Breastfeeding and cardiometabolic markers at age 12: a population-based birth cohort study.

BACKGROUND: There is growing evidence for a protective effect of breastfeeding against overweight and diabetes. It is less clear though, whether breastfed infants also have a more favorable cardiometabolic profile in childhood. OBJECTIVE: We investigated whether children who were breastfed in infancy had more favorable cardiometabolic markers at 12 years of age than children who were never breastfed and received formula milk instead, and whether associations depended on the duration of breastfeeding. METHODS: In 1509 participants of the population-based PIAMA birth cohort study, cardiometabolic markers were measured at 12 years of age. Duration of breastfeeding in weeks was assessed through parental questionnaires at 3 months and 1 year of age. Multivariable linear regression analysis was used to investigate associations of breastfeeding (any vs. never breastfeeding and duration of breastfeeding in categories <3 months, 3 to <6 months, and ≥6 months breastfeeding vs. never breastfeeding) with systolic and diastolic blood pressure (SBP and DBP, in Z-scores adjusted for age, sex, and height), total-to-high-density lipoprotein cholesterol (TC/HDLC), glycated hemoglobin (HbA1c, in mmol/mol), body mass index (BMI, in Z-scores adjusted for age and sex) and waist circumference (WC, in cm). Multivariable logistic regression was used to investigate the association of breastfeeding with odds of being overweight. RESULTS: 1288 of 1509 children (85.3%) received any breastmilk in infancy. Breastfed children had a lower SBP Z-score (-0.21 SD (≈ -2.29 mmHg), 95% CI -0.37, -0.06), a lower DBP Z-score (-0.10 SD (≈ -1.19 mmHg), 95% CI -0.20, -0.00), a smaller WC (-1.12 cm, 95% CI -2.20; -0.04), and lower odds of being overweight (OR 0.61, 95% CI 0.38, 0.97) than never breastfed children. These associations were not different between children with shorter and longer duration of breastfeeding. No statistically significant differences in TC/HDLC, HbA1c, and BMI were observed between breastfed and never breastfed children. CONCLUSIONS: We observed that breastfeeding was associated with a lower blood pressure, a smaller waist circumference and a lower risk of overweight in 12-year old children. These associations were independent of the duration of breastfeeding. No associations were observed between breastfeeding and other cardiometabolic markers.

Childhood infections and common carotid intima media thickness in adolescence.

Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.

Increased risk of asthma in overweight children born large for gestational age.

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.

Trajectories of metabolic risk factors and biochemical markers prior to the onset of type 2 diabetes: the population-based longitudinal Doetinchem study.

BACKGROUND: Risk factors often develop at young age and are maintained over time, but it is not fully understood how risk factors develop over time preceding type 2 diabetes. We examined how levels and trajectories of metabolic risk factors and biochemical markers prior to diagnosis differ between persons with and without type 2 diabetes over 15-20 years. METHODS: A total of 355 incident type 2 diabetes cases (285 self-reported, 70 with random glucose ⩾11.1 mmol l-1) and 2130 controls were identified in a prospective cohort between 1987-2012. Risk factors were measured at 5-year intervals. Trajectories preceding case ascertainment were analysed using generalised estimating equations. RESULTS: Among participants with a 21-year follow-up period, those with type 2 diabetes had higher levels of metabolic risk factors and biochemical markers 15-20 years before case ascertainment. Subsequent trajectories were more unfavourable in participants with type 2 diabetes for body mass index (BMI), HDL cholesterol and glucose (P<0.01), and to a lesser extent for waist circumference, diastolic and systolic blood pressure, triglycerides, alanine aminotransferase, gamma glutamyltransferase, C-reactive protein, uric acid and estimated glomerular filtration rate compared with participants without type 2 diabetes. Among persons with type 2 diabetes, BMI increased by 5-8% over 15 years, whereas the increase among persons without type 2 diabetes was 0-2% (P<0.01). The observed differences in trajectories of metabolic risk factors and biochemical markers were largely attenuated after inclusion of BMI in the models. Results were similar for men and women. CONCLUSIONS: Participants with diabetes had more unfavourable levels of metabolic risk factors and biochemical markers already 15-20 years before diagnosis and worse subsequent trajectories than others. Our results highlight the need, in particular, for maintenance of a healthy weight from young adulthood onwards for diabetes prevention.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Patient selection for cardiac surgery: Time to consider subgroups within risk categories?

