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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.

Early-life exposure to inorganic arsenic (iAs) may adversely impact health later in life. To date, evidence of iAs adverse effects on children's neurodevelopment comes mainly from populations highly exposed to contaminated water with conflicting results. Little is known about those effects among populations with low iAs exposure from food intake. We investigated the cross-sectional association between exposure to iAs and neurodevelopment scores among children living in Spain whose main route of exposure was diet. Arsenic species concentrations in urine from 400 children was determined, and the sum of urinary iAs, dimethylarsinic acid, and monomethylarsonic acid was used to estimate iAs exposure. The McCarthy Scales of Children's Abilities was used to assess children's neuropsychological development at about 4-5 years of age. The median (interquartile range) of children's sum of urinary iAs, MMA, and DMA was 4.85 (2.74-7.54) μg/L, and in adjusted linear regression analyses the natural logarithm transformed concentrations showed an inverse association with children's motor functions (β, [95% confidence interval]; global scores (-2.29, [-3.95, -0.63])), gross scores (-1.92, [-3.52, -0.31]) and fine scores (-1.54, [-3.06, -0.03]). In stratified analyses by sex, negative associations were observed with the scores in the quantitative index (-2.59, [-5.36, 0.17]) and working memory function (-2.56, [-5.36, 0.24]) only in boys. Our study suggests that relatively low iAs exposure may impair children's neuropsychological development and that sex-related differences may be present in susceptibility to iAs related effects; however, our findings should be interpreted with caution given the possibility of residual confounding., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 th 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.

Inorganic arsenic (i-As) has been related to wide-ranging health effects in children, leading to lifelong concerns. Proportionally, dietary i-As exposure dominates in regions with low arsenic drinking water. This study aims to investigate the relation between rice and seafood consumption and urinary arsenic species during childhood and to assess the proportion of urinary i-As metabolites. Urinary arsenic species concentration in 400 4-year-old children living in four geographical areas of Spain, in addition to repeated measures from 100 children at 7 years of age are included in this study. Rice and seafood products intake was collected from children's parents using a validated food frequency questionnaire (FFQ). At 4 years of age, children's urine i-As and monomethylarsonic acid (MMA) concentrations increased with rice product consumption (p-value = 0.010 and 0.018, respectively), and urinary arsenobetaine (AsB) with seafood consumption (p = 0.002). Four-year-old children had a higher consumption of both rice and seafood per body weight and a higher urinary %MMA (p-value = 0.001) and lower % dimethylarsinic acid (DMA) (p-value = 0.017). This study suggests increased dietary i-As exposure related to rice product consumption among children living in Spain, and the younger ones may be especially vulnerable to the health impacts of this exposure also considering that they might have a lower i-As methylation capacity than older children. In contrast, seafood consumption did not appear to influence the presence of potentially toxic arsenic species in this population of children., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Natural environments, including green spaces, may have beneficial impacts on brain development. However, longitudinal evidence of an association between long-term exposure to green spaces and cognitive development (including attention) in children is limited., Objectives: We evaluated the association between lifelong residential exposure to green space and attention during preschool and early primary school years., Methods: This longitudinal study was based on data from two well-established population-based birth cohorts in Spain. We assessed lifelong exposure to residential surrounding greenness and tree cover as the average of satellite-based normalized difference vegetation index and vegetation continuous fields, respectively, surrounding the child's residential addresses at birth, 4-5 y, and 7 y. Attention was characterized using two computer-based tests: Conners' Kiddie Continuous Performance Test (K-CPT) at 4-5 y (n=888) and Attentional Network Task (ANT) at 7 y (n=987). We used adjusted mixed effects models with cohort random effects to estimate associations between exposure to greenness and attention at ages 4-5 and 7 y., Results: Higher lifelong residential surrounding greenness was associated with fewer K-CPT omission errors and lower K-CPT hit reaction time-standard error (HRT-SE) at 4-5 y and lower ANT HRT-SE at 7 y, consistent with better attention. This exposure was not associated with K-CPT commission errors or with ANT omission or commission errors. Associations with residential surrounding tree cover also were close to the null, or were negative (for ANT HRT-SE) but not statistically significant., Conclusion: Exposure to residential surrounding greenness was associated with better scores on tests of attention at 4-5 y and 7 y of age in our longitudinal cohort. https://doi.org/10.1289/EHP694.

Objective: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources., Methods: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated., Results: The geometric means of TSH, TT3, FT4 and mercury were 1.1μU/L, 2.4nmol/L, 10.5pmol/L and 7.7μg/L, respectively. Mercury levels were marginally significantly associated with TT3 (β: -0.05; 95%CI: -0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (-0.08; 95%CI: -0.15, -0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant., Conclusion: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of this study is to describe the total hair mercury concentrations and their determinants in preschool Spanish children, as well as to explore the trend in mercury exposure from birth to the age four. This evolution has been scarcely studied in other birth cohort studies. The study population was 580 four year old children participating in the INMA (i.e. Childhood and Environment) birth cohort study in Valencia (2008-2009). Total mercury concentration at age four was measured in hair samples by atomic absorption spectrometry. Fish consumption and other covariates were obtained by questionnaire. Multivariate linear regression models were conducted in order to explore the association between mercury exposure and fish consumption, socio-demographic characteristics and prenatal exposure to mercury. The geometric mean was 1.10 µg/g (95%CI: 1.02, 1.19). Nineteen percent of children had mercury concentrations above the equivalent to the Provisional Tolerable Weekly Intake proposed by WHO. Mercury concentration was associated with increasing maternal age, fish consumption and cord blood mercury levels, as well as decreasing parity. Children whose mothers worked had higher mercury levels than those with non working mothers. Swordfish, lean fish and canned fish were the fish categories most associated with hair mercury concentrations. We observed a decreasing trend in mercury concentrations between birth and age four. In conclusion, the children participating in this study had high hair mercury concentrations compared to reported studies on children from other European countries and similar to other countries with high fish consumption. The INMA study design allows the evaluation of the exposure to mercury longitudinally and enables this information to be used for biomonitoring purposes and dietary recommendations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To describe the time trend in atmospheric lead concentrations in Spain, from before lead was banned as a gasoline additive to the present, and to determine the trend in lead body burden in the Spanish child population., Methods: We obtained the annual average for atmospheric lead levels in several Spanish cities from the 1980s to the present. A literature search was conducted to identify published studies on lead concentrations in populations of Spanish children., Results: Overall, atmospheric lead levels decreased, particularly between 1991 and 1999. This downward trend was related to a decrease in lead concentrations in Spanish children from 1989, the year in which the first study of childhood lead exposure was published, until the present. The decreased concentrations in both air and in children was most probably a result of legislative measures regulating the maximum amount of lead in gasoline in 1987 until a complete ban in August 2001., Conclusions: From a public health point of view, the banning of leaded gasoline has significantly increased health protection in the Spanish population., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)

Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive., Objective: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery., Methods: Mother-child cohorts set up in five Spanish areas during the years 2000-2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis., Results: Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was -0.45 g (95% confidence interval: -1.36, 0.45 g) for chloroform and 0.16 g (-1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery., Conclusions: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.

