Publications by authors named "Mikel Basterrechea"

48 Publications

Maternal sleep duration and neonate birth weight: A population-based cohort study.

Int J Gynaecol Obstet 2021 Mar 23. Epub 2021 Mar 23.

Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.

Objective: To investigate the association between maternal sleep duration (an important health indicator) and neonate birth weight.

Methods: The study included 2536 mother-neonate pairs of a Spanish birth cohort (2004-2006, INMA project). The exposures were questionnaire-based measures of sleep duration before and during pregnancy. The primary outcome was neonate birth weight score (g) standardized to 40 weeks of gestation.

Results: In women sleeping for <7 h/day before pregnancy, each additional hour of sleep increased birth weight score by 44.7 g (P = 0.049) in the minimally adjusted model, although findings were not statistically significant after considering other potential confounders (P > 0.05). However, increasing sleep duration for the group of mothers who slept for more than 9 h/day decreased birth weight score by 39.2 g per additional hour (P = 0.001). Findings were similar after adjusting for several sociodemographic confounders and maternal depression-anxiety clinical history as an intermediate factor. Similar but attenuated associations were observed with sleep duration in the second trimester of pregnancy.

Conclusion: The relationship between maternal sleep duration before and during pregnancy and neonate birth weight is an inverse U-shaped curve. Excessive sleep duration may adversely affect neonate health through its impact on birth weight.
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http://dx.doi.org/10.1002/ijgo.13685DOI Listing
March 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

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

Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain).

Environ Res 2020 02 19;181:108943. Epub 2019 Nov 19.

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. Electronic address:

We assessed whether prenatal selenium (Se) exposure is associated with anthropometry at birth, placental weight and gestational age. Study subjects were 1249 mother-child pairs from the Valencia and Gipuzkoa cohorts of the Spanish Childhood and Environment Project (INMA, 2003-2008). Se was determined in serum samples taken at the first trimester of pregnancy. Socio-demographic and dietary characteristics were also collected by questionnaires. Mean (SD) serum Se concentration was 79.57 (9.64) μg/L. Se showed weak associations with both head circumference and gestational age. The association between serum Se concentration and birth weight and length was negative, and direct for placental weight and probability of preterm birth, although the coefficients did not reach statistical significance. Individuals with total mercury (THg) levels >15 μg/L reversed the serum Se concentration effect on head circumference. Significant interactions were found between sex and both gestational age and prematurity. Spontaneous birth gestational ages were estimated to be lower for males and their probability of prematurity was higher. In conclusion, prenatal Se exposure may be associated with lower head circumference and lower gestational ages at spontaneous birth. Interactions with THg exposure and gender should be considered when assessing these relationships.
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http://dx.doi.org/10.1016/j.envres.2019.108943DOI Listing
February 2020

Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy.

JAMA Netw Open 2019 10 2;2(10):e1912902. Epub 2019 Oct 2.

ISGlobal, Barcelona, Spain.

Importance: Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid's role in fetal brain development.

Objective: To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy.

Design, Setting, And Participants: In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019.

Main Outcomes And Measures: Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines.

Results: Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-μg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 μm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-μg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 μg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study.

Conclusions And Relevance: The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.12902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806433PMC
October 2019

Maternal Thyroid Function in Early Pregnancy and Child Attention-Deficit Hyperactivity Disorder: An Individual-Participant Meta-Analysis.

Thyroid 2019 09;29(9):1316-1326

Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre - Sophia Children's Hospital, Rotterdam, The Netherlands.

Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). A total of 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA;  = 1073, Spain), Generation R ( = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC;  = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0-1.3],  = 0.060 and OR 0.9 [CI 0.9-1.1],  = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0-1.4],  = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. We found no clear evidence of an association between maternal thyroid function and child ADHD.
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http://dx.doi.org/10.1089/thy.2018.0794DOI Listing
September 2019

Prenatal exposure to organochlorine compounds and lung function during childhood.

Environ Int 2019 10 27;131:105049. Epub 2019 Jul 27.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address:

Introduction: Prenatal exposure to organochlorine compounds (OCs) can increase the risk of reported respiratory symptoms in children. It remains unclear whether these compounds can also impact on lung function. We assessed the association between prenatal exposure to OCs and lung function during childhood.

