Publications by authors named "Ana Esplugues"

45 Publications

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study.

Sci Total Environ 2021 Mar 20;782:146654. Epub 2021 Mar 20.

Epidemiology and Environmental Health Joint Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, FISABIO-Universitat Jaume I-Universitat de València, Av. Catalunya 21, 46020 Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Av. Monforte de Lemos, 3-5. Pabellón 11, 28029 Madrid, Spain.

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionnaires administered to parents. Associations were investigated by logistic regression adjusted for socio-demographic and lifestyle-related variables in each cohort and subsequent meta-analysis. We tested effect modification by factors related to individual susceptibility, diet and co-exposure with other pollutants. The geometric mean of cord blood and hair total mercury was 8.20 μg/L and 0.97 μg/g, respectively. No statistically significant association between pre or postnatal mercury exposure and respiratory and allergy outcomes was found. Notwithstanding, lower maternal intake of fruits and vegetables increased the risk of some respiratory outcomes due to the prenatal exposure to mercury (p < 0.05). Moreover, an inverse association between prenatal mercury exposure and some respiratory outcomes was observed among children with higher maternal exposure to organocholorine compounds or smoking (p < 0.05). Also, sex and postnatal smoking exposure modulated mercury postnatal effects on persistent cough (p < 0.05). In conclusion, no association between pre and postnatal mercury exposure and respiratory and allergy problems among the whole population at study was found. However, diet and other toxicants could modulate this relation, especially during prenatal period. More research on this topic is warranted due to the limited evidence.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146654DOI Listing
March 2021

Urinary arsenic species and methylation efficiency during pregnancy: Concentrations and associated factors in Spanish pregnant women.

Environ Res 2021 May 17;196:110889. Epub 2021 Feb 17.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Background: Arsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency.

Objectives: To describe the urinary concentrations of the different As species and evaluate the methylation efficiency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women.

Methods: Participants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003-2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Sociodemographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis.

Results: Median urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 μg/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., β [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA).

Discussion: Certain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.
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http://dx.doi.org/10.1016/j.envres.2021.110889DOI Listing
May 2021

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

J Allergy Clin Immunol 2021 Mar 15;147(3):1031-1040. Epub 2020 Dec 15.

Centre for Individualized Infection Medicine, CiiM, a joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.

Objective: We sought to identify DNA methylation profiles associated with childhood allergy.

Methods: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses.

Results: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium.

Conclusion: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.
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http://dx.doi.org/10.1016/j.jaci.2020.11.044DOI Listing
March 2021

Urban environment during early-life and blood pressure in young children.

Environ Int 2021 01 21;146:106174. Epub 2020 Oct 21.

ISGlobal, Doctor Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: The urban environment is characterised by many exposures that may influence hypertension development from early life onwards, but there is no systematic evaluation of their impact on child blood pressure (BP).

Methods: Systolic and diastolic blood pressure were measured in 4,279 children aged 4-5 years from a multi-centre European cohort (France, Greece, Spain, and UK). Urban environment exposures were estimated during pregnancy and childhood, including air pollution, built environment, natural spaces, traffic, noise, meteorology, and socioeconomic deprivation index. Single- and multiple-exposure linear regression models and a cluster analysis were carried out.

Results: In multiple exposure models, higher child BP, in particular diastolic BP, was observed in association with higher exposure to air pollution, noise and ambient temperature during pregnancy, and with higher exposure to air pollution and higher building density during childhood (e.g., mean change [95% confidence interval] for an interquartile range increase in prenatal NO = 0.7 mmHg[0.3;1.2]). Lower BP was observed in association with higher temperature and better street connectivity during childhood (e.g., temperature = -1.1[-1.6;-0.6]). Some of these associations were not robust in the sensitivity analyses. Mother-child pairs were grouped into six urban environment exposure clusters. Compared to the cluster representing the least harmful urban environment, the two clusters representing the most harmful environment (high in air pollution, traffic, noise, and low in green space) were both associated with higher diastolic BP (1.3[0.1;2.6] and 1.5[0.5;2.5]).

Conclusion: This first large systematic study suggests that living in a harmful urban environment may impact BP regulation in children. These findings reinforce the importance of designing cities that promote healthy environments to reduce long-term risk of hypertension and other cardiovascular diseases.
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http://dx.doi.org/10.1016/j.envint.2020.106174DOI Listing
January 2021

Exposure to mercury among 9-year-old children and neurobehavioural function.

