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1.
Int J Epidemiol ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578044

RESUMO

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.

2.
Environ Int ; 130: 104835, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226565

RESUMO

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.

3.
Environ Res ; 174: 135-142, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075694

RESUMO

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 (ß, [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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30920622

RESUMO

CONTEXT: While the consequences of severe iodine deficiency are beyond doubt, the effects of mild-to-moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. OBJECTIVE: To study the association between maternal iodine status during pregnancy and child IQ and to identify vulnerable time-windows of exposure to suboptimal iodine availability. DESIGN: Meta-analysis of individual-participant data from three prospective population-based birth cohorts: Generation R (The Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002-2006, 2003-2008, and 1990-1992, respectively. SETTING: General community. PARTICIPANTS: 6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancy, fertility treatment, medication affecting the thyroid, and pre-existing thyroid disease. INTERVENTION(S): None. MAIN OUTCOME MEASURE: Child non-verbal and verbal IQ assessed at 1.5-8 years of age. RESULTS: There was a positive curvilinear association of the urinary iodine-to-creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat < 150 µg/g was not associated with lower non-verbal IQ [-0.6 points, 95% CI -1.7 to 0.4, P=0.246] or lower verbal IQ [-0.6, 95% CI -1.3 to 0.1, P=0.082]. Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation. CONCLUSIONS: Fetal brain development is vulnerable to mild-to-moderate iodine deficiency, particularly in the first trimester. Our results show that any potential randomized, controlled trial investigating the effect of iodine supplementation in mild-to-moderate iodine deficient women on child neurodevelopment, should start with supplementation not later than the first trimester.

5.
Int J Hyg Environ Health ; 222(3): 503-512, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30713056

RESUMO

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 ±â€¯standard deviation of maternal Cu concentrations was 1606 ±â€¯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.

6.
Int J Hyg Environ Health ; 222(3): 468-478, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30638867

RESUMO

OBJECTIVE: To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain. METHODS: Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated. RESULTS: Elevated placental Cd levels (>5.79 vs. <3.30 ng/g) were associated with reduced birth weight (-111.8 g, 95%CI = -215.6; -8.06, p-trend = 0.01) and length (-0.62 cm, 95%CI = -1.20; -0.04, p-trend = 0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI = 1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI = 0.78; 0.96) of preterm delivery in males (Pinteraction = 0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (-0.49 cm, 95%CI = -1.00; 0.03) in females (Pinteraction = 0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI = 0.01; 0.07) in the global sample and in head circumference (0.05 cm, 95%CI = -0.01; 0.10) in females (Pinteraction = 0.03). Elevated Cr levels (>99.6 vs. <56.1 ng/g) were associated with reduced birth length (-0.68 cm, 95%CI = -1.33; -0.04, p-trend = 0.02) