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Background: Quantification of the burden of overweight on the healthcare system is becoming increasingly urgent for health policy, but accurate estimates are hard to obtain., Methods: In order to assess healthcare utilisation and expenditure of overweight and non-overweight children, we linked, on an individual basis, data on body mass index from a birth cohort study with administrative health insurance claims data. In children aged 14-15 years, we compared utilisation and expenditure on general practice care, dental care, hospital/specialist care, prescribed medication, allied healthcare and mental healthcare of overweight children (overweight at age 11 and 14, n=80) and non-overweight children (no overweight at age 11 and 14, n=1253)., Results: For overweight children, mean 1-year healthcare expenditure was €837 per child and for non-overweight children €616. This difference was mainly due to significant differences in utilisation of hospital care (49% vs 37%) and mental healthcare (14% vs 7%) and to a lesser extent to higher expenditure per user., Conclusion: Our results indicate the potential value of linking survey data to claims data in order to obtain insight into the healthcare costs of childhood overweight. Further studies should elucidate whether the observed differences are causally related to overweight., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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 (FEV 1 ) and forced vital capacity (FVC) growth from ages eight to 16 and FEV 1 and FVC at age 16. We estimated residential concentrations of nitrogen dioxide (NO 2 ), "soot" and particulate matter (PM x , where x is the 50% cut-off aerodynamic diameter in µm) with diameters of <2.5 µm (PM 2.5 ), <10 µm (PM 10 ) and 2.5-10 µm (PM coarse ) during the preschool, primary school and secondary school time windows by land use regression models. Associations with (growth in) FEV 1 and FVC were analysed by linear (mixed effects) regression.Higher air pollution exposure was associated with reduced FEV 1 growth ( e.g. adjusted difference -0.26% (95% CI -0.49 to -0.03%) per interquartile range increase in secondary school PM 2.5 ) and lower FEV 1 (adjusted difference -2.36% (95% CI -3.76 to -0.94%)), but was not adversely associated with FVC. Associations with FEV 1 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., Competing Interests: Conflict of interest: G.H. Koppelman reports grants from the Lung Foundation of the Netherlands, during the conduct of the study; grants from the Lung Foundation of the Netherlands, the Ubbo Emmius Foundation, the TETRI Foundation and TEVA Netherlands, outside the submitted work. All funds were paid to G.H. Koppelman's institution., (Copyright ©ERS 2018.)

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., Competing Interests: Conflict of interest: L. Duijts reports grants from European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (the ALPHABET project (number 696295; 2017) and ZonMW The Netherlands (number 529051014; 2017)) and grants from the European Union's Horizon 2020 programme (the LIFECYCLE project, grant agreement number 733206; 2016), during the conduct of the study. Conflict of interest: B. Gerhard reports grants from the EU FP7, during the conduct of the study. Conflict of interest: H. Inskip reports grants (salary) from the UK Medical Research Council, grants from the British Heart Foundation, the UK Food Standards Agency, the British Lung Foundation, Arthritis Research UK, the NIHR Southampton Biomedical Research Centre and the European Union's Seventh Framework Programme (FP7/2007-2013, project EarlyNutrition under grant agreement number 289346), during the conduct of the study; and members of H. Inskip's team have received funding from Nestec, Abbott Nutrition and Danone Nutricia for various projects to which she is linked, but she has received no direct funding herself. Conflict of interest: S. Lau reports grants and personal fees (honoraria) from Symbiopharm and Allergopharma, personal fees (honoraria) and non-financial support (advisory board work) from DBV, personal fees from ALK, and non-financial support (advisory board work) from Boehringer and Merck, outside the submitted work. Conflict of interest: D. Maier reports grants from the European Commission (FP7 MeDALL, 261357), during the conduct of the study., (Copyright ©ERS 2018.)

Purpose: To investigate whether early introduction of complementary foods (CF) is associated with an increased risk of overweight during childhood, and whether this association differs between formula-fed and breastfed infants., Methods: We included 2611 participants that were born at term from a Dutch population-based birth cohort (n = 3963) designed to investigate the development of asthma and allergies. Parents kept records of their infant's age when CF were first introduced. Weight and height were parent reported yearly from age 1 to 8 years, and at ages 11, 14 and 17 years. We used multivariate generalized estimating equations analysis to investigate the association between timing of CF introduction (before 4 months vs at or after 4 months of age) and overweight at ages 1-17 years., Results: Children with CF introduction before 4 months had higher odds of being overweight during childhood than children with CF introduction at or after 4 months (OR 1.32, 95% CI 1.19, 1.47). This association was observed in formula-fed infants (OR 1.51, 95% CI 1.17, 1.94) and breastfed infants (OR 1.32, 95% CI 1.19, 1.47). The duration of breastfeeding modified the association between CF introduction and overweight: children breastfed for shorter than 4 months, but not children breastfed for 4 months or longer with CF introduction before 4 months had higher odds of being overweight (OR 1.37, 95% CI 1.19, 1.57 and 1.07, 95% CI 0.87, 1.32, respectively), compared to those with CF introduction at or after 4 months., Conclusions: In children born at term, formula-fed infants and infants who were breastfed for shorter than 4 months, but not infants who were breastfed for 4 months or longer, had a higher risk of being overweight during childhood when being introduced to CF before 4 months of age.

Background: Air pollution has been found to adversely affect children's lung function. Forced expiratory volume in 1 s and forced vital capacity from spirometry have been studied most frequently, but measurements of airway resistance may provide additional information. We assessed associations of long-term air pollution exposure with airway resistance., Methods: We measured airway resistance at age 8 with the interrupter resistance technique (R int ) in participants of the Dutch PIAMA birth cohort study. We linked R int with estimated annual average air pollution concentrations [nitrogen oxides (NO 2 , NO x ), PM 2.5 absorbance ("soot"), and particulate matter < 2.5 μm (PM 2.5 ), < 10 μm (PM 10 ) and 2.5-10 μm (PM coarse )] at the birth address and current home address (n = 983). Associations between air pollution exposure and interrupter resistance (R int ) were assessed using multiple linear regression adjusting for potential confounders., Results: We found that higher levels of NO 2 at the current address were associated with higher R int [adj. mean difference (95% confidence interval) per interquartile range increase in NO 2 : 0.018 (0.001, 0.035) kPa·s·L - 1 ]. Similar trends were observed for the other pollutants, except, PM 10 . No association was found between R int and exposure at the birth address., Conclusions: Our results support the hypothesis that air pollution exposure is associated with a lower lung function in schoolchildren.

Background: Green space may influence health through several pathways, for example, increased physical activity, enhanced social cohesion, reduced stress, and improved air quality. For green space to increase physical activity and social cohesion, spending time in green spaces is likely to be important., Objectives: We examined whether adolescents visit green spaces and for what purposes. Furthermore, we assessed the predictors of green space visits., Methods: In this cross-sectional study, data for 1911 participants of the Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort were analyzed. At age 17, adolescents reported how often they visited green spaces for physical activities, social activities, relaxation, and to experience nature and quietness. We assessed the predictors of green space visits altogether and for different purposes by log-binomial regression., Results: Fifty-three percent of the adolescents visited green spaces at least once a week in summer, mostly for physical and social activities. Adolescents reporting that a green environment was (very) important to them visited green spaces most frequently {adjusted prevalence ratio (PR) [95% confidence interval (CI)] very vs. not important: 6.84 (5.10, 9.17) for physical activities and 4.76 (3.72, 6.09) for social activities}. Boys and adolescents with highly educated fathers visited green spaces more often for physical and social activities. Adolescents who own a dog visited green spaces more often to experience nature and quietness. Green space visits were not associated with the objectively measured quantity of residential green space, i.e., the average normalized difference vegetation index (NDVI) and percentages of urban, agricultural, and natural green space in circular buffers around the adolescents' homes., Conclusions: Subjective variables are stronger predictors of green space visits in adolescents than the objectively measured quantity of residential green space. https://doi.org/10.1289/EHP2429.

Background: The role of tobacco smoke exposure in the development and persistence of asthma and rhinoconjunctivitis through childhood into adolescence is unclear., Objectives: We assessed the associations of parental smoking from fetal life through adolescence with asthma and rhinoconjunctivitis during childhood and adolescence., Methods: We analyzed data for 10,860 participants of five European birth cohort studies from the Mechanisms of the Development of Allergy (MeDALL) consortium. Parental smoking habits and health outcomes (early transient, persistent, and adolescent-onset asthma and rhinoconjunctivitis) were based on questionnaires covering the period from pregnancy to 14-16 y of age. Data were combined and analyzed using a one-stage and two-stage individual participant data meta-analysis., Results: Overall, any maternal smoking during pregnancy tended to be associated with an increased odds of prevalent asthma [adjusted odds ratio (aOR)=1.19 (95% CI: 0.98, 1.43)], but not prevalent rhinoconjunctivitis [aOR=1.05 (95% CI: 0.90, 1.22)], during childhood and adolescence. In analyses with phenotypes related to age of onset and persistence of disease, any maternal smoking during pregnancy was associated with early transient asthma [aOR=1.79 (95% CI: 1.14, 2.83)]. Maternal smoking of ≥10 cigarettes/day during pregnancy was associated with persistent asthma [aOR=1.66 (95% CI: 1.29, 2.15)] and persistent rhinoconjunctivitis [aOR=1.55 (95% CI, 1.09, 2.20)]. Tobacco smoke exposure during fetal life, infancy, childhood, and adolescence was not associated with adolescent-onset asthma or rhinoconjunctivitis., Conclusions: Findings from this combined analysis of five European birth cohorts strengthen evidence linking early exposure to tobacco smoke with asthma during childhood and adolescence. Children with high early-life exposure were more likely than unexposed children to have early transient and persistent asthma and persistent rhinoconjunctivitis. https://doi.org/10.1289/EHP2738.

Background: Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data., Methods: In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis., Findings: We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001., Interpretation: The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently., (© 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.)

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In epidemiological studies, exposure to green space is inconsistently associated with being overweight and physical activity, possibly because studies differ widely in their definition of green space exposure, inclusion of important confounders, study population and data analysis., Objectives: We evaluated whether the association of green space with being overweight and physical activity depended upon definition of greenspace., Methods: We conducted a cross-sectional study using data from a Dutch national health survey of 387,195 adults. Distance to the nearest park entrance and surrounding green space, based on the Normalized Difference Vegetation Index (NDVI) or a detailed Dutch land-use database (TOP10NL), was calculated for each residential address. We used logistic regression analyses to study the association of green space exposure with being overweight and being moderately or vigorously physically active outdoors at least 150min/week (self-reported). To study the shape of the association, we specified natural splines and quintiles., Results: The distance to the nearest park entrance was not associated with being overweight or outdoor physical activity. Associations of surrounding green space with being overweight or outdoor physical activity were highly non-linear. For NDVI surrounding greenness, we observed significantly decreased odds of being overweight [300m buffer, odds ratio (OR) = 0.88; 95% CI: 0.86, 0.91] and increased odds for outdoor physical activity [300m buffer, OR = 1.14; 95% CI: 1.10, 1.17] in the highest quintile compared to the lowest quintile. For TOP10NL surrounding green space, associations were mostly non-significant. Associations were generally stronger for subjects living in less urban areas and for the smaller buffers., Conclusion: Associations of green space with being overweight and outdoor physical activity differed considerably between different green space definitions. Associations were strongest for NDVI surrounding greenness., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis., Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses., Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses., Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Second hand smoke (SHS) exposure is associated with increased incidence and severity of childhood asthma. We investigated whether, in turn, asthma diagnosis in a child is associated with cessation of smoking exposure in the child's home. In the PIAMA birth cohort (n=3963), parents reported on smoking in their home and on asthma diagnosis in their child, annually from birth to 8 years. We used generalized estimating equations to assess the association between asthma diagnosis in a child and cessation of smoking in the child's home. Among children with residential SHS exposure, smoking stopped in 23.7% of the homes of children with newly diagnosed asthma as compared with 16.2% of the homes of children without asthma diagnosis (P=0.014). For children with an asthma diagnosis, the relative risk of smoking cessation in their home was 1.36 (one-sided 95% confidence interval: 1.09, inf.) and changed little after adjustment for maternal education, parental allergy and child's age. In most smokers' households (76.3%), smoking continued when the child got an asthma diagnosis. Nevertheless, an asthma diagnosis in the child increased the probability of a smoke-free home for the child and its parents and siblings. Cross-sectional associations between SHS exposure and asthma may underestimate true associations, because exposure may have been reduced following diagnosis of the disease.

Background: Being born large for gestational age (LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children., Objective: We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association., Methods: Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma., Results: Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non-LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24)., Conclusions: We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma., (© 2017 John Wiley & Sons Ltd.)

Objective: To examine the association between pubertal timing and cardiometabolic markers among adolescents., Study Design: We used data from Dutch adolescents participating in a birth cohort study. The study population for the current study consisted of 799 adolescents of whom data were available for at least 1 of the exposure variables (pubertal timing and/or age at menarche) and any of the cardiometabolic markers (waist circumference, cholesterol, blood pressure [BP], glycated hemoglobin) measured at age 16 years. Adolescents self-reported pubertal development at ages 11, 14, and 16 years. We categorized participants with early (84 girls, 88 boys), intermediate (240 girls, 211 boys), or late pubertal timing (89 girls, 85 boys). We estimated differences in cardiometabolic markers using linear regression analysis., Results: Girls with early pubertal timing had 1.54 cm larger waist circumference (95% CI .05; 3.03) and 3.98 mm Hg higher systolic BP (95% CI 1.69; 6.27) at age 16 years than girls with intermediate pubertal timing. The association with systolic BP remained after adjusting for childhood body mass index (BMI) (age 8 years) but attenuated after adjusting for BMI in adolescence (age 16 years). Boys with early pubertal timing had 0.79 mmol/mol lower glycated hemoglobin (95%CI -1.38; -0.20) than boys with intermediate pubertal timing., Conclusions: Girls with early pubertal timing had unfavorable BP levels at age 16 years, independent of BMI in childhood. Girls and boys with late pubertal timing had a tendency for lower waist circumference, but no differences in other cardiometabolic markers. Late pubertal timing does not appear to be a risk factor for unfavorable cardiometabolic markers in adolescence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Secondhand smoke (SHS) exposure is a modifiable risk factor associated with childhood asthma. Associations with adolescent asthma and the relevance of the timing and patterns of exposure are unclear. Knowledge of critical windows of exposure is important for targeted interventions., Methods: We used data until age 17 from 1454 children of the Dutch population-based PIAMA birth cohort. Residential SHS exposure was assessed through parental questionnaires completed at ages 3 months, 1-8 (yearly), 11, 14, and 17 years. Lifetime exposure was determined as; a) time window-specific exposure (prenatal, infancy, preschool, primary school, and secondary school); b) lifetime cumulative exposure; c) longitudinal exposure patterns using latent class growth modeling (LCGM). Generalized estimation equations and logistic regression were used to analyze associations between exposure and asthma at ages 4 to 17 years, adjusting for potential confounders., Results: With all three methods, we consistently found no association between SHS exposure and asthma at ages 4 to 17 years e.g. adjusted overall odds ratio (95% confidence interval) 0.67 (0.41-1.12), 1.00 (0.66-1.51) and 0.67 (0.41-1.11) for prenatal maternal active smoking, infancy, and preschool school time window exposures, respectively., Conclusion: We assessed lifetime SHS exposure using different methods. Different timing and patterns of SHS exposure were not associated with an increased risk of asthma in childhood and adolescence in our study. More longitudinal studies could investigate effects of lifetime SHS exposure on asthma in adolescence and later life.

Objectives: This longitudinal study examines children's health-related characteristics in relation to discrepancies between their educational potential assessed by a cognitive test in primary school at age 11 and their attained secondary school level at age 14., Methods: Data were used from 1510 participants of the Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort. Multiple multinomial logistic regression analyses were used to estimate the associations between indicators of physical health, psychosocial health, lifestyle, sleeping patterns and stressful life events and attending a higher or lower level of secondary education than indicated by the cognitive test., Results: We found no evidence that physical health contributes to discrepancies between the potential and attained level of secondary education, but attention disorders and stressful life events (nasty experiences and parents' divorce) were associated with educational attainment below children's potential level. Furthermore, substance use (alcohol, drugs and smoking) were strongly associated with attending a lower level of secondary education than expected (odds ratios from 2.2 (CI: 1.5-3.3) to 5.0 (CI: 2.8-8.7))., Conclusion: In this general population study, attention disorders, stressful life events and especially substance use seemed to be more important than physical health for the discrepancy between expected and attained level of secondary education. The longitudinal design of the present study and the broad range of health-related factors that were studied, adds insights to the process of health-selection., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To investigate whether children delivered by cesarean had a higher risk of being overweight from early until late childhood and whether they had a higher blood pressure in adolescence compared with children delivered vaginally., Study Design: We used data from a Dutch birth cohort study with prenatal inclusion in 1996 and 1997. Mode of delivery (cesarean or vaginal delivery) was ascertained at 3 months after birth by questionnaire. During clinical examinations, height and weight (at age 4, 8, 12, and 16 years) and blood pressure (at age 12 and 16 years) were measured. We used mixed model analysis to estimate associations of cesarean delivery with overweight and blood pressure z scores in 2641 children who participated in at least 1 of the 4 examinations., Results: Children born by cesarean delivery (n = 236, 8.9%) had a 1.52 (95% CI 1.18, 1.96) higher odds of being overweight throughout childhood than children delivered vaginally. Children born by cesarean delivery had no higher systolic blood pressure z-score (0.11 SD, 95% CI -0.04, 0.26), nor a different diastolic blood pressure z-score (-0.00 SD, 95% CI -0.10, 0.09) in adolescence than children delivered vaginally., Conclusions: Compared with children delivered vaginally, children delivered by cesarean had a 52% higher risk of being overweight throughout childhood, but this was not accompanied by a higher blood pressure in adolescence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Breastfeeding has been associated with improved cognition. It remains unclear whether long-chain polyunsaturated fatty acids (LC-PUFAs) play a role in this association. We assessed the association between LC-PUFA concentrations in infant feeding and school performance at age 12., Methods: Within a population-based birth cohort, we compared school performance of 277 non-breastfed children and 157 children who had fatty acid composition of their mothers' breast milk measured. Two indicators of school performance were: (1) the score on a standardized achievement test and (2) the teacher's advice regarding a child's potential performance level in secondary education. Linear regression and multinomial logistic regression analyses were performed to assess the independent association between LC-PUFA content of breast milk and school performance., Results: Girls, who received breast milk with a relative high content (above the median) of docosahexaenoic acid (DHA), had a higher Cito-test score (β = 2.96 points, 95 % CI 0.24; 5.69) than non-breastfed girls. Among the breastfed girls, each percentage point of higher content of total n-3 LC-PUFA (β = 4.55, 95 % CI 0.43; 8.66) and DHA (β = 7.09, 95 % CI 0.9; 13.3) was associated with a higher Cito-test score. The association between LC-PUFA content and teacher school advice showed a similar pattern. There was no association between LC-PUFA content and school performance in boys., Conclusion: Although a large part of the association between infant milk feeding and cognition seems to be explained by sociodemographic and lifestyle-related factors, a relative high content of n-3 PUFAs, especially DHA, in breast milk is associated with better school performance in 12-year-old girls but not in boys., Competing Interests: The authors declare that they have no conflict of interest. Ethics statement The study protocol was approved by the medical ethics committees of the participating institutes and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All parents gave written informed consent.