Environ Int 2021 01 20;146:106173. Epub 2020 Oct 20.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Mercury (Hg) is an environmental neurotoxicant whose main route of exposure in humans is the consumption of seafood. The aim of this study was to explore the relationship between Hg exposure at 9 years old and behaviour assessed at 9 and 11 years old. Study subjects were mother-child pairs participating in the INMA (Environment and Childhood) Project in Valencia (Spain). Total Hg (THg) was measured in hair samples from the children at 9 years old. Behaviour and emotions were assessed at 9 (n = 472) years and 11 (n = 385) years of age using the Child Behaviour Checklist test (CBCL) and the Conners Parents Rating Scale-Revised: Short Form (CPRS-R:S). Furthermore, the attention function was assessed by the Attention Network Test at 11 years old. Socio-demographic, lifestyle and dietary information was collected through questionnaires during pregnancy and childhood. Polymorphism in BDNF, APOE and GSTP1 were genotyped in cord blood DNA. Multivariable negative binomial regression models were built in order to study the association between THg concentrations and the scores obtained by the children at 9 and 11 years old. Effect modification by sex and genetic polymorphisms was assessed. The association between Hg levels and CBCL scores was positive (worse neurobehavioural development) for the CBCL internalizing and total problem scales (Incidence Rate Ratio [95% confidence interval] = 1.07 [1.01, 1.13] and 1.05 [0.99, 1.11], respectively). The association between Hg and the externalizing and total problems CBCL scales and the Attention Deficit Hyperactivity Disorder (ADHD) index of the CPRS-R:S was different according to sex, with boys obtaining worse scores with increasing Hg, compared to girls. Statistically significant interactions were also observed for genetic polymorphisms affecting the association between early exposure to Hg and both CBCL and CPRS-R:S scores. In conclusion, postnatal Hg exposure is associated with poorer neurobehavioural development in 9- and 11-year-old children. Sex and the presence of certain genetic polymorphisms modified this association.
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http://dx.doi.org/10.1016/j.envint.2020.106173DOI Listing
January 2021

Early childhood growth is associated with lung function at 7 years: a prospective population-based study.

Eur Respir J 2020 12 24;56(6). Epub 2020 Dec 24.

ISGlobal, Barcelona, Spain.

Previous studies have related early postnatal growth with later lung function but their interpretation is limited by the methods used to assess a child's growth. We aimed to assess the association of early childhood growth, measured by body mass index (BMI) trajectories up to 4 years, with lung function at 7 years.We included 1257 children from the Spanish Infancia y Medio Ambiente population-based birth cohort. Early childhood growth was classified into five categories based on BMI trajectories up to 4 years previously identified using latent class growth analysis. These trajectories differed in birth size ("lower", "average", "higher") and in BMI gain velocity ("slower", "accelerated"). We related these trajectories to lung function (forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC and forced expiratory flow at 25%-75% of FVC (FEF)) at 7 years, using multivariable mixed regression.Compared to children with average birth size and slower BMI gain (reference), children with higher birth size and accelerated BMI gain had a higher FVC % pred (3.3%, 95% CI 1.0%-5.6%) and a lower FEV/FVC % pred (-1.5%, 95% CI -2.9%--0.1%) at 7 years. Similar associations were observed for children with lower birth size and accelerated BMI gain. Children with lower birth size and slower BMI gain had lower FVC % pred at 7 years. No association was found for FEFIndependently of birth size, children with accelerated BMI gain in early childhood had higher lung function at 7 years but showed airflow limitation. Children with lower birth size and slower BMI gain in early childhood had lower lung function at 7 years.
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http://dx.doi.org/10.1183/13993003.00157-2020DOI Listing
December 2020

[Evaluation of a pilot program of physical activity prescription in primary care in the Valencian Community (Spain)].

Gac Sanit 2020 Aug 22. Epub 2020 Aug 22.

Oficina Valenciana d'Acció Comunitària per a la Salut, Direcció General de Salut Pública i Adiccions, Generalitat Valenciana, València, España; Grupo ALES-FISABIO, València, España.

Objective: Assess the prescription process, adherence and impact on health measured in improvement of self-esteem and health-related quality of life, as short-term health indicators, from a pilot study of prescription of physical activity assets for 3 months.

Method: Quasi-experimental study before-after without a control group, for the evaluation of the pilot phase (November 2017 and May 2018) of the program Conecta Actius per a la Salut in the Valencian Community (Spain). The physical activity prescription was performed and a questionnaire was completed at the beginning (T0) and at 3 months (T1). A descriptive analysis was carried out by sex and educational level where the differences between T0 and T1 were calculated using chi square and the Wilcoxon test of two dependent samples.

Results: The sample was 82 in T0 and 78 people in T1. The analysis shows an improvement between quality of life (7%; p ≤0.001), health perception (12,5%; p ≤0.001) and self-esteem (5,9%; p ≤0.001) between T0 and T1. The improvement proportion in Health perception is greater in women than in men for the three measured scales and in those who have a higher educational level or have been prescribed in centers that offer a single asset.

Conclusion: Pilot study shows short-term health benefits after the physical activity prescription. Specifically, there is an improvement in the quality of life, health perception and self-esteem of the population.
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http://dx.doi.org/10.1016/j.gaceta.2020.04.021DOI Listing
August 2020

Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma: A meta-analysis of European birth cohorts.

Environ Int 2020 03 18;136:105474. Epub 2020 Jan 18.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; INSERM, U1168, VIMA: Aging and Chronic Diseases, Epidemiological and Public Health Approaches, Villejuif, France; Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, F-78180 Montigny le Bretonneux, France; Université Rennes, INSERM, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.

Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades.

Objective: We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries.

Methods: Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrogen dioxide (NO), nitrogen oxides, mass of particulate matter with an aerodynamic diameter <10 μm (PM), 10-2.5 μm (PM) and <2.5 μm (PM), and PM absorbance were assigned to the birth, four- and eight-year home addresses using highly defined spatial air pollution exposure models. Cohort-specific cross-sectional associations were assessed using logistic regression models adjusted for demographic and environmental covariates and combined in a random effects meta-analysis.

