http://repub.eur.nl/res/aut/4139/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39624/ 2013-04-01T00:00:00Z http://repub.eur.nl/res/pub/37398/ 2012-10-01T00:00:00Z Breastfed individuals have a lower blood pressure than formula-fed individuals. Supplementation with n-3 long-chain polyunsaturated fatty acids in adults is also associated with a lower blood pressure. We studied whether children receiving human milk with a relatively high content of n-3 long-chain polyunsaturated fatty acids have a lower blood pressure at age 12 years, and, if so, whether this association is explained by the n-3 long-chain polyunsaturated fatty acids content in erythrocyte membranes at age 12 years. Within a 12-year follow-up of a population-based birth cohort, we compared blood pressure of 205 never-breastfed children and 109 children who had fatty acid composition of their mothers' breast milk measured during lactation. In addition, 973 children had information on erythrocyte fatty acid composition and blood pressure at age 12 years. Children who received human milk with an n-3 long-chain polyunsaturated fatty acids content above the median (ie, 0.51 weight percentage) had a 4.79-mm Hg lower systolic (95% CI, -7.64 to -1.94) and a 2.47-mm Hg lower diastolic (95% CI, -4.45 to -0.49) blood pressure at age 12 years than never-breastfed children. N-3 long-chain polyunsaturated fatty acids levels in human milk below the median value and current n-3 long-chain polyunsaturated fatty acid status were not associated with blood pressure at age 12 years. Thus, a relatively high content of n-3 long-chain polyunsaturated fatty acids in human milk is associated with a lower blood pressure in children at age 12 years, a finding not explained by current n-3 long-chain polyunsaturated fatty acids status. http://repub.eur.nl/res/pub/31999/ 2012-01-01T00:00:00Z http://repub.eur.nl/res/pub/34786/ 2012-01-01T00:00:00Z Background Systemic inflammation is suggested as a mechanism by which overweight might induce asthma. However, few studies have linked childhood overweight, inflammation and asthma. Objective To study the association between body mass index (BMI), asthma symptoms and pro-inflammatory proteins. Methods High-sensitivity C-reactive protein (hs-CRP), complement factor 3 (C3) and 4 (C4) concentrations, and body weight and height were available for 359 4-year-old children participating in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Data on asthma symptoms were obtained by yearly questionnaires. Logistic regression and generalized estimating equations were used to analyse the cross-sectional and prospective associations between BMI, asthma symptoms and pro-inflammatory proteins. Results BMI was associated with asthma symptoms {odds ratio [OR] 1.43 [95% confidence interval (CI): 1.08-1.88] per BMI standard deviation scores [SDS]}. The inclusion of hs-CRP, C3 and C4 in the statistical models did not change this association. C3 was cross-sectionally associated with frequent asthma symptoms [OR per interquartile range of C3: 1.97 (95% CI: 1.20-3.24)] and prospectively with asthma symptoms [OR: 1.48 (95%CI: 1.04-2.09)], independent of BMI SDS. Conclusions and Clinical Relevance We showed no evidence for a role of hs-CRP, C3 and C4 in the association between BMI and asthma symptoms. C3 concentrations were associated with (frequent) asthma symptoms, independent of BMI. http://repub.eur.nl/res/pub/30844/ 2011-11-01T00:00:00Z Objective: Under and overtreatment of asthma may be a serious problem especially in young children, but the evidence is scarce and no longitudinal data are available. Our aim was to investigate whether inhaled medication use in young children was in agreement with asthma symptoms at the age of 2-8yr. Methods: Data were used from the 'Prevention and Incidence of Asthma and Mite Allergy' birth cohort, consisting of 3963 children born in the Netherlands. Between age 2 and 8yr, children were followed up using annual postal questionnaires. Age-specific prevalences of asthma symptoms were assessed and compared with reported use of inhaled bronchodilators and/or corticosteroids. Results: The proportion of current wheeze decreased with age. About a third of 'current wheezers' did not use any inhaled medication during the years in which symptoms were reported. At 8yr, 30% of children with reported 'severe current asthma symptoms' were not using inhaled corticosteroids. On the other hand, up to 50% of children with inhaled corticosteroids for at least 2yr did not report any wheezing during those 2yr. Conclusion: The proportion of symptomatic children without appropriate treatment was substantial throughout childhood, even when parents reported prolonged or severe symptoms. Treatment of asymptomatic children with inhaled corticosteroids increased with age and accounted for up to a third of all inhaled steroid use at 8yr. These findings suggest that under and overtreatment of asthma in children was common. http://repub.eur.nl/res/pub/31253/ 2011-08-01T00:00:00Z http://repub.eur.nl/res/pub/34039/ 2011-08-01T00:00:00Z Background: Despite existing effective treatment options, asthma is uncontrolled in a considerable proportion of patients. The aim of this study was to identify determinants of uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study. Methods: One hundred seventy children using inhaled corticosteroids in the previous 12months at age 8 were included. Uncontrolled asthma was defined as: ≥3 items present in the past month: (1) day-time or (2) night-time asthma symptoms, (3) limitations in activities, (4) rescue medication use, (5) FEV1<80% predicted and (6) unscheduled physician visits because of asthma. Binomial regression was performed to study five groups of determinants representing asthma control: child and parental characteristics, environmental factors, therapy adherence and parental perception towards medication use (Beliefs about Medicines Questionnaire). Results: Seventy seven children (45%) had uncontrolled asthma. Low maternal education (RR 1.6, 95% CI: 1.0-2.4) was associated with uncontrolled asthma. Parental necessity beliefs about medication use to maintain present and future health and parental concerns about potential adverse consequences of medication were also associated with uncontrolled asthma (RR 1.6, 95% CI: 1.1-2.2; and 1.6, 95% CI: 1.0-2.5, respectively). Conclusions: Environmental factors and therapy adherence were not associated with asthma control. In our cohort, uncontrolled asthma is associated with low maternal education and with strong parental beliefs about medication necessity and higher concern about potential side effects of medication. http://repub.eur.nl/res/pub/26707/ 2011-06-01T00:00:00Z Objective. To develop a decision rule by which children with a high risk to develop overweight can be distinguished at birth from children at low risk. Design, setting and participants. Data of 1 687 Dutch children born in 1996/1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) longitudinal birth cohort study were analysed. Perinatal candidate predictors of overweight at 8 years of age were selected and a prediction model was developed using stepwise model selection based on the Akaike Information Criterion (AIC). The prediction model was internally validated using resampling techniques. Outcome measure. Overweight at the age of 8 years. Results. A total of 13.9% (n = 253) of the children were overweight at 8 years of age. Independent positive predictors of overweight were paternal and maternal body mass index, female gender, smoking in the parental house, birth weight and hospital delivery. From the model, a decision rule was derived by which an overweight score could be calculated. Of the children with an overweight score below 89.45, only 2.7% were overweight at the age of 8, whereas in children with an overweight score above 105.02 the prevalence of overweight was 35.4%. Conclusion. The risk of overweight at the age of 8 years can be predicted with six characteristics that are available at birth. The decision rule developed in this study may help to target early preventive measures against overweight in high-risk children. http://repub.eur.nl/res/pub/33431/ 2011-06-01T00:00:00Z Background: Asthma has its origins in early childhood, but different patterns of childhood wheezing vary in their associations with subsequent asthma, atopy, and bronchial hyperresponsiveness (BHR). Novel wheezing phenotypes have been identified on the basis of analyses of longitudinal data from the Avon Longitudinal Study of Parents And Children (ALSPAC). It is unclear whether these phenotypes can be replicated in other birth cohorts. Objective: To compare wheezing phenotypes identified in the first 8 years of life in the ALSPAC study and the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study. Methods: We used longitudinal latent class analysis to identify phenotypes on the basis of repeated reports of wheezing from 0 to 8 years in 5760 children from the ALSPAC study and 2810 children from the PIAMA study. Phenotypes were compared between cohorts. Associations with asthma, atopy, BHR, and lung function were analyzed by using weighted regression analyses. Results: The model with the best fit to PIAMA data in the first 8 years of life was a 5-class model. Phenotypes identified in the PIAMA study had wheezing patterns that were similar to those previously reported in ALSPAC, adding further evidence to the existence of an intermediate-onset phenotype with onset of wheeze after 2 years of age. Associations