Aims/hypothesis: Despite the overlap in occurrence of cardiovascular disease (CVD) and type 2 diabetes and their risk factors, family history of these diseases has not yet been investigated simultaneously in relation to cardiometabolic markers in offspring. We examined how a family history of CVD and/or diabetes relates to cardiometabolic markers in offspring, and to what extent these diseases independently contribute to cardiometabolic markers., Methods: We used data from 1,374 12-year-old children and their parents participating in a birth cohort study in the Netherlands. Family history of CVD (myocardial infarction [MI] and stroke) and diabetes were reported by the parents. Children were classified as 'no', 'moderate' or 'strong' family history, based on early/late onset of disease in parents and grandparents. Cardiometabolic markers were measured at 12 years of age: waist circumference, cholesterol, blood pressure and HbA1c., Results: Compared with those with no family history, children with a strong family history of MI and/or stroke and/or diabetes (29% of the study population) had 0.13 mmol/l higher total cholesterol (TC) (95% CI 0.03, 0.23) and 0.18 higher TC/HDL-cholesterol (HDLC) ratio (95% CI 0.04, 0.32). A strong family history of MI or diabetes was independently associated with unfavourable cardiometabolic markers specific to those diseases. These associations remained after adjusting for BMI. Children with a moderate family history had no unfavourable cardiometabolic markers., Conclusions/interpretation: One-third of the children had a strong family history of CVD and/or diabetes. These children had higher TC levels and TC/HDLC ratios than children with no family history. A strong family history of MI or diabetes was independently associated with unfavourable cardiometabolic markers specific to those diseases.

Background: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma., Objective: We sought to assess the hypothesis that these associations are explained by reduced airway patency., Methods: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma., Results: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma., Conclusions: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear., Objective: To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity., Design, Setting, and Participants: Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26,184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years., Exposures: Consumption of fish during pregnancy., Main Outcomes and Measures: We estimated offspring body mass index percentile trajectories from 3 months after birth to 6 years of age. We defined rapid infant growth as a weight gain z score greater than 0.67 from birth to 2 years and childhood overweight/obesity at 4 and 6 years as body mass index in the 85th percentile or higher for age and sex. We calculated cohort-specific effect estimates and combined them by random-effects meta-analysis., Results: This multicenter, population-based birth cohort study included the 26,184 pregnant women and their children. The median fish intake during pregnancy ranged from 0.5 times/week in Belgium to 4.45 times/week in Spain. Women who ate fish more than 3 times/week during pregnancy gave birth to offspring with higher body mass index values from infancy through middle childhood compared with women with lower fish intake (3 times/week or less). High fish intake during pregnancy (>3 times/week) was associated with increased risk of rapid infant growth, with an adjusted odds ratio (aOR) of 1.22 (95% CI, 1.05-1.42) and increased risk of offspring overweight/obesity at 4 years (aOR, 1.14 [95% CI, 0.99-1.32]) and 6 years (aOR, 1.22 [95% CI, 1.01-1.47]) compared with an intake of once per week or less. Interaction analysis showed that the effect of high fish intake during pregnancy on rapid infant growth was greater among girls (aOR, 1.31 [95% CI, 1.08-1.59]) than among boys (aOR, 1.11 [95% CI, 0.92-1.34]; P = .02 for interaction)., Conclusions and Relevance: High maternal fish intake during pregnancy was associated with increased risk of rapid growth in infancy and childhood obesity. Our findings are in line with the fish intake limit proposed by the US Food and Drug Administration and Environmental Protection Agency., Competing Interests: Disclosures: None reported.

Purpose: This study aimed to investigate the association between maternal fish consumption during pregnancy and BMI in children and the development of this association between birth and 14 years of age, taking into account relevant mother and child covariates., Methods: The study population consisted of 3684 Dutch children born in 1996-1997 who participated in the PIAMA birth cohort study. Maternal fish consumption during pregnancy and the child's body weight and height (up to 11 times) were reported by questionnaire. Generalized estimating equations were used to investigate whether BMI of children differed according to maternal fish consumption during pregnancy., Results: The crude overall association between maternal fish consumption during pregnancy and BMI in children was non-significant (P = 0.17), but differed by the child's age (P interaction = 0.03). Children of mothers who consumed fish ≥1×/week during pregnancy (n = 909) had statistically significant lower mean BMI z scores than children of mothers who never consumed fish (n = 1025) at the ages 4, 7, 8.5, and 11.5 years. Adjustment for maternal covariates (particularly pre-pregnancy BMI) attenuated the differences, which remained statistically significant at the age of 7 years only (mean difference in BMI z score: -0.14 95 % CI -0.25; -0.03). Additional adjustment for child covariates hardly affected the results., Conclusions: In a population with relatively low fish consumption, higher fish consumption by pregnant women seems rather an indicator for more healthy maternal characteristics in general than a causal factor for the lower BMI in their children.

