Publications by authors named "Ferran Ballester"

211 Publications

Prenatal arsenic exposure, arsenic methylation efficiency, and neuropsychological development among preschool children in a Spanish birth cohort.

Environ Res 2021 Oct 15:112208. Epub 2021 Oct 15.

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: Prenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive.

Objectives: To explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements.

Materials And Methods: Study subjects were 807 mother-child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B and B).

Results: The geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) μg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. β [CI95%] = -1.37 [-2.33, -0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency.

Discussion: An inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.
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http://dx.doi.org/10.1016/j.envres.2021.112208DOI Listing
October 2021

Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children.

Environ Res 2021 Oct 8:112181. Epub 2021 Oct 8.

Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain; Department of Preventive Medicine and Public Health, Faculty of Medicine, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain.

Background: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW).

Method: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McCarthy Scales (age of 4). Multiple linear regression analyses were carried out adjusting for a wide range of covariates related to the child, mother, family context and other potential neurotoxicants.

Results: No association was found between MUFcr levels and Bayley Mental Development Index score. Nevertheless, regarding the McCarthy scales, it was found that per unit (mg/g) of MUFcr across the whole pregnancy, scores in boys were greater for the verbal, performance, numeric and memory domains (β = 13.86, CI 95%: 3.91, 23.82), (β = 5.86, CI 95%: 0.32, 11.39), (β = 6.22, CI 95%: 0.65, 11.79) and (β = 11.63, CI 95%: 2.62, 20.63) respectively and for General Cognitive Index (β = 15.4, CI 95%: 6.32, 24.48). For girls there was not any cognitive score significantly associated with MUFcr, being the sex-F interactions significant (P interaction <0.05). Including other toxicants levels, quality of family context or deprivation index did not substantially change the results.

Conclusions: In boys, positive associations were observed between MUFcr and scores in cognitive domains at the age of 4. These findings are inconsistent with those from some previous studies and indicate the need for other population-based studies to confirm or overturn these results at low levels of F in CDW.
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http://dx.doi.org/10.1016/j.envres.2021.112181DOI Listing
October 2021

Serum metal levels in a population of Spanish pregnant women.

Gac Sanit 2021 Oct 6. Epub 2021 Oct 6.

Biodonostia, Health Research Institute, Donostia, Gipuzkoa, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Department of Health of the Basque Government, Public Health Division of Gipuzkoa, Donostia, Gipuzkoa, Spain.

Objective: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy.

Method: Cross-sectional study with 1279 participants from the INMA cohorts.

Results: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B supplementation (p=0.006).

Conclusions: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.
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http://dx.doi.org/10.1016/j.gaceta.2021.07.006DOI Listing
October 2021

DNA methylation changes associated with prenatal mercury exposure: A meta-analysis of prospective cohort studies from PACE consortium.

Environ Res 2021 Sep 22;204(Pt B):112093. Epub 2021 Sep 22.

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 a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10, p-value = 5.87 × 10) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10) in GRK1 and cg02212000 (β = -0.001, p-value = 8.13 × 10) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
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http://dx.doi.org/10.1016/j.envres.2021.112093DOI Listing
September 2021

Exposure to metals and metalloids among pregnant women from Spain: Levels and associated factors.

Chemosphere 2021 Aug 6;286(Pt 2):131809. Epub 2021 Aug 6.

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: Humans are regularly exposed to metals and metalloids present in air, water, food, soil and domestic materials. Most of them can cross the placental barrier and cause adverse impacts on the developing foetus.

Objectives: To describe the prenatal concentrations of metals and metalloids and to study the associated sociodemographic, environmental and dietary factors in pregnant Spanish women.

Methods: Subjects were 1346 pregnant women of the INMA Project, for whom the following metals arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), thallium (Tl) and zinc (Zn) were determined in urine, at both the first and the third trimesters of gestation. Sociodemographic, dietary and environmental information was collected through questionnaires during pregnancy. Multiple linear mixed models were built in order to study the association between each metal and metalloid concentrations and the sociodemographic, environmental and dietary factors.