with asthma, atopy, BHR, and lung function were remarkably similar in the 2 cohorts. Conclusion: Wheezing phenotypes identified by using longitudinal latent class analysis were comparable in 2 large birth cohorts. Study of genetic and environmental factors associated with different phenotypes may help elucidate the origins of asthma. http://repub.eur.nl/res/pub/25468/ 2011-05-19T00:00:00Z Background: Overweight develops gradually as a result of a long term surplus on the balance between energy intake and energy expenditure. Aim of this study was to quantify the positive energy balance responsible for excess body weight gain (energy gap) in young overweight children. Methods. Reported data on weight and height were used of 2190 Dutch children participating in the PIAMA birth cohort study. Accumulated body energy was estimated from the weight gain observed between age 2 and age 5-7. Energy gap was calculated as the difference in positive energy balance between children with and without overweight assuming an energy efficiency of 50%. Results: Ten percent of the children were overweight at the age of 5-7 years. For these children, median weight gain during 4-years follow-up was 13.3 kg, as compared to 8.5 kg in the group of children who had a normal weight at the end of the study. A daily energy gap of 289-320 kJ (69-77 kcal) was responsible for the excess weight gain or weight maintenance in the majority of the children who were overweight at the age of 5-7 years. The increase in daily energy requirement to maintain the 4.8 kilograms excess weight gain among overweight children at the end of the study was approximately 1371 kJ. Conclusions: An energy gap of about 289-320 kJ per day over a number of years can make the difference between normal weight and overweight in young children. Closing the energy gap in overweight children can be achieved by relatively small behavior changes. However, much more effort is required to lose the excess weight gained. http://repub.eur.nl/res/pub/34080/ 2011-05-01T00:00:00Z Diet may affect the development of asthma. We investigated whether asthma or atopy outcomes at 8 yrs of age were associated with long-term dietary exposure, and whether associations were different for consumption at early or later age. The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort enrolled 4,146 participants at baseline, who were followed up to 8 yrs of age. Dietary intakes of interest were fruit, vegetables, brown/wholemeal bread, fish, milk, butter and margarine. Associations between food intake at early (2-3 yrs) and later (7-8 yrs) age, and long-term intake, asthma and atopy at 8 yrs of age were calculated by logistic regression. Complete longitudinal dietary data for at least one of the food groups were available for 2,870 children. Fruit consumption at early age was associated with reduced asthma symptoms (OR per 1 consumption day per week increase 0.93, 95% CI 0.85-1.00). Long-term fruit intake was inversely associated with asthma symptoms (OR 0.90, 95% CI 0.82-0.99) and sensitisation to inhaled allergens (OR 0.90, 95% CI 0.82-0.99). We found no consistent associations between diet and outcomes for other foods. This study indicates no consistent effects of increased early or late consumption, or long-term intake of certain foods on asthma and atopy in 8-yr-olds, with a possible exception for fruit. Copyright http://repub.eur.nl/res/pub/33512/ 2011-03-01T00:00:00Z Background: IL-1 receptor-like 1 (IL1RL1) is a membrane receptor involved in TH2 inflammatory responses and eosinophilia. Single nucleotide polymorphisms (SNPs) in IL1RL1 have been associated with blood eosinophil counts in a genome-wide association study and with asthma in family-based and case-control studies. Objective: We assessed in the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) whether IL1RL1 SNPs associate with levels of its soluble transcript IL1RL1 (IL1RL1-a) in serum, blood eosinophil counts, and asthma prevalence from birth to age 8 years, and whether IL1RL1-a serum levels associate with blood eosinophil counts. Methods: Fifteen IL1RL1 SNPs were genotyped. Serum IL1RL1-a levels were measured in 2 independent subsets within PIAMA, at 4 and 8 years. Blood eosinophil counts were measured in 4-year-old children. Results: In 2 independent subsets of children, 13 of 15 SNPs were associated with serum IL1RL1-a levels at ages 4 and 8 years with a consistent direction of effect for each allele. Rs11685480 allele A and rs1420102 allele A were significantly associated with lower numbers of blood eosinophils. In the total cohort, rs1041973 allele A was associated with a decreased risk of developing asthma (odds ratio, 0.70; 95% CI, 0.54-0.90). Rs1420101, recently identified in a genome-wide association study in the Icelandic population, was not associated with asthma in this study. IL1RL1-a levels were not associated with eosinophil counts. Conclusion: We demonstrate that IL1RL1 polymorphisms are associated with serum IL1RL1-a, blood eosinophils, and asthma in childhood. http://repub.eur.nl/res/pub/31723/ 2011-02-01T00:00:00Z http://repub.eur.nl/res/pub/28148/ 2010-12-01T00:00:00Z In children, the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) is reportedly constant or falls linearly with age, whereas the ratio of residual volume (RV) to total lung capacity (TLC) remains constant. This seems counter-intuitive given the changes in airway properties, body proportions, thoracic shape and respiratory muscle function that occur during growth. The age dependence of lung volumes, FEV1/FVC and RV/TLC were studied in children worldwide. Spirometric data were available for 22,412 healthy youths (51.4% male) aged 4-20 yrs from 15 centres, and RV and TLC data for 2,253 youths (56.7% male) from four centres; three sets included sitting height (SH). Data were fitted as a function of age, height and SH. In childhood, FVC outgrows TLC and FEV1, leading to falls in FEV1/FVC and RV/TLC; these trends are reversed in adolescence. Taking into account SH materially reduces differences in pulmonary function within and between ethnic groups. The highest FEV1/FVC ratios occur in those shortest for their age. When interpreting lung function test results, the changing pattern in FEV1/FVC and RV/TLC should be considered. Prediction equations for children and adolescents should take into account sex, height, age, ethnic group, and, ideally, also SH. Copyright http://repub.eur.nl/res/pub/21604/ 2010-11-01T00:00:00Z Purpose: This study was conducted to assess the validity of parental reported use of inhaled corticosteroids (ICS) in children. Methods: ICS users were identified within the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and the PIAMA pharmacy sub-cohort which is nested within the PIAMA study. Complete medication histories were available for the first 8 years of life for children within the PIAMA pharmacy sub-cohort. Parental reported ICS use was measured by using data from questionnaires. ICS use in the pharmacy records was determined by using the Anatomical Therapeutic Chemical (ATC) codes. The proportion of overall agreement and kappa statistics with their corresponding 95% confidence intervals were calculated to quantify agreement between self-reported medication use and pharmacy prescription data. Results: At all ages overall agreement was very high (>97%) and Cohen's kappa's ranged from 0.80 to 0.88 which also reflects excellent agreement between parental reported use of ICS and pharmacy prescription data. Conclusions: Our finding suggests that parental report of medication use is a reliable source of data to asses ICS use in children. The questionnaire-based medication data collected within the PIAMA study can be used to study asthma medication use in a large group of children. http://repub.eur.nl/res/pub/28284/ 2010-10-01T00:00:00Z Wheeze has many underlying pathophysiologies in childhood, but is the main reason for anti-asthma drugs prescription. This study was conducted to describe asthma medication use patterns among children in their first eight years of life. Longitudinal medication use data from 777 children participating in the PIAMA study were used. Medication patterns were described for four groups that started therapy before the third birthday, when the peak in prescriptions occurred in our cohort; short-acting β-agonists (SABA), inhaled corticosteroids (ICS), SABA + ICS or none of these. One third (n = 255) of the children received a first SABA or ICS prescription before age 8. Only three children (1.2%) used medication continuously during follow-up. Of the children who started SABA, 53.8% discontinued within 1-2 years. Of the children who started ICS before age 3, 42.1% discontinued within 1-2 years and 31.6% received additional SABA. 41.5% of the children who started SABA + ICS used this short-term (≤1-2 years) and 21.5% long-term (≥3 years). Fifteen percent of children who did not start asthma therapy in their first 3 years of life did receive prescriptions between age 3 and 8. Children prescribed SABA + ICS before age 3 had the highest prevalence of hyper responsiveness at age 8, and similar prevalence of atopy as the other groups. Asthma medication is prescribed frequently in the first 8 years of life, particularly before age 3, and only few children use it continuously. ICS and SABA prescription occurs especially in those who were more likely to develop signs of asthma at age 8. http://repub.eur.nl/res/pub/27632/ 2010-09-01T00:00:00Z Rationale: For clinicians it remains very difficult to