Methods: We included 1308 mother-child pairs enrolled in a prospective cohort study. Prenatal concentrations of p,p'-dichlorodiphenyltrichloroethane [p,p'-DDT], p,p'-dichlorodiphenyldichloroethylene [p,p'-DDE], hexachlorobenzene [HCB], and seven polychlorinated biphenyls [PCBs] were measured in cord blood. Spirometry was performed in the offspring at ages 4 (n = 636) and 7 years (n = 1192).

Results: More than 80% of samples presented quantifiable levels of p,p'-DDE, HCB, PCB-138, PCB-153, and PCB-180; p,p'-DDE was the compound with the highest median concentrations. At 4 years, prenatal p,p'-DDE exposure was associated with a decrease in forced expiratory volume in 1 s (FEV) in all quartiles of exposure (e.g., third quartile [0.23-0.34 ng/mL]: β for FEV -53.61 mL, 95% CI -89.87, -17.35, vs. the lowest). Prenatal p,p'-DDE levels also decreased forced vital capacity (FVC) and FEV/FVC, but associations did not reach statistical significance in most exposure quartiles. At 7 years, p,p'-DDE was associated with a decrease in FVC and FEV in only the second quartile of exposure (e.g. β for FEV -36.96 mL, 95% CI -66.22, -7.70, vs. the lowest). Prenatal exposure to HCB was associated with decreased FVC and FEV, but in only the second quartile and at 7 years (e.g. [0.07-0.14 ng/mL]: β for FEV -25.79 mL, 95% CI -55.98, 4.39, vs. the lowest). PCBs were not consistently associated with lung function.

Conclusion: Prenatal exposure to p,p'-DDE may decrease lung function during childhood, especially FEV and at medium levels of exposure. Further and deeper knowledge on the impact of environmental chemicals during pregnancy on lung development is needed.
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http://dx.doi.org/10.1016/j.envint.2019.105049DOI Listing
October 2019

First-trimester maternal concentrations of polyfluoroalkyl substances and fetal growth throughout pregnancy.

Environ Int 2019 09 25;130:104830. Epub 2019 Jun 25.

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; Department of Nursing and Chiropody, Universitat de València, Valencia, Spain. Electronic address:

Background: Several studies have investigated the possible association between prenatal exposure to perfluoroalkyl substances (PFASs) and birth anthropometry. However, none has assessed fetal size longitudinally. We studied the possible association between PFASs and fetal biometry.

Methods: In 1230 mother-child pairs of three cohorts from the Spanish INMA-Project, we analyzed perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in first-trimester maternal plasma (collection: 2003-2008). We measured abdominal circumference (AC), femur length (FL), biparietal diameter (BPD), and estimated fetal weight (EFW) by ultrasounds at 12, 20, and 34 gestational weeks. We conducted multivariable linear regression analyses between log-transformed (PFASs) and SD-scores of fetal parameters in each cohort and subsequent meta-analysis. We also assessed effect modification by sex and maternal smoking.

Results: PFHxS, PFOA, PFOS, and PFNA medians were: 0.58, 2.35, 6.05, and 0.65 ng/mL, respectively. There were no associations for the whole population in any trimester of pregnancy. However, we found an indication that maternal smoking modified the effect in different directions depending on the PFAS. Among smokers (31%), we found negative associations between both PFOA and PFNA and FL or EFW at week 20 (% change ranging between -6.8% and -5.7% per twofold PFAS increase) and positive associations between PFHxS or PFOS and BPD at week 34 (6.8% and 6.3%, respectively).

Conclusions: Results did not suggest an overall association between prenatal PFASs and fetal growth. The results among smokers should be taken with caution and further studies are warranted to elucidate the possible role of smoking in this association.
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http://dx.doi.org/10.1016/j.envint.2019.05.024DOI Listing
September 2019

DNA methylation in childhood asthma: an epigenome-wide meta-analysis.

Lancet Respir Med 2018 05 26;6(5):379-388. Epub 2018 Feb 26.

ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma.

Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting.

Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p<1·14 × 10) after meta-analysis. Consistently lower methylation levels were observed at all associated loci across childhood from age 4 to 16 years in participants with asthma, but not in cord blood at birth. All 14 CpG sites were significantly associated with asthma in the second replication study using whole-blood DNA, and were strongly associated with asthma in purified eosinophils. Whole-blood transcriptional signatures associated with these CpG sites indicated increased activation of eosinophils, effector and memory CD8 T cells and natural killer cells, and reduced number of naive T cells. Five of the 14 CpG sites were associated with asthma in respiratory epithelial cells, indicating cross-tissue epigenetic effects.