Results: The overall prevalence of pediatric eczema, rhinoconjunctivitis and asthma at four years was 15.4%, 5.9% and 12.4%. We found no increase in the prevalence of these outcomes at four or eight years with increasing air pollution exposure. For example, the meta-analysis adjusted odds ratios (95% confidence intervals) for eczema, rhinoconjunctivitis and asthma at four years were 0.94 (0.81, 1.09), 0.90 (0.75, 1.09), and 0.91 (0.74, 1.11), respectively, per 10 μg/m increase in NO at the birth address, and 1.00 (0.81, 1.23), 0.70 (0.49, 1.00) and 0.88 (0.54, 1.45), respectively, per 5 μg/m increase in PM at the birth address.

Discussion: In this large meta-analysis of five birth cohorts, we found no indication of adverse effects of long-term air pollution exposure on the prevalence of current pediatric eczema, rhinoconjunctivitis or asthma.
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http://dx.doi.org/10.1016/j.envint.2020.105474DOI Listing
March 2020

[Descriptive analysis of mobile phone applications on breastfeeding].

An Pediatr (Barc) 2020 May 21;92(5):302-305. Epub 2019 May 21.

Facultat d' Infermeria i Podologia, Universitat de València. Unidad Mixta de Investigación en Epidemiología, Ambiente y Salud. FISABIO - Universitat Jaume I -Universitat de València. CIBERESP, Valencia, España.

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http://dx.doi.org/10.1016/j.anpedi.2019.03.009DOI Listing
May 2020

[Exposure to nitrogen dioxide and respiratory health at 2 years in the INMA-Valencia cohort].

Gac Sanit 2018 Nov - Dec;32(6):507-512. Epub 2017 Jul 26.

Departament d'Infermeria, Universitat de València, Valencia, España; Unidad Mixta de Investigación en Epidemiología y Salud Ambiental, FISABIO-Universitat Jaume I-Universitat de València, Valencia, España; CIBER de Epidemiología y Salud Pública (CIBERESP), España. Electronic address:

Objective: To analyze the association between exposure to nitrogen dioxide (NO) during pregnancy and the postnatal period up to the age of 2 years old and the incidence of respiratory problems in children from the INMA-Valencia cohort.

Methods: The study population included 624 children from the INMA-Valencia cohort. Individual exposure to NO was estimated in different environments outside the home during pregnancy and up to the age of 2 using empirical measurement and data from geo-statistical methods. Respiratory symptoms were obtained from a questionnaire applied at the age of two. The association between NO exposure and respiratory symptoms was performed using multivariate logistic regression.

Results: The cumulative incidence was 16.3% for persistent cough, 34.9% for wheezing and 27.6% for lower respiratory tract infections. No association was found between respiratory symptoms and exposure to NO in any of the children. However an association between NO exposure and persistent cough was found at two years of life in the children with a parental history of allergy.

Conclusion: NO exposure would lead to persistent cough in children with a parental history of allergies.
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http://dx.doi.org/10.1016/j.gaceta.2017.05.012DOI Listing
June 2019

Infants' indoor and outdoor residential exposure to benzene and respiratory health in a Spanish cohort.

Environ Pollut 2017 Mar 4;222:486-494. Epub 2017 Jan 4.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I, Universitat de València, Avenida de Catalunya 21, 46020, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain.

Benzene exposure represents a potential risk for children's health. Apart from being a known carcinogen for humans (group 1 according to IARC), there is scientific evidence suggesting a relationship between benzene exposure and respiratory problems in children. But results are still inconclusive and inconsistent. This study aims to assess the determinants of exposure to indoor and outdoor residential benzene levels and its relationship with respiratory health in infants. Participants were 1-year-old infants (N = 352) from the INMA cohort from Valencia (Spain). Residential benzene exposure levels were measured inside and outside dwellings by means of passive samplers in a 15-day campaign. Persistent cough, low respiratory tract infections and wheezing during the first year of life, and covariates (dwelling traits, lifestyle factors and sociodemographic data) were obtained from parental questionnaires. Multiple Tobit regression and logistic regression models were performed to assess factors associated to residential exposure levels and health associations, respectively. Indoor levels were higher than outdoor ones (1.46 and 0.77 μg/m, respectively; p < 0.01). A considerable percentage of dwellings, 42% and 21% indoors and outdoors respectively, surpassed the WHO guideline of 1.7 μg/m derived from a lifetime risk of leukemia above 1/100 000. Monitoring season, maternal country of birth and parental tobacco consumption were associated with residential benzene exposure (indoor and outdoors). Additionally, indoor levels were associated with mother's age and type of heating, and outdoor levels were linked with zone of residence and distance from industrial areas. After adjustment for confounding factors, no significant associations were found between residential benzene exposure levels and respiratory health in infants. Hence, our study did not support the hypothesis for the benzene exposure effect on respiratory health in children. Even so, it highlights a public health concern related to the personal exposure levels, since a considerable number of children surpassed the abovementioned WHO guideline for benzene exposure.
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http://dx.doi.org/10.1016/j.envpol.2016.11.065DOI Listing
March 2017

Exposure to ambient air pollution during pregnancy and preterm birth: A Spanish multicenter birth cohort study.

Environ Res 2016 May 4;147:50-8. Epub 2016 Feb 4.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Avenida de Catalunya 21, 46020 Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Background And Objective: Preterm birth is a major determinant of infant mortality and morbidity. Air pollution has been suggested as a risk factor for preterm delivery; however, the scientific evidence on this impact remains inconsistent. We assessed the association between residential exposure to air pollution during pregnancy and preterm birth (gestational age at delivery <37 weeks) in Spain.