predict whether preschool children with symptoms suggestive of asthma will develop asthma in later childhood. Objective: To investigate whether measurement of fraction of exhaled nitric oxide (FENO), interrupter resistance (Rint) or specific immunoglobulin E (IgE) in 4-year-old children with suggestive symptoms can predict asthma symptoms up to age 8 years. Methods: Children were recruited from the PIAMA birth cohort. All children with symptoms suggestive of asthma at age 3 or 4 years, who were invited for medical examination at age 4 (n=848), were eligible. Associations of FENO(n=308), Rint (n=482) and specific IgE (n=380) at 4 years with wheezing and asthma at the ages of 5-8 years were assessed using repeated measurement analyses. The added predictive value of these objective tests was then investigated by including parameters for clinical history in the model. Results: FENOand specific IgE measured at 4 years were associated with wheezing and asthma at 8 years. Both tests also remained significant predictors after mutual adjustment and adjustment for clinical history: OR on wheezing at 8 years for FENO(10log-scale, per IQR) 1.6 (95% CI 1.1 to 2.2) and for specific IgE 2.8 (95% CI 1.9 to 4.1). Rint was significantly associated with wheezing at age 6, but not at 7 and 8 years. Conclusions: In preschool children with symptoms suggestive of asthma, both FENOand specific IgE measured at age 4, but not Rint, improved the prediction of asthma symptoms until the age of 8 years, independent of clinical history. http://repub.eur.nl/res/pub/27473/ 2010-08-01T00:00:00Z Background: Epidemiological studies have reported adverse effects of ambient air pollution on the prevalence of asthma. Laboratory studies have suggested that innate immune responses are involved. Objective: A study was undertaken to determine whether the Toll-like receptor 2 and 4 genes (TLR2 and TLR4) influence the susceptibility to adverse effects of traffic-related air pollution with respect to the prevalence of childhood asthma. Methods: Haplotype tagging single nucleotide polymorphisms (SNPs) in the TLR2 (n=4) and TLR4 genes (n=9) were genotyped in 916 children from the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Exposure to particulate matter (PM2.5), soot and nitrogen dioxide (NO2) at the birth address was estimated by land use regression models. Interactions between levels of pollutants and SNPs in relation to annual questionnaire reports of asthma diagnosis and symptoms from birth up to 8 years of age were analysed longitudinally by generalised estimating equations. Results: Two TLR2 SNPs and four TLR4 SNPs significantly modified the effect of air pollution on the prevalence of doctor-diagnosed asthma from birth up to 8 years of age. The risk of having doctor-diagnosed asthma increased with increasing PM2.5levels in children with at least one copy of the TLR2 rs4696480 A allele (OR 2.0 (95% CI 1.2 to 3.1) for an interquartile range increase in exposure). Similar observations were present with the following TLR4 genotypes: rs2770150 TC (OR 2.0 (95% CI 1.1 to 3.6)), rs10759931 GG (OR 2.6 (95% CI 1.4 to 4.9)), rs6478317 GG (OR 2.2 (95% CI 1.2 to 4.3)), rs10759932 CT or CC (OR 2.9 (95% CI 1.2 to 6.9)) and rs1927911 TT (OR 4.4 (95% CI 1.7 to 11.7)). Conclusions: Variant alleles of TLR2 and TLR4 genes influence the susceptibility to adverse effects of traffic-related air pollution on childhood asthma. http://repub.eur.nl/res/pub/20320/ 2010-06-01T00:00:00Z Background: Exposure to environmental tobacco smoke (ETS) is known to increase the risk of respiratory tract infections (RTI). Some children, however, may be more susceptible to the harmful effects of ETS than others. We examined whether early atopic status (defi ned by elevated neonatal total IgE (tIgE) or symptoms of atopic dermatitis) modifi ed the association between ETS exposure and RTI. Methods: The data of 2863 children from the Prevention and Incidence of Asthma and Mite Allergy birth cohort were collected to the age of 4 years. Neonatal tIgE was collected from a subset of 914 children, and clinical information by yearly parental questionnaires. The effect of pre- and/or postnatal ETS exposure, early atopic status and interaction between these factors was studied for various RTI. Results: Children with elevated tIgE or atopic dermatitis and prenatal ETS exposure have a strongly increased risk of frequent RTI (aOR 6.18 (95% CI 1.45 to 26.34) and 5.69 (2.01 to 16.04), respectively; interaction p=0.006 and p=0.14, respectively) compared to non-atopic children without prenatal ETS exposure. Similar results were seen for lower RTI and otitis. This effect was less evident for postnatal ETS. Conclusion: Early atopic status enhances the risk of RTI in children with prenatal ETS exposure. This suggests that host factors modify the association between ETS and RTI. http://repub.eur.nl/res/pub/28497/ 2010-04-15T00:00:00Z Background. There is ample evidence that childhood overweight is associated with increased risk of chronic disease in adulthood. The aim of this study was to investigate associations between childhood overweight and common childhood health problems. Methods. Data were used from a general population sample of 3960 8-year-old children, participating in the Dutch PIAMA birth cohort study. Weight and height, measured by the investigators, were used to define BMI status (thinness, normal weight, moderate overweight, obesity). BMI status was studied cross-sectionally in relation to the following parental reported outcomes: a general health index, GP visits, school absenteeism due to illness, health-related functional limitations, doctor diagnosed respiratory infections and use of antibiotics. Results. Obesity was significantly associated with a lower general health score, more GP visits, more school absenteeism and more health-related limitations, (adjusted odds ratios around 2.0 for most outcomes). Obesity was also significantly associated with bronchitis (adjusted odds ratio (aOR) and 95% confidence intervals (95%CI): 5.29 (2.58;10.85) and with the use of antibiotics (aOR (95%CI): 1.79 (1.09;2.93)). Associations with flu/serious cold, ear infection and throat infection were positive, but not statistically significant. Moderate overweight was not significantly associated with the health outcomes studied. Conclusion. Childhood obesity is not merely a risk factor for disease in adulthood, but obese children may experience more illness and health related problems already in childhood. The high prevalence of the outcomes studied implies a high burden of disease in terms of absolute numbers of sick children. http://repub.eur.nl/res/pub/27901/ 2010-04-01T00:00:00Z Objective:The aim of this study was to investigate the association between maternal overweight before pregnancy and offspring asthma in an ongoing birth cohort study. Maternal overweight may affect the pulmonary and immunological development of the fetus in utero because of the increased levels of inflammatory factors associated with being overweight and thereby increase the asthma risk in childhood.Design:Birth cohort study with follow-up until 8 years of age.Subjects:The study population included 3963 children and their mothers who participated in the Prevention and Incidence of Asthma and Mite Allergy study.Measurements:Maternal overweight before pregnancy was defined as a body mass index (BMI) above 25 kg m 2. Data on wheeze, dyspnea and prescription of inhaled corticosteroids of the child were reported yearly by the parents in a questionnaire. Sensitization to inhalant allergens and bronchial hyperresponsiveness (BHR) were determined at 8 years. Effect modification by predisposition for asthma in the child was tested. Data were analyzed by logistic regression and generalized estimating equations analyses.Results:At 8 years, 14.4% (n571) of the children had asthma. In total, 20.9% (n830) of the mothers were overweight before pregnancy. In children predisposed for asthma (n1058), maternal overweight before pregnancy was associated with an increased risk of asthma in the child at 8 years (OR1.52, 95% CI: 1.05-2.18) after adjustment for confounding factors, birth weight and the child's BMI. No association was observed in children without a predisposition (OR0.86, 95% CI: 0.60-1.23). There was no association with sensitization or BHR.Conclusion: Children with a predisposition for asthma may have a higher risk to develop asthma during childhood when their mothers are overweight before pregnancy, irrespective of the child's BMI. http://repub.eur.nl/res/pub/32732/ 2010-03-15T00:00:00Z Rationale: The role of air pollution exposure in the development of asthma, allergies,andrelatedsymptomsremains unclear,duein part to the limited number of prospective cohort studies with sufficiently long follow-ups addressing this problem. Objectives: We studied the association between traffic-related air pollution and the development of asthma, allergy, and related symptoms in a prospective birth cohort study with a unique 8-year follow-up. Methods: Annual questionnaire reports of asthma, hay fever, and related symptoms during the first 8 years of life were analyzed for 3,863 children. At age 8, measurements of allergic sensitization and bronchial hyperresponsiveness were performed for subpopulations (n = 1,700 and 936, respectively). Individual exposures to nitrogen dioxide (NO2), particulate matter (PM2.5), and soot at the birth address were estimated by land-use regression models. Associations between exposure to traffic-related air pollution