Background and Aims: Because their lungs and immune system are not completely developed, children are more susceptible to respiratory disease and more vulnerable to ambient pollution. We assessed the relation between prenatal and postnatal nitrogen dioxide (NO(2)) levels and the development of lower respiratory tract infections (LRTI), wheezing and persistent cough during the first year of life., Methods: The study population consisted of 352 children from a birth cohort in Valencia, Spain. Prenatal exposure to NO(2), a marker of traffic related air pollution was measured at 93 sampling sites spread over the study area during four different sampling periods of 7 days each. It was modeled for each residential address through land use regression using the empirical measurements and data from geographic information systems. Postnatal exposure was measured once inside and outside each home using passive samplers for a period of 14 days. Outcomes studied were any episode of LRTI during the child's first year of life diagnosed by a doctor (bronchitis, bronchiolitis or pneumonia), wheezing (defined as whistling sounds coming from the chest), and persistent cough (more than three consecutive weeks). Outcomes and potential confounders were obtained from structured questionnaires. Multiple logistic regression was used to identify associations., Results: The cumulative incidence (CI) at first year of life was 30.4% for LRTI (23.0% bronchiolitis, 11.9% bronchitis and 1.4% pneumonia), 26.1% for wheezing and 6.3% for persistent cough. The adjusted odds ratio (95% confidence interval) per 10μg/m(3) increment in postnatal outdoor NO(2) concentration was 1.40 (1.02-1.92) for persistent cough. We also found some pattern of association with LRTI, bronchiolitis, bronchitis, wheezing and persistent cough in different prenatal periods, although it was not statistically significant., Conclusions: Our results indicate that exposure to outdoor, but not indoor, NO(2) during the first year of life increases the risk of persistent cough., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects., Objectives: To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project., Methods: One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols., Results: Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education., Conclusions: Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Numerous studies have focused on the effects of exposure to air pollution on health; however, certain subsets of the population tend to be more exposed to such pollutants depending on their social or demographic characteristics. In addition, exposure to toxicants during pregnancy may play a deleterious role in fetal development as fetuses are especially vulnerable to external insults. The present study was carried out within the framework of the INMA (Infancia y Medio Ambiente or Childhood and the Environment) multicenter cohort study with the objective of identifying the social, demographic, and life-style factors associated with nitrogen dioxide (NO(2)) exposure in the subjects in the cohort. The study comprised 785 pregnant women who formed part of the INMA cohort in Valencia, Spain. Outdoor levels of NO(2) were measured at 93 sampling sites spread over the study area during four different sampling periods lasting 7 days each. Multiple regression models were used for mapping outdoor NO(2) throughout the area. Individual exposure was assigned as: 1) the estimated outdoor NO(2) levels at home, and 2) the average of estimated outdoor NO(2) levels at home and work, weighted according to the time spent in each environment. The subjects' socio-demographic and life-style information was obtained through a questionnaire. In the multiple linear analyses, the outdoor NO(2) levels assigned to each home were taken to be the dependent variable. Other variables included in the model were: age, country of origin, smoking during pregnancy, parity, season of the year, and social class. These same variables remained in the model when the dependent variable was changed to the NO(2) levels adjusted for the subjects' time-activity patterns. We found that younger women, those coming from Latin American countries, and those belonging to the lower social strata were exposed to higher NO(2) levels, both as measured outside their homes as well as when time-activity patterns were taken into account. These subgroups also have a higher probability of being exposed to NO(2) levels over 40 μg/m(3), which is the annual limit for maximum safe exposure, as established by European Directive 2008/50/EC., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Polybromodiphenyl ethers (PBDEs) were analyzed in blood serum of pregnant women and in cord blood serum of their newborns from a general population cohort (n = 174; Valencia, Spain). The most abundant PBDE congeners identified were BDE 47, BDE 99, BDE 153, BDE 154 and BDE 209. Their cord blood serum concentrations were about 45% of those in maternal serum but after lipid normalization about the same concentrations were observed in both types of samples. Thus, median of total PBDEs was 9.6 ng/g lipid in cord serum (range between not detected and 140 ng/g lipid) and 9.6 ng/g lipid in maternal serum (range between not detected and 120 ng/g lipid). The distributions of these compounds were dominated by BDE 47 in both cases. In cord blood serum the decreasing order of abundance was BDE 47>BDE 99>BDE 209>BDE 153>BDE 154. The congener composition in maternal serum followed a similar trend: BDE 47>BDE 153>BDE 154>BDE 209>BDE 99. The congener concentrations exhibited a higher degree of correlation in cord blood than in maternal serum. Use of the maternal determinants for categorization of the observed maternal and fetal PBDE concentrations only showed significant associations for the levels in umbilical cord. Neonates from rural areas exhibited statistically significantly lower concentrations than those from urban, semi-urban or metropolitan sites. Maternal serum also showed this difference but the higher dispersion of the concentrations in maternal serum did not afford its recognition with statistical significance. The lower qualitative and quantitative variability in the PBDE concentrations of cord blood serum than maternal serum suggest that the latter is reflecting PBDE contributions from a wider diversity of sources than the former whereas cord blood sera seem to represent the long term standing stock of these compounds accumulated in the maternal tissues., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Unlabelled: Nitrogen dioxide (NO2) is produced from the exhausts of vehicles and gas appliances and is known to pose certain health risks. In this study, we characterize the exposure to this substance during the first year of life, which is an important period of development. To this end, we used passive samplers to measure indoor and outdoor NO2 levels for 2 weeks in the homes of 352 children. To compensate for the fact that NO2 levels were measured only once in each home, a correction factor was calculated to assign each child an outdoor NO2 exposure value for the first year of life. The outdoor NO2 concentrations were 26.1 microg/m(3) while those measured indoors averaged 18.0 microg/m(3). A multivariate linear regression analysis showed that the main determinants of outdoor NO2 levels were the degree of urbanization and the frequency of vehicle traffic at the location of the residence while for indoor NO2 levels the principal determinants were the type of cooking range and water heater present in the home, the season of the year, and both the country of origin and educational level of the mother., Practical Implications: Exposure to NO2 has been related to respiratory and other health problems among children. Precise identification of the main sources of both indoor and outdoor NO2 should shed light on appropriate intervention periods and methods. Our results indicate that while population density and traffic-related variables are the main determinants of outdoor NO2 levels, the use of gas appliances have the greatest impact on indoor levels. Strategies should thus be developed to reduce such exposure, especially with regard to reducing emissions from vehicle traffic.