Methods: This study was based on 2409 pregnant women participating in the INMA birth cohorts in Asturias, Gipuzkoa, Sabadell and Valencia. Ambient levels of nitrogen dioxide (NO2) and benzene were estimated for each woman's residence for each trimester and for the whole pregnancy, using temporally adjusted land-use regression models. The association between air pollution exposure and preterm birth was assessed for each cohort separately by means of logistic regression models controlling for potential confounders, under single- and two-pollutant models, for all the women in the study and for those spending more than 15h/day at home. Combined estimates of the association across cohorts were obtained through meta-analysis.

Results: Throughout the whole sample, suggestive but no statistically significant associations were found between exposure and preterm birth. For pregnant women spending more time at home significant associations were found for both pollutants, under single- and two-pollutant models. Under the last ones, NO2 exposure during the second trimester and the whole pregnancy was associated with a higher risk of preterm delivery (OR=1.58, (95%CI: 1.04-2.42) per 10μg/m(3) increase). Benzene exposure during the third trimester was also associated with preterm birth in that subsample (OR=1.45, (95%CI: 1.00-2.09) per 1μg/m(3) increase).

Conclusion: We found suggestive associations between NO2 and benzene exposure during pregnancy and preterm birth. Estimates of the association were higher among women who spent more time at home, probably reflecting a better exposure assessment in this group.
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http://dx.doi.org/10.1016/j.envres.2016.01.037DOI Listing
May 2016

Vitamin D Status in Pregnancy and Determinants in a Southern European Cohort Study.

Paediatr Perinat Epidemiol 2016 May 5;30(3):217-28. Epub 2016 Feb 5.

CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

Background: Population-based data on vitamin D status in pregnancy in southern European countries are scarce. We assessed the prevalence and determinants of vitamin D insufficiency and deficiency in pregnancy in Spain.

Methods: Plasma 25-hydroxyvitamin D3 (25(OH)D3) concentration was measured at the first trimester of gestation in 2,036 pregnant women from several geographical areas of Spain (latitude 39-42°N). Uni- and multivariable regression models were conducted to identify predictors of circulating 25(OH)D3 concentration and vitamin D insufficiency (20-30 ng/mL) and deficiency (<20 ng/mL).

Results: Thirty-one per cent and 18% of women were vitamin D insufficient and deficient, respectively. Season at blood collection, latitude, age, social class, tobacco smoking, physical activity and use of vitamin D supplements were identified as independent determinants of 25(OH)D3 concentration. Lower risk of vitamin D insufficiency and deficiency was associated with summer season at blood collection (RR for insufficiency = 0.34, confidence intervals (CI) 0.25, 0.48; and RR for deficiency = 0.07, 95% CI 0.04, 0.12), southern latitude (RR for insufficiency = 0.71, 95% CI 0.50, 1.02; RR for deficiency = 0.60, 95% CI 0.38, 0.94); use of vitamin D supplements (RR for insufficiency = 0.50, 95% CI 0.35, 0.71; RR for deficiency = 0.24, 95% CI 0.14, 0.41); and strong physical activity (RR for insufficiency = 0.80, 95% CI 0.58, 1.09; and RR for deficiency = 0.67, 95% CI 0.46, 1.03). Higher risk of vitamin D deficiency was related to lower social class (RR = 1.94, 95% CI 1.19, 3.16) and smoking (RR = 1.76, 95% CI 1.23, 2.54).

Conclusions: Vitamin D insufficiency and deficiency are highly prevalent in pregnancy. Recommendations and policies to detect and prevent hypovitaminosis D during pregnancy should be developed taking into account the associated factors.
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http://dx.doi.org/10.1111/ppe.12281DOI Listing
May 2016

Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children.

J Allergy Clin Immunol 2016 Apr 11;137(4):1026-1035. Epub 2015 Nov 11.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and Sach's Children Hospital, Stockholm, Switzerland.

Background: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma.

Objective: We sought to assess the hypothesis that these associations are explained by reduced airway patency.

Methods: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma.

Results: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma.

Conclusions: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.
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http://dx.doi.org/10.1016/j.jaci.2015.08.050DOI Listing
April 2016

Water hardness and eczema at 1 and 4 y of age in the INMA birth cohort.

Environ Res 2015 Oct;142:579-85

Centre for Research in Environmental Epidemiology (CREAL), Barcelona Biomedical Research Park, 88 Doctor Aiguader, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), 80 Doctor Aiguader, Barcelona 08003, Spain; IMIM (Hospital del Mar Medical Research Institute), 88 Doctor Aiguader, Barcelona 08003, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), 3-5 Melchor Fernández Almagro, Madrid 28029, Spain. Electronic address:

Background: Exposure to hard water has been suggested as a risk factor for eczema in childhood, based on limited evidence from two ecologic and two cross-sectional studies.

Objectives: We evaluate this hypothesis for the first time in early infancy using prospective data from a mother-child cohort study.

Methods: We used data from the INMA cohorts in Gipuzkoa, Sabadell and Valencia, Spain (N=1638). Current and ever eczema, bathing frequency and duration and covariables were collected by questionnaires at 14 months (14 m) and 4 years (4 y). Calcium carbonate (CaCO3) level in municipal water was assigned to home addresses at birth, 14 m and 4 y. We calculated Odds Ratio (OR) of eczema related to CaCO3 at home, bath exposure and a combination of both.