Interpretation: Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context.

Funding: EU and the Seventh Framework Programme (the MeDALL project).
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http://dx.doi.org/10.1016/S2213-2600(18)30052-3DOI Listing
May 2018

Maternal Metabolic Health Parameters During Pregnancy in Relation to Early Childhood BMI Trajectories.

Obesity (Silver Spring) 2018 03 5;26(3):588-596. Epub 2018 Feb 5.

ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.

Objective: The objective of this study was to evaluate the associations between maternal metabolic parameters and early childhood BMI trajectories.

Methods: Two thousand two hundred fifty-one children born in Spain between 2004 and 2008 were analyzed. Five BMI z score trajectories from birth to age 4 years were identified by using latent class growth analysis. Multinomial regression assessed the associations between maternal metabolic parameters and offspring's BMI trajectories.

Results: Children in the reference BMI trajectory had average size at birth followed by a slower BMI gain. Maternal prepregnancy obesity was associated with trajectories of accelerated BMI gain departing from either higher (relative risk ratio [RRR] = 1.77; 95% CI: 1.07-2.91) or lower size at birth (RRR = 1.91; 95% CI: 1.17-3.12). Gestational weight gain (GWG) above clinical guidelines was associated with a trajectory of higher birth size followed by accelerated BMI gain (RRR = 2.14; 95% CI: 1.53-2.97). Maternal serum triglycerides were negatively associated with BMI trajectories departing from lower birth sizes. Gestational diabetes, maternal serum cholesterol, and C-reactive protein were unrelated to children's BMI trajectories.

Conclusions: Maternal prepregnancy obesity, GWG, and serum triglycerides are associated with longitudinal BMI trajectories in early childhood that may increase disease risk in later life. Health initiatives should promote healthy weight status before and during pregnancy to improve maternal and child health.
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http://dx.doi.org/10.1002/oby.22095DOI Listing
March 2018

Iodine intake from supplements and diet during pregnancy and child cognitive and motor development: the INMA Mother and Child Cohort Study.

J Epidemiol Community Health 2018 03 26;72(3):216-222. Epub 2017 Dec 26.

CIBER Epidemiología y Salud Pública (CIBERESP), Spain.

Background: The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4-5 years.

Methods: We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4-5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children's Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC~Cr).

Results: Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC~Cr <100 µg/L had 3.93 (95% CI -6.18 to -1.69) general cognitive scores lower than the reference (150-249 µg/L). Dietary iodine was inversely associated with motor scores and milk but not other dairy products or seafood consumption accounted for this association (beta: -1.36; 95% CI -2.12 to -0.61; per one daily milk serving).

Conclusions: We found an association between low maternal urinary iodine and lower cognitive scores in childhood, although only when corrected for creatinine, adding to the evidence that iodine deficiency may have potential harmful effects on neurodevelopment. Iodine supplementation does not appear to improve child's neurodevelopment at 4-5 years.
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http://dx.doi.org/10.1136/jech-2017-209830DOI Listing
March 2018

Variations in the prevalence of childhood asthma and wheeze in MeDALL cohorts in Europe.

ERJ Open Res 2017 Jul 3;3(3). Epub 2017 Jul 3.

Bradford Institute for Health Research, Bradford, UK.

While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, individual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe. We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education, parental smoking, pets, parental asthma, doctor-diagnosed allergic rhinitis, doctor-diagnosed eczema and wheeze severity. At age 4 years, asthma prevalence varied from 1.72% in Germany to 13.48% in England and the prevalence of wheeze varied from 9.82% in Greece to 55.37% in Spain. Adjusted estimates of the proportion of 4-year-old children with wheeze diagnosed with asthma remained highest in England (38.14%, 95% CI 31.38-44.90%) and lowest in Spain (15.94%, 95% CI 6.16-25.71%). The large differences in prevalence rates of asthma, wheeze and wheeze with asthma at age 4 years between European cohorts may indicate that childhood asthma is more readily diagnosed in some countries while going unrecognised elsewhere.
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http://dx.doi.org/10.1183/23120541.00150-2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566268PMC
July 2017

Comparison of urinary iodine levels in women of childbearing age during and after pregnancy.

Eur J Nutr 2018 Aug 29;57(5):1807-1816. Epub 2017 Apr 29.

Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Purpose: Median urinary iodine concentration (UIC) is used to describe the iodine status of a population. However, the link between UIC and iodine intake may vary during pregnancy. The aim of this study was to compare UIC during and after pregnancy, adjusting for factors that affect iodine intake.

Methods: Two repeated measures of UIC and data on maternal iodine intake estimated through questionnaires were collected during pregnancy and 1-4 years after pregnancy in a subsample of women (n = 598) from a mother and child cohort study in Spain. Random-effects interval regression was used to assess the changes in UIC according to pregnancy status.

Results: Median UIC was similar during (133 μg/L) and after pregnancy (139 μg/L). After adjusting for iodised salt, iodine supplement consumption, and socio-demographic related variables, UIC was 24.0% (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was maintained in a subsample of women with exhaustive information on diet (n = 291): 26.2%, 95% CI 10.3, 44.4.

Conclusions: In an iodine sufficient area for the general population, iodine excretion was lower during than after pregnancy when factors affecting iodine intake were controlled for. Current recommendations of median UIC during pregnancy are based on the equivalence between iodine intake and UIC estimated from studies in non-pregnant populations, which might lead to overestimation of iodine deficiency during gestation. Further studies should evaluate the equivalence between iodine intake and its urinary excretion during pregnancy.
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http://dx.doi.org/10.1007/s00394-017-1465-4DOI Listing
August 2018

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.

Int J Epidemiol 2017 10;46(5):1465-1477

Cancer Epidemiology Unit, University of Turin and CPO-Piemonte, Turin, Italy.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1093/ije/dyx007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251679PMC
October 2017

Prenatal mercury exposure and birth outcomes.

Environ Res 2016 Nov 21;151:11-20. Epub 2016 Jul 21.

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

Background: Results regarding the association between mercury exposure and anthropometry at birth, gestational length and placental weight are inconsistent, as is the role of seafood intake in these associations.

Objective: We assessed whether prenatal mercury exposure is associated with anthropometry at birth, placental weight and gestational length in a population with a relatively high exposure to mercury from seafood consumption.

Methods: Total mercury (T-Hg) was determined in cord blood from 1869 newborns with birth outcome measures, within the Spanish multicenter INMA cohort from 2004 to 2008. We adjusted cohort specific linear and Cox regression models to evaluate the association between T-Hg and birth anthropometry (weight, length, and head circumference), placental weight and gestational length. Non-spontaneous labor was taken to be censoring in the survival analysis. Final estimates were obtained using meta-analysis.

Results: Geometric mean T-Hg was 8.2μg/L. A doubling of T-Hg was associated with a 7.7g decrease in placental weight (95% CI: -13.6, -1.8) and marginally with head circumference (beta: -0.052cm, 95% CI: -0.109, 0.005). T-Hg was also inversely related to weight and length, although with weaker estimates. Mercury exposure was not associated with the length of gestation. The inverse relation between T-Hg and growth was enhanced when the intake of different seafood groups was adjusted for in the models.

Conclusions: Prenatal mercury exposure may be associated with reduced placental and fetal growth. Confounding by fish intake should be considered when assessing these relationships.
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http://dx.doi.org/10.1016/j.envres.2016.07.003DOI Listing
November 2016

Urban regeneration as population health intervention: a health impact assessment in the Bay of Pasaia (Spain).

Int J Equity Health 2016 09 15;15(1):145. Epub 2016 Sep 15.

Department of Sociology 2, University of the Basque Country (UPV/EHU), Leioa, Spain.

Background: An important health issue in urban areas is how changes arising from the regeneration of city-areas affect social determinants of health and equity. This paper examines the impacts attributable to a new fish market and to delays in the regeneration of a port area in a deteriorated region of the Bay of Pasaia (Spain). Potential differential impacts on local residents and socially vulnerable groups were evaluated to determine health inequalities.

Methods: An in-depth, prospective and concurrent Health-Impact-Assessment (HIA) focused on equity was conducted by the regional Public Health Department, following the Merseyside guidelines. Data from different sources was triangulated and impacts were identified using qualitative and quantitative methods.

Results: The intervention area is characterised by poor social, environmental, and health indicators. The distinctness of the two projects generates contrasting health and inequality impacts: generally positive for the new fish market and negative for the port area. The former creates recreational spaces and improves urban quality and social cohesion. By contrast, inaction and stagnation of the project in the port area perpetuates deterioration, a lack of safety, and poor health, as well as increased social frustration.

