Monique Mommers

Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy.

BACKGROUND Both gastrointestinal microbiota composition and cesarean section have been linked to atopic manifestations. However, results are inconsistent, and the hypothesized intermediate role of the microbiota in the association between birth mode and atopic manifestations has not been studied yet. OBJECTIVES We sought to investigate the relationship between microbiota composition, mode and place of delivery, and atopic manifestations. METHODS The Child, Parent and Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on birth characteristics, lifestyle factors, and atopic manifestations collected through repeated questionnaires from birth until age 7 years. Fecal samples were collected at age 1 month (n = 1176) to determine microbiota composition, and blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n = 384) years to determine specific IgE levels. RESULTS Colonization by Clostridium difficile at age 1 month was associated with wheeze and eczema throughout the first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home delivery compared with vaginal hospital delivery was associated with a decreased risk of eczema, sensitization to food allergens, and asthma. After stratification for parental history of atopy, the decreased risk of sensitization to food allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only found for children with atopic parents. Mediation analysis showed that the effects of mode and place of delivery on atopic outcomes were mediated by C difficile colonization. CONCLUSION Mode and place of delivery affect the gastrointestinal microbiota composition, which subsequently influences the risk of atopic manifestations.

Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990–2010: A Systematic Review of Epidemiological Studies

The prevalence of atopic eczema has been found to have increased greatly in some parts of the world. Building on a systematic review of global disease trends in asthma, our objective was to study trends in incidence and prevalence of atopic eczema. Disease trends are important for health service planning and for generating hypotheses regarding the aetiology of chronic disorders. We conducted a systematic search for high quality reports of cohort, repeated cross-sectional and routine healthcare database-based studies in seven electronic databases. Studies were required to report on at least two measures of the incidence and/or prevalence of atopic eczema between 1990 and 2010 and needed to use comparable methods at all assessment points. We retrieved 2,464 citations, from which we included 69 reports. Assessing global trends was complicated by the use of a range of outcome measures across studies and possible changes in diagnostic criteria over time. Notwithstanding these difficulties, there was evidence suggesting that the prevalence of atopic eczema was increasing in Africa, eastern Asia, western Europe and parts of northern Europe (i.e. the UK). No clear trends were identified in other regions. There was inadequate study coverage worldwide, particularly for repeated measures of atopic eczema incidence. Further epidemiological work is needed to investigate trends in what is now one of the most common long-term disorders globally. A range of relevant measures of incidence and prevalence, careful use of definitions and description of diagnostic criteria, improved study design, more comprehensive reporting and appropriate interpretation of these data are all essential to ensure that this important field of epidemiological enquiry progresses in a scientifically robust manner.

Folic Acid Use in Pregnancy and the Development of Atopy, Asthma, and Lung Function in Childhood

BACKGROUND: Recently, folic acid supplementation during pregnancy was implicated as a potential risk factor for atopic diseases in childhood. OBJECTIVE: To investigate whether folic acid supplementation and higher intracellular folic acid (ICF) levels during pregnancy increase the risk of childhood atopic diseases. METHODS: In the KOALA Birth Cohort Study (N = 2834), data on eczema and wheeze were collected by using repeated questionnaires at 3, 7, 12, and 24 months, 4 to 5 years, and 6 to 7 years after delivery. Atopic dermatitis and total and specific immunoglobulin E levels were determined at age 2 years and asthma and lung function at age 6 to 7 years. We defined folic acid use as stand-alone and/or multivitamin supplements according to the period of use before and/or during pregnancy. ICF levels were determined in blood samples taken at ∼35 weeks of pregnancy (n = 837). Multivariable logistic and linear regression analyses were conducted, with generalized estimating equation models for repeated outcomes. RESULTS: Maternal folic acid supplement use during pregnancy was not associated with increased risk of wheeze, lung function, asthma, or related atopic outcomes in the offspring. Maternal ICF level in late pregnancy was inversely associated with asthma risk at age 6 to 7 years in a dose-dependent manner (P for trend = .05). CONCLUSIONS: Our results do not confirm any meaningful association between folic acid supplement use during pregnancy and atopic diseases in the offspring. Higher ICF levels in pregnancy tended, at most, toward a small decreased risk for developing asthma.