Results: Prevalence of eczema ever was 18.4% at 14 m and 33.4% at 4 y. Mean CaCO3 ranged from 51.6 to 272.8 mg/L among areas. No association was detected between water hardness at home and current or ever eczema. Adjusted OR was 0.79 (95%CI=0.45, 1.39) at 14 m and 0.93 (0.56, 1.52) at 4 y among children in the highest vs. lowest tertiles of CaCO3. Bath exposure alone or in combination with water hardness did not increase the OR of eczema at 14 m or 4 y either.

Conclusions: We did not find an association between eczema and water hardness at home or bathing exposure during the first four years of life. This first cohort study in a critical age period with improved exposure assessment does not confirm the association suggested among children by previous studies.
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http://dx.doi.org/10.1016/j.envres.2015.07.013DOI Listing
October 2015

Health effects of the 2012 Valencia (Spain) wildfires on children in a cohort study.

Environ Geochem Health 2016 Jun 29;38(3):703-12. Epub 2015 Jul 29.

Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO - Public Health, Avda Catalunya, 21, 46020, Valencia, Spain.

In July 2012, two simultaneous wildfires burnt a big area in Valencia (Spain), where a birth cohort study (INMA) is being developed. The heavy smoke covered the whole INMA study area for several days. We aimed at evaluating the 2012 Valencia wildfire effects on the health of children enrolled in the INMA-Valencia cohort. Two weeks after the extinction of the wildfires, a phone survey was conducted and finally 460 individuals were enrolled. We considered a wildfire period (12-day interval when they were active) and a control period (12-day interval just before wildfires). Parents were asked about respiratory symptoms experienced during both periods, and during wildfires only about the preventive measures adopted and the perception of exposure, along with individual data collected through the different follow-up surveys of the cohort. Conditional logistic regression models were applied, and we included interaction terms for asthma/rhinitis and level of perception of exposure; 82.4 % perceived smoke smell outdoors, 40 % indoors and more than 90 % of the families observed the presence of ash. An adjusted odds ratio of 3.11 [95 % confidence interval 1.62-5.97] for itchy/watery eyes and 3.02 [1.41-6.44] for sore throat was obtained. Significant interaction terms for rhinitis and asthma in itchy/watery eyes and sneezing, and only asthma for sore throat were obtained. Exposure to wildfire smoke was associated with increased respiratory symptoms in this child population, particularly affecting susceptible individuals with asthma or rhinitis.
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http://dx.doi.org/10.1007/s10653-015-9753-5DOI Listing
June 2016

Prenatal Exposure to NO2 and Ultrasound Measures of Fetal Growth in the Spanish INMA Cohort.

Environ Health Perspect 2016 Feb 26;124(2):235-42. Epub 2015 Jun 26.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain.

Background: Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability.

Objective: The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study.

Methods: Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis.

Results: A 10-μg/m(3) increase in average exposure to NO2 during weeks 0-12 was associated with reduced growth at weeks 0-12 in AC (-2.1%; 95% CI: -3.7, -0.6) and EFW (-1.6%; 95% CI: -3.0, -0.3). The same exposure was inversely associated with reduced growth at weeks 20-34 in BPD (-2.6%; 95% CI: -3.9, -1.2), AC (-1.8%; 95% CI: -3.3, -0.2), and EFW (-2.1%; 95% CI: -3.7, -0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers.

Conclusions: Maternal exposure to NO2 in early pregnancy was associated with reduced fetal growth based on ultrasound measures of growth during pregnancy and measures of size at birth.
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http://dx.doi.org/10.1289/ehp.1409423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749079PMC
February 2016

Maternal complications in pregnancy and wheezing in early childhood: a pooled analysis of 14 birth cohorts.

Int J Epidemiol 2015 Feb 27;44(1):199-208. Epub 2015 Jan 27.

Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Città della Salute e della Scienza University Hospital, CPO Piedmont, Italy, Inserm, Epidemiology of Allergic and Respiratory diseases (EPAR) Department, U707 and UPMC, EPAR UMR-S 707, Medical School Saint-Antoine, Univ6, Sorbonne Universités Paris, France, Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School and EPIUnit - Institute of Public Health, Porto, Portugal, CIBER Epidemiología y Salud Pública (CIBERESP); Subdirección de Salud Pública de Gipuzkoa; Departamento de Sanidad del Gobierno Vasco; Biodonostia, Donostia Ospitalea, Donostia - San Sebastián, Basque Country, Spain, The Generation R Study, Erasmus Medical Center; Department of Epidemiology, Erasmus Medical Center; Department of Pediatrics, Division of Respiratory Medicine and Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands, University of Valencia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP); Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO, Valencia, Spain, Department of Biomedical and Neuromotor Sciences, University of Bologna - Alma Mater Studiorum, Bologna, Italy, Department of Epidemiology, Lazio Regional Health Service, Rome, Italy, Centre for Research in Environmental Epidemiology (CREAL), Barcelona; Hospital del Mar Research Institute (IMIM), Barcelona, Spanish Consortium for Research on Epidemiology (CIBERESP), Barcelona, Spain, MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom, Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark, Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands, Department of Medical Microbiology, NUTRIM School for Nutrition, Toxicology and Metabolism

Background: Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient.

Methods: A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring. Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index ≥ 30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12-24 months of age. Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model.