Conclusions: In addition to assessing the health impacts of both projects this HIA promoted intersectoral partnerships, boosted a holistic and positive view of health and incorporated health and equity into the political discourse. Community-level participatory action enabled public health institutions to respond to new urban planning challenges and responsibilities in a more democratic manner.
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http://dx.doi.org/10.1186/s12939-016-0424-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024480PMC
September 2016

Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts.

JAMA Pediatr 2016 Apr;170(4):381-90

Department of Public Health, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.

Importance: Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear.

Objective: To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity.

Design, Setting, And Participants: Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26,184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years.

Exposures: Consumption of fish during pregnancy.

Main Outcomes And Measures: We estimated offspring body mass index percentile trajectories from 3 months after birth to 6 years of age. We defined rapid infant growth as a weight gain z score greater than 0.67 from birth to 2 years and childhood overweight/obesity at 4 and 6 years as body mass index in the 85th percentile or higher for age and sex. We calculated cohort-specific effect estimates and combined them by random-effects meta-analysis.

Results: This multicenter, population-based birth cohort study included the 26,184 pregnant women and their children. The median fish intake during pregnancy ranged from 0.5 times/week in Belgium to 4.45 times/week in Spain. Women who ate fish more than 3 times/week during pregnancy gave birth to offspring with higher body mass index values from infancy through middle childhood compared with women with lower fish intake (3 times/week or less). High fish intake during pregnancy (>3 times/week) was associated with increased risk of rapid infant growth, with an adjusted odds ratio (aOR) of 1.22 (95% CI, 1.05-1.42) and increased risk of offspring overweight/obesity at 4 years (aOR, 1.14 [95% CI, 0.99-1.32]) and 6 years (aOR, 1.22 [95% CI, 1.01-1.47]) compared with an intake of once per week or less. Interaction analysis showed that the effect of high fish intake during pregnancy on rapid infant growth was greater among girls (aOR, 1.31 [95% CI, 1.08-1.59]) than among boys (aOR, 1.11 [95% CI, 0.92-1.34]; P = .02 for interaction).

Conclusions And Relevance: High maternal fish intake during pregnancy was associated with increased risk of rapid growth in infancy and childhood obesity. Our findings are in line with the fish intake limit proposed by the US Food and Drug Administration and Environmental Protection Agency.
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http://dx.doi.org/10.1001/jamapediatrics.2015.4430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103635PMC
April 2016

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

Transfer of perfluoroalkyl substances from mother to fetus in a Spanish birth cohort.

Environ Res 2015 Oct 7;142:471-8. Epub 2015 Aug 7.

Centre for Research in Environmental Epidemiology (CREAL), Doctor Aiguader, 88, 08003 Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain.

Introduction: Prenatal exposure to perfluoroalkyl substances (PFAS) might affect child health; thus estimating PFAS fetal burden is relevant. PFAS fetal burden is best estimated in cord samples; previous studies have used either maternal plasma or serum during pregnancy as proxy, but their validity is not clear. We aimed to evaluate PFAS transfer between mother and fetus and determine its predictors in a Spanish birth cohort.

Methods: We measured perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA) in maternal blood and cord serum from 66 mother-child pairs. We used Spearman's rank coefficients to correlate PFAS concentrations in first trimester maternal plasma and serum, with cord serum samples. We assessed PFAS placental transfer by calculating maternal to cord ratios and examined their association with maternal socio-demographic characteristics and child sex using linear regression models.

Results: Median concentrations of PFAS (ng/mL) of PFHxS, PFOS, PFOA, and PFNA in maternal plasma (0.79, 6.18, 2.85 and 0.84, respectively) and serum (0.84, 6.99, 2.97 and 0.85) were higher than in cord serum (0.40, 1.86, 1.90 and 0.32). PFBS was not detected. Positive Spearman's correlations (p-values<0.001) were found between maternal plasma and serum (⍴≥0.80), maternal plasma and cord (⍴≥0.66), and maternal serum and cord samples (⍴≥0.67). Maternal plasma to cord ratios were above 1 (PFHxS: 2.35 [95%CI: 2.05, 2.70], PFOS: 3.33 [3.05, 3.62], PFOA: 1.37 [1.27, 1.48], PFNA: 2.39 [2.18, 2.63]); maternal serum to cord ratios were similar. Maternal to cord ratios decreased with maternal age, but not with other socio-demographic factors.