Background: Risk of cardiovascular and metabolic disease is higher in adults who were relatively thin at birth and had subsequent accelerated weight gain. This specific pattern of weight gain may relate to unfavorable cardiometabolic markers already in childhood. We prospectively assessed whether children with different patterns of overweight development from age 3 months to 11 years had distinct levels of cardiometabolic markers at age 12 years., Subjects/methods: We used data of 1500 children participating in the PIAMA birth cohort that started in 1996/1997. Parents reported height and weight during 10 waves of follow-up from age 3 months to 11 years. Four distinct overweight development patterns were derived using longitudinal latent class analysis; 'never'; 'early transient'; 'gradually developing' and 'persistent' overweight. Cardiometabolic markers (total-to-high-density lipoprotein cholesterol (TC/HDLC) ratio, blood pressure (BP), glycated hemoglobin (HbA1c)) were assessed at age 12 years in 1500 children., Results: Children who developed overweight gradually and children with persistent overweight throughout childhood, at age 12 years had a 2-3-fold higher risk of having high (>90th centile) TC/HDLC ratio, systolic and diastolic BP, compared with children who were never overweight. In children who gradually developed overweight, TC/HDLC ratio was 0.75 higher (95% confidence interval (CI) 0.54-0.96); systolic BP 4.90 mmHg higher (95% CI 2.45-7.36) and diastolic BP 1.78 mmHg higher (95% CI 0.07-3.49) than in children who never had overweight. Estimates for children with persistent overweight were similar., Conclusions: Children with gradually developing overweight, and those with persistent overweight had unfavorable cholesterol and blood pressure levels already at age 12 years, whereas children with early transient overweight avoided these unfavorable outcomes. Our results support the hypothesis that specific overweight patterns predispose to an adverse cardiometabolic profile, which is already apparent in early adolescence before progressing to adult cardiometabolic disease.

Background: Previous published analyses have focused on the effect of air pollution on asthma and rhinoconjunctivitis throughout early and middle childhood. However, the role of exposure to air pollution in the development of childhood and adolescent asthma and rhinoconjunctivitis remains unclear. We aimed to assess the longitudinal associations between exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence., Methods: We did a population-based birth cohort study of 14 126 participants from four prospective birth cohort studies from Germany, Sweden, and the Netherlands with 14–16 years of follow-up. We linked repeated questionnaire reports of asthma and rhinoconjunctivitis with annual average air pollution concentrations (nitrogen dioxide [NO2], particulate matter [PM] with a diameter of less than 2·5 μm [PM2·5], less than 10 μm [PM10], and between 2·5 μm and 10 μm [PMcoarse], and PM2·5 absorbance [indicator of soot]) at the participants' home addresses. We analysed longitudinal associations of air pollution exposure at participants' birth addresses and addresses at the time of follow-up with asthma and rhinoconjunctivitis incidence and prevalence in cohort-specific analyses, with subsequent meta-analysis and pooled analyses., Findings: Overall, the risk of incident asthma up to age 14–16 years increased with increasing exposure to NO2 (adjusted meta-analysis odds ratio [OR] 1·13 per 10 μg/m3 [95% CI 1·02–1·25]) and PM2·5 absorbance (1·29 per 1 unit [1·00–1·66]) at the birth address. A similar, albeit non-significant, trend was shown for PM2·5 and incident asthma (meta-analysis OR 1·25 per 5 μg/m3 [95% CI 0·94–1·66]). These associations with asthma were more consistent after age 4 years than before that age. There was no indication of an adverse effect of air pollution on rhinoconjunctivitis., Interpretation: Exposure to air pollution early in life might contribute to the development of asthma throughout childhood and adolescence, particularly after age 4 years, when asthma can be more reliably diagnosed. Reductions in levels of air pollution could help to prevent the development of asthma in children., Funding: The European Union.

Background: Levels of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs in breast milk are associated with the development of allergic diseases up to school age. However, it is unknown whether this relationship persists when the child becomes older. We therefore studied the association between levels of n-3 PUFAs and n-6 PUFAs in breast milk of allergic- and nonallergic mothers and asthma, eczema and sensitization up to the age of 14 years., Methods: The study was nested in the ongoing PIAMA birth cohort. At the child's age of 3 months, 276 mothers provided a breast milk sample. Asthma (N total = 269) and eczema (N total = 274) were self-reported up to the child's age of 14 years. Specific serum IgE levels were measured at the ages of 4, 8 and 12 years (N total = 216). Generalized estimating equations analyses were used to take account of repeated observations., Results: Asthma up to the age of 14 years is less prevalent in children of allergic mothers receiving breast milk with higher levels of n-3 long chain polyunsaturated (LCP) fatty acids (OR 0.50; 95% CI 0.31-0.79), and more prevalent in children of nonallergic mothers receiving breast milk with higher levels of n-6LCP (OR 1.86; 95% CI 1.14-3.03). Weaker associations in similar direction were observed for eczema and sensitization. Direction of associations were consistent and of similar magnitude throughout childhood., Conclusion: The association between breast milk fatty acid composition and asthma, eczema and sensitization persists up to the age of 14 years in children of both allergic and nonallergic mothers., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Maternal gestational weight gain (GWG) is a risk factor for the development of overweight in her child. It is unknown whether GWG programs the child's health or whether GWG indicates a shared familial lifestyle during childhood. To disentangle these influences, we studied the association of GWG and postdelivery maternal weight change simultaneously with child's weight development., Methods: We used data from 3367 children participating in a birth cohort that started in 1996 in the Netherlands. Weight and height were self-reported. GWG was categorized as "inadequate," "adequate," and "excessive." Multivariable regression and mixed models were used to study maternal and child weight changes., Results: Children of mothers with excessive GWG had a higher BMI z score and overweight prevalence (odds ratio [OR] 1.20; 95% confidence interval [CI], 0.99 to 1.46) throughout childhood. Children of mothers with a high (≥1 kg/year) postdelivery weight gain had a 0.14 (95% CI, -0.08 to 0.36) higher change in BMI z score between age 1 and 14 years than children of mothers with a low (<0.5 kg/year) postdelivery weight gain. Children of mothers with excessive GWG in combination with a high postdelivery weight gain had the highest BMI z score and overweight risk at age 14 years (OR 3.53; 95% CI, 1.70 to 7.33)., Conclusions: Maternal GWG and postdelivery weight gain contribute to child's weight development up to adolescence independently., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and absence of wheeze., Methods: Data of 3,252 children from the PIAMA birth cohort were studied. Parents reported the presence of nocturnal dry cough, wheeze, and doctor-diagnosed asthma in the past 12 months yearly, from birth up to the age of 8 years., Results: Nocturnal dry cough without wheeze was significantly associated with doctor-diagnosed asthma at age 8, except for age 1 (range of Relative Risks (RR) at ages 2-7: 1.8 (age 5) - 7.1 (age 7), all P-values <0.048). As expected, wheeze without nocturnal dry cough was strongly associated with doctor-diagnosed asthma at age 8 (range of RR: 2.0 (age 1) - 22.2 (age 7), all P-values <0.003). Of interest, nocturnal dry cough with wheeze showed the strongest association with doctor-diagnosed asthma at age 8 (range of RR: 3.7 (age 1) - 26.0 (age 7), all P-values <0.001). The relative excess risk of asthma at age 8 due to interaction of nocturnal dry cough with wheeze at age 1 year was 1.8 (0.1-3.6, P < 0.01)., Conclusion: Nocturnal dry cough and wheeze in early childhood are both independently associated with asthma at school age. The presence of both nocturnal dry cough and wheeze at age 1 almost doubles the risk of asthma at age 8 compared to wheeze alone., (© 2014 Wiley Periodicals, Inc.)