Results: The study included 85509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98-1.06) and 1.20 (95% CI: 0.98-1.47) for hypertensive disorders; 1.09 (95% CI: 1.01-1.18) and 1.23 (95% CI: 1.07-1.43) for preeclampsia; 1.04 (95% CI: 0.97-1.13) and 1.24 (95% CI: 0.86-1.79) for diabetes; 1.08 (95% CI: 1.05-1.11) and 1.19 (95% CI: 1.12-1.26) for overweight; 1.12 (95% CI: 1.08-1.17) and 1.16 (95% CI: 0.97-1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P=0.027).

Conclusions: Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring.
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http://dx.doi.org/10.1093/ije/dyu260DOI Listing
February 2015

[Trends in environmental risks in the context of the economic crisis. SESPAS report 2014].

Gac Sanit 2014 Jun;28 Suppl 1:51-7

Departamento de Enfermería, Universitat de València, València, España; Área de Investigación en Ambiente y Salud, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)-Salud Pública, València, España; CIBER de Epidemiología y Salud Pública (CIBERESP), España.

This article aims to analyze the impact of the economic and financial crisis on environmental determinants of health. The World Health Organization estimates that between 13% and 27% of the disease burden in countries could be prevented by improving the environment. These effects are larger in vulnerable populations, especially among the poorest. In the last decade, outdoor air pollution (the most significant environmental health risk in most European countries) has declined, mostly due to the European policy of reducing emissions and to the decrease in activity following the economic crisis. During the last few years, this improvement in air quality has occurred simultaneously with a reduction in investment in environmental protection and could therefore be offset in the medium-term. The economic crisis has not reduced the trend for higher temperatures in Spain and Europe because climate change is a global phenomenon that is not directly related to local emissions. To reduce the risk of an increase in the health impact of environmental factors, certain key aspects should be considered, such as the need to maintain or develop adequate monitoring and control systems and the opportunity to implement policies that help improve the quality of the environment and reduce the vulnerability of different population groups in a cross-disciplinary framework of transparency and citizen participation.
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http://dx.doi.org/10.1016/j.gaceta.2014.03.004DOI Listing
June 2014

Prenatal exposure to DDE and PCB 153 and respiratory health in early childhood: a meta-analysis.

Epidemiology 2014 Jul;25(4):544-53

From the aCentre for Research in Environmental Epidemiology, Barcelona, Spain; bCIBER Epidemiología y Salud Pública, Spain; cIMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; dUniversitat Pompeu Fabra, Barcelona, Spain; eUniversity of Valencia, Spain; fCenter for Public Health Research (CSISP-FISABIO), Valencia, Spain; gSubdirección de Salud Pública de Gipuzkoa, Departamento de Sanidad del Gobierno Vasco, Spain; hBiodonostia, Donostia Ospitalea, Donostia-San Sebastián, Basque Country, Spain; iDepartment of Occupational and Environmental Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; jDepartment of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece; kINSERM, U1085 IRSET, University of Rennes I, Rennes, France; lNorwegian Institute of Public Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; mEnvironmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; nNational Institute for Health and Welfare, Department of Environmental Health, Chemical Exposure Unit, Finland; oRuhr University Bochum, Department of Hygiene, Social and Environmental Medicine, Bochum, Germany; pIUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; qSlovak Medical University, Faculty of Public Health, Bratislava, Slovak Republic; rDepartment of Epidemiology and Public Health, University Hospital, Rennes, France; sLaboratory of Environmental Toxicology, Norwegian School of Veterinary Science, Oslo, Norway; and tDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; and uArea de Salud de Menorca, IB-SALUT, Menorca, Spain.

Background: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts.

Methods: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses.

Results: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust.

Conclusion: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.
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http://dx.doi.org/10.1097/EDE.0000000000000097DOI Listing
July 2014

The development of the MeDALL Core Questionnaires for a harmonized follow-up assessment of eleven European birth cohorts on asthma and allergies.

Int Arch Allergy Immunol 2014 1;163(3):215-24. Epub 2014 Mar 1.

Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Germany.

Background: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts.

Methods: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up.

Results: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children.

Conclusions: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe.
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http://dx.doi.org/10.1159/000357732DOI Listing
May 2014

Prenatal exposure to cooking gas and respiratory health in infants is modified by tobacco smoke exposure and diet in the INMA birth cohort study.

Environ Health 2013 Dec 1;12:100. Epub 2013 Dec 1.

CIBER Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain.

Background: Studies that have evaluated the association between exposure to gas appliances emissions at home with respiratory health in children obtained heterogeneous and limited results. The aim of this study is to analyze the association between the use of gas cooking at home during pregnancy and respiratory problems in children during their first year of life.

Methods: In the years 2003 through 2008 pregnant women were enrolled in 4 Spanish areas and visited in different age-points following a common protocol. Outcomes studied (from a questionnaire) were any episode of lower respiratory tract infection (LRTI), wheezing, persistent cough, chestiness and otitis. The association between exposure to gas cooking at home and respiratory outcomes was assessed using logistic regression and adjusting by confounding variables. Some potential effect modifiers (i.e. smoking, fruit and vegetables consumption) were examined.