and repeated measures of health outcomes were assessed by repeated-measures logistic regression analysis. Effects are presented for an interquartile range increase in exposure after adjusting for covariates. Measurements and Main Results: Annual prevalence was 3 to 6% for asthma and 12 to 23% for asthma symptoms. Annual incidence of asthma was 6%at age 1, and 1 to 2%at later ages. PM2.5levels were associated with a significant increase in incidence of asthma (odds ratio [OR], 1.28;95%confidenceinterval [CI], 1.10-1.49), prevalence of asthma (OR, 1.26; 95% CI, 1.04-1.51), and prevalence of asthma symptoms (OR, 1.15; 95% CI, 1.02-1.28). Findings were similar for NO2 and soot. Associations were stronger for children who had not moved since birth. Positive associations with hay fever were found in nonmovers only. No associations were found with atopic eczema, allergic sensitization, and bronchial hyperresponsiveness. Conclusions: Exposure to traffic-related air pollution may cause asthma in children. http://repub.eur.nl/res/pub/19875/ 2010-03-01T00:00:00Z Objective. Many studies evaluated asthma medication use in children in a cross-sectional manner, yet little is known about longitudinal use patterns. This study describes the formation of a longitudinal data set on asthma medication use and shows first results regarding the prevalence and incidence of medication use. Methods. The PIAMA (Prevention and Incidence of Asthma and Mite Allergy) study is a prospective birth cohort study among 3963 Dutch children. Recruitment took place in 1996-1997. The data of the PIAMA birth cohort study were complemented with pharmacy data. Prescription information of family members was used to determine whether medication histories were complete from birth until age 8. The prevalence and incidence of asthma medication use was studied in children for whom complete medication histories were available. Results. A first prescription for asthma medication was filled before age 8 by 280 (36%) children, with 88% starting therapy before age 5. Of all children who started therapy, 91.1% received short-acting β2-agonists and 61.1% inhaled corticosteroids. Conclusion. The applied method of data collection rendered a data set including 777 children with complete medication histories for their first 8 years of life. This data set provides the opportunity to study longitudinal medication use patterns. First analyses show that asthma medication is initiated in a rather high percentage of children in this cohort and mainly at an age at which an asthma diagnosis cannot yet be firmly established. http://repub.eur.nl/res/pub/21430/ 2010-01-01T00:00:00Z Background: Maternal exposure to air pollution has been associated with adverse pregnancy outcomes. Few studies took into account the spatial and temporal variation of air pollution levels. Objectives: To evaluate the impact of maternal exposure to traffic-related air pollution during pregnancy on preterm birth and term birth weight using a spatio-temporal exposure model. Methods: We estimated maternal residential exposure to nitrogen dioxide (NO2), particulate matter (PM2.5) and soot during pregnancy (entire pregnancy, 1st trimester, and last month) for 3853 singleton births within the Dutch PIAMA prospective birth cohort study by means of temporally adjusted land-use regression models. Associations between air pollution concentrations and preterm birth and term birth weight were analyzed by means of logistic and linear regression models with and without adjustment for maternal physical, lifestyle, and socio-demographic characteristics. Results: We found positive, statistically non-significant associations between exposure to soot during entire pregnancy and during the last month of pregnancy and preterm birth [adj. OR (95% CI) per interquartile range increase in exposure 1.08 (0.88-1.34) and 1.09 (0.93-1.27), respectively]. There was no indication of an adverse effect of air pollution exposure on term birth weight. Conclusions: In this study, maternal exposure to traffic-related air pollution during pregnancy was not associated with term birth weight. There was a tendency towards an increased risk of preterm birth with increasing air pollution exposure, but statistical power was low. http://repub.eur.nl/res/pub/21795/ 2010-01-01T00:00:00Z http://repub.eur.nl/res/pub/24794/ 2009-12-01T00:00:00Z Background: Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear. Methods: FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure. Results: The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4-2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8-7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6-25.9, 6.0; 95% CI: 3.2-11.3 and 5.4; 95% CI: 1.2-23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5-10.5). Conclusions: FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization. http://repub.eur.nl/res/pub/16732/ 2009-11-01T00:00:00Z The association between helminth infections and childhood atopic diseases remains controversial. The majority of studies have been carried out in tropical areas, whereas less information is available from western countries with low intensity of helminth infections. In the Netherlands, the infection of pigs with Ascaris suum is very common, particularly on pig farms with outdoor facilities. This helminth can also infect humans, causing visceral larva migrans. This study aims at determining the prevalence of antibodies against A. suum and its association with allergic symptoms and sensitisation in a population of 4-year-old children living in the Netherlands. Blood samples from 629 children from the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study were examined for Ascaris antibodies. Data on allergic symptoms and sensitisation were collected using questionnaires and radioallergosorbent tests (RAST). A total of 45 out of 629 (7%) were found to be Ascaris-seropositive. In addition, a positive association between Ascaris seropositivity and wheeze in the last year, doctor-diagnosed asthma and food and aero-allergen sensitisation was found. These results support the hypothesis that low-level or transient infection with helminths enhances allergic reactivity. http://repub.eur.nl/res/pub/17097/ 2009-11-01T00:00:00Z Background: Clinicians have difficulty in diagnosing asthma in preschool children with suggestive symptoms. Objective: We sought to develop a clinical asthma prediction score for preschool children who have asthma-like symptoms for the first time. Methods: The Prevalence and Incidence of Asthma and Mite Allergy birth cohort followed 3,963 children for 8 years. Between 0 and 4 years of age, 2,171 (55%) children reported "wheezing," "coughing at night without a cold," or both. In these children possible predictor variables for asthma were assessed at the age respiratory symptoms were first reported. Asthma was defined as wheezing, inhaled steroid prescription, or a doctor's diagnosis of asthma at both age 7 and 8 years of age. Results: Eleven percent of children with symptoms at 0 to 4 years of age had asthma at 7 to 8 years of age. Eight clinical parameters independently predicted asthma at 7 to 8 years of age: male sex, postterm delivery, parental education and inhaled medication, wheezing frequency, wheeze/dyspnea apart from colds, respiratory infections, and eczema. In 72% of the cases, the model accurately discriminated between asthmatic and nonasthmatic children. A clinical risk score was developed (range, 0-55 points). Symptomatic children with a score of less than 10 points had a 3% risk, whereas children with a score of 30 points or greater had a 42% risk of asthma. Conclusion: A risk score based on 8 readily available clinical parameters at the time preschool children first reported asthma-like symptoms predicted the risk of asthma at 7 to 8 years of age. http://repub.eur.nl/res/pub/24800/ 2009-11-01T00:00:00Z The guidelines of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) for standardized measurements of exhaled nitric oxide (NO) state that for online measurements the inhaled air should be free of NO. As it is not always possible to create an NO-free environment, inhalation through an NO-scrubber is used. To describe the relationship between ambient NO and measurements of fractional exhaled NO (FENO) and nasal NO (nNO) investigated according to the ATS-ERS guidelines in a large population of children. The present work makes use of data collected during the 8-yr follow-up of the Dutch PIAMA birth cohort study. FENO and nNO were measured in three hospitals in a total of 1005 children with a NIOX chemiluminescence analyser. In two hospitals, almost half of the measured ambient NO levels exceeded 5 p.p.b. Maximum levels were >100 p.p.b. in all hospitals. Despite its large variation, ambient NO did not have an effect on FENO, but it did have a significant impact on nNO in two of the three centres. The currently recommended technique including inhalation through an NO scrubber effectively deals with variable levels of ambient NO on FENO. In contrast, ambient NO has an effect on measurements of nNO. http://repub.eur.nl/res/pub/17504/ 2009-09-15T00:00:00Z Rationale: Daycare exposes young children to more infections early in life and may thereby prevent the development of asthma and allergy. Objectives: To prospectively study the effect of daycare on the development of asthma and allergic sensitization during the first 8 years of life. Methods: In the Prevention and Incidence of Asthma and Mite Allergy birth cohort 3,963 newborn