Conclusions: Our results suggest that PFAS fetal body burden can be assessed using as proxy maternal plasma or serum collected early in pregnancy. Maternal age might influence PFAS placental transfer.
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http://dx.doi.org/10.1016/j.envres.2015.07.020DOI Listing
October 2015

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

Organochlorine Compounds and Ultrasound Measurements of Fetal Growth in the INMA Cohort (Spain).

Environ Health Perspect 2016 Jan 9;124(1):157-63. Epub 2015 Jun 9.

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

Background: Several studies have reported decreases in birth size associated with exposure to organochlorine compounds (OCs), but uncertainties remain regarding the critical windows of prenatal exposure and the effects on fetal body segments.

Objective: We examined the relationship between prenatal OC concentrations and fetal anthropometry.

Methods: We measured 4,4´-dichlorodiphenyldichloroethylene (4,4´-DDE), hexachlorobenzene (HCB), and polychlorinated biphenyl (PCB) congeners (138, 153, and 180) in 2,369 maternal and 1,140 cord serum samples in four Spanish cohorts (2003-2008). We used linear mixed models to obtain longitudinal growth curves for estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL) adjusted by parental and fetal characteristics. We calculated standard deviation (SD) scores of growth at 0-12, 12-20, and 20-34 weeks of gestation as well as size at gestational week 34 for the four parameters. We studied the association between OCs and the fetal outcomes by cohort-specific linear models and subsequent meta-analyses.

Results: PCBs were associated with a reduction in AC up to mid-pregnancy, and BPD and FL from gestational week 20 onward. An inverse association was also found between HCB and AC growth in early pregnancy. The reduction of these parameters ranged from -4% to -2% for a doubling in the OC concentrations. No association between 4,4´-DDE and fetal growth was observed.

Conclusions: To our knowledge, this is the first study to report an association between prenatal exposure to some PCBs and HCB and fetal growth: AC during the first two trimesters of pregnancy, and BPD and FL later in pregnancy.

Citation: Lopez-Espinosa MJ, Murcia M, Iñiguez C, Vizcaino E, Costa O, Fernández-Somoano A, Basterrechea M, Lertxundi A, Guxens M, Gascon M, Goñi-Irigoyen F, Grimalt JO, Tardón A, Ballester F. 2016. Organochlorine compounds and ultrasound measurements of fetal growth in the INMA cohort (Spain). Environ Health Perspect 124:157-163; http://dx.doi.org/10.1289/ehp.1408907.
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http://dx.doi.org/10.1289/ehp.1408907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710595PMC
January 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

Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, Spain.

Paediatr Perinat Epidemiol 2015 Mar 7;29(2):113-22. Epub 2015 Jan 7.

Pharmacy, University Cardenal Herrera-CEU, Valencia, Spain.

Background: Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery.

Methods: We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4  < 5 th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4  > 95 th percentile and TSH normal), and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery.

Results: An inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (β = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes.

Conclusions: High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range.
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http://dx.doi.org/10.1111/ppe.12172DOI Listing
March 2015

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

Thorax 2015 Jan 20;70(1):64-73. Epub 2014 Oct 20.

Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Spain.

Background: Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers.

Methods: Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed.

Results: Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class.

Conclusions: Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age.
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http://dx.doi.org/10.1136/thoraxjnl-2014-205413DOI Listing
January 2015

Prenatal exposure to PCB-153, p,p'-DDE and birth outcomes in 9000 mother-child pairs: exposure-response relationship and effect modifiers.

Environ Int 2015 Jan 11;74:23-31. Epub 2014 Oct 11.

Department of Hygiene, Social and Environmental Medicine, Ruhr University Bochum, Bochum, Germany.

Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p'-DDE) can impair fetal growth; however, the exposure-response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure-response relationship between PCB-153 and p-p'-DDE and birth outcomes; to evaluate whether any no exposure-effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother-child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure-response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194g (95% CI -314, -74) per 1μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure-response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association.
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http://dx.doi.org/10.1016/j.envint.2014.09.013DOI Listing
January 2015

[Prevalence of factors associated with the duration of exclusive breastfeeding during the first 6 months of life in the INMA birth cohort in Gipuzkoa].

Gac Sanit 2015 Jan-Feb;29(1):4-9. Epub 2014 Sep 23.