Background: Performance in primary school is a determinant of children's educational attainment and their socio-economic position and health inequalities in adulthood. We examined the relationship between five common childhood health conditions (asthma symptoms, eczema, general health, frequent respiratory infections, and overweight), health related school absence and family socio-economic status on children's school performance., Methods: We used data from 1,865 children in the Dutch PIAMA birth cohort study. School performance was measured as the teacher's assessment of a suitable secondary school level for the child, and the child's score on a standardized achievement test (Cito Test). Both school performance indicators were standardised using Z-scores. Childhood health was indicated by eczema, asthma symptoms, general health, frequent respiratory infections, overweight, and health related school absence. Children's health conditions were reported repeatedly between the age of one to eleven. School absenteeism was reported at age eleven. Highest attained educational level of the mother and father indicated family socio-economic status. We used linear regression models with heteroskedasticity-robust standard errors for our analyses with adjustment for sex of the child., Results: The health indicators used in our study were not associated with children's school performance, independently from parental educational level, with the exception of asthma symptoms (-0.03 z-score / -0.04 z-score with Cito Test score after adjusting for respectively maternal and paternal education) and missing more than 5 schooldays due to illness (-0.18 z-score with Cito Test score and -0.17 z-score with school level assessment after adjustment for paternal education). The effect estimates for these health indicators were much smaller though than the effect estimates for parental education, which was strongly associated with children's school performance., Conclusion: Children's school performance was affected only slightly by a number of common childhood health problems, but was strongly associated with parental education.

Background: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data., Methods: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs)., Results: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts., Conclusions: Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences., (© 2015 John Wiley & Sons Ltd.)

Background: In adults, overweight is associated with reduced lung function, in children evidence on this association is conflicting. We examined the association of body mass index (BMI) and waist circumference (WC) at age 12, and of persistently (at ages 8 and 12 years) high BMI and large WC, with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at age 12., Methods: Height, weight, WC and FVC and FEV1 were measured during a medical examination in 1288 12-year-olds participating in the PIAMA birth cohort study. 1090 children also had BMI and WC measured at age 8. The associations between BMI and WC and FVC, FEV1, and FEV1/FVC ratio were studied using local and linear regression analyses, separately for girls and boys. The regression models were adjusted for age, height, and pubertal development and maternal educational level., Results: High BMI and large WC (sd-score >90th percentile) were associated with higher FVC; in girls these associations were statistically significant (4.6% (95% CI: 1.5, 7.9) and 3.6% (95% CI: 0.6, 6.8) respectively in adjusted models). Similar associations were observed for persistently high BMI or large WC: girls with a high BMI or large WC at both 8 and 12 years had statistically significantly higher FVC at age 12 years (BMI: 4.9% (95% CI 0.9, 9.1), WC: 5.0% (95% CI 0.7, 9.6)) than girls with normal BMI or WC at both ages. No statistically significant associations were observed between (persistently) high BMI or large WC and FEV1. The FEV1/FVC ratio was statistically significantly lower in children with a high BMI or large WC than in children with a normal BMI or WC. Girls and boys with a persistently high BMI or large WC status had statistically significantly lower FEV1/FVC ratios., Conclusion: At 12 years of age, a persistently high BMI or large WC is not yet associated with lower FVC and FEV1, suggesting that this association, that is commonly observed in adults, develops at a later age.

Objective: HbA1c is associated with cardiovascular risk in persons without diabetes and cardiovascular risk accumulates over the life course. Therefore, insight in factors determining HbA1c from childhood onwards is important. We investigated (lifestyle) determinants of HbA1c at age 12 years and the effects of growth on change in HbA1c and the tracking of HbA1c between the age of 8 and 12 years., Study Design and Methods: Anthropometric measurements were taken and HbA1c levels were assessed in 955 children without diabetes aged around 12 years participating in the PIAMA birth cohort study. In 363 of these children HbA1c was also measured at age 8 years. Data on parents and children were collected prospectively by questionnaires., Results: We found no significant association between known risk factors for diabetes and HbA1c at age 12 years. Mean(SD) change in HbA1c between ages 8 and 12 years was 0.6(0.7) mmol/mol per year (or 0.1(0.1) %/yr). Anthropometric measures at age 8 and their change between age 8 and 12 years were not associated with the change in HbA1c. 68.9% of the children remained in the same quintile or had an HbA1c one quintile higher or lower at age 8 years compared to age 12 years., Conclusion: The lack of association between known risk factors for diabetes and HbA1c suggest that HbA1c in children without diabetes is relatively unaffected by factors associated with glycaemia. HbA1c at age 8 years is by far the most important predictor of HbA1c at age 12. Therefore, the ranking of HbA1c levels appear to be fairly stable over time.

