULTS: After an average follow-up of 14.6 y, 1477 verified incident cases of type 2 diabetes were documented. Compared with no consumption, pure fruit juice consumption was not significantly associated with type 2 diabetes, with adjusted HRs ranging from 0.92 (95% CI: 0.79, 1.09) to 1.03 (95% CI: 0.83, 1.26). The associations did not differ between participants with low and high fruit consumption. None of the categories of fruit consumption were associated with type 2 diabetes (lowest quintile as reference). Adjusted HRs ranged between 0.93 (95% CI: 0.78, 1.10) and 1.00 (95% CI: 0.84, 1.19). Adjustment for the Dutch Healthy Diet Index, as an overall measure of dietary quality, strongly attenuated the observed associations of type 2 diabetes with both fruit juice and fruit consumption. CONCLUSIONS: We found no evidence for associations between pure fruit juice and fruit consumption and diabetes risk after adjustment for overall dietary quality for participants in the EPIC-NL study. This trial was registered at https://www.trialregister.nl/trial/6939 as NL6939.

Development of a prediction model to target screening for high blood pressure in children.

Targeted screening for childhood high blood pressure may be more feasible than routine blood pressure measurement in all children to avoid unnecessary harms, overdiagnosis or costs. Targeting maybe based e.g. on being overweight, but information on other predictors may also be useful. Therefore, we aimed to develop a multivariable diagnostic prediction model to select children aged 9-10 years for blood pressure measurement. Data from 5359 children in a population-based prospective cohort study were used. High blood pressure was defined as systolic or diastolic blood pressure ≥ 95th percentile for gender, age, and height. Logistic regression with backward selection was used to identify the strongest predictors related to pregnancy, child, and parent characteristics. Internal validation was performed using bootstrapping. 227 children (4.2%) had high blood pressure. The diagnostic model included maternal hypertensive disease during pregnancy, maternal BMI, maternal educational level, parental hypertension, parental smoking, child birth weight standard deviation score (SDS), child BMI SDS, and child ethnicity. The area under the ROC curve was 0.73, compared to 0.65 when using only child overweight. Using the model and a cut-off of 5% for predicted risk, sensitivity and specificity were 59% and 76%; using child overweight only, sensitivity and specificity were 47% and 84%. In conclusion, our diagnostic prediction model uses easily obtainable information to identify children at increased risk of high blood pressure, offering an opportunity for targeted screening. This model enables to detect a higher proportion of children with high blood pressure than a strategy based on child overweight only.

The joint effect of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants' term birth weight.

BACKGROUND: It is well known that maternal smoking during pregnancy and maternal pre-pregnancy overweight have opposite effects on the infants' birth weight. We report on the association of the combination between both risk factors and the infants' birth weight. METHODS: We studied 3241 infants born at term in the PIAMA birth cohort. Maternal smoking during pregnancy and pre-pregnancy height and weight were self-reported. Multivariable regression analysis was performed to assess the associations between infants of mothers who only smoked during pregnancy, who only had pre-pregnancy overweight and who had both risk factors simultaneously, on term birth weight and the risk of being SGA or LGA. RESULTS: Of 3241 infants, 421 infants (13%) were born to smoking, non-overweight mothers, 514 (15.8%) to non-smoking, overweight mothers, 129 (4%) to smoking and overweight mothers and 2177 (67%) to non-smoking, non-overweight mothers (reference group). Infants of mothers who smoked and also had pre-pregnancy overweight had similar term birth weight (- 26.6 g, 95%CI: - 113.0, 59.8), SGA risk (OR = 1.06, 95%CI: 0.56, 2.04), and LGA risk (OR = 1.09, 95%CI: 0.61, 1.96) as the reference group. CONCLUSIONS: Our findings suggested that the effects of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants' birth weight cancel each other out. Therefore, birth weight may not be a good indicator of an infant's health status in perinatal practice because it may mask potential health risks due to these maternal risk factors when both present together.

Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Role of timing of exposure to pets and dampness or mould on asthma and sensitization in adolescence.