Instituto de investigación Sanitaria, BIODONOSTIA, San Sebastián, Guipúzcoa, España; Subdirección de Salud Pública de Gipuzkoa, Gobierno Vasco, San Sebastián, Guipúzcoa, España; CIBER de Epidemiología y Salud Pública (CIBERESP), España; Dirección de Salud Pública y Adicciones, Departamento de Salud del Gobierno Vasco, Vitoria-Gasteiz, Álava, España. Electronic address:

Objective: To estimate the prevalence of exclusive breastfeeding (EB) during the first 6 months of life in the Gipuzkoa birth cohort, identify the reasons for abandonment of EB, and establish the associated factors.

Methods: The study population consisted of 638 pregnant women from the INMA-Gipuzkoa (Infancia y Medio Ambiente, www.proyectoinma.org) birth cohort, who were followed up from the third trimester of pregnancy until the child was aged 14 months. To determine the factors related to abandonment of EB, logistic regression models were used in two different stages (4 months or early stage and 6 months or late stage).

Results: The prevalence of EB within the Gipuzkoa cohort was 84.8% after hospital discharge, 53.7% at 4 months of life and 15.4% at 6 months of life. The reasons given by the mothers for early EB cessation were: breastfeeding problems, low weight gain and hypogalactia. Other factors influencing the early phase were the intention to provide EB, parity, area of residence and social class. Abandonment in the late stage was influenced by the length of maternity leave.

Conclusions: From a public health perspective, the results of this study could help health professionals to develop strategies to support breastfeeding mothers, taking into account the main reasons for early and late abandonment.
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http://dx.doi.org/10.1016/j.gaceta.2014.08.002DOI Listing
December 2016

[Health impact assessment of regeneration projects in Pasaia Bay (Spain): perceptions of the affected population].

Gac Sanit 2014 Nov-Dec;28(6):442-9. Epub 2014 Aug 6.

Servicio de Estudios e Investigación Sanitaria, Departamento de Salud, Gobierno Vasco, Vitoria-Gasteiz, Araba, España; CIBER de Epidemiología y Salud Pública (CIBERESP), España.

Aim: To determine the health impact perceived by residents and social players involved in two urban regeneration interventions (a new fish market and the redevelopment of North/West Herrera) in Pasaia Bay (Gipuzkoa, Spain) that have been the subject of a health impact assessment (HIA).

Method: Qualitative methodology was used with theoretical and intentional sampling. Information was obtained through 18 personal interviews and five discussion groups and was analyzed in accordance with the sociological analysis model of discourse. The preliminary results were triangulated and contrasted among the team members and those taking part in the study.

Results: Four interrelated areas of health impact were identified: urban quality, connectivity, social cohesion, and-to a lesser extent-employment. Specific aspects for improvement were indicated for each field, as well as the influence of the sociopolitical context and conceptions of health. Other significant findings were the impact of the process of carrying out the building work and the distinct perspectives due to the differing roles and social profiles of participants.

Conclusions: Knowledge of the perceptions and expectations of affected individuals through qualitative methods provides novel elements and interrelations that are needed to apply HIA as a tool for improving health and for citizen participation.
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http://dx.doi.org/10.1016/j.gaceta.2014.06.009DOI Listing
December 2016

Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta.

Environ Int 2014 Oct 28;71:81-7. Epub 2014 Jun 28.

Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.

Background: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks.

Objectives: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation.

Methods: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated.

Results: A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value<0.001), while no significant effects were found in girls (p-value=0.134).

Conclusions: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
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http://dx.doi.org/10.1016/j.envint.2014.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122792PMC
October 2014

[Shigella sonnei outbreak in a school in Northern Spain].

Enferm Infecc Microbiol Clin 2015 Mar 5;33(3):145-8. Epub 2014 May 5.

Subdirección de Salud Pública de Gipuzkoa, Gobierno Vasco, Donostia-San Sebastián, Gipuzkoa, España.

In October 2012, an outbreak of acute gastroenteritis caused by Shigella sonnei was detected in a nursery and primary school in the north of Spain affecting 112 people: 63.7% were pupils and teachers and 35.7% their co-habitants. The source was a sick child who had travelled to an endemic country, and the key trigger factor was inadequate hygiene in one of the toilets of the school. The enforcement of strict hygiene measures was essential for controlling the outbreak.
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http://dx.doi.org/10.1016/j.eimc.2014.02.024DOI Listing
March 2015

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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July 2014