Results: The most detected compounds were As, Co, Mo, Sb, Se and Zn at both trimesters. Zn was the element found in the highest concentrations at both trimesters and Tl was detected in the lowest concentrations. We observed significant associations between As, Cd, Cu, Sb, Tl and Zn concentrations and working situation, social class and age. Seafood, meat, fruits, nuts, vegetables and alcohol intake affected the levels of all the metals but Cd and Cu. Proximity to industrial areas, fields and air pollution were related to all metals except Cd, Sb and Se.

Conclusions: This is the first large prospective longitudinal study on the exposure to metals and metalloids during pregnancy and associated factors to include several cohorts in Spain. The present study shows that some modifiable lifestyles, food intakes and environmental factors could be associated with prenatal exposure to metal(loid)s, which may be considered in further studies to assess their relationship with neonatal health outcomes.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131809DOI Listing
August 2021

Maternal Perfluoroalkyl Substances, Thyroid Hormones, and Genes: A Spanish Cross-sectional Study.

Environ Sci Technol 2021 Jul 27. Epub 2021 Jul 27.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-University Jaume I-University of Valencia, 46019 Valencia, Spain.

Results of studies on perfluoroalkyl substances (PFASs) and thyroid hormones (THs) are heterogeneous, and the mechanisms underlying the action of PFASs to target THs have not been fully characterized. We examined the relation between first-trimester maternal PFAS and TH levels and the role played by polymorphisms in the iodothyronine deiodinase 1 (1) and 2 (2) genes in this association. Our sample comprised 919 pregnant Spanish women (recruitment = 2003-2008) with measurements of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4), and we genotyped for single-nucleotide polymorphisms in the 1 (rs2235544) and 2 (rs12885300) genes. We performed multivariate regression analyses between PFASs and THs and included the interaction term PFAS-genotypes in the models. PFHxS was associated with an increase in TSH (% change in outcome [95% CI] per 2-fold PFAS increase = 6.09 [-0.71, 13.4]), and PFOA and PFNA were associated with a decrease in TT3 (-7.17 [-13.5, -0.39] and -6.28 [-12.3, 0.12], respectively). We found stronger associations between PFOA, PFNA, and TT3 for 1-CC and 2-CT genotypes, although interaction -values were not significant. In conclusion, this study found evidence of an inverse association between PFOA and TT3 levels. No clear effect modification by enzyme genes was observed.
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http://dx.doi.org/10.1021/acs.est.1c01452DOI Listing
July 2021

Prenatal perfluoroalkyl substance exposure and neuropsychological development throughout childhood: The INMA Project.

J Hazard Mater 2021 08 20;416:125185. Epub 2021 Jan 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; Faculty of Nursing and Chiropody, Universitat de València, Valencia, Spain. Electronic address:

Background: Perfluoroalkyl substances (PFASs) have been related to neurodevelopmental toxicity in animals. However, human studies are inconclusive.

Objectives: To evaluate the association between prenatal PFAS exposure and neuropsychological development during childhood.

Methods: 1240 mother-child pairs from the Spanish INMA Project were analyzed. Perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) were measured in first-trimester maternal plasma. Neuropsychological development was assessed at 14 months, 4-5 and 7 years covering four domains: general cognitive, general motor, attention, and working memory. Associations were studied by means of multivariable regression analyses.

Results: PFHxS, PFOA, PFOS, and PFNA medians were: 0.6, 2.4, 6.1, and 0.7 ng/mL. Higher PFAS prenatal exposure was associated with worse motor development at 14 months, especially in the case of PFHxS (β[95%CI]: -1.49[-2.73, -0.24]) and to a lesser extent PFOS (-1.25[-2.62, 0.12]). There was also a marginal positive association between general cognitive development at 4-5 years and PFOS (1.17[-0.10, 2.43]) and PFNA (0.99[-0.13, 2.12]). No clear associations for other neuropsychological outcomes or any sex differences were found.

Discussion: This study shows no clear-cut evidence of an association between prenatal PFAS exposure and adverse neuropsychological development in children up to the age of 7 years.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125185DOI Listing
August 2021

Prenatal manganese serum levels and neurodevelopment at 4 years of age.

Environ Res 2021 06 12;197:111172. Epub 2021 Apr 12.

Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Paseo Doctor Begiristain s/n, 20014, San Sebastian, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029, Madrid, Spain; Department of Preventive Medicine and Public Health, Faculty of Medicine, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain.

Background: The excess of manganese (Mn) causes severe deleterious effects in the central nervous system, and the developing brain is especially sensitive to Mn overload. However, results of prospective studies regarding Mn neurodevelopmental effects remain inconclusive. The present study aims at studying the association of prenatal Mn exposure and neurodevelopment at 4-5 years of age.

Methods: Mn serum concentration was measured in 1465 pregnant women from the INMA (INfancia y MedioAmbiente, Environment and Childhood) Project. Neurodevelopment was assessed using a standardized version of the McCarthy Scales of Children's Abilities (MSCA). Multivariate regression models were used for data analysis.

Results: No association was found between Mn levels in serum and any of the McCarthy scales. However, the stratification by sex showed a positive and beneficial association of prenatal Mn levels and the verbal, quantitative and general-cognitive scales in girls (β (95%CI): 4 (0.03, 7.96), 4.5 (0.43, 8.57) and 4.32 (0.6, 8.05), respectively).

Conclusions: A beneficial association was found for the first time between prenatal Mn levels measured in serum and neurodevelopment of female offspring at 4 years of age, which could have implications on public health policies, specifically on the establishment of policies promoting prenatal health related to dietary deficits of micronutrients such as Mn.
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http://dx.doi.org/10.1016/j.envres.2021.111172DOI Listing
June 2021

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

Sci Total Environ 2021 Aug 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
August 2021

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

Environ Res 2021 05 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

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

Postnatal exposure to mercury and neuropsychological development among preschooler children.

Eur J Epidemiol 2020 Mar 13;35(3):259-271. Epub 2020 Mar 13.

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.

The objective of this study was to describe the postnatal exposure to Hg and to evaluate its association with neuropsychological development among preschool children. The study population are 4-5 years old children (n = 1252) participant in the Spanish INMA Project. Total Hg was measured in cord blood and in hair samples taken at 4 years of age (2008-2012). Neuropsychological development was assessed using the McCarthy Scales of Children's Abilities (MSCA). Information on covariates and possible confounders was obtained by questionnaires during pregnancy and childhood. Generalized additive and linear regression models were built in order to assess the relationship between MSCA scores and Hg exposure. We also evaluated the magnitude of the possible bias generated from measurement error in seafood intake estimate from questionnaire and Hg determination. The geometric mean of hair Hg was 0.98 µg/g [95% confidence interval (CI) 0.94, 1.03]. In the regression analysis, the association between Hg and the MSCA scores was positive for all the scales and statistically significant for the verbal (β = 0.89; 95%CI 0.38, 1.39), memory (β = 0.42; 95%CI 0.09, 0.76) and general cognitive scales (β = 1.35; 95%CI 0.45, 2.25). However, these associations were clearly attenuated when we adjusted by the children's fish intake variables or when took into account theoretical scenarios of low precision in fish intake and Hg measurements. Hg levels in this Spanish population were high in comparison with other European countries; however, we did not observe adverse effects on child neuropsychological development associated with this postnatal exposure to Hg.
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http://dx.doi.org/10.1007/s10654-020-00620-9DOI Listing
March 2020

Prenatal manganese exposure and neuropsychological development in early childhood in the INMA cohort.

Int J Hyg Environ Health 2020 03 7;224:113443. Epub 2020 Jan 7.

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:

Introduction: Manganese (Mn) is an essential element, diet being its main source. Some epidemiological studies have found that a prenatal excess of Mn could negatively affect neuropsychological development during infancy, but the evidence is inconclusive. The aim of this study was to explore the relationship between maternal serum Mn concentrations and child neuropsychological development assessed at 1 year of age.

Methods: study subjects were 1179 mother-child pairs from two Spanish cohorts (Valencia and Gipuzkoa) of the INMA (Environment and Childhood) Project. Mn was measured in serum samples collected during the first trimester of pregnancy. Child neuropsychological development was assessed using the Bayley Scales of Infant Development, composed of both mental and psychomotor scales. Sociodemographic, lifestyle and dietary information was collected through questionnaires during pregnancy and during the child's first year of life. Serum Mn was log-2 transformed. Multivariable linear regression models were built. Generalized additive models were used to assess the shape of the relation between prenatal exposure to Mn and the neuropsychological test scores.