children were followed prospectively for 8 years. Daycare use and respiratory health were assessed yearly by questionnaires. At 8 years, sensitization to airborne allergens and airway responsiveness were measured. Daycare was defined as early (aged 0-2 yr), late (aged 2-4 yr), or none (no daycare before age 4 yr). Associations of daycare and/or older siblings with asthma symptoms (wheezing, shortness of breath, and inhaled steroids taken in the last year), airway responsiveness, and allergic sensitization were assessed in a longitudinal repeated-event analysis. Measurements and Main Results: Children with early daycare had more wheezing in the first years of life, but less wheezing and steroid use between 4 and 8 years of age. At the age of 8 years, early daycare was not protective for asthma symptoms (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.74-1.32), allergic sensitization (aOR 0.86; 95% CI, 0.63-1.18), or airway hyperresponsiveness (aOR, 0.80; 95% CI, 0.57-1.14). The transient reduction in airway symptoms between age 4 and 8 years was only observed in children without older siblings. Conclusion: Early daycare is associated with an increase in airway symptoms until the age of 4 years, and fewer symptoms between the ages of 4 and 8 years. We found no protection against asthma symptoms, hyperresponsiveness, or allergic sensitization at the age of 8 years. http://repub.eur.nl/res/pub/24793/ 2009-08-01T00:00:00Z Background: Recall bias may provide discrepant relationships of pet exposure with sensitization and asthma development. We studied prospectively effects of pets at home on development of sensitization, asthma and respiratory symptoms from birth up to age 8 years. Methods: Event history analysis was performed on annually registered data of 2951 children, participating in the PIAMA birth cohort study. Results: Children with a cat or dog at home at 3 months of age had a significantly lower prevalence of sensitization to inhalant allergens at age 8, but not of asthma. A cat decreased the risk of house dust mite sensitization at age 8 [odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.49-0.95], a dog of pollen sensitization (OR = 0.49, 95% CI: 0.29-0.83). A cat or dog at home did not significantly affect asthma incidence in each subsequent year. From 2 years of age onwards, the incidence of wheeze (OR = 1.52, 95% CI: 1.12-2.05) and a dry cough at night (OR = 1.28, 95% CI: 1.05-1.57) was higher in children with a dog, whereas removal of a dog increased the risk of developing asthma symptoms. Comparing analyses using prospectively and retrospectively collected data on diagnosed asthma showed important recall bias. Conclusions: Our prospective study shows a protective effect of early presence of pets at home on sensitization to inhalant allergens, but no prevention of asthma development. Furthermore, children with pets had more frequent transient or intermittent asthma symptoms. Parental report of asthma by recall may provide spurious results of these associations. http://repub.eur.nl/res/pub/24910/ 2009-07-01T00:00:00Z Background: It is unclear how the association between breast feeding and asthma develops with age of the child and how this association over time is influenced by maternal or paternal allergy. These factors - the age of the child and maternal or paternal allergy - might partly explain the conflicting results observed in cross-sectional studies. Methods: The study population consisted of 3115 Dutch children born in 1996/1997 who participated in the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Data on breast feeding and asthma (based on wheeze, dyspnoea and prescription of inhaled steroids) were collected by yearly questionnaires. At 8 years, specific immunoglobulin E (IgE) to airborne allergens and bronchial responsiveness were measured. Data were analysed by logistic regression and generalised estimating equations (GEEs), and stratified by maternal and paternal allergic status. Results: 35% (n=1081) of the children were breast fed for >16 weeks. At 8 years of age, 12.6% (n=392) had asthma. Breast feeding (>16 weeks vs no breast feeding) was significantly associated with a lower asthma prevalence from 3 to 8 years of age, in children of both non-allergic and allergic mothers. The inverse association between breast feeding and sensitisation to airborne allergens at 8 years was non-significant. Breast feeding was not associated with bronchial hyper-responsiveness. No interaction between breast feeding and gender, maternal allergy or paternal allergy was observed in any of the associations. Conclusions: Breast feeding is associated with a lower asthma risk in children until 8 years of age without evidence of attenuation and regardless of the family history of allergy. http://repub.eur.nl/res/pub/16304/ 2009-06-01T00:00:00Z Introduction: ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV1) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. Aim: To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene-environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. Methods: Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV1 and BHR at age 8 years; asthma was based on questionnaire data at age 8. Results: In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV1% predicted. Conclusions: We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation. http://repub.eur.nl/res/pub/24404/ 2009-06-01T00:00:00Z Background: Asthma may be more prevalent in overweight children. However, how early overweight and changes in weight status during childhood affect the asthma risk is unclear. Objectives: To investigate overweight and changes in overweight status in children age 1 to 8 years in relation to asthma symptoms in childhood. Methods: We studied 3756 children who participated in a large birth cohort study. The parents reported their children's weight and height, and wheeze, dyspnea, and prescription of inhaled corticosteroids in yearly questionnaires. Sensitization to inhalant allergens and bronchial hyperresponsiveness (BHR) were determined at 8 years. Results: At 8 years, 275 children (7.3%) wheezed, 361 (9.6%) had dyspnea, and 268 (7.1%) had a prescription of inhaled corticosteroids in the preceding year. Children who had a persistent high body mass index (BMI, weight/height2) during childhood or a high BMI at 6 to 7 years had a significantly increased risk of dyspnea (adjusted odds ratio, 1.68; 95% CI, 1.18-2.39, for a high BMI at 6-7 years) and measured BHR (adjusted odds ratio, 1.66; 95% CI, 1.10-2.52) at 8 years. Children with a high BMI at a young age, but who developed a normal BMI at 6 to 7 years, did not have an increased risk of dyspnea or BHR at 8 years. BMI was not associated with sensitization. Conclusion: Children with a current high BMI are at increased risk to have dyspnea and BHR at 8 years. A high BMI at an earlier age is not related to an increased risk if the child has become normal weight at 6 to 7 years. http://repub.eur.nl/res/pub/25401/ 2009-04-01T00:00:00Z OBJECTIVE. Studies among patients have shown accelerated weight gain after (adeno)tonsillectomy.* Whether (adeno)tonsillectomy is also a risk factor for the development of overweight is unknown. We investigated the association between (adeno)tonsillectomy and the subsequent development of overweight in the general population. METHODS. The study population consisted of 3963 children participating in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort. Data on weight and height, adenoidectomy and tonsillectomy, and covariates (gender, birth weight, maternal education, maternal overweight, maternal smoking during pregnancy, breastfeeding, and smoking in the home) were obtained from annual questionnaires completed by the parents. In addition to the questionnaire data, weight and height were measured by the investigators when the children were 8 years old. RESULTS. (Adeno)tonsillectomy between 0 and 7 years of age was significantly associated with overweight and obesity at age 8. Overweight at the age of 2 years was not associated with increased risk of (adeno)tonsillectomy in later years, indicating that the association between (adeno)tonsillectomy and overweight was not explained by preexisting overweight. Longitudinal data on weight and height in the years before and after surgery suggest that (adeno)tonsillectomy forms a turning point between a period of growth faltering and a period of catch-up growth, which might explain the increased risk to develop overweight after the operation. CONCLUSION. Children who undergo (adeno)tonsillectomy are at increased risk to develop overweight in the years after surgery. Copyright http://repub.eur.nl/res/pub/15836/ 2009-03-01T00:00:00Z Ficolins are pattern-recognition molecules that appear to be relevant for innate immune defence against infections. The ficolin genes in Caucasians are polymorphic and genetic variations may have functional consequences, both in relation to function and concentration. Low levels of Ficolin-2 have been suggested to associate with recurrent respiratory tract infections (RTI), whereas data on Ficolin-3 are still very limited. We investigated the association between variation in genes encoding Ficolin-2 (FCN2) and Ficolin-3 (FCN3) and frequency of RTI during the first 4 years of life. The study population consisted of 900 children from a large, population-based birth cohort of Dutch children, followed prospectively from birth to 4 years of age. The number of RTI was assessed by annual parental questionnaires. Nine single nucleotide polymorphisms in FCN2 and two in FCN3, all based on functionality or haplotype-tagging characteristics, were determined and haplotypes constructed. We found that single nucleotide polymorphisms in FCN2 and FCN3 were not associated with increased risk of RTI during the first 4 years of life. No difference existed between haplotype-frequencies of FCN2 and FCN3 in children grouped according to the reported number of RTI. In conclusion, at a population level, genetic variation in ficolin genes FCN2 and FCN3 do not seem to contribute to the risk of RTI in Caucasian children. http://repub.eur.nl/res/pub/24911/ 2009-02-01T00:00:00Z Background: Caesarean section might be a risk factor for asthma because of delayed microbial colonisation, but the association remains controversial. A study was undertaken to investigate prospectively whether children born by caesarean section are more at risk of having asthma in childhood and sensitisation at the age of 8 years, taking into account the allergic status of the parents. Methods: 2917 children who participated in a birth cohort study were followed for 8 years. The definition of asthma included wheeze, dyspnoea and prescription of inhaled steroids. In a subgroup (n = 1454), serum IgE antibodies for inhalant and food allergens were measured at 8 years. Results: In the total study population, 12.4% (n = 362) of the children had asthma at the age of 8 years. Caesarean section, with a total prevalence of 8.5%, was associated with an increased risk of asthma (OR 1.79; 95% CI 1.27 to 2.51). This association was stronger among predisposed children (with two allergic parents: OR 2.91; 95% CI 1.20 to 7.05; with only one: OR 1.86; 95% CI 1.12 to 3.09) than in children with non-allergic parents (OR 1.36; 95% CI 0.77 to 2.42). The association between caesarean section and sensitisation at the age of 8 years was significant only in children of non-allergic parents (OR 2.14; 95% CI 1.16 to 3.98). Conclusions: Children born by caesarean section have a higher risk of asthma than those born by vaginal delivery, particularly children of allergic parents. Caesarean section increases the risk for sensitisation to common allergens in children with non-allergic parents only. http://repub.eur.nl/res/pub/25459/ 2009-01-01T00:00:00Z The long-chain PUFA (LCPUFA) content of an infant's diet might affect early weight gain. In early trials on supplementation of formula feeding n-3 LCPUFA affected weight gain adversely. n-6 LCPUFA are thought to promote adipose tissue development and might be associated with higher weight gain. We studied the association between the natural n-3 and n-6 LCPUFA content of breast milk of Dutch women and weight and BMI gain of their breast-fed infants in the first year of life. The children in this study were enrolled in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and were born in 1996-1997 in the Netherlands. Parents reported their child's weight and length in a questionnaire. Of a subgroup of the total population breast-milk samples were collected (n 244). The fatty acid composition of breast milk was determined by GLC and expressed as weight percentages. Linear regression was used for data analysis. Mean gain in weight, length and BMI per week from birth to 1 year of age was 119.5 (sd 16.1) g, 0.48 (sd 0.05) cm and 0.06 (sd 0.03) kg/m2, respectively. The associations between n-6 and n-3 LCPUFA in breast milk, and infant weight, length and BMI gain were weak and inconsistent. The n-3 and n-6 LCPUFA content in breast milk did not affect weight or BMI gain in the first year of life in breast-fed term infants. http://repub.eur.nl/res/pub/32352/ 2008-12-15T00:00:00Z Rationale: Single and serial spirometric data are commonly compared with predicted values to assess pulmonary function and normal lung growth. Objectives: Do reference equations adequately describe pulmonary function in a population and in growing individuals? Methods: We applied five sets of reference equations with appropriate age ranges to cross-sectional data of FEV1, FVC, and FEV1/FVC from the United States, Estonia, and The Netherlands (1,487 boys and 1,340 girls, 6 to 18 years of age), and to serial measurements in Dutch (430 girls and 769 boys, 6 to 19 years of age) and in German and Austrian children (1,305 girls and 1,303 boys, 6 to 13 years of age). Measurements and Main Results: Compared with reference equations from Polgar and Zapletal, cross-sectional FEV1and FVC declined between the ages of 6 and 12 and then increased, leading to a spurious change of up to 25% predicted; this pattern was most pronounced in boys. In cross-sectional data this trend was much weaker when using reference equations from Hankinson, Quanjer, and Stanojevic, and these equations provided a good fit from the age of 12 upward. In longitudinal data (i.e., within individuals), the trend was more pronounced for FEV1in boys than in girls. No set of equations provideda satisfactoryfit in the lower limits of normal, but Hankinson and Stanojevic equations performed best. Conclusions: Spirometric reference equations that use only height for predicting pulmonary function are unsuitable for describing the progression of pulmonary function. Those that incorporate height and age demonstrate some discrepancy with longitudinal data. Failure to take these spurious trends into account leads to significant errors in estimating the natural course of respiratory disease, in allocating patients to treatment groups, or in assessing long-term effects of drug intervention in school children and adolescents. http://repub.eur.nl/res/pub/14149/ 2008-12-01T00:00:00Z Background. Low mannan-binding lectin (MBL) levels, caused by MBL2 polymorphisms, are suggested to contribute to susceptibility to respiratory tract infections (RTIs), particularly early in life. Large-scale replication of previous associations is needed, however. We investigated the association between MBL2 polymorphisms and the frequency of RTI in a large population-based birth cohort of white children. Methods. The frequency of RTI was prospectively assessed by annual parental questionnaires until children were 4 years of age. Thirteen polymorphisms in MBL2 were determined in 987 Dutch children. Haplotypes, previously shown to be associated with functional levels of MBL, were constructed, and their associations with the frequency of RTI during year 1, year 2, and the first 4 years of life were assessed. High-producing, intermediate-producing, and deficient MBL2 genotypes were defined on the basis of exon 1 and Y/X promoter polymorphisms. Results. No differences were found between investigated polymorphisms and haplotype frequencies in the population as a whole or between the groups with frequent, moderately frequent, or no RTIs reported. Deficient MBL2 genotypes were not associated with an increased risk of RTI (odds ratio, 0.71 [95% confidence interval, 0.25 to 2.05]) during years 1-4 of life. This was also true when year 1 and year 2 were studied separately. Conclusion. These results suggest that, at the population level, MBL2 polymorphisms do not contribute to the risk of questionnaire-reported RTI in white children. http://repub.eur.nl/res/pub/14422/ 2008-11-01T00:00:00Z Breastfeeding has been associated with a reduced risk of overweight later in life. This study investigates whether differences in diet and lifestyle at 7 years of age between breastfed and formula-fed children can explain the difference in overweight prevalence at 8 years of age. We studied 2,043 Dutch children born in 1996-1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Data on breastfeeding duration and diet and lifestyle factors at 7 years were collected using questionnaires. Weight and height were measured at 8 years. Overweight was defined according to international gender- and age-specific standards. Compared to nonbreastfed children (15.5%, n = 316), children breastfed for >16 weeks (38.0%, n = 776) consumed fruit and vegetables significantly more often and meat, white bread, carbonated soft drinks, chocolate bars, and fried snacks less often. Overall, breastfed children were less likely to have an unhealthy diet (adjusted prevalence ratio: 0.77, 95% confidence interval: 0.61-0.98). The associations could only partly be explained by maternal education, maternal overweight, and smoking during pregnancy. At 8 years, 14.5% (n = 297) of the children were overweight. Breastfeeding for >16 weeks was significantly associated with a lower overweight risk at 8 years (adjusted odds ratio: 0.67, 95% confidence interval: 0.47-0.97), and the association hardly changed after adjustment for diet (adjusted odds ratio: 0.71, 95% confidence interval: 0.49-1.03). Breastfed children had a healthier diet at 7 years compared to nonbreastfed children, but this difference could not explain the lower overweight risk at 8 years in breastfed children. © 2008 The Obesity Society. http://repub.eur.nl/res/pub/15937/ 2008-10-01T00:00:00Z Objective: In young children with asthmatic symptoms diagnostic difficulties lead to use of trials of asthma medication as a diagnostic tool. Our aim is to quantify the persistent use of asthma medication, initiated in the first year of life and identify determinants of this persistent use. Patients and methods: We identified 165 children within the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort who used asthma medication before the age of one. Persistent use was investigated during three years after the first prescription. A Cox regression analysis was performed to identify