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We sought to determine whether prenatal co-exposure to As, Cd, Hg, Mn, and Pb was associated with impaired neurodevelopment in preschool children from the Spanish Environment and Childhood (INMA) Project, using the placenta as exposure matrix. We measured metal levels in placenta tissue samples randomly selected from five of the seven population-based birth cohorts participating in the INMA Project, collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was carried through the use of the McCarthy Scales of Children's Abilities (MSCA) at the age of 4-5 years. Data on placental metal levels, MSCA scores, and relevant covariates was available for 302 children. Mn was detected in all placental samples, Cd in nearly all placentas (99%) and As, Hg, and Pb in 22%, 58%, and 17% of the placentas, respectively. After adjusting for potential confounders, detectable As levels were associated with decrements in global and verbal executive functions and quantitative abilities; detectable Hg was associated with lower scores on the verbal function of posterior cortex in a dose-response manner, and non-linearly related to poorer motor function and gross motor skills; and Mn levels were associated with decrement in perceptual-performance skills in a dose-response manner but with better memory span and quantitative skills. A synergistic interactive effect was found between As and Pb with respect to the general cognitive score, whereas an antagonistic interaction was found between Mn and Hg. Prenatal exposure to As and Hg may be a risk factor for cognitive and motor impairment in children, while the effects of Cd and Mn on neurodevelopment are less clear. Future studies should examine combined and interactive effects of exposure to multiple metals during vulnerable periods of brain development prospectively. (C) 2017 Elsevier B.V. All rights reserved.

Inorganic arsenic (i-As) is a non-threshold human carcinogen that has been associated with several adverse health outcomes. Exposure to i-As is of particular concern among pregnant women, infants and children, as they are specifically vulnerable to the adverse health effects of i-As, and in utero and early-life exposure, even low to moderate levels of i-As, may have a marked effect throughout the lifespan. Ion chromatography-mass spectrometry detection (IC-ICP-MS) was used to analyse urinary arsenic speciation, as an exposure biomarker, in samples of 4-year-old children with relatively low-level arsenic exposure living in different regions in Spain including Asturias, Gipuzkoa, Sabadell and Valencia. The profile of arsenic metabolites in urine was also determined in samples taken during pregnancy (1st trimester) and in the children from Valencia of 7 years old. The median of the main arsenic species found in the 4-year-old children was 9.71 mu g/l (arsenobetaine-AsB), 3.97 mu g/l (dimethylarsinic acid-DMA), 0.44 mu g/l (monomethylarsonic acid-MMA) and 0.35 mu g/l (i-As). Statistically significant differences were found in urinary AsB, MMA and i-As according to the study regions in the 4-year-old, and also in DMA among pregnant women and their children. Spearman's correlation coefficient among urinary arsenic metabolites was calculated, and, in general, a strong methylation capacity to methylate i-As to MMA was observed.

Background: The association between prenatal air pollution exposure and postnatal growth has hardly been explored. Mitochondrial DNA (mtDNA), as a marker of oxidative stress, and growth at birth can play an intermediate role in this association. Objective: In a subset of the Spanish birth cohort INMA we assessed first whether prenatal nitrogen dioxide (NO2) exposure is associated with infant growth. Secondly, we evaluated whether growth at birth (length and weight) could play a mediating role in this association. Finally, the mediation role of placental mitochondrial DNA content in this association was assessed. Methods: In 336 INMA children, relative placental mtDNA content was measured. Land-use regression models were used to estimate prenatal NO2 exposure. Infant growth (height and weight) was assessed at birth, at 6 months of age, and at 1 year of age. We used multiple linear regression models and performed mediation analyses. The proportion of mediation was calculated as the ratio of indirect effect to total effect. Results: Prenatal NO2 exposure was inversely associated with all infant growth parameters. A 10 mu g/m(3) increment in prenatal NO2 exposure during trimester 1 of pregnancy was significantly inversely associated with height at 6 months of age (-6.6%; 95%CI: -11.4, -1.9) and weight at 1 year of age (-4.2%; 95%CI: -8.3, -0.1). These associations were mediated by birth length (31.7%; 95%CI: 34.5, 14.3) and weight (53.7%; 95%CI: 65.3, -0.3), respectively. Furthermore, 5.5% (95%CI: 10.0, -0.2) of the association between trimester 1 NO2 exposure and length at 6 months of age could be mediated by placental mtDNA content. Conclusions: Our results suggest that impaired fetal growth caused by prenatal air pollution exposure can lead to impaired infant growth during the first year of life. Furthermore, molecular adaptations in placental mtDNA are associated with postnatal consequences of air pollution induced alterations in growth.

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.

Introduction: Exposure to organochlorine compounds (OCs) may interfere with thyroid hormone (TH) homeostasis. The disruption of the deiodinase (DIO) enzymes has been proposed as a mechanism of action. Aim: To evaluate the association between exposure to OCs and TH status in pregnant women, as well as to explore the role of genetic variations in the DIO1 and DIO2 genes. Methods: The study population (n = 1128) was composed of pregnant women who participated in the INMA Project (Spain, 2003-2006). Hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (4,4'-DDE), b-hexachlorocyclohexane (b-HCH), polychlorobiphenyl (PCB) congeners 138, 153 and 180, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) were measured in serum samples taken during the first trimester of pregnancy (mean [standard deviation (SD)]: 13.5 [2] weeks of gestation). Polymorphisms in DIO1 (rs2235544) and DIO2 (rs12885300) were genotyped in maternal DNA. Sociodemographic and dietary characteristics were obtained by questionnaire. Results: A 2-fold increase in HCB was associated with lower TT3 (% change = -1.48; 95% CI: -2.36, -0.60). Women in the third tertile for b-HCH had lower TT3 (% change=-3.19; 95% CI:-5.64,-0.67). The interactions between DIO1 rs2235544 and PCB153 and b-HCH were statistically significant. The inverse association between PCB153 and TT3 was the strongest among women with AA genotype. Women with CC genotype presented the strongest inverse association between b-HCH and FT4. Conclusion: Exposure to HCB and b-HCH was associated to a disruption in maternal TT3. The DIO1 rs2235544 SNP modified the association between exposure to some of the OCs (specifically b-HCH and PCB153) and maternal thyroid hormone levels. These results strengthen the hypothesis that DIO enzymes play a role in explaining the disruption of thyroid hormones in relation to exposure to OCs. (C) 2016 Elsevier Ltd. All rights reserved.

Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children's body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10-600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n=12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in vitro (DIV) resulted in protein carbonylation and in cell death at concentrations >= 200 nM and >= 300 nM, respectively. Exposure of CCN and CGC to non-cytotoxic MeHg concentrations for 5 DIV induced an early concentration-dependent decrease in cofilin phosphorylation. Furthermore, in both cell types actin was translocated from the cytosol to the mitochondria whereas cofilin translocation was found only in CGC. Translocation of cofilin and actin to mitochondria in CGC occurred from 30 nM MeHg onwards. We also found an increased expression of cortactin and LIMK1 mRNA in CGC but not in CCN. All these effects were prevented by the antioxidant probucol. Cofilin phosphorylation was significantly decreased and a trend for decreased activity of glutathione reductase and glutathione peroxidase was found in the fetal side of human placental samples from the highest (20-40 mu g/L) MeHg-exposed group when compared with the low (

Benzene exposure represents a potential risk for children's health. Apart from being a known carcinogen for humans (group 1 according to IARC), there is scientific evidence suggesting a relationship between benzene exposure and respiratory problems in children. But results are still inconclusive and inconsistent. This study aims to assess the determinants of exposure to indoor and outdoor residential benzene levels and its relationship with respiratory health in infants. Participants were 1-year-old infants (N = 352) from the INMA cohort from Valencia (Spain). Residential benzene exposure levels were measured inside and outside dwellings by means of passive samplers in a 15-day campaign. Persistent cough, low respiratory tract infections and wheezing during the first year of life, and covariates (dwelling traits, lifestyle factors and sociodemographic data) were obtained from parental questionnaires. Multiple Tobit regression and logistic regression models were performed to assess factors associated to residential exposure levels and health associations, respectively. Indoor levels were higher than outdoor ones (1.46 and 0.77 mu g/m(3), respectively; p < 0.01). A considerable percentage of dwellings, 42% and 21% indoors and outdoors respectively, surpassed the WHO guideline of 1.7 mu g/m(3) derived from a lifetime risk of leukemia above 1/100 000. Monitoring season, maternal country of birth and parental tobacco consumption were associated with residential benzene exposure (indoor and outdoors). Additionally, indoor levels were associated with mother's age and type of heating, and outdoor levels were linked with zone of residence and distance from industrial areas. After adjustment for confounding factors, no significant associations were found between residential benzene exposure levels and respiratory health in infants. Hence, our study did not support the hypothesis for the benzene exposure effect on respiratory health in children. Even so, it highlights a public health concern related to the personal exposure levels, since a considerable number of children surpassed the abovementioned WHO guideline for benzene exposure. (C) 2016 The Authors. Published by Elsevier Ltd.

