European Birth Cohort Studies Research Articles

Socioeconomic position during pregnancy and pre-school exposome in children from eight European birth cohort studies

Distribution of environmental hazards and vulnerability to their effects vary across socioeconomic groups. Our objective was to analyse the relationship between child socioeconomic position (SEP) at birth and the external exposome at pre-school age (0–4 years).This study included more than 60,000 children from eight cohorts in eleven European cities (Oslo, Copenhagen, Bristol, Bradford, Rotterdam, Nancy, Poitiers, Gipuzkoa, Sabadell, Valencia and Turin). SEP was measured through maternal education and a standardised indicator of household income. Three child exposome domains were investigated: behavioral, diet and urban environment. We fitted separate logistic regression model for each exposome variable - dichotomised using the city-specific median - on SEP (medium/low vs high) adjusting for maternal age, country of birth and parity. Analyses were carried out separately in each study-area.Low-SEP children had, consistently across study-areas, lower Odds Ratios (ORs) of breastfeeding, consumption of eggs, fish, fruit, vegetables and higher ORs of TV screen time, pet ownership, exposure to second-hand smoke, consumption of dairy, potatoes, sweet beverages, savory biscuits and crisps, fats and carbohydrates. For example, maternal education-breastfeeding OR (95% Confidence Interval (CI)) ranged from 0.18 (0.14–0.24) in Bristol to 0.73 (0.58–0.90) in Oslo. SEP was also strongly associated with the urban environment with marked between-city heterogeneity. For example, income-PM2.5 OR (95%CI) ranged from 0.69 (0.47–1.02) in Sabadell to 2.44 (2.16–2.72) in Oslo.Already at pre-school age, children with lower SEP have consistently poorer diets and behaviours, which might influence their future health and wellbeing. SEP-urban environment relationships are strongly context-dependent.

Parental lifestyle patterns around pregnancy and risk of childhood obesity in four European birth cohort studies

BackgroundA high prevalence of excess weight in children younger than 5 years suggests the involvement of early-life risk factors. The preconception and pregnancy periods are crucial stages for the implementation of interventions to prevent childhood obesity. Most studies so far have evaluated the effects of early-life factors separately, with only a few investigating the combined effect of parental lifestyle factors. Our objective was to fill the literature gap regarding parental lifestyle factors in the preconception and pregnancy periods and to study their association with the risk of overweight in children after the age of 5 years. MethodsWe harmonised and interpreted data from four European mother–offspring cohorts (EDEN [comprising 1900 families], Elfe [comprising 18 000 families], Lifeways [comprising 1100 families], and Generation R [comprising 9500 families]). Written informed consent was obtained from parents of all involved children. Lifestyle factor data collected through questionnaires comprised parental smoking, BMI, gestational weight gain, diet, physical activity, and sedentary behaviour. We applied principal component analyses to identify multiple lifestyle patterns in preconception and pregnancy. Their association with child BMI z-score and risk of overweight (including obesity, overweight and obesity, as defined by the International Task Force reference) between the ages of 5 and 12 years were assessed using cohort-specific multivariable linear and logistic regression models (adjusted for confounders including parental age, education level, employment status, geographic origin, parity, and household income). FindingsAmong the various lifestyle patterns identified in all cohorts, the two that better explained variance were high parental smoking plus low maternal diet quality or high maternal sedentary behaviour, and high parental BMI plus low gestational weight gain. Overall, we observed that patterns characterised by high parental BMI, smoking, low-quality diet, or sedentary lifestyle before or during pregnancy were associated with higher BMI z-scores and risk of overweight and obesity in children aged 5–12 years. InterpretationOur data contribute to a better understanding of how parental lifestyle factors might be associated with the risk of childhood obesity. These findings are valuable to inform future family-based and multi-behavioural child obesity prevention strategies in early life. FundingEuropean Union's Horizon 2020 under the ERA-NET Cofund action (reference 727565) and European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, EndObesity).

Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review.

BackgroundThere are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks.MethodsBased on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks.ResultsThirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996.ConclusionThere is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.Supplementary informationThe online version contains supplementary material available at https://doi.org/10.1265/ehpm.21-00033.

Prenatal and postnatal exposure to persistent organic pollutants and attention-deficit and hyperactivity disorder: a pooled analysis of seven European birth cohort studies.

Attention-deficit/hyperactivity disorder (ADHD) is increasing worldwide for reasons largely unknown and environmental chemicals with neurotoxic properties, such as persistent organic pollutants (POPs), have been proposed to play a role. We investigated the association between prenatal and postnatal exposure to polychlorinated biphenyl-153 (PCB-153), p-p´-dichlorodiphenyldichloroethylene (p-p'-DDE) and hexachlorobenzene (HCB) and ADHD in childhood. We pooled seven European birth cohort studies encompassing 4437 mother-child pairs from the general population with concentrations of PCB-153, p-p´-DDE and HCB measured in cord blood, maternal blood or milk. We then calculated prenatal (birth) and postnatal (3, 6, 12 and 24 months) POP concentrations using a pharmacokinetic model. The operational definition of ADHD varied across cohorts and ranged from doctor diagnosis obtained from patient registries to maternal or teachers reports. We used multilevel (mixed) logistic regression models to estimate the associations between exposure to POPs at birth, 3, 6, 12 and 24 months and ADHD. The global prevalence of ADHD in our study was 6%. The mean age at assessment of ADHD was 5.8 years (range: 3.8-9.5 years). We found no association between exposure to PCB-153, p-p´-DDE and HCB at any age point between birth and 24 months and ADHD, in the pooled analyses (pooled odds ratios ranging from 1.00 to 1.01). A number of sensitivity analyses gave basically the same results. In the largest study to date of 4437 children in seven European birth cohorts, we did not observe any association between either pre- or postnatal exposure (up to 24 months) to PCB-153, p-p´-DDE and HCB and the risk of ADHD before the age of 10 years.

Maternal Smoking during Pregnancy and Early Childhood and Development of Asthma and Rhinoconjunctivitis - a MeDALL Project.

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

Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts.

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

Inclusion of migrants and ethnic minorities in European birth cohort studies-a scoping review.

Migrant and ethnic minority groups constitute substantial parts of European populations. They frequently experience health disadvantages relative to the respective majority populations. Birth cohort studies can help to disentangle social and biological factors producing these health inequalities over the life course. We investigated whether birth cohorts in European countries (i) assess migration history and ethnicity in the study design; and (ii) use this information in data analyses. A scoping review was performed in which European birth cohort studies were identified using dedicated web-based registries, MEDLINE and EMBASE. Two reviewers systematically assessed all identified birth cohorts and selected those fulfilling defined inclusion criteria (e.g. enrolment after 1980). Publications and websites were screened for information on the inclusion of migrants and ethnic minorities. To obtain more detailed information, researchers of enrolled birth cohorts were contacted individually. Eighty-eight birth cohorts were identified in 20 European countries, with more than 486 250 children enrolled in total. Sixty-two studies (70.5%) reported collecting data about migration history or ethnic background. Twenty-three studies (26%) used information on migration history or ethnicity for data analyses or plan to do so in future. The majority of European birth cohorts assessed participants' migration history or ethnic background; however, this information was seldom used for comparative analyses in trying to disentangle reasons for health inequalities. Also, heterogeneous indicators were used. Better use of data already available, as well as harmonization of data collection on migration history and ethnicity, could yield interesting insights into the production of health inequalities.

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

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. 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. 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. 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. 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.

Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study

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

Inclusion of ethnic minority groups in European birth cohort studies – a systematic overview

Background Health inequalities exist between ethnic minority groups and majority populations. Cohort studies can help understanding ethnic disparities in health; particularly birth cohort studies can enable a view over the life course and differentiate between causal and non-causal associations. We aimed to establish whether birth cohorts in European countries i) consider ethnic background in their study design and ii) use information on ethnicity for data analysis. Methods Review of …

Air pollution exposure during pregnancy and childhood cognitive and psychomotor development in 6 European birth cohort studies. The ESCAPE Project.

Background: Accumulating evidence from experimental studies suggests that air pollution may have an impact on the development of the central nervous system. Aims: To assess whether air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. Methods: Collaborative study of 6 European population-based birth cohorts (GENERATION R (The Netherlands), DUISBURG (Germany), EDEN (France, 2 areas), GASPII (Italy), RHEA (Greece), and INMA (Spain, 5 areas)). Mother-child pairs were recruited from 1997 to 2008. Air pollution levels (nitrogen oxides (NO2, NOx), particulate matter with diameters of less than 2.5µm (PM2.5), less than 10µm (PM10), and 2.5-10µm (PMcoarse), and PM2.5 absorbance) at birth addresses were estimated by land-use regression models based on monitoring campaigns mostly performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods using routine background monitoring network sites. General cognition, language, and psychomotor development were assessed between 1 and 6 years of age. Adjusted area-specific effect estimates were combined using random-effects meta-analysis. Results: A total of 9,482 children were included. Air pollution exposure during pregnancy was negatively associated with psychomotor development. Decreases of global psychomotor development score by 0.62 points (95% Confidence Interval -1.16; -0.09) and 1.66 points (95% Confidence Interval -3.49; 0.16) were found per each increase by 10?g/m3 in NO2 and by 5?g/m3 in PM2.5 pregnancy levels, respectively. Similar trends were observed in most areas. No association was found between air pollution exposure during pregnancy and general cognition or language development. Conclusions: Air pollution exposure during pregnancy was associated with delayed psychomotor development during childhood. Follow-up at older ages should explore catch-up and whether air pollution is related to cognitive development beyond psychomotor development.

How are European birth-cohort studies engaging and consulting with young cohort members?

BackgroundBirth cohort studies, where parents consent for their child to be enrolled in a longitudinal study prior to or soon after birth, are a powerful study design in epidemiology and developmental research. Participation often continues into adulthood. Where participants are enrolled as infants, provision should be made for consent, consultation and involvement in study design as they age. This study aims to audit and describe the extent and types of consultation and engagement currently used in birth cohorts in Europe.MethodsSeventy study groups (representing 84 cohorts) were contacted to ask about their practice in engaging and involving study members. Information was gathered from study websites and publications, 15 cohorts provided additional information via email and 17 cohorts were interviewed over the phone.ResultsThe cohorts identified confirm the growth of this study design, with more than half beginning since 1990, and 4 since 2011. Most studies maintain a website open to the general public, although many are written for the scientific community only. Five studies have web pages specifically for young cohort members and one study provides a dedicated page for fathers. Cohorts send newsletters, cards, and summaries of findings to participants to stay in touch. Six cohorts use Facebook for this purpose. Five cohorts provide feedback opportunities for participants after completing a round of data collection. We know of just 8 cohorts who have a mechanism for consulting with parents and 3 a mechanism for consulting with young people themselves, although these were ‘one off’ consultations for some groups. Barriers to further consultation with cohort members were: concerns about impact on quality of research, ethical constraints, resource limitations, lack of importance, and previous adverse experiences.ConclusionsAlthough the children in some of the cohorts are still young (born in the last 10 years) many are old enough to include some element of consultation. Barriers to greater participation identified here have been overcome in some cohorts and in other fields. Within the scope of their funding and resources, birth cohort studies should consider ways in which they could increase engagement, consultation, and co-production with research participants.

Maternal pre-pregnancy overweight and obesity, and child neuropsychological development: two Southern European birth cohort studies

Maternal pre-pregnancy obesity may be associated with impaired infant neuropsychological development; however, there are few studies and it is unclear if reported associations are due to intrauterine mechanisms. We assessed whether maternal pre-pregnancy overweight and obesity were associated with cognitive and psychomotor development scores (mean 100 ± 15) of children aged 11-22 months in two birth cohorts: Environment and Childhood (INMA, Spain; n = 1967) and Mother-Child (RHEA, Greece: n = 412). Paternal body mass index (BMI) was used as a negative control exposure. The percentage of overweight and obese mothers was 18% and 8%, respectively, in INMA and 20% and 11% in RHEA, respectively. Maternal pre-pregnancy obesity was associated with reduced infant cognitive development scores in both INMA (score reduction: -2.72; 95% CI: -5.35, -0.10) and RHEA (score reduction: -3.71; 95% CI: -8.45, 1.02), after adjusting for socioeconomic variables and paternal BMI. There was evidence in both cohorts of a dose-response relationship with continuous maternal BMI. Paternal overweight/obesity was not associated with infant cognitive development. Associations with psychomotor scores were not consistent between cohorts, and were stronger for paternal than maternal BMI in RHEA. This study in two birth cohorts with moderately high obesity prevalence suggests that maternal pre-pregnancy obesity is associated with reduced child cognitive development at early ages. This association appears more likely to be due to maternal than shared family and social mechanisms, but further research is needed to disentangle a direct intrauterine effect from other maternal confounding factors.

Environmental exposure assessment in European birth cohorts: results from the ENRIECO project

Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.

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

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. The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies. Within the EU-funded network of excellence GA(2)LEN, we performed meta-analyses with data from 12 ongoing European birth cohort studies on asthma and allergy. Each of the birth cohort studies enrolled between 485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis, eczema) of parents and siblings, parental education, access to ground floor, and number of people living at home were assessed by questionnaires. Among the 25 056 families from seven European countries cats (14.9%) were more common than dogs (12.0%). Allergic family history significantly reduced the odds to own a cat (adjusted combined random-effect OR 0.91; 95% CI 0.85-0.99), or dog (0.90; 0.86-0.94). A higher parental educational level had even more pronounced effects on cat (0.84; 0.71-0.98), and dog ownership (0.61; 0.54-0.70). Elder siblings reduced the odds to own cats, but not dogs. Convenient ground access significantly increased the odds, whereas crowding at home was not associated with cat or dog ownership. The chances to own a cat or dog were significantly reduced in allergic families, in parents with a higher educational level, and in homes without convenient ground access. In addition to parental allergies, social and housing factors should be considered as potential confounders in studies on pet exposure and allergic diseases.

Celebration: William Farr (1807 1883) an appreciation on the 200th anniversary of his birth

wheezing in south Asian and white children: prevalence and clinical significance. J Allergy Clin Immunol 2006;118:528–30. 30 Chauliac ES, Silverman M, Zwahlen M, Strippoli M-PF, Brooke AM, Kuehni CE. The therapy of pre-school wheeze: appropriate and fair? Pediatr Pulmonol 2006;41:829–38. 31 Spycher BD, Silverman M, Minder C, Kuehni CE. Phenotype definition in childhood wheezing illness: a data-driven approach. Eur Respir J 2006;28 (Suppl 50):267s. 32 Spycher BD, Silverman M, Brooke AM, Minder C, Kuehni CE. A multidimensional data-driven approach to phenotype definition in childhood wheeze and cough, Submitted for publication. 33 Staley KG, Stover C, Strippoli M-PF, Spycher BD, Silverman M, Kuehni CE. Mannan-binding lectin in young children with asthma differs by level of severity. J Allergy Clin Immunol 2007;119:503–5. 34 Kuehni CE, Brooke AM, Silverman M. Prevalence of wheeze during childhood: Retrospective and prospective assessment. Eur Respir J 2000;16:81–85. 35 Michel G, Silverman M, Strippoli M-PF et al. Parental understanding of ‘‘wheeze’’ and its impact on asthma estimates. Eur Respir J 2006;28:1124–30. 36 Kuehni CE, Strippoli M-PF, Zwahlen M, Silverman M. Association between reported exposure to road traffic and respiratory symptoms in children: evidence of bias. Int J Epidemiol 2006;35:779–86. 37 Keil T, Kulig M, Simpson A et al. European birth cohort studies on asthma and atopic diseases: I. Comparison of study designs—a GALEN initiative. Allergy 2006;61:221–28. 38 Keil T, Kulig M, Simpson A et al. European birth cohort studies on asthma and atopic diseases: II. Comparison of outcomes and exposures—a GA2LEN initiative. Allergy 2006;61:1104–11.