Physical Activity and Asthma: A Systematic Review and Meta-Analysis

Introduction This review aims to give an overview of available published evidence concerning the association between physical activity and asthma in children, adolescents and adults. Methods We included all original articles in which both physical activity and asthma were assessed in case-control, cross-sectional or longitudinal (cohort) studies. Excluded were studies concerning physical fitness, studies in athletes, therapeutic or rehabilitation intervention studies such as physical training or exercise in asthma patients. Methodological quality of the included articles was assessed according to the Newcastle-Ottawa Scale (NOS). Results A literature search was performed until June 2011 and resulted in 6,951 publications derived from PubMed and 1,978 publications from EMBASE. In total, 39 studies met the inclusion criteria: 5 longitudinal studies (total number of subjects n = 85,117) with physical activity at baseline as exposure, and asthma incidence as outcome. Thirty-four cross-sectional studies (n = 661,222) were included. Pooling of the longitudinal studies showed that subjects with higher physical activity levels had lower incidence of asthma (odds ratio 0.88 (95% CI: 0.77–1.01)). When restricting pooling to the 4 prospective studies with moderate to good study quality (defined as NOS≥5) the pooled odds ratio only changed slightly (0.87 (95% CI: 0.77–0.99)). In the cross-sectional studies, due to large clinical variability and heterogeneity, further statistical analysis was not possible. Conclusions The available evidence indicates that physical activity is a possible protective factor against asthma development. The heterogeneity suggests that possible relevant effects remain hidden in critical age periods, sex differences, or extremes of levels of physical activity (e.g. sedentary). Future longitudinal studies should address these issues.

Asthmatic Symptoms, Physical Activity, and Overweight in Young Children: A Cohort Study

OBJECTIVE. Prevalence of asthma and overweight has increased simultaneously during the past decades. Several studies have reported an association between these two health problems, but it is unclear whether this relation is causal. We hypothesize that children with asthmatic symptoms are less physically active, which may contribute to the development of overweight. PATIENTS AND METHODS. The study included children from the KOALA Birth Cohort Study who were invited at 4 to 5 years of age to wear an Actigraph accelerometer for 5 days (n = 305; 152 boys). Information on wheezing was gathered by repeated questionnaires completed by parents at child ages 7 months and 1, 2, and 4 to 5 years. Questionnaires on physical activity were completed at child age 4 to 5 years, and height, weight, and abdominal circumference were measured. Accelerometer data were expressed as mean counts per minute, minutes per day performing vigorous activity, and moderate-to-vigorous physical activity during ≥1 minute. RESULTS. Children who had wheezed in the last 12 months showed very similar activity levels compared with children who had never wheezed. By contrast, boys who had wheezed at least once but not in the last 12 months were more physically active than boys who had never wheezed (geometric mean: 694 vs 625 cpm; adjusted geometric mean ratio: 1.11). This was not found for girls. Similar results were found in parent-reported physical activity data. No association was found between wheezing at any age and overweight at the age of 4 to 5 years. CONCLUSIONS. These results do not support our hypothesis and previous studies that showed that wheezing children are less physically active. Our data provide no evidence that asthmatic symptoms induce a lower physical activity level and more overweight. Additional research could concentrate on the effect of physical activity and overweight on the development of asthmatic symptoms.

Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.

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

Trends in the prevalence of respiratory symptoms and treatment in Dutch children over a 12 year period: results of the fourth consecutive survey

Background: Although there is considerable evidence that the prevalence of childhood asthma has increased over the last decades, it is not clear if this trend is still ongoing. A study was undertaken to investigate whether previously observed trends in the prevalence of respiratory symptoms, physician visits, medication use, and absence from school in Dutch children aged 8–9 years persisted in 2001. Methods: Parents of 1154 children aged 8–9 years eligible for a routine physical examination in 2001 were asked to complete a questionnaire on the respiratory health of their child. Results: In 2001, 1102 children (95.5%) participated in the survey. Similarly high response rates were obtained in the surveys of 1989, 1993 and 1997, with 1794, 1526 and 1670 children aged 8–9 years participating in the respective surveys. The decreasing trend previously observed for recent wheeze between 1989 and 1997 persisted into 2001, particularly in boys. After increasing between 1989 and 1997, the prevalence of shortness of breath with wheeze decreased between 1997 and 2001. The proportion of wheezy children using medication increased between 1989 and 2001 in boys (42.9% v 64.8%; p = 0.003), but the increase was not statistically significant in girls (34.0% v 45.7%; p = 0.096). Conclusion: The prevalence of recent wheeze in Dutch school children has declined steadily since 1989. The rising prevalence of medication use in symptomatic children over time may reflect better asthma control and may partly explain the concurrently decreasing trend in the prevalence of asthma symptoms in our study population.

The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study

Objective:To investigate whether the intestinal microbiota composition in early infancy is associated with subsequent weight development in children.Methods:Analyses were conducted within the KOALA Birth Cohort Study (n=2834). This cohort originates from two recruitments groups: pregnant women with a conventional lifestyle (no selection based on lifestyle) and pregnant women recruited through alternative channels (organic shops, anthroposophic clinicians/midwives, Steiner schools and relevant magazines). From 909 one-month-old infants, fecal samples were collected and analyzed by quantitative PCR targeting bifidobacteria, Bacteroides fragilis group, Clostridium difficile, Escherichia coli, Lactobacilli and total bacteria counts. Between the ages of 1 and 10 years, parent-reported weight and height was collected at 7 time points. Age- and gender-standardized body mass index (BMI) z-scores were calculated. Data were analyzed using generalized estimating equation.Results:Colonization with B. fragilis group was borderline significantly associated with a higher BMI z-score of 0.15 (95% confidence interval (CI): −0.02 to 0.31), in the conventional subcohort. After stratification for fiber intake (Pforinteraction=0.003), colonization with B. fragilis group was associated with a 0.34 higher BMI z-score among children with a low-fiber intake in this subcohort (95% CI: 0.17–0.53). Higher counts among colonized children were positively associated with BMI z-score only in children within the conventional subcohort and a high-fiber diet (BMI z-score 0.08; 95% CI: 0.01–0.14), but inversely associated in children with a low-fiber diet (BMI z-score −0.05; 95% CI: −0.10 to 0.00), and in children recruited through alternative channels (BMI z-score −0.10; 95% CI: −0.17 to −0.03). The other bacteria were not associated with BMI z-scores, regardless of subcohort.Conclusion:Using a targeted approach, we conclude that the intestinal microbiota, particularly the B. fragilis group, is associated with childhood weight development. To identify the potential impact of additional bacterial taxa, further prospective studies applying an unconstrained in-depth characterization of the microbiota are needed.

Meta-analysis of determinants for pet ownership in 12 European birth cohorts on asthma and allergies: a GA2LEN initiative

Background:  Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors.

Variants of the FADS1 FADS2 gene cluster, blood levels of polyunsaturated fatty acids and eczema in children within the first 2 years of life.

Background Association of genetic-variants in the FADS1-FADS2-gene-cluster with fatty-acid-composition in blood of adult-populations is well established. We analyze this genetic-association in two children-cohort-studies. In addition, the association between variants in the FADS-gene-cluster and blood-fatty-acid-composition with eczema was studied. Methods and Principal Findings Data of two population-based-birth-cohorts in the Netherlands and Germany (KOALA, LISA) were pooled (n = 879) and analyzed by (logistic) regression regarding the mutual influence of single-nucleotide-polymorphisms (SNPs) in the FADS-gene-cluster (rs174545, rs174546, rs174556, rs174561, rs3834458), on polyunsaturated fatty acids (PUFA) in blood and parent-reported eczema until the age of 2 years. All SNPs were highly significantly associated with all PUFAs except for alpha-linolenic-acid and eicosapentaenoic-acid, also after correction for multiple-testing. All tested SNPs showed associations with eczema in the LISA-study, but not in the KOALA-study. None of the PUFAs was significantly associated with eczema neither in the pooled nor in the analyses stratified by study-cohort. Conclusions and Significance PUFA-composition in young childrens blood is under strong control of the FADS-gene-cluster. Inconsistent results were found for a link between these genetic-variants with eczema. PUFA in blood was not associated with eczema. Thus the hypothesis of an inflammatory-link between PUFA and eczema by the metabolic-pathway of LC-PUFAs as precursors for inflammatory prostaglandins and leukotrienes could not be confirmed by these data.