Background: In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children's environmental health research will face in the coming years. Results: The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. Conclusions: INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children. (C) 2017 Elsevier GmbH. All rights reserved.

Background: Results regarding the association between mercury exposure and anthropometry at birth, gestational length and placental weight are inconsistent, as is the role of seafood intake in these associations. Objective: We assessed whether prenatal mercury exposure is associated with anthropometry at birth, placental weight and gestational length in a population with a relatively high exposure to mercury from seafood consumption. Methods: Total mercury (T-Hg) was determined in cord blood from 1869 newborns with birth outcome measures, within the Spanish multicenter INMA cohort from 2004 to 2008. We adjusted cohort specific linear and Cox regression models to evaluate the association between T-Hg and birth anthropometry (weight, length, and head circumference), placental weight and gestational length. Non-spontaneous labor was taken to be censoring in the survival analysis. Final estimates were obtained using meta analysis. Results: Geometric mean T-Hg was 8.2 mu g/L. A doubling of T-Hg was associated with a 7.7 g decrease in placental weight (95% CI: -13.6, -1.8) and marginally with head circumference (beta: -0.052 cm, 95% CI: -0.109, 0.005). T-Hg was also inversely related to weight and length, although with weaker estimates. Mercury exposure was not associated with the length of gestation. The inverse relation between T-Hg and growth was enhanced when the intake of different seafood groups was adjusted for in the models. Conclusions: Prenatal mercury exposure may be associated with reduced placental and fetal growth. Confounding by fish intake should be considered when assessing these relationships. (C) 2016 Elsevier Inc. All rights reserved.

Background Attention function filters and selects behaviorally relevant information. This capacity is impaired in some psychiatric disorders and has been proposed as an endophenotype for Attention-Deficit/Hyperactivity Disorder; however, its genetic basis remains largely unknown. This study aimed to identify single nucleotide polymorphism (SNPs) associated with attention function. Materials and Methods The discovery sample included 1655 children (7-12 years) and the replication sample included 546 children (5-8 years). Five attention outcomes were assessed using the computerized Attentional Network Test (ANT): alerting, orienting, executive attention, Hit Reaction time (HRT) and the standard error of HRT (HRTSE). A Genome-wide Association Study was conducted for each outcome. Gene set enrichment analyses were performed to detect biological pathways associated with attention outcomes. Additional neuroimaging analyses were conducted to test neural effects of detected SNPs of interest. Results Thirteen loci showed suggestive evidence of association with attention function (P

This study aimed to describe the degree of annoyance among pregnant women in a Spanish cohort and to examine associations with proximity to traffic, NO2 and benzene exposure. We included 2457 participants from the Spanish Childhood and Environment study. Individual exposures to outdoor NO2 and benzene were estimated, temporally adjusted for pregnancy. Interviews about sociodemographic variables, noise and air pollution were carried out. Levels of annoyance were assessed using a scale from 0 (none) to 10 (strong and unbearable); a level of 8 to 10 was considered high. The reported prevalence of high annoyance levels from air pollution was 11.2% and 15.0% from noise; the two variables were moderately correlated (0.606). Significant correlations between NO2 and annoyance from air pollution (0.154) and that from noise (0.181) were observed. Annoyance owing to noise and air pollution had a low prevalence in our Spanish population compared with other European populations. Both factors were associated with proximity to traffic. In multivariate models, annoyance from air pollution was related to NO2, building age, and country of birth; annoyance from noise was only related to the first two. The health burden of these exposures can be increased by stress caused by the perception of pollution sources.

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height. R.M.F. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust grant 085541/Z/08/Z). T.H.P. is supported by The Danish Council for Independent Research Medical Sciences (FSS) The Alfred Benzon Foundation. B.F. is supported by an Oak Foundation fellowship. M.M. is a Wellcome Trust Senior Investigator (Wellcome Trust grant 090532) and a NIHR Senior Investigator. T.M.F. is supported by the European Research Council grant: SZ-245 50371- GLUCOSEGENES-FP7-IDEAS-ERC. F.R. (VIDI 016.136.367) and V.W.V.J. (VIDI 016.136.361) received grants from the Netherlands Organization for Health Research and Development.