factors associated with persistent use. Results: A total of 58.8% of children continued using asthma medication after the first prescription and 10.3% continued during three years. Children with doctor-diagnosed asthma (Hazard ratio of discontinuation (HR) = 0.64, 95% CI: 0.45-0.91) or prescribed inhaled corticosteroids in the first year of life (HR of discontinuation = 0.59, 95% CI: 0.40-0.86) were 1.6-1.7 times more likely to continue using asthma medication. Conclusions: Persistence of asthma medication, prescribed in the first year of life is very low and is positively associated with doctor-diagnosed asthma and use of inhaled corticosteroids. Characterizing persistent users of asthma medication is important to understand prescribing of asthma medication in this age group. http://repub.eur.nl/res/pub/32502/ 2008-07-15T00:00:00Z Rationale: Maternal diet during pregnancy has the potentialto affect airway development and to promote T-helper-2-cell responses during fetal life. This might increase the riskofdeveloping childhood asthma or allergy. Objectives:We investigated the influence of maternal food consumption during pregnancy on childhood asthma outcomes from 1 to 8 years of age. Methods: A birth cohort study consisting of a baseline of 4,146 pregnant women(1,327 atopic and 2,819nonatopic).These women were asked about their frequency of consumption of fruit, vegeta-bles, fish, egg, milk, milk products, nuts, and nut products during the last month. Their children were followed until 8 years of age. Longitudinal analyses were conducted to assess associations between maternal diet during pregnancy and childhood asthma outcomes over 8 years. Measurements and Main Results: Complete data were obtained for 2,832 children. There were no associations between maternal vegetable, fish, egg, milk or milk products, and nut consumption and longitudinal childhood outcomes. Daily consumptionofnut products increased the risk of childhood wheeze (odds ratio [OR] daily versus rare consumption, 1.42; 95% confidence interval [95% CI], 1.06-1.89), dyspnea (OR, 1.58; 95% CI, 1.16-2.15), steroid use (OR, 1.62; 95% CI, 1.06-2.46), and asthma symptoms (OR, 1.47; 95% CI, 1.08-1.99). Conclusions: Results of this study indicate an increased risk of daily versus rare consumption of nut products during pregnancy on child-hood asthma outcomes.These findings need to be replicated by other studies before dietary advice can be given to pregnant women. http://repub.eur.nl/res/pub/30350/ 2008-07-15T00:00:00Z Studies have presented conflicting associations between cat allergen exposure and sensitisation and atopic disease. We therefore investigated the association between the observed domestic cat allergen level and cat sensitisation in young children in four study populations from three European countries. We recruited children from a nested case-control study, which is composed of four ongoing birth cohorts conducted in three European countries. Children at 2-4 years of age in the four cohorts who were sensitised to cat allergens (n=106) were compared with 554 non-sensitised children (controls). House dust samples were collected when the children were 5 to 7 years old, and cat allergen levels were measured in ng/g dust and ng/m2surface area. In the German study population we found a positive association between domestic cat allergen in house dust and cat sensitisation (OR (CI)=3.01 (1.16, 7.99)) while in the Swedish study population, we found a negative association (OR (CI)=0.41 (0.16, 0.98)). No association was found in the Dutch study population (OR (CI)=0.83 (0.22, 2.93)). Looking into the family history of cat keeping, we found the lowest prevalence of cat sensitisation in children who were cat owners at the age of blood sampling (11%) and the highest prevalence was found in those who have had a cat but not anymore, at the age of blood sampling (41%). The mixed results may be explained by differences in age and avoidance patterns. http://repub.eur.nl/res/pub/30376/ 2008-02-26T00:00:00Z Background. In pre-school children a diagnosis of asthma is not easily made and only a minority of wheezing children will develop persistent atopic asthma. According to the general consensus a diagnosis of asthma becomes more certain with increasing age. Therefore the congruence between asthma medication use and doctor-diagnosed asthma is expected to increase with age. The aim of this study is to evaluate the relationship between prescribing of asthma medication and doctor-diagnosed asthma in children age 0-17. Methods. We studied all 74,580 children below 18 years of age, belonging to 95 GP practices within the second Dutch national survey of general practice (DNSGP-2), in which GPs registered all physician-patient contacts during the year 2001. Status on prescribing of asthma medication (at least one prescription for beta2-agonists, inhaled corticosteroids, cromones or montelukast) and doctor-diagnosed asthma (coded according to the International Classification of Primary Care) was determined. Results. In total 7.5% of children received asthma medication and 4.1% had a diagnosis of asthma. Only 49% of all children receiving asthma medication was diagnosed as an asthmatic. Subgroup analyses on age, gender and therapy groups showed that the Positive Predictive Value (PPV) differs significantly between therapy groups only. The likelihood of having doctor-diagnosed asthma increased when a child received combination therapy of short acting beta2-agonists and inhaled corticosteroids (PPV = 0.64) and with the number of prescriptions (3 prescriptions or more, PPV = 0.66). Both prescribing of asthma medication and doctor-diagnosed asthma declined with age but the congruence between the two measures did not increase with age. Conclusion. In this study, less than half of all children receiving asthma medication had a registered diagnosis of asthma. Detailed subgroup analyses show that a diagnosis of asthma was present in at most 66%, even in groups of children treated intensively with asthma medication. Although age strongly influences the chance of being treated, remarkably, the congruence between prescribing of asthma medication and doctor-diagnosed asthma does not increase with age. http://repub.eur.nl/res/pub/36734/ 2007-08-01T00:00:00Z Background: In adults, body weight tends to be underestimated when based on self-reported data. Whether this discrepancy between measured and reported data exists in healthy young children is unclear. We studied whether parental reported body weight and height of 4-year-old children corresponded with measured body weight and height. In addition, we studied the determinants and the consequences of differences between reported and measured data. Methods: Data on body weight and height of 864 4-year-old Dutch children born in 1996/1997 enrolled in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study were collected via a questionnaire and a medical examination. Overweight was defined according to standard international age and gender specific definitions. Results: Mean differences between measured and reported body weight, height, and body mass index (BMI) were small. Parents of children with a low BMI tended to over report body weight while parents of children with a high BMI tended to underreport body weight. Whereas 9.5% of the children were overweight according to reported BMI, the prevalence of overweight was 13.4% based on measured BMI. Over 45% of the overweight children according to measured BMI were missed when reported BMI was used. Conclusion: These findings suggest that overweight prevalence rates in children are underestimated when based on reported weight and height. http://repub.eur.nl/res/pub/36893/ 2007-07-06T00:00:00Z Background. A higher prevalence of respiratory symptoms and an associated increase in health care utilization among children with parents who smoke is to be expected. From previous studies however, it appears that parents who smoke may underutilize health services for their children, especially with respect to respiratory care. This study explores the validity and generalizability of the previous assumption. Methods. Data were obtained from a Dutch birth-cohort study; the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) project. Information regarding parental smoking, the child's respiratory symptoms and health care use and potential confounders were obtained by postal questionnaires. Multivariate logistic models were used to relate parental smoking to the child's respiratory symptoms and health care use. Results. The study comprised 3,564, 4-year old children. In the crude analysis, respiratory symptoms were more frequent among children with a parent who smoked, while health care utilization for respiratory symptoms was not significantly different between children with or without a parent who smoked. In the multivariate analyses, maternal smoking had a larger impact on the child's respiratory symptoms and health care use as compared to paternal smoking. Maternal smoking was positively associated with mild respiratory symptoms of the child, adjusted odds ratio [AOR] 1.50 (1.19-1.91), but not with severe respiratory symptoms AOR 1.03 (0.75-1.40). Among children with mild respiratory symptoms, children with a mother who smoked were less likely to be taken to the general practitioner (GP) for respiratory symptoms, than children with mothers who did not smoke, AOR 0.58 (0.33-1.01). This finding was less pronounced among children with severe respiratory symptoms AOR 0.86 (0.49-1.52). Neither GP visits for non-respiratory symptoms nor specialized care for respiratory disease were significantly associated with parental smoking. Conclusion. Mothers who smoke appear to underutilize health care for their children with mild respiratory symptoms. Health care workers should be informed about this phenomenon. Inquiring after the respiratory health of the children during regular visits to healthy baby clinics may help to track potential underutilization of care. http://repub.eur.nl/res/pub/36453/ 2007-06-01T00:00:00Z It has been suggested that early childhood exposure to microbial agents decreases the risk of allergies in children. The current authors studied the association between microbial agents in house dust and allergic sensitisation in children aged 2-4 yrs. Nested case-control studies were performed within ongoing birth cohort studies in Germany, the Netherlands and Sweden and ∼180 sensitised and 180 nonsensitised children were selected per country. Levels of bacterial endotoxin, β(1,3)-glucans and fungal extracellular polysaccharides (EPS) were measured in dust samples from the children's mattresses and the living-room floors. Combined across countries, higher amounts of mattress dust and higher mattress dust loads of endotoxin, β(1,3)-glucans and EPS were associated with a significantly decreased risk of sensitisation to inhalant allergens. After mutual adjustment, only the protective effect of the amount of mattress dust remained significant (odds ratio (95% confidence interval) 0.57(0.39-0.84)). Higher amounts of mattress dust may decrease the risk of allergic sensitisation to inhalant allergens. The effect might be partly attributable to endotoxin, β(1,3)-glucans and extracellular polysaccharides, but could also reflect (additional) protective effects of (microbial) agents other than the ones measured. It is not possible to distinguish with certainty which component relates to the effect, since their levels are highly correlated. Copyright http://repub.eur.nl/res/pub/36645/ 2007-05-15T00:00:00Z Rationale: The relation between birth weight and respiratory symptoms and asthma in children remains unclear. Previous studies focused on a relation at separate ages. A longitudinal analysis may lead to a better understanding. Objectives: To estimate the effect of birth weight on the development and course of respiratory symptoms and asthma in the first 7 years of life. Methods: In a prospective birth cohort study, 3,628 children with a gestational age 37 weeks or more were monitored for 7 years. Parental questionnaires were used to assess respiratory health yearly. Associations of birth weight with respiratory symptoms (wheezing, coughing, respiratory infections) and doctor's diagnosis of asthma were assessed in a repeated-event analysis. Measurements and Main Results: Lower birth weight was associated with more respiratory symptoms (odds ratio [OR] per kg decrease in birth weight, 1.21; 95% confidence interval [CI], 1.09-1.34). The effect of birth weight increased from age 1 to 5, but decreased thereafter and was no longer significant at the age of 7. The effect of birth weight on respiratory symptoms was significantly greater among children exposed to tobacco smoke in their home than among nonexposed children (OR at 5 yr: 1.21 [95% CI, 1.02-1.44] and 1.52 [95% CI, 1.23-1.87], respectively). Birth weight and a doctor's diagnosis of asthma were not related (OR, 1.06; 95% CI, 0.82-1.37). Conclusions: A lower birth weight in children born at term is associated with a transiently increased risk of respiratory symptoms. This effect is enhanced by environmental tobacco smoke exposure. http://repub.eur.nl/res/pub/36471/ 2007-05-01T00:00:00Z Few studies have addressed associations between traffic-related air pollution and respiratory disease in young children. The present authors assessed the development of asthmatic/allergic symptoms and respiratory infections during the first 4 yrs of life in a birth cohort study (n=∼4,000). Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM2.5, particles with a 50% cut-off aerodynamic diameter of 2.5 μm and soot) were assigned to birthplace home addresses with a land-use regression model. They were linked by logistic regression to questionnaire data on doctor-diagnosed asthma, bronchitis, influenza and eczema and to self-reported wheeze, dry night-time cough, ear/nose/ throat infections and skin rash. Total and specific immunoglobulin (Ig)E to common allergens were measured in a subgroup (n=713). Adjusted odds ratios (95% confidence intervals) per interquartile pollution range were elevated for wheeze (1.2 (1.0-1.4) for soot), doctor-diagnosed asthma (1.3 (1.0-1.7)), ear/nose/throat infections (1.2 (1.0-1.3)) and flu/serious colds (1.2 (1.0-1.4)). No consistent associations were observed for other end-points. Positive associations between air pollution and specific sensitisation to common food allergens (1.6 (1.2-2.2) for soot), but not total IgE, were found in the subgroup with IgE measurements. Traffic-related pollution was associated with, respiratory infections and some measures of asthma and allergy during the first 4 yrs of life. Copyright http://repub.eur.nl/res/pub/35501/ 2007-04-01T00:00:00Z Compared with nonbreastfed children, breastfed children tend to have a lower body mass index (BMI) at about 1 year of age. How the BMI of breastfed children develops after the first year when this difference in BMI at 1 year of age is considered is not clear. The authors studied the association between breastfeeding and BMI development from 1 to 7 years of age independently of BMI at 1 year of age. Longitudinal BMI data reported by parents of 2,347 Dutch children born in 1996-1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study were collected. Linear regression and mixed-effects models were used for data analyses. Mean BMI at 1 year of age was 17.2 kg/m2(standard deviation, 1.4). Compared with nonbreastfed children, children breastfed for >16 weeks had a lower BMI at 1 year of age, after adjustment for confounders (β = -0.22, 95% confidence interval: -0.39, -0.06). The association between breastfeeding and BMI between 1 and 7 years of age was negligible, while a high BMI at 1 year of age was strongly associated with a high BMI between 1 and 7 years of age in the same model. These findings suggest that the lower BMI and lower risk of overweight among breastfed children later in life are already achieved at 1 year of age. Copyright http://repub.eur.nl/res/pub/8517/ 2002-01-01T00:00:00Z AIMS: To evaluate ethnic differences in the prevalence of respiratory and skin symptoms in the first two years of life. METHODS: A total of 4146 children participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study. Parents completed questionnaires on respiratory and skin symptoms, ethnic background, and other potential confounders during pregnancy, and at 3 months, 1 year, and 2 years of age. RESULTS: In the first year, "non-Dutch" children (compared with "Dutch" children) had a higher prevalence of runny nose with itchy/watery eyes (11.0% versus 5.0%). In the second year, a higher prevalence of wheeze at least once (26.7% versus 18.5%), night cough without a cold (24.6% versus 15.5%), runny nose without a cold (34.1% versus 21.3%), and runny nose with itchy/watery eyes (13.7% versus 4.6%) was found. Adjustment for various confounders, especially adjustment for socioeconomic factors, reduced most associations between ethnicity and respiratory symptoms. Only runny nose with itchy/watery eyes in the second year of life was independently associated with non-Dutch ethnicity (adjusted odds ratio 2.89, 95% CI 1.3-6.4). CONCLUSIONS: Non-Dutch children more often had respiratory symptoms in the first two years of life than Dutch children. This could largely be explained by differences in socioeconomic status. Follow up of the cohort will determine whether this higher prevalence of respiratory symptoms in children with non-Dutch ethnicity represents an increased risk of developing allergic disease rather than non-specific or infection related respiratory symptoms. http://repub.eur.nl/res/pub/9766/ 2001-01-01T00:00:00Z OBJECTIVE: To investigate the association between contacts with other children and the development of respiratory infections in the first year of life in children with or without genetic predisposition for allergy. METHODS: Children (n = 4146) who participate in a prospective birth cohort study (Prevention and Incidence of Asthma and Mite Allergy study) were investigated. Questionnaires were used to obtain information on doctor-diagnosed upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI), child care attendance, having siblings, family history of allergic disease, and various potential confounders. RESULTS: Child care attendance in the first year of life was associated with doctor-diagnosed URTI (adjusted odds ratio [AOR]: 2.7; 95% confidence interval [CI]: 2.1-3.4 for large child care facility vs no child care) and doctor-diagnosed LRTI (AOR: 5.6; 95% CI: 3.9-7.9). Having siblings was associated with doctor-diagnosed LRTI (AOR: 2.6; 95% CI: 2.0-3.4). In addition, children who have allergic parents and attend child care or have older siblings have a higher risk of developing doctor-diagnosed LRTI than do children who have nonallergic parents. CONCLUSIONS: Child care attendance or having siblings increases the risk of developing doctor-diagnosed LRTI in the first year of life to a greater extent in allergy-prone children than in children who are not allergy prone.