Background: Breastfeeding has been linked to a reduction in the prevalence of allergy and asthma. However, studies on this relationship vary in outcome, which may partly be related to differences in breast milk composition. In particular breast milk composition may differ between allergic and non-allergic mothers. Important components that may be involved are breast milk proteins, as these are known to regulate immune development in the newborn. The objective of this study was therefore to explore differences in the proteins of breast milk from 20 allergic and non-allergic mothers. The results from this comparison may then be used to generate hypotheses on proteins associated with allergy in their offspring., Methods: Milk samples from allergic and non-allergic mothers were obtained from the PIAMA project, a prospective birth cohort study on incidence, risk factors, and prevention of asthma and inhalant allergy. Non-targeted proteomics technology, based on liquid chromatography and mass spectrometry, was used to compare breast milk from allergic and non-allergic mothers., Results: Nineteen proteins, out of a total of 364 proteins identified in both groups, differed significantly in concentration between the breast milk of allergic and non-allergic mothers. Protease inhibitors and apolipoproteins were present in much higher concentrations in breast milk of allergic than non-allergic mothers. These proteins have been suggested to be linked to allergy and asthma., Conclusions: The non-targeted milk proteomic analysis employed has provided new targets for future studies on the relation between breast milk composition and allergy.

Background/objectives: Recently, a few studies have linked soft drink consumption to increased asthma risk, but the contribution of different types of soft drinks is unknown. We investigated cross-sectional associations between six different types of soft drinks and asthma in 11-year-old children., Subjects/methods: We analyzed data of 2406 children participating in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort. At age 11, children self-reported consumption of sugar-added drinks, diet drinks, sweetened milk drinks, 100% fruit juice, energy drinks and sport drinks. The definition of asthma was based on parental reports of wheezing, prescription of inhaled corticosteroids and doctor's diagnosis of asthma., Results: The prevalence of asthma in this study was 5.8%. In adjusted logistic regression analyses, asthma risk was increased for high (⩾10 glasses/week (gl/wk) versus low (<4 gl/wk) consumption of 100% fruit juice (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.21-3.60), sugar-added drinks (OR: 1.56, 95%CI: 0.95-2.56) and for very high (>21.5 gl/wk) versus low (<12.5 gl/wk) total sugar-containing beverage (SCB) consumption (OR: 1.91, 95%CI: 1.04-3.48). Consumption of other beverages and consumption of fruit were not associated with increased asthma risk. No evidence for mediation of the observed associations by body mass index was found., Conclusions: This study indicates that high consumption of 100% fruit juice and total SCBs is associated with increased asthma risk in children. The positive association between consumption of 100% fruit juice and asthma is an unexpected finding that needs confirmation in future studies.

Aims: Elevation of a child's blood pressure may cause possible health risks in later life. There is evidence for adverse effects of exposure to air pollution and noise on blood pressure in adults. Little is known about these associations in children. We investigated the associations of air pollution and noise exposure with blood pressure in 12-year-olds., Methods: Blood pressure was measured at age 12 years in 1432 participants of the PIAMA birth cohort study. Annual average exposure to traffic-related air pollution [NO2, mass concentrations of particulate matter with diameters of less than 2.5 µm (PM2.5) and less than 10 µm (PM10), and PM2.5 absorbance] at the participants' home and school addresses at the time of blood pressure measurements was estimated by land-use regression models. Air pollution exposure on the days preceding blood pressure measurements was estimated from routine air monitoring data. Long-term noise exposure was assessed by linking addresses to modelled equivalent road traffic noise levels. Associations of exposures with blood pressure were analysed by linear regression. Effects are presented for an interquartile range increase in exposure., Results: Long-term exposure to NO2 and PM2.5 absorbance were associated with increased diastolic blood pressure, in children who lived at the same address since birth [adjusted mean difference (95% confidence interval) [mmHg] 0.83 (0.06 to 1.61) and 0.75 (-0.08 to 1.58), respectively], but not with systolic blood pressure. We found no association of blood pressure with short-term air pollution or noise exposure., Conclusions: Long-term exposure to traffic-related air pollution may increase diastolic blood pressure in children., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background/aims: Visfatin has been suggested as a marker of visceral adiposity. We hypothesized that visfatin, but not leptin, would be specifically associated with visceral adiposity. We investigated the relation of serum visfatin and leptin with measures of adiposity and body fat distribution in children., Methods: Serum leptin and visfatin levels were measured in 1,022 12-year-old children participating in the PIAMA birth cohort. BMI, waist, hip and upper arm circumference were available for all children. Multiple linear regression analyses were conducted to study associations between different anthropometric indices and log serum visfatin and leptin levels., Results: All anthropometric indices showed positive and strong dose-response relationships with serum leptin. Visfatin was increased only in children with a high waist-to-hip ratio. The effect size was small compared to those observed for leptin and the association was present in overweight children (n = 133) but not in normal weight children., Conclusion: Serum leptin levels strongly increased with increasing adiposity, but were not related to a specific type of fat distribution. In contrast, serum visfatin was associated only with high waist-to-hip ratio in overweight children. Based on our study we would currently not recommend visfatin as a marker of visceral adiposity in the general population of children., (© 2015 S. Karger AG, Basel.)

Background: There is evidence for a relation of TV viewing with adiposity and increased cardiometabolic risk factors in children and adolescents. It is unclear to what extent this relation is mediated by snacking and lack of physical activity. We determined whether associations of screen time with adiposity and cardiometabolic markers were mediated by these behaviours., Methods: Children from a population-representative Dutch birth cohort (n=1447) reported screen time and other lifestyle factors by a questionnaire around the age of 11 years (range 10-14) and had anthropometry and cardiometabolic markers measured around the age of 12 years (range 12-14). Adjusted associations of screen time with snacking, physical activity, adiposity and cardiometabolic markers (total-to-high-density lipoprotein cholesterol (TC/HDLC) ratio, blood pressure, glycated haemoglobin) were assessed by using formal mediation analysis. We tested the hypothesized paths by structural equation modeling, which allows quantification of the indirect effects associated with potential mediators., Results: Children with ⩾20 h screen time per week consumed more snacks (1.9 vs 1.3 portions per day) and were less physically active (4.3 vs 4.8 days per week) than children with maximum 6 h screen time. Screen time was directly associated with higher adiposity (standardized β=0.10-0.12 depending on the outcome, P<0.001), and indirectly through less physical activity. The association of screen time with TC/HDLC ratio was almost completely mediated by adiposity (β=0.39, P<0.0001), and to a minor extent by physical activity (β=-0.06, P=0.02). There was no direct association of screen time with TC/HDLC ratio., Conclusions: The adverse association of screen time with adiposity was partly mediated by physical activity, but not by snacking. The association of screen time with TC/HDLC ratio was almost completely mediated by adiposity. Our results may suggest that future efforts in society and public health should be directed to replace screen time with physical activity for reducing children's adiposity and cardiometabolic risk.

Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results., Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years)., Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes., Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27)., Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Purpose: We investigated the use of asthma medication by children and the association of use as recommended by guidelines with modifiable risk factors: parental attitudes, knowledge of asthma medication and information provided by health care providers., Methods: Questionnaire data were obtained from parents of 229 8-year-old children participating in the prevention and incidence of asthma and mite allergy birth cohort who used asthma medication in the past 12 months. They reported on their child's medication use, their own knowledge and attitudes towards the medication and their satisfaction with the information they received from health care providers., Results: Irregular use of inhaled corticosteroids (ICS) was common: 40% of the parents only gave their child ICS when the child felt breathless and 52% only 'when the child needed it'; 15% of the parents tried to avoid giving medication, and about 25% of the parents sometimes discontinued medication. Parental knowledge of how asthma medication should be given was a major determinant of guideline-recommended use: Of the parents who knew that anti-inflammatory drugs should be taken everyday (53% of all parents), 84% reported that they actually gave their child the medicines everyday as compared with 25% of the parents who did not know this. Guideline-recommended use was also significantly associated with parental satisfaction with the amount of information received from health care providers. These associations were independent of maternal school education., Conclusions: Our findings suggest that substantial improvements in the use of asthma medication are feasible, and this could considerably improve the effectiveness of current asthma treatment., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants., Objective: We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies., Design: The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis., Results: Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ≥ 3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts., Conclusion: This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.

Background: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years., Methods: In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years., Findings: We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years., Interpretation: Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We investigated associations of time in bed and multiple sleep quality characteristics with cardiometabolic markers in children. Data from the prevention and incidence of asthma and mite allergy study, a population-based prospective birth-cohort study started in 1996-1997 in the Netherlands, were analysed. In total 1481 children aged 11-12 years completed a questionnaire (including questions on sleep) and underwent a medical examination. We measured body mass index, waist circumference, total- and high-density lipoprotein cholesterol, blood pressure and glycated haemoglobin. Results showed that in girls, some sleep characteristics were related to anthropometrics (body mass index, waist circumference) and cholesterol. Girls who had a long time in bed (11-12.5 h) had 0.16 lower body mass index z-score (95% confidence interval -0.31; -0.01) and 0.99 cm smaller waist circumference (95% confidence interval -2.01; -0.13) compared with girls who spent 10-10.5 h in bed. Girls who went to bed late and rose early had 0.16 mm higher total cholesterol (95% confidence interval 0.01; 0.31) and 0.08 mm higher high-density lipoprotein cholesterol (95% confidence interval 0.01; 0.14) than 'early to bed/early rise' girls. Girls with night-time awakenings had 0.14 mm higher total cholesterol (95% confidence interval 0.03; 0.25) than girls without night-time awakenings. Girls who felt sleepy/tired ≥1 day per week had 0.10 mm lower high-density lipoprotein cholesterol (95% confidence interval -0.16; -0.04) and 0.17 mm higher total cholesterol/high-density lipoprotein cholesterol ratio (95% confidence interval 0.02; 0.32) than girls who did not feel sleepy. No associations were found for boys. Sleep characteristics were not related to blood pressure and glycated haemoglobin, and effect sizes of the associations in girls were small. Therefore, we consider it premature to propose that improved sleep could reduce cardiovascular risk during childhood., (© 2013 European Sleep Research Society.)

Background: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts., Methods: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up., Results: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children., Conclusions: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe., (© 2014 S. Karger AG, Basel.)

Background: A considerable proportion of children with early-life overweight attain a normal weight. To recognize infants at risk of persistent overweight, we compared early-life factors of children with a longitudinal pattern of persistent overweight to children with a pattern of overweight in early but not in later childhood., Methods: In 3,550 children participating in a birth cohort that started in 1996/1997 in the Netherlands, body mass index was repeatedly assessed until age 11 and dichotomized into with/without overweight. Latent class growth modeling was used to distinguish trajectories. Our analysis was focused on the comparison of early-life factors in children in a persistent overweight pattern with those in an overweight reduction pattern using multivariable log-binomial regression analyses., Results: Children (n = 133) in the persistent overweight pattern were more likely to have overweight parents [relative risk (RR)mother: 1.85, 95% CI: 1.37-2.49: RRfather: 1.75, 95% CI: 1.21-2.55] than children in the overweight reduction pattern (n = 303). Maternal education, child's gender, ethnicity, birth weight, breast-feeding and maternal smoking during pregnancy did not differ between the trajectories., Conclusion: Health care practitioners should focus on high-weight infants with overweight parents, as these children are less likely to resolve their overweight., (© 2014 S. Karger AG, Basel.)

Background: It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood., Objective: We investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6- to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects., Methods: The association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n = 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts., Results: AGER showed replicated association with FEV1/FVC ratio. TNS1 associated with more TEW in PIAMA and lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD., Conclusion: Our findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life., (Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.)

Background: Several experimental studies showed consistent evidence for decreased energy expenditure at higher ambient temperatures. Based on this, an association between thermal exposure and body weight may be expected. However, the effect of thermal exposure on body weight has hardly been studied. Therefore, this study investigated the association between indoor temperature and body mass index (BMI) in children in real life., Methods: This longitudinal observational study included 3 963 children from the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort that started in 1996. These children were followed from birth until the age of 11 years. Winter indoor temperature (living room and bedroom) was reported at baseline and BMI z-scores were available at 10 consecutive ages. Missing data were multiply imputed. Associations between indoor temperature and BMI were analyzed using generalized estimating equations (GEE), adjusted for confounders and stratified by gender. In a subgroup of 104 children, bedroom temperature was also measured with data loggers., Results: Mean reported living room and bedroom temperature were 20.3°C and 17.4°C, respectively. Reported and measured bedroom temperatures were positively correlated (r = 0.42, p = 0.001).Neither reported living room temperature (-0.03 ≤ β ≥ 0.04) and bedroom temperature (-0.01 ≤ β ≥ 0.02) nor measured bedroom temperature (-0.04 ≤ β ≥ 0.05) were associated with BMI z-score between the age of 3 months and 11 years., Conclusions: This study in children did not support the hypothesized association between indoor temperature and BMI in a real life setting.