Our aim was to investigate the relation between PBDEs and fetal growth or newborn anthropometry in a Spanish cohort (2003-2008). PBDE congeners (BDE-47, -99, -153, -154, and -209) were determined in serum of 670 mothers at gestational week 12 and in 534 umbilical cord samples. Abdominal circumference (AC), estimated fetal weight (EFW), femur length (FL), and biparietal diameter (BPD) during gestation were measured by ultrasounds. At birth, weight (BW), head circumference (HC), and length (BL) were also measured. We assessed growth in the intervals between 12-20 and 20-34 weeks of gestation and size at birth by standard deviation (SD)-scores adjusted for constitutional characteristics. We conducted multivariate linear regression analyses between PBDE congeners and their sum (Sigma PBDEs) and outcomes. We found statistically significant inverse associations between Sigma PBDEs and AC, EFW, and BPD at weeks 20-34 and HC at birth. Regarding congeners, the association was clearer with BDE-99, with inverse associations being found with AC, EFW, and BPD at weeks 20-34, and with BW and HC at delivery. These outcomes decreased between 1.3% and 3.5% for each 2-fold PBDE increase. Concerning matrices, we found statistically significant inverse associations with BPD, HC, and BW when using maternal serum, and for AC and EFW with cord serum. In conclusion, PBDEs may impair fetal growth in late pregnancy and reduce birth size.

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

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 mu g/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. (C) 2014 Elsevier Inc. All rights reserved.

La exposición a dosis altas de mercurio durante periodos vulnerables (como el embarazo y la infancia) puede tener serias consecuencias para el desarrollo cognitivo, tal como se ha constatado tras los episodios de envenenamiento agudo ocurridos en Japón e Irak. El consumo de ciertos tipos de pescado es la fuente principal de exposición a mercurio de la población general. Existe una creciente preocupación por los posibles efectos neurotóxicos del mercurio, especialmente a edades tempranas en poblaciones donde el consumo de pescado es moderado-alto. La evidencia científica hasta el momento no es concluyente. En el ámbito español, el Proyecto INMA (Infancia y Medio Ambiente) ha proporcionado información sobre los niveles de exposición prenatal a mercurio de 1800 recién nacidos de Valencia, Sabadell, Asturias y Guipúzcoa. En general, los niveles resultaron elevados, con un 24% de los niños con niveles superiores a las dosis recomendadas por la Organización Mundial de la Salud y un 64% por encima de la recomendación de la Agencia de Protección Ambiental de Estados Unidos. Los resultados en el segundo año de vida, sin embargo, no muestran un incremento en el riesgo de efectos adversos en el desarrollo cognitivo de los niños. Diversas agencias han desarrollado recomendaciones de consumo de pescado dirigidas a mujeres embarazadas y población infantil, debido a la presencia de mercurio. No obstante, sería conveniente reforzar estas recomendaciones, teniendo en cuenta el pescado como fuente de nutrientes esenciales para el desarrollo en las fases tempranas de la vida, consensuadas para todas las comunidades autónomas y la administración estatal. Exposure to high levels of mercury during vulnerable periods (such as pregnancy and childhood) may have serious consequences for cognitive development, as observed after acute poisoning episodes in Japan and Irak. The main source of mercury exposure in the general population is consumption of certain types of fish. There is growing concern about the possible neurotoxic effects of mercury, especially in younger children in populations where fish intake is moderate to high. The scientific evidence to date is inconclusive. In Spain, the Childhood and Environment (Infancia y Medio Ambiente [INMA]) project has provided information on levels of prenatal exposure to mercury among 1800 newborns from Valencia, Sabadell, Asturias and Guipúzcoa. In general, levels were high, being above the World Health Organization's recommended dose in 24% of children and above the recommended levels of the U.S. Environmental Protection Agency in 64%. However, the results did not indicate a significant association between prenatal mercury exposure and delayed cognitive development during the second year of life. Various agencies have developed recommendations on fish consumption for pregnant women and children, due to the presence of mercury. These recommendations should be strengthened, since there is general consensus among all regional and national public administrations that fish is an essential source of nutrients for development in the early stages of life.

Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive. Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure. The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of the Bayley Scales of Infant Development (BSID) test in children aged around 14-months of a subsample (N = 1175) of the Spanish INMA birth cohort, and to compare this with the effects of prenatal exposure. Although in the present study population PCB-153, DDE and HCB exposure increased within the first months of postnatal life, no associations were found between different periods of postnatal exposure to these compounds and mental or psychomotor scores. Increasing prenatal PCB-153 concentrations were associated with worse mental and psychomotor scores, although significance was only reached for psychomotor development (beta [95%CI] = -1.36 [-2.61, -0.11]). Indeed, the association between exposure and effects observed during prenatal life weakened gradually across periods of postnatal life. Results of the present study suggest that, although breastfeeding increases children's blood persistent organic pollutants (POPs) levels during postnatal life, deleterious effects of PCB-153 on neuropsychological development are mainly attributable to prenatal exposure. (c) 2012 Elsevier Inc. All rights reserved.

Socioeconomic disadvantage can be harmful for mother's health and can influence child's health long term. The aim of this study is to analyse social inequalities between pregnant women from four INMA (INfancia y Medio Ambiente) cohorts. The analysis included 2,607 pregnant women recruited between 2004 and 2008 from four INMA cohorts. Data on maternal characteristics were collected through two questionnaires completed in the first and third trimester of pregnancy. The relationship between socioeconomic status (SES) and maternal health, dietary intake, lifestyle habits and self-care related variables was modelled using logistic regression analysis. 33.5 % of women had a university level of education and 47 % had high occupational class. Women with higher SES reported healthier habits, fewer complications during pregnancy, better weight gain control and attended more prenatal appointments than women with lower SES. The risk of sedentary behaviour and passive smoking was higher among women with a lower level of education (OR = 1.7, 95 % CI 1.3-2.2 and OR = 1.6, 95 % CI 1.2-2.3, respectively) and with less skilled occupations (OR = 1.7, 95 % CI 1.4-2.0 and OR = 1.2, 95 % CI 1.0-1.5, respectively). Although both SES indicators-occupation and education-act as social determinants of diet, occupation was a more powerful determinant than education. For other lifestyle and self-caring variables, education was a more powerful predictor than occupation. Social inequalities were observed in health, habits and self-care during pregnancy. Proper care during pregnancy requires the control of common clinical variables and the knowledge of socioeconomic conditions of the pregnant women.

Objetivo: Describir la evolución temporal de las concentraciones de plomo en el aire en España, desde antes de su prohibición como aditivo de la gasolina hasta la actualidad, así como estudiar la evolución de la carga corporal de plomo en la población infantil española. Métodos: Se obtuvieron las concentraciones medias anuales de plomo en el aire en diversas ciudades españolas, desde la década de 1980 hasta la actualidad. Se realizó una búsqueda bibliográfica con el fin de identificar estudios publicados sobre concentraciones de plomo en la población infantil española. Resultados: En general se observó una disminución de las concentraciones de plomo, de mayor magnitud entre 1991 y 1999. Esta evolución decreciente se asocia con una disminución de las concentraciones de plomo en la población infantil española, desde 1989 (año en que se publica el primer estudio sobre exposición infantil al plomo) hasta hoy. La disminución, tanto en el aire como en la población infantil, es muy probable que sea consecuencia de las medidas legislativas que han regulado la cantidad máxima de plomo en la gasolina, desde 1987 hasta su prohibición total en agosto de 2001. Conclusiones: Desde el punto de vista de la salud pública, la prohibición del uso de gasolina con plomo fue una acción que aumentó la protección de la salud de la población española. 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.

OBJECTIVE: To investigate whether circulating 25-hydroxyvitamin D-3 [25(OH)D-3] concentration in pregnancy is associated with neuropsychological development in infants. METHODS: The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D-3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5 +/- 2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11-23) by using the Bayley Scales of Infant Development. beta-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D-3 were calculated by using linear regression analysis. RESULTS: The median plasma value of 25(OH)D-3 in pregnancy was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D-3 concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D-3 concentrations in pregnancy >30 ng/mL showed higher mental score (beta = 2.60; 95% CI 0.63-4.56) and higher psychomotor score (beta = 2.32; 95% CI 0.36-4.28) in comparison with those of mothers with 25(OH)D-3 concentrations