Results: geometric mean and 95% confidence interval (95% CI) of maternal serum Mn was 1.50 (1.48-1.53) μg/L. Levels of Mn were higher among non-working mothers and in those with a higher consumption of nuts. The association between maternal Mn levels and child neuropsychological development was negative in the multivariable models for the mental (β [95% CI] = -0.39 [-2.73, 1.95]) and psychomotor scales (β [95% CI] = -0.92 [-3.48, 1.65]), although the coefficients were not statistically significant. The best shape describing the relationship between Mn and the Bayley scales was linear in both cases.

Conclusion: This study shows a null association between maternal prenatal levels of Mn and neuropsychological development at one year after birth in two cohorts within the INMA study.
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http://dx.doi.org/10.1016/j.ijheh.2019.113443DOI 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

Exposure to ultrafine particles in children until 18 years of age: A systematic review.

Indoor Air 2020 01 3;30(1):7-23. Epub 2019 Dec 3.

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

Airborne ultrafine particles (UFP) have been related to adverse health effects, but exposure in vulnerable population groups such as children is still not well understood. We aim to review the scientific literature regarding personal exposure to UFP in different microenvironments in populations until 18 years of age. The bibliographical search was carried out in July 2019 using the online database PubMed and was completed with references in articles found in the search. We selected the studies that used continuous counters and measured UFP levels in both specific microenvironment (houses, schools, transport, etc) and personal exposure. Finally, 32 studies fulfilled the criteria: of these, 10 analyzed personal exposure and 22 examined UFP levels in the microenvironment (especially in schools or nurseries (18/22)) and five in various microenvironments (including dwellings and means of transport, where exposure levels were higher). The characteristics of the microenvironments with the greatest levels of UFP were being close to heavy traffic or near cooking and cleaning activities. This review revealed the wide differences in exposure assessment methodologies that could lead to a lack of uniform and comparable information about the real UFP exposure in children.
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http://dx.doi.org/10.1111/ina.12620DOI Listing
January 2020

Maternal seafood consumption during pregnancy and child attention outcomes: a cohort study with gene effect modification by PUFA-related genes.

Int J Epidemiol 2020 04;49(2):559-571

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

Background: There is a need to test the fetal programming theoretical framework in nutritional epidemiology. We evaluated whether maternal seafood intake during pregnancy was associated with 8-year-old attention outcomes after adjusting for previous child seafood intake and cognitive function. We also explored effect modification by several single nucleotide polymorphisms (SNPs) related with polyunsaturated fatty acid (PUFA) metabolism.

Methods: Our final analyses included 1644 mother-child pairs from the prospective INMA (INfancia y Medio Ambiente) cohort study (Spain, recruitment between 2003 and 2008). We used food frequency questionnaires to assess prenatal and postnatal seafood consumption of the mother-child pairs. We evaluated attention function of the children through the computer-based Attention Network Test (ANT) and we used the number of omission errors and the hit reaction time standard error (HRT-SE). Parents reported child attention deficit hyperactivity disorder (ADHD) symptoms using the Revised Conners' Parent Rating Scale Short Form (CPRS-R: S). We measured seven candidate SNPs in a subsample of 845 children. We estimated associations using regression models, adjusting for family characteristics, child seafood intake and cognitive functions at early ages, and to explore SNP effect modifications.

Results: Higher total seafood intake during early pregnancy was associated with a reduction of child ANT omission errors, 5th quintile (median = 854 g/week) vs 1st quintile (median = 195 g/week), incidence risk ratio (IRR) 0.76; 95% CI = 0.61, 0.94. Similar results were observed after adjusting the models for child seafood intake and previous cognitive status. Lean, large and small fatty fish showed similar results, and generally similar but less robust associations were observed with the other attention outcomes. Shellfish and canned tuna showed weaker associations. The association patterns were weaker in late pregnancy and null in child seafood consumption. Child rs1260326 (glucokinase regulator, GCKR) and child/maternal rs2281591 (fatty acid elongase 2, ELOVL2) polymorphisms showed nominal P-value for interactions <0.10 between total seafood intake and ANT outcomes.