Results: Among the 2003 children included in the study, a total of 731 (36.6%) had a LRTI episode, 693 (34.6%) experienced wheezing, 302 (15.5%) a persistent cough, 939 (47.4%) chestiness and 620 (31.2%) had an episode of otitis during their first year of life. Gas cookers were present in 45.5% of homes. Exposure to gas cooking in homes was not associated with respiratory outcomes Odds Ratios (OR) were close to 1 and not statistically significant. However, a positive association was found for otitis among infants whose mothers reported low intakes of fruit and vegetables during pregnancy [OR (95% CI) = 1.38 (1.01-1.9)] and also wheezing and chestiness were associated with gas cookers among those children whose mothers smoked during pregnancy.

Conclusions: In susceptible subjects (those whose mothers smoke and consumed below average fruit and vegetables) we found an association between exposure to gas cooking during pregnancy and risk of wheezing, chestiness and otitis during the first year of life. But more research is needed regarding not only gas cooking and respiratory health but also the possible effect modifier role of diet and tobacco.
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http://dx.doi.org/10.1186/1476-069X-12-100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883519PMC
December 2013

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

Environ Health Perspect 2014 Jan 22;122(1):107-13. Epub 2013 Oct 22.

Institute of Epidemiology I, Helmholtz Zentrum München, German Research Centre for Environmental Health, Munich, Germany.

Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood.

Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts--BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)--and to derive combined effect estimates using meta-analysis.

Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter≤2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5-10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates.

Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR=1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR=1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR=1.09; 95% CI: 1.02, 1.16 per 10-μg/m3).

Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media.
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http://dx.doi.org/10.1289/ehp.1306755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888562PMC
January 2014

Swimming pool attendance, respiratory symptoms and infections in the first year of life.

Eur J Pediatr 2013 Jul 7;172(7):977-85. Epub 2013 Mar 7.

CREAL-Centre for Research in Environmental Epidemiology, Barcelona Biomedical Research Park, Dr. Aiguader, 88, 08003 Barcelona, Spain.

Unlabelled: We evaluated the relationship between indoor and outdoor swimming pool attendance and respiratory symptoms and infections during the first year of life. A population-based mother-child cohort study was conducted in four Spanish areas (INMA project). Study subjects were recruited at pregnancy, followed to delivery and 14 months after birth. Information on swimming pool attendance and health manifestations during the first year of life was collected at 14 months: low respiratory tract infection (LRTI), persistent cough, wheezing, atopic eczema and otitis. Odds ratios and 95 % confidence interval (OR 95 %CI) were calculated by logistic regression adjusting for confounders. Among the 2,205 babies included, 37 % reported having LRTI, 37 % wheezing, 16 % persistent cough, 22 % atopic eczema, 33 % otitis and 50 % attended swimming pools during the first year of life. Around 40 % went to outdoor pools in summer with a median cumulative duration of 7.5 h/year, and 20 % attended indoor pools with a median cumulative duration of 18 h/year. Pool attendance differed by area, season of birth and sociodemographic characteristics, and was not associated with LRTI, wheezing, persistent cough, atopic eczema or otitis. Adjusted OR of wheezing and LRTI were, respectively, 1.06 (95 %CI, 0.88-1.28) and 1.09 (0.90-1.31) for babies attending vs. babies not attending pools. Stratification by type of swimming pool, cumulative duration or parental atopy did not modify the results.

Conclusion: No association was detected between pool attendance and LRTI, wheezing, persistent cough, atopic eczema or otitis during the first year of life in Spain.
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http://dx.doi.org/10.1007/s00431-013-1975-xDOI Listing
July 2013

Prenatal and postnatal residential usage of insecticides in a multicenter birth cohort in Spain.

Sci Total Environ 2013 Feb 19;445-446:273-80. Epub 2013 Jan 19.

Centre for Public Health Research (CSISP), Av. Catalunya 21, 46020 Valencia, Spain.

This study aimed to describe the residential use of insecticides in a birth cohort in Spain. Study subjects were 2,456 women enrolled into the INMA (Environment and Childhood) birth cohort followed prospectively during pregnancy and in the early postnatal period. The women were recruited at the beginning of their pregnancy between 2003 and 2008 in four regions of Spain. Socio-demographic, environmental and lifestyle information was obtained at two interviews during pregnancy, one at the first (mean:13.8±2.6 weeks of gestation) and the other at the third trimester (mean: 33.3±2.3 weeks of gestation). Information about prenatal use of indoor and outdoor insecticides (type, timing, place of application, place of storage) was obtained from the second interview. In a 3rd interview (mean: 16.2±6.9 months of age of children), information about postnatal indoor and outdoor insecticide use was obtained. Regression models examined the association between demographic and lifestyle factors and pesticide use to determine which characteristics predicted use prenatally and postnatally. Fifty-four percent of women reported using indoor insecticides during pregnancy, 45% in their bedroom and 47% elsewhere in the house. Plug-in devices were the most frequent application methods used in the pregnant woman's bedroom and insecticide sprays elsewhere in the house. The maternal factors related to prenatal use of indoor insecticides were parity, country of birth, educational level, region of residence, having a garden or yard with plants, and living near an agricultural area. These products continued to be used postnatally, although 20% of the women stopped using them. Foetuses and children are especially vulnerable to pesticide exposure; thus knowing how pesticides are used during pregnancy and infancy may be a starting point for the study of their potential effects on health as well as useful for designing preventive actions.
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http://dx.doi.org/10.1016/j.scitotenv.2012.12.031DOI Listing
February 2013

Early-life exposure to outdoor air pollution and respiratory health, ear infections, and eczema in infants from the INMA study.