BACKGROUND: Pet and dampness or mould exposure are considered risk factors for asthma and sensitization. It is unclear whether timing of exposure to these factors is differentially associated with asthma risk and sensitization in adolescence. OBJECTIVE: We investigated the role of timing of pet and dampness or mould exposure in asthma and sensitization in adolescence. Understanding this role is essential to build targeted prevention strategies. METHODS: We used data from 1871 participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. Residential exposure to pets, dampness or mould was assessed by repeated parental questionnaires. We used asthma data from the 17-year questionnaire and sensitization data from the 16-year medical examination. We characterized timing using longitudinal exposure patterns from pregnancy till age 17 using longitudinal latent class growth modelling. We used logistic regression models to analyse associations of exposure patterns with asthma at age 17 and sensitization at age 16. RESULTS: For none of the time windows, exposure to pets and dampness or mould was associated with asthma at age 17, but a lower sensitization risk at age 16 was suggested, for example the odds ratio (95% confidence interval) for sensitization was 0.63 (0.35-1.11) and 0.69 (0.44-1.08) for early life and persistently high pet exposure, respectively, compared with very low exposure. An inverse association was also suggested for sensitization and moderate early childhood dampness or mould exposure (0.71 [0.42-1.19]). CONCLUSION AND CLINICAL RELEVANCE: Different timing of pet and dampness or mould exposure was not associated with asthma, but lower risk of sensitization in adolescence was suggested, which could be partly attributable to reversed causation. Current findings are not sufficient to recommend pet avoidance to prevent allergic disease. More prospective studies are needed to obtain insights that can be used in clinical practice.

Pure fruit juice and fruit consumption and the risk of CVD: the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study.

Dietary guidelines for pure fruit juice consumption differ between countries, regarding the question whether pure fruit juice is an acceptable alternative for fruit. Currently, little is known about pure fruit juice consumption and the risk of CVD. In this prospective cohort study, we studied the association of pure fruit juice and fruit consumption with the incidence of fatal and non-fatal CVD, CHD and stroke and investigated the differences in association with pure fruit juice consumption between low and high fruit consumers. A validated FFQ was used to estimate dietary intake of 34 560 participants (26·0 % men and 74·0 % women) aged 20-69 years from the European Prospective Investigation into Cancer and Nutrition-Netherlands study. Adjusted hazard ratios (HR) were estimated using Cox regression after average follow-up of 14·6 years. Compared with no consumption, pure fruit juice consumption up to 7 glasses/week - but not consumption of ≥8 glasses - was significantly associated with reduced risk of CVD and CHD, with HR from 0·83 (95 % CI 0·73, 0·95) to 0·88 (95 % CI 0·80, 0·97). Consumption of 1-4 and 4-8 glasses/week was significantly associated with lower risk of stroke with HR of 0·80 (95 % CI 0·64, 0·99) and 0·76 (95 % CI 0·61, 0·94), respectively. Associations did not differ considerably between low and high fruit consumers. The highest three quintiles of fruit consumption (≥121 g/d) were significantly associated with lower incidence of CVD, with HR of 0·87 (95 % CI 0·78, 0·97) and 0·88 (95 % CI 0·80, 0·98). In conclusion, although we observed favourable associations of moderate pure fruit juice consumption with CVD, for now consumption of whole fruit should be preferred because the evidence of the health benefits of fruit is more conclusive.

Does breast milk adiponectin affect BMI and cardio-metabolic markers in childhood?

Observational studies suggest that breast-feeding is associated with a more favourable BMI and cardio-metabolic markers, but potential underlying mechanisms are unclear. As serum adiponectin has an important function in adults for glucose and lipid metabolism, we assessed 251 participants of the Prevention and Incidence of Asthma and Mite Allergy birth cohort whether breast milk adiponectin is associated with childhood BMI and cardio-metabolic markers. We measured adiponectin levels in breast milk collected around 3 months after birth of the child and subsequently obtained weight and height repeatedly up to the age of 17 years. A medical examination (including blood pressure, glycated Hb and cholesterol) was performed at the age of 8, 12 and 16 years. We used multivariable mixed models to assess the association between breast milk adiponectin and BMI and cardio-metabolic markers at these ages. In models adjusted for exact age of breast milk collection, maternal age, presence of siblings, maternal BMI, pregnancy weight gain and child's birth weight, each unit increase in log breast milk adiponectin (in ng/ml) was associated with a 0·28 lower BMI z score (95 % CI -0·56, 0·00) at 3 months. After the age of 1 year, there was a tendency towards a higher BMI z score with increased breast milk adiponectin at some ages, but this pattern was not consistent throughout childhood. There were no associations between breast milk adiponectin and any of the cardio-metabolic markers in childhood. We conclude that in our study with follow-up until 17 years of age, breast milk adiponectin has no long-term effect on BMI and cardio-metabolic health during childhood.

Residential surrounding green, air pollution, traffic noise and self-perceived general health.