Conclusions: After adjusting for previous child cognitive functions and child seafood intake, high pregnancy consumption (total, lean, small and large fatty fish) was independently associated with improvements of some 8-year-old attention outcomes. Genetic effect modification analyses suggest PUFA intake from seafood as a potential biological mechanism of such association.
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http://dx.doi.org/10.1093/ije/dyz197DOI Listing
April 2020

Prenatal and postnatal exposure to air pollution and emotional and aggressive symptoms in children from 8 European birth cohorts.

Environ Int 2019 10 18;131:104927. Epub 2019 Jul 18.

ISGlobal, Barcelona, Spain; Pompeu Fabra University, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia's Children's Hospital, Rotterdam, the Netherlands. Electronic address:

Background: The association between air pollution exposure and emotional and behavioural problems in children is unclear. We aimed to assess prenatal and postnatal exposure to several air pollutants and child's depressive and anxiety symptoms, and aggressive symptoms in children of 7-11 years.

Methods: We analysed data of 13182 children from 8 European population-based birth cohorts. Concentrations of nitrogen dioxide (NO), nitrogen oxides (NO), particulate matter (PM) with diameters of ≤10 μm (PM), ≤ 2.5 μm (PM), and between 10 and 2.5 μm (PM), the absorbance of PM filters (PMabs), and polycyclic aromatic hydrocarbons (PAHs) were estimated at residential addresses of each participant. Depressive and anxiety symptoms and aggressive symptoms were assessed at 7-11 years of age using parent reported tests. Children were classified in borderline/clinical range or clinical range using validated cut offs. Region specific models were adjusted for various socio-economic and lifestyle characteristics and then combined using random effect meta-analysis. Multiple imputation and inverse probability weighting methods were applied to correct for potential attrition bias.

Results: A total of 1896 (14.4%) children were classified as having depressive and anxiety symptoms in the borderline/clinical range, and 1778 (13.4%) as having aggressive symptoms in the borderline/clinical range. Overall, 1108 (8.4%) and 870 (6.6%) children were classified as having depressive and anxiety symptoms, and aggressive symptoms in the clinical range, respectively. Prenatal exposure to air pollution was not associated with depressive and anxiety symptoms in the borderline/clinical range (e.g. OR 1.02 [95%CI 0.95 to 1.10] per 10 μg/m higher NO) nor with aggressive symptoms in the borderline/clinical range (e.g. OR 1.04 [95%CI 0.96 to 1.12] per 10 μg/m higher NO). Similar results were observed for the symptoms in the clinical range, and for postnatal exposures to air pollution.

Conclusions: Overall, our results suggest that prenatal and postnatal exposure to air pollution is not associated with depressive and anxiety symptoms or aggressive symptoms in children of 7 to 11 years old.
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http://dx.doi.org/10.1016/j.envint.2019.104927DOI Listing
October 2019

Associations of black carbon with lung function and airway inflammation in schoolchildren.

Environ Int 2019 10 10;131:104984. Epub 2019 Jul 10.

Inserm U1153-CRESS HERA Team, Faculté de Pharmacie de Paris, Université Paris Descartes, France; Ville de Paris, Direction de l'Action Sociale, de l'Enfance et de la Santé, Cellule Cohorte PARIS, Paris, France. Electronic address:

Background: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms.

Methods: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined.

Results: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV for an inter-quartile range of 1160 ng/m exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase].

Conclusion: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure.
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http://dx.doi.org/10.1016/j.envint.2019.104984DOI Listing
October 2019

Prenatal exposure to perfluoroalkyl substances, immune-related outcomes, and lung function in children from a Spanish birth cohort study.

Int J Hyg Environ Health 2019 07 28;222(6):945-954. Epub 2019 Jun 28.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain.

Background: Prenatal exposure to perfluoroalkyl substances (PFASs) has been associated with impaired immune and respiratory health during childhood but the evidence is inconsistent and limited for lung function. We studied the association between prenatal PFASs exposure and immune and respiratory health, including lung function, up to age 7 years in the Spanish INMA birth cohort study.