Environ Health Perspect 2013 Mar 5;121(3):387-92. Epub 2012 Dec 5.

Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health.

Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12-18 months of age in a Spanish birth cohort of 2,199 infants.

Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO(2)) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations.

Results: A 10-µg/m(3) increase in average NO(2) during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO(2) were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO(2), the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period.

Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.
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http://dx.doi.org/10.1289/ehp.1205281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621204PMC
March 2013

The use of household cleaning products during pregnancy and lower respiratory tract infections and wheezing during early life.

Int J Public Health 2013 Oct 11;58(5):757-64. Epub 2012 Oct 11.

Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain,

Objective: To evaluate the effects of household use of cleaning products during pregnancy on infant wheezing and lower respiratory tract infections (LRTI).

Methods: In four prospective Spanish birth cohorts (n = 2,292), pregnant women reported the use of household cleaning products. When infants were 12-18 months old, current cleaning product use and infant's wheezing and LRTI were reported. Cohort-specific associations between the use of specific products and respiratory outcomes were evaluated using multivariable regression analyses and estimates were combined using random-effects meta-analyses.

Results: The period prevalence of LRTI was higher when sprays (combined odds ratio (OR) = 1.29; 95 % confidence interval (CI) 1.04-1.59) or air fresheners (OR = 1.29; CI 1.03-1.63) were used during pregnancy. The odds of wheezing increased with spray (OR = 1.37; CI 1.10-1.69) and solvent (OR = 1.30; CI 1.03-1.62) use. The associations between spray and air freshener use during pregnancy and both outcomes remained apparent when these products were not used after pregnancy. Nevertheless, the estimates were higher when post-natal exposure was included.

Conclusion: The use of cleaning sprays, air fresheners and solvents during pregnancy may increase the risk of wheezing and infections in the offspring.
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http://dx.doi.org/10.1007/s00038-012-0417-2DOI Listing
October 2013

Prenatal exposure to traffic-related air pollution and fetal growth in a cohort of pregnant women.

Occup Environ Med 2012 Oct 27;69(10):736-44. Epub 2012 Jul 27.

High Center for Public Health Research-CSISP, Avda, Cataluña no 21, Valencia 46020, Spain.

Objectives: Scant evidence is available on effects of air pollution on longitudinally measured fetal biometry, and thus it remains unclear as to whether there are critical windows of exposure or specificity of effects. Our objective was to examine the association between exposure to nitrogen dioxide (NO2) during pregnancy and fetal and neonatal anthropometry in a cohort of Spanish women.

Methods: Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses. Biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) were evaluated in each trimester by ultrasound. As neonatal outcomes, weight, length and head circumference were analysed. SD scores adjusted by gestational age, mother characteristics and fetus sex were calculated at 12, 20 and 32 weeks of gestation as well as at birth. The association between fetal growth and average exposure to NO2 in the relevant windows was investigated using regression models, adjusted for socio-demographic and lifestyle-related variables.

Results: Exposure to NO2 was inversely associated with BPD, AC and EFW at week 32 and with growth in these parameters in weeks 20-32. BPD and FL were also affected earlier, at week 20. NO2 levels above the median (38 μg/m3) reduced size at week 32 by around 9% in all parameters except for FL (6%). The critical windows of exposure were in early pregnancy, before 20 weeks. Exposure in this period was also inversely associated with neonatal length and head circumference.

Conclusions: Maternal exposure to NO2 is associated with impaired fetal growth from mid-gestation onwards.
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http://dx.doi.org/10.1136/oemed-2011-100550DOI Listing
October 2012

[The spatial distribution of population exposure to outdoor air pollution in Valencia (Spain) and its association with a privation index].

Gac Sanit 2013 Mar-Apr;27(2):143-8. Epub 2012 Jul 9.

CIBER de Epidemiología y Salud Pública (CIBERESP), España.

Objective: To evaluate spatial variation in exposure to nitrogen dioxide (NO2) air pollution in the city of Valencia, Spain, and its association with socioeconomic deprivation and age.

Methods: Census tract population data were obtained from the National Statistics Institute of Spain. Outdoor NO2 was monitored in 100 sites in the study area, through the use of passive samplers, in three campaigns between 2002 and April 2004. Land use regression (LUR) was used to obtain a map of NO2 levels. The LUR predictions were compared with the NO2 level obtained by: a) the nearest sampler of the monitoring network, b) the nearest passive sampler, c) the mean distance-weighted levels of the samplers in the neighborhood, and d) the NO2 level obtained by using Kriging. For each census tract, the NO2 levels were obtained. The association of NO2 air pollution exposure with population age (≥65 years) and the 5-category deprivation index was analyzed.

Results: The LUR models showed less error than the other prediction methods. The safety levels proposed by the World Health Organization were exceeded in more than 99% of the population. An inverse relationship was found between NO2 levels and the deprivation index (β = -2.01μg/m(3) in the most deprived quintile compared with lower deprivation, 95%CI: -3.07; -0.95) and a direct relationship was found with age (β = 0.12μg/m(3) per unit increase in percentage of the population ≥ 65 years, 95%CI: 0.08; 0.16).

Conclusions: The method allowed pollution maps to be obtained and the association between NO2 levels and sociodemographic characteristics to be described.
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http://dx.doi.org/10.1016/j.gaceta.2012.05.010DOI Listing
February 2014