There is a growing concern about the possible adverse effects of exposure to air pollution on health during pregnancy. Therefore, a priority of the INMA (environment and childhood) study was to estimate personal exposure to traffic-related air pollution. In the cohort from Valencia (n=855), ambient levels of NO(2) were measured at 93 sampling sites spread over the study area during four different sampling periods of 7 days each. Multiple regression models were used to map ambient NO(2) over the area. Geographical data and predictions from kriging obtained by the "let one out" procedure were used as predictors. Individual exposure was assigned as 1) the estimated ambient NO(2) level at the home address and 2) the average of estimated ambient NO(2) levels at home and work addresses, weighted by the time spent in each environment. Estimations were temporally customized using the NO(2) levels registered daily by the regional Air Pollution Monitoring Network. The entire pregnancy and each trimester were taken as exposure windows. The model for the mean levels of NO(2) during the sampling periods explained 81% of the variation in NO(2) levels. Relative percent differences between the two models of personal exposure assignment were less than 9% for more than 90% of the participants; however the rest of them showed marked differences. Personal exposure estimates were slightly higher in the second model. In both cases, exposure during the whole pregnancy was strongly correlated with exposure in the second trimester. Considering periods shorter than the entire pregnancy will provide us the opportunity to identify specific windows of susceptibility.

Abstract: Background: Mercury is a ubiquitous heavy metal that may negatively affect human health. It is desirable to investigate mercury exposure in vulnerable populations. Objective: To determine the concentrations of total mercury (T-Hg) in cord blood and to evaluate the role of maternal fish consumption in a Spanish mother and child cohort. Methods: A total of 1883 mother and child pairs from a population-based cohort were included between 2004 and 2008. T-Hg concentrations were measured in whole cord blood and maternal seafood consumption was ascertained by means of a food-frequency questionnaire. Linear regression was used in stratified analyses, while a joint model was adjusted using a mixed-effects linear model. Results: Maternal daily seafood consumption was 78g/d and the geometric mean for T-Hg was 8.2μg/L. Maternal fish intake during pregnancy, mother''s age, country of origin, educational level, employment status and parity, as well as area of study and season of delivery, were associated with cord blood T-Hg levels. A doubling in consumption of large oily fish was associated with an increase of 11.4% (95%CI: 3.8 to 19.6%) in cord blood T-Hg levels, followed by an increase of 8.4% (95%CI: 5.7 to 11.2%) in the case of canned tuna and 8.3% (95%CI: 5.5 to 11.1%) in that of lean fish. Conclusion: A high proportion of newborns had elevated concentrations of cord blood T-Hg according to the current US-EPA reference dose (5.8μg/L for methylmercury). Mercury concentrations were related to maternal fish consumption, with large oily fish being the main contributor. [Copyright &y& Elsevier]