Methods: We assessed four PFASs in maternal plasma samples collected during the 1st trimester of pregnancy (years: 2003-2008): perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA). Mothers reported the occurrence (yes/no) of lower respiratory tract infections, wheezing, asthma, and eczema in the previous 12 months at 1.5 and 4 years of the child (n = 1188) and at 7 years (n = 1071). At ages 4 (n = 503) and 7 (n = 992) years lung function was assessed using spirometry tests.

Results: The most abundant PFASs were PFOS and PFOA (geometric means: 5.80 and 2.31 ng/mL, respectively). The relative risk of asthma during childhood per each doubling in PFNA concentration was 0.74 (95 CI%: 0.57, 0.96). The relative risk of eczema during childhood per every doubling in PFOS concentration was 0.86 (95 CI%: 0.75, 0.98). Higher PFOA concentrations were associated with lower forced vital capacity and lower forced expiratory volume in 1 s z-scores at 4 years [β (95 CI %): -0.17 (-0.34, -0.01) and -0.13 (-0.29, 0.03), respectively], but not at 7 years.

Conclusion: This longitudinal study suggests that different PFASs may affect the developing immune and respiratory systems differently. Prenatal exposure to PFNA and PFOS may be associated with reduced risk of respiratory and immune outcomes, particularly asthma and eczema whereas exposure to PFOA may be associated with reduced lung function in young children. These mixed results need to be replicated in follow-up studies at later ages.
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http://dx.doi.org/10.1016/j.ijheh.2019.06.005DOI Listing
July 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

Exposure to mercury among 9-year-old Spanish children: Associated factors and trend throughout childhood.

Environ Int 2019 09 19;130:104835. Epub 2019 Jun 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:

Mercury is considered a neurotoxicant and human exposure occurs mainly from the consumption of marine species. We aimed to describe total mercury concentrations (THg) and associated factors in 9-year old children, as well as to explore the trend in THg from 4 to 9 years of age. The study population consisted of 9-year-old children participating in the INMA (Environment and Childhood) birth cohort study in Valencia, Spain (n = 405, 2013-2014). THg in hair samples was measured by atomic absorption spectrometry at the age of 4 and 9 years. Sociodemographic and dietary data was obtained through questionnaires. Multiple linear regression was used to explore the association between THg and covariates. The geometric mean (95% confidence interval) of hair THg at 9 years old was 0.89 μg/g (0.81, 0.98). Thirteen percent of children had THg above the equivalent to the Provisional Tolerable Weekly Intake proposed by the World Health Organization. THg were higher among children whose mothers had a healthy body mass index before pregnancy. Children with non-smoker mothers and worker fathers had also higher THg. Children's fish intake at 9 years-old was positively associated with THg, being swordfish, canned tuna and lean fish (i.e. hake, sea bream and sole) the most associated categories. Levels decreased by around 22% between 4 and 9 years old. Birth cohort studies, such as the INMA Project, allow the longitudinal evaluation of Hg exposure and the possible effects on children's health. This information can be used to formulate diet recommendations in vulnerable populations.
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http://dx.doi.org/10.1016/j.envint.2019.05.029DOI Listing
September 2019

Influence of the Urban Exposome on Birth Weight.

Environ Health Perspect 2019 04;127(4):47007

4 Team of environmental epidemiology applied to reproduction and respiratory health, Institut national de la santé et de la recherche médicale (Inserm, National Institute of Health & Medical Research), Institute for Advanced Biosciences (IAB), CNRS, Université Grenoble Alpes , Grenoble, France.

Background: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life.

Objective: We evaluated the association of the urban exposome with birth weight.

Methods: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associations with either continuous birth weight or term low birth weight (TLBW) risk, we primarily relied on the Deletion-Substitution-Addition (DSA) algorithm, which is an extension of the stepwise variable selection method. Second, we used an exposure-by-exposure exposome-wide association studies (ExWAS) method accounting for multiple hypotheses testing to report associations not adjusted for coexposures.