Self-perceived general health (SGH) is one of the most inclusive and widely used measures of health status and a powerful predictor of mortality. However, only a limited number of studies evaluated associations of combined environmental exposures on SGH. Our aim was to evaluate associations of combined residential exposure to surrounding green, air pollution and traffic noise with poor SGH in the Netherlands. We linked data on long-term residential exposure to surrounding green based on the Normalized Difference Vegetation Index (NDVI) and a land-use database (TOP10NL), air pollutant concentrations (including particulate matter (PM10, PM2.5), and nitrogen dioxide (NO2)) and road- and rail-traffic noise with a Dutch national health survey, resulting in a study population of 354,827 adults. We analyzed associations of single and combined exposures with poor SGH. In single-exposure models, NDVI within 300 m was inversely associated with poor SGH [odds ratio (OR) = 0.91, 95% CI: 0.89, 0.94 per IQR increase], while NO2 was positively associated with poor SGH (OR = 1.07, 95% CI: 1.04, 1.11 per IQR increase). In multi-exposure models, associations with surrounding green and air pollution generally remained, but attenuated. Joint odds ratios (JOR) of combined exposure to air pollution, rail-traffic noise and decreased surrounding green were higher than the odds ratios of single-exposure models. Studies including only one of these correlated exposures may overestimate the risk of poor SGH attributed to the studied exposure, while underestimating the risk of combined exposures.

The associations of air pollution, traffic noise and green space with overweight throughout childhood: The PIAMA birth cohort study.

BACKGROUND: Air pollution, traffic noise and absence of green space may contribute to the development of overweight in children. OBJECTIVES: To investigate the combined associations of air pollution, traffic noise and green space with overweight throughout childhood. METHODS: We used data for 3680 participants of the Dutch PIAMA birth cohort. We estimated exposure to air pollution, traffic noise and green space (i.e. the average Normalized Difference Vegetation Index (NDVI) and percentages of green space in circular buffers of 300 m and 3000 m) at the children's home addresses at the time of parental reported weight and height measurements. Associations of these exposures with overweight from age 3 to 17 years were analyzed by generalized linear mixed models, adjusting for potential confounders. Odds ratios (OR's) are presented for an interquartile range increase in exposure. RESULTS: odds of being overweight increased with increasing exposure to NO2 (adjusted OR 1.40 [95% confidence interval (CI) 1.12-1.74] per 8.90 µg/m3) and tended to decrease with increasing exposure to green space in a 3000 m buffer (adjusted OR 0.86 [95% CI 0.71-1.04] per 0.13 increase in the NDVI; adjusted OR 0.86 [95% CI 0.71-1.03] per 29.5% increase in the total percentage of green space). After adjustment for NO2, the associations with green space in a 3000 m buffer weakened. No associations of traffic noise with overweight throughout childhood were found. In children living in an urban area, living further away from a park was associated with a lower odds of being overweight (adjusted OR 0.67 [95% CI 0.52-0.85] per 359.6 m). CONCLUSIONS: Exposure to traffic-related air pollution, but not traffic noise or green space, may contribute to childhood overweight. Future studies examining the associations of green space with childhood overweight should account for air pollution exposure.

Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

BACKGROUND: Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms. OBJECTIVES: We sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts. METHODS: The presence of AD was examined in 2 birth cohort studies including 9894 children from the United Kingdom (ALSPAC) and 3652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity. RESULTS: Six latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the 2 cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male sex. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognized class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified. CONCLUSIONS: Six classes based on temporal trajectories of rash were consistently identified in 2 population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.

Air pollution exposure and lung function until age 16 years: the PIAMA birth cohort study.

Evidence for the effects of air pollution exposure on lung function growth into adolescence is scarce. We investigated associations of air pollution exposure with lung function and lung function growth until age 16.We conducted both longitudinal (n=915) and cross-sectional (n=721) analyses of associations of air pollution exposure with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) growth from ages eight to 16 and FEV1 and FVC at age 16. We estimated residential concentrations of nitrogen dioxide (NO2), "soot" and particulate matter (PMx, where x is the 50% cut-off aerodynamic diameter in µm) with diameters of <2.5 µm (PM2.5), <10 µm (PM10) and 2.5-10 µm (PMcoarse) during the preschool, primary school and secondary school time windows by land use regression models. Associations with (growth in) FEV1 and FVC were analysed by linear (mixed effects) regression.Higher air pollution exposure was associated with reduced FEV1 growth (e.g. adjusted difference -0.26% (95% CI -0.49 to -0.03%) per interquartile range increase in secondary school PM2.5) and lower FEV1 (adjusted difference -2.36% (95% CI -3.76 to -0.94%)), but was not adversely associated with FVC. Associations with FEV1 were stronger in boys than girls and were not modified by asthma status.Higher air pollution exposure may lead to increased airway obstruction, but not reduced lung volume in adolescence.

Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts.

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.