Vulnerability of the central nervous system to mercury is increased during early development. This study aimed to evaluate whether cord blood total mercury levels may have a negative effect on both mental and psychomotor development in a maternal-birth cohort from moderate-high fish consumption areas. Study subjects were 1,683 child participants in the INMA (Environment and Childhood) Project from 4 areas of Spain between 2003 and 2010. Cord blood total mercury levels were analyzed by atomic absorption spectrometry. Infant neurodevelopment was assessed around age 14 months by the Bayley Scales of Infant Development. Sociodemographic, lifestyle, and dietary information was obtained by questionnaire during pregnancy. The geometric mean of total mercury levels was 8.4 mu g/L (95% confidence interval (CI): 8.1, 8.7). In multivariate analysis, a doubling in total mercury levels did not show an association withmental (beta = 0.1, 95% CI: -0.68, 0.88) or psychomotor (beta = -0.05, 95% CI: -0.79, 0.68) developmental delay; however, stratified findings by sex suggest a negative association between prenatal exposure to total mercury and psychomotor development among female infants (beta = -1.09, 95% CI: -2.21, 0.03), although follow-up is required to confirm these results.

Introduction and Objective: Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). Methods: A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. >= vs = 2 mu g/dL were found (5.9%). Geometric mean and maximum were 1.06 mu g/dL and 19 mu g/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels >= 2 mu g/dL Conclusion: In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. (C) 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. (C) 2011 Elsevier Ltd. 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 mu g/L (Valencia) to 114.7 mu g/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.

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 NO2 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 NO2 over the area. Geographical data and predictions from kriging obtained by the "let one out" procedure were used a:; predictors. Individual exposure was assigned as 1) the estimated ambient NO2 level at the home address and 2) the average of estimated ambient NO2 levels at home and work addresses, weighted by the time spent in each environment. Estimations were temporally customised using the NO2 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 NO2 during the sampling periods explained 81% of the variation in NO2 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. (C) 2009 Elsevier B.V. All rights reserved.

Objectives: To describe the degree of annoyance caused by air pollution and noise in pregnant women in a birth cohort; to determine the modifying factors and their relation with exposure to ambient nitrogen dioxide (NO,). Methods: The study population was 855 pregnant women in Valencia, Spain. Annoyance caused by air pollution and noise, and explanatory factors were obtained from 786 pregnant women through a questionnaire. NO2 levels were determined combining measurements at 93 points within the area of study and using geostatistical techniques (kriging). Results: In all 7.9% of the women reported high annoyance caused by air pollution and 13.1% high annoyance caused by noise. There was a significant difference in the degree of annoyance due to both air pollution and noise depending on the area where the women lived and their working status. The degree of annoyance correlated better with measured NO, at the municipality level (air pollution: r = 0.53; noise: r = 0.44) than at the individual level (air pollution and noise: r = 0.21). On multivariate analysis, being a housewife, higher NO2 levels and high traffic density were associated with higher degrees of annoyance. Conclusions: There was a high percentage of women who perceived medium-high annoyance due to noise and air pollution. Annoyance caused by environmental pollutants could lead to some psychological effects, which impair the quality of life, or even physiological ones, which affect prenatal development. (C) 2007 Elsevier Ltd. All rights reserved.

Assessing the adverse effects on human health of persistent organic pollutants (POPs) and the impact of policies aiming to reduce human exposure to POPs warrants monitoring body concentrations of POPs in representative samples of subjects. While numerous ad hoc studies are being conducted to understand POPs effects, only a few countries are conducting nationwide surveillance programs of human concentrations of POPs, and even less countries do so in representative samples of the general population. We tried to identify all studies worldwide that analyzed the distribution of concentrations of POPs in a representative sample of the general population, and we synthesized the studies' main characteristics, as design, population, and chemicals analyzed. The most comprehensive studies are the National Reports on Human Exposure to Environmental Chemicals (USA), the German Environmental Survey, and the Arctic Monitoring and Assessment Programme. Population-wide studies exist as well in New Zealand, Australia, Japan, Flanders (Belgium) and die Canary Islands (Spain). Most such studies are linked with health surveys, which is a highly-relevant additional strength. Only the German and Flemish studies analyzed POPs by educational level, while studies in the USA offer results by ethnic group. The full distribution of POPs concentrations is unknown in many countries. Knowledge gaps include also the interplay of age, gender, period and cohort effects on the prevalence of exposures observed by cross-sectional surveys. Local and global efforts to minimize POPs contamination, like the Stockholm convention, warrant nationwide monitoring of concentrations of POPs in representative samples of the general population. Results of this review show how such studies may be developed and used. (C) 2007 Elsevier Ltd. All rights reserved.

No systematic review is available on studies conducted in Spain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane, (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrations of DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individuals may be over 200-fold higher than those of others. The actual magnitude of human contamination by PTS and their trends across Spain -as well as the geographic and social heterogeneity- remain largely unknown.

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.