Results: The most consistent statistically significant associations were observed between increasing green space exposure estimated as Normalized Difference Vegetation Index (NDVI) and increased birth weight and decreased TLBW risk. Furthermore, we observed statistically significant associations among presence of public bus line, land use Shannon's Evenness Index, and traffic density and birth weight in our DSA analysis.

Conclusion: This investigation is the first large urban exposome study of birth weight that tests many environmental urban exposures. It confirmed previously reported associations for NDVI and generated new hypotheses for a number of built-environment exposures. https://doi.org/10.1289/EHP3971.
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http://dx.doi.org/10.1289/EHP3971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785228PMC
April 2019

Associations of Maternal Cell-Phone Use During Pregnancy With Pregnancy Duration and Fetal Growth in 4 Birth Cohorts.

Am J Epidemiol 2019 07;188(7):1270-1280

Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.

Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996-2002), the Netherlands (2003-2004), Spain (2003-2008), and South Korea (2006-2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure-response relationships were found for shorter pregnancy duration (P < 0.001) and preterm birth (P = 0.003). We observed no association with fetal growth or birth weight. Maternal cell-phone use during pregnancy may be associated with shorter pregnancy duration and increased risk of preterm birth, but these results should be interpreted with caution, since they may reflect stress during pregnancy or other residual confounding rather than a direct effect of cell-phone exposure.
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http://dx.doi.org/10.1093/aje/kwz092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601518PMC
July 2019

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.

PLoS Med 2019 02 11;16(2):e1002744. Epub 2019 Feb 11.

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.

Background: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.

Methods And Findings: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.

Conclusions: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.
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http://dx.doi.org/10.1371/journal.pmed.1002744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370184PMC
February 2019

Maternal copper status and neuropsychological development in infants and preschool children.

Int J Hyg Environ Health 2019 04 1;222(3):503-512. Epub 2019 Feb 1.

Epidemiology and Environmental Health Joint Research Unit, 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. Electronic address:

Introduction: Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development.

Methods: Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) and the McCarthy Scales of Children's Abilities (MSCA) at 5 years of age (n = 490). Covariates were obtained by questionnaires during pregnancy and childhood. Multivariate linear and non-linear models were built in order to study the association between maternal Cu and child neuropsychological development.

Results: The mean ± standard deviation of maternal Cu concentrations was 1606 ± 272 μg/L. In the multivariate analysis, a negative linear association was found between maternal Cu concentrations and both the BSID mental scale (beta = -0.051; 95% confidence intervals [CI]: -0.102, -0.001) and the MSCA verbal scale (beta = -0.044; 95%CI:-0.094, 0.006). Boys obtained poorer scores than girls, with increasing Cu at 12 months (interaction p-value = 0.040 for the mental scale and 0.074 for the psychomotor scale). This effect modification disappeared at 5 years of age. The association between Cu and the MSCA scores (verbal, perceptive performance, global memory and motor, general cognitive, and executive function scales) was negative for those children with lowest maternal iron concentrations (<938μg/L).

Conclusion: The Cu concentrations observed in our study were within the reference range established for healthy pregnant women in previous studies. The results of this study contribute to the body of scientific knowledge with important information on the possible neurotoxic capability of Cu during pregnancy.
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http://dx.doi.org/10.1016/j.ijheh.2019.01.007DOI Listing
April 2019

Chronic mercury exposure and blood pressure in children and adolescents: a systematic review.

Environ Sci Pollut Res Int 2019 Jan 6;26(3):2238-2252. Epub 2018 Dec 6.

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

The aim of this paper is to systematically review the scientific literature on the possible relation of chronic mercury exposure and blood pressure among children and adolescents. We searched for observational studies in 6 electronic databases and grey literature for English, French or Spanish language studies published up to 30 November 2017. We performed a quality assessment of primary studies. We identified 8 articles involving 5 cohorts, 1 cross-sectional study and 1 case-control study. The participants had mean ages of between 3 and 17 years. Mercury was analysed in different matrices and periods of exposure. Four articles evaluated prenatal exposure, 2 evaluated both prenatal and postnatal exposures and 2 postnatal exposure. Blood pressure was measured according to different protocols. The association between mercury and blood pressure was adjusted by different covariates in each study. Four articles found a positive significant association between chronic mercury exposure and blood pressure in children or adolescents. Among these 4 articles, three of them evaluated prenatal exposure. There are still few studies assessing chronic mercury exposure and blood pressure in children and adolescents with inconsistency in results. Designs are very heterogeneous, which hampers their comparability. Evidence of this association is scarce and further research is needed.
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http://dx.doi.org/10.1007/s11356-018-3796-yDOI Listing
January 2019

The role of parental social class, education and unemployment on child cognitive development.