BACKGROUND: Medical guidelines increasingly use risk stratification and implicitly assume that individuals classified in the same risk category form a homogeneous group, while individuals with similar, or even identical, predicted risks can still be very different. We evaluate a strategy to identify homogeneous subgroups typically comprising predicted risk categories to allow further tailoring of treatment allocation and illustrate this strategy empirically for cardiac surgery patients with high postoperative mortality risk. METHODS: Using a dataset of cardiac surgery patients (n=6517) we applied cluster analysis to identify homogenous subgroups of patients comprising the high postoperative mortality risk group (EuroSCORE ≥ 15%). Cluster analyses were performed separately within younger (<75 years) and older (≥ 75 years) patients. Validity measures were calculated to evaluate quality and robustness of the identified subgroups. RESULTS: Within younger patients two distinct and robust subgroups were identified, differing mainly in preoperative state and indication of recent myocardial infarction or unstable angina. In older patients, two distinct and robust subgroups were identified as well, differing mainly in preoperative state, presence of chronic pulmonary disease, previous cardiac surgery, neurological dysfunction disease and pulmonary hypertension. CONCLUSIONS: We illustrated a feasible method to identify homogeneous subgroups of individuals typically comprising risk categories. This allows a single treatment strategy--optimal only on average, across all individuals in a risk category--to be replaced by subgroup-specific treatment strategies, bringing us another step closer to individualized care. Discussions on allocation of cardiac surgery patients to different interventions may benefit from focusing on such specific subgroups.

Overweight patterns throughout childhood and cardiometabolic markers in early adolescence.

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.

Breast milk fatty acid composition has a long-term effect on the risk of asthma, eczema, and sensitization.

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.

Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts: an allergic comorbidity cluster.

BACKGROUND: Asthma, rhinitis and eczema often co-occur in children, but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis and eczema using unsupervised statistical techniques. METHODS: We included 17 209 children at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age of onset and treatments of asthma, rhinitis and eczema; immunoglobulin E sensitization; weight; and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organizing maps. RESULTS: Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70% and 79% of children, respectively) was characterized by a low prevalence of symptoms and sensitization, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitization. Ninety-nine percentage of children with comorbidities (co-occurrence of asthma, rhinitis and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses. CONCLUSION: At 4 and 8 years, at the population level, asthma, rhinitis and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Associations of sugar-containing beverages with asthma prevalence in 11-year-old children: the PIAMA birth cohort.

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.

Screen time, adiposity and cardiometabolic markers: mediation by physical activity, not snacking, among 11-year-old children.

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 ß=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 (ß=0.39, P<0.0001), and to a minor extent by physical activity (ß=-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.

Diagnosis of diabetes mellitus or cardiovascular disease and lifestyle changes - the Doetinchem cohort study.

OBJECTIVE: To study whether being diagnosed with a cardiovascular disease (CVD) or diabetes mellitus (DM) is associated with improvements in lifestyles. METHODS: We used data from the Doetinchem Cohort Study, a prospective study among 6386 Dutch men and women initially aged 20-59years who were examined four times over 15years (1987-2007). Logistic and linear regression models were used to assess the effect of a self-reported diagnosis of CVD (n=403) or DM (n=221) on smoking, alcohol consumption, weight, diet and physical activity. RESULTS: Self-reported diagnosis of CVD increased rates of smoking cessation (OR=2.2, 95%CI 1.6 - 3.1). Adults reporting a diagnosis of DM (relatively) decreased weight (3.2%, 95%CI 2.2 - 4.2), (relatively) decreased energy intake (4.2%, 95%CI 0.7 - 7.7), decreased energy percentage from saturated fat (0.4%, 95%CI 0.0 - 0.9) and increased fish consumption (2.8 g/day, 95%CI 0.4 - 5.1). A self-reported diagnosis of CVD or DM was not associated with changes in physical activity. CONCLUSION: A diagnosis of CVD or DM may act, along with possible effects of medical treatment, as a trigger to adopt a healthier lifestyle in terms of smoking cessation, healthier diet and weight loss.

Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project.

BACKGROUND: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood. OBJECTIVES: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts--BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)--and to derive combined effect estimates using meta-analysis. METHODS: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter≤2.5 µm (PM2.5), PM2.5 absorbance, PM10, PM2.5-10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates. RESULTS: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR=1.30; 95% CI: 1.02, 1.65 per 10-µg/m3 increase in NO2 and OR=1.76; 95% CI: 1.00, 3.09 per 10-µg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR=1.09; 95% CI: 1.02, 1.16 per 10-µg/m3). CONCLUSION: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media.

Perinatal risk factors for wheezing phenotypes in the first 8 years of life.

BACKGROUND: A novel data-driven approach was used to identify wheezing phenotypes in pre-schoolchildren aged 0-8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes. OBJECTIVE: The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention. METHODS: In the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with 'never/infrequent wheeze' as reference category. RESULTS: Complete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day-care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy. CONCLUSION AND CLINICAL RELEVANCE: We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day-care attendance and breastfeeding, and may be important targets for prevention programmes.

Modelling obesity outcomes: reducing obesity risk in adulthood may have greater impact than reducing obesity prevalence in childhood.

A common policy response to the rise in obesity prevalence is to undertake interventions in childhood, but it is an open question whether this is more effective than reducing the risk of becoming obese during adulthood. In this paper, we model the effect on health outcomes of (i) reducing the prevalence of obesity when entering adulthood; (ii) reducing the risk of becoming obese throughout adult life; and (iii) combinations of both approaches. We found that, while all approaches reduce the prevalence of chronic diseases and improve life expectancy, a given percentage reduction in obesity prevalence achieved during childhood had a smaller effect than the same percentage reduction in the risk of becoming obese applied throughout adulthood. A small increase in the probability of becoming obese during adulthood offsets a substantial reduction in prevalence of overweight/obesity achieved during childhood, with the gains from a 50% reduction in child obesity prevalence offset by a 10% increase in the probability of becoming obese in adulthood. We conclude that both policy approaches can improve the health profile throughout the life course of a cohort, but they are not equivalent, and a large reduction in child obesity prevalence may be reversed by a small increase in the risk of becoming overweight or obese in adulthood.

Childhood wheezing phenotypes and FeNO in atopic children at age 8.

BACKGROUND: Fractional exhaled Nitric Oxide (FeNO) is a surrogate biomarker of the degree of eosinophilic airway inflammation. Using longitudinal latent class analysis, five wheezing phenotypes have been identified, characterized by different ages of onset and prognosis. OBJECTIVES: To assess FeNO measured at 4 and 8 years in children with different phenotypes of wheeze and atopy. METHODS: Children participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study, a prospective birth cohort in the Netherlands. Respiratory health was assessed yearly by questionnaires until the age of 8 years; these data were used to identify five wheezing phenotypes. Associations between FeNO and wheezing phenotypes were investigated using weighted linear regression. RESULTS: Data on wheezing phenotypes and FeNO at 4 and 8 years were available in 588 and 973 children respectively. Compared with the phenotype of never and transient wheeze, FeNO at 4 years was higher in intermediate onset and persistent wheeze. FeNO at 8 years of age differed significantly between all phenotypes, with highest FeNO values for persistent, intermediate onset, and late onset wheeze. Rise in FeNO from 4 to 8 years in intermediate and late onset wheezers was significantly higher compared to FeNO rise in never and transient wheezers. Stratified analyses showed that the increase in FeNO in persistent, intermediate, and late onset wheeze was only present in children with allergic sensitization at 8 years. CONCLUSIONS AND CLINICAL RELEVANCE: The FeNO measured at 8 years was associated with specific wheezing phenotypes, only among atopic children.