European birth cohort studies on asthma and atopic diseases: II. Comparison of outcomes and exposures – a GA2LEN initiative

The Global Allergy and Asthma European Network (GA2LEN) is a consortium of 26 leading European research centres committed to establish a European research area of excellence in the field of allergy and asthma. One of the GA2LEN work packages was designed to identify and compare the existing European birth cohort studies on asthma and atopic diseases. The present review compares their subjective and objective outcomes as well as exposure variables. A common database was established to assess study characteristics of observational birth cohort studies designed to examine asthma and atopic diseases. Data were collected by visiting most of the participating research teams and interviewing all relevant study personnel. For each study, the type of objective/subjective outcome parameters and potentially influential factors were recorded precisely for every time point during follow-up. Eighteen birth cohort studies on asthma and atopic diseases were identified in eight European countries. Thirteen studies collected data on specific immunoglobulin E (IgE) to various inhalant and food allergens, whereas 12 performed skin prick tests (many at several time points during follow up). Several studies measured lung function, but across the cohorts no comparable standard procedures were used. For subjective evaluation of asthma and allergic rhinitis most studies applied the ISAAC questionnaire (sometimes modified), whereas the assessment of eczema was rather heterogeneous across the studies. This GA2LEN initiative established a unique common database of 18 European birth cohorts on asthma and atopic diseases. For selected cohorts, it seems that pooling data and performing common analyses may be possible to examine associations between certain exposure variables (e.g. pet ownership, tobacco smoke exposure and day-care) and selected outcome measures for atopy, asthma or allergic rhinitis (e.g. sensitization assessed by IgE or skin prick tests, doctor's diagnosis of asthma, parental perception regarding asthma/wheezing or hay fever symptoms).

European birth cohort studies on asthma and atopic diseases: I. Comparison of study designs – a GA2LEN initiative

The reasons for the rise in asthma and allergies remain unclear. To identify risk or protective factors, it is essential to carry out longitudinal epidemiological studies, preferably birth cohort studies. In Europe, several birth cohort studies on asthma and atopic diseases have been initiated over the last two decades. One of the work packages within the Global Allergy and Asthma European Network (GA(2)LEN) project was designed to identify and compare European birth cohorts on asthma and atopic diseases. The present review (part I) describes their objectives, study settings, recruitment process and follow-up rates. A subsequent review (part II) will compare outcome and exposure parameters. For each birth cohort, we collected detailed information regarding recruitment process, study setting, baseline data (pregnancy, birth, parents/siblings) as well as follow-up rates, outcome and exposure parameters at each time point. We identified and assessed 18 European birth cohorts on asthma, allergic rhinitis and eczema. Six of these studies also focused on food allergies. The birth cohorts were mostly initiated in the 1990s with predominantly urban/metropolitan settings. Many studies were able to maintain high follow-up rates, even after five or more years. Due to the unique cooperation within the GA(2)LEN project a common database was established containing study characteristics of European birth cohorts on asthma and atopic diseases. This can be used as a basis for evaluating the possibility to pool data and perform meta-analyses, as well as to recommend criteria for conducting future birth cohorts.

Birthweight and blood pressure in five European birth cohort studies: an investigation of confounding factors

It has been suggested that the association between birthweight and blood pressure has been overstated as a result of publication bias and, within studies, a lack of adjustment for potentially important maternal and socioeconomic confounding factors and 'overadjustment' for current body size. This study investigates the impact of potential confounding variables on the birthweight-blood pressure association in birth cohort studies from different time periods and geographical locations in Europe. Data from five European birth cohort studies (from Finland, the UK, and the Faroe Islands) taking part in the European Birth-Lifecourse-Studies (EURO-BLCS) project were analysed. Birthweight was measured at birth in all cohorts and confounding variable information was collected prospectively at subsequent follow-ups in all cohorts. Regression models were used to assess the unadjusted association between birthweight and blood pressure and then to assess the impact of potential maternal and socioeconomic confounding variables and adjustment for later body size. Analyses were carried out in the same way across all five cohorts. Birthweight was consistently negatively associated with systolic blood pressure (SBP) across all cohorts. Gestational age and possibly maternal pre-pregnancy weight, but not socioeconomic status, may be important confounding factors of the relationship between birthweight and SBP. The size of the birthweight-SBP association in adulthood may be larger than in childhood before adjustment for current body size, although a cohort effect cannot be ruled out. This study highlights the value of future cross-cohort comparisons in the investigation of the foetal origins of adult disease.