Gac Sanit 2020 Jan - Feb;34(1):51-60. Epub 2018 Nov 1.

Unidad Mixta de Investigación en Epidemiología, Ambiente y Salud FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Área de Investigación de Servicios en Salud, FISABIO Salud Pública, Valencia, Spain; Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Spain.

Objective: Assessing the association between socioeconomic gradient and cognitive development among children of a Spanish birth cohort aged 5-6 years from a gender perspective.

Method: Cognitive development was assessed on 525 children aged 5-6 years in the INMA-Valencia cohort, with the Global Cognitive Score (GCS) from McCarthy Scales of Children's Abilities. Information on social class, education level and employment was collected for both parents in addition to other sociodemographic factors, parental, family and child characteristics. The relationship between maternal and paternal socioeconomic gradient and cognitive development was assessed by linear regressions and comparing the variance explained by each indicator measured in the mother and father.

Results: Maternal socioeconomic gradient indicators explained more variance on GCS than paternal. Maternal education and paternal social class had an important individual effect that stayed after adjusting by other parental, child and family determinants. In the multivariable analysis, maternal education, age and intelligence, paternal social class and the child's age and sex were significantly associated with cognitive development.

Conclusions: Diverse socioeconomic gradient factors have an important influence on cognitive development, maternal education being the strongest determinant. Policies should be implemented to mitigate the negative effects of this gradient on child development.
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http://dx.doi.org/10.1016/j.gaceta.2018.07.014DOI Listing
November 2020

Human Early Life Exposome (HELIX) study: a European population-based exposome cohort.

BMJ Open 2018 09 10;8(9):e021311. Epub 2018 Sep 10.

Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.

Purpose: Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations.

Participants: The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level).

Findings To Date: Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder.

Future Plans: HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.
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http://dx.doi.org/10.1136/bmjopen-2017-021311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144482PMC
September 2018

Influence of paid maternity leave on return to work after childbirth.

Med Lav 2018 08 28;109(4):243-252. Epub 2018 Aug 28.

Mutua ASEPEYO.

Background: Paid maternity leave (ML) has been associated with better health outcomes in mothers and newborns. However, its protective role in mothers' employment after childbirth remains unclear.

Objective: To assess the association between paid ML and being employed 1-year after childbirth.

Methods: As part of the INfancia y Medio Ambiente (INMA) cohort study, 507 Spanish women employed at 12th week of pregnancy, were asked about their employment status and job characteristics at 32nd week of pregnancy. One year after childbirth, they were re-interviewed about their employment status and if they had taken paid ML. Incidence of maternal employment 1-year after childbirth was estimated. Crude and adjusted associations with paid ML were assessed by logistic regression, and characterized by odds ratios (ORs) with associated 95% CIs.

Results: Information was obtained from 398 women. Of those, 290 (72.9%) were employed 1-year after childbirth. Incidence of maternal employment was lower for those who: i) didn't take paid ML, ii) were younger than 27 years; iii) had temporary contract, iv) had part-time jobs, v) reported less-favoured familiar social class, and vi) left the job before 32 weeks of pregnancy. Being employed 1-year after childbirth was more common in those who took paid ML (OR 2.7, 95%CI 1.6-4.5), also after adjusting for staying at work until advanced stages of pregnancy (OR 1.8, 95%CI 1.0-3.1).

Conclusions: Taking paid ML seems to be associated with higher maternal employment rates 1-year after childbirth. Therefore, our findings suggest that protection of maternity might positively influence women's labour market participation after childbirth.
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Source
http://dx.doi.org/10.23749/mdl.v109i4.7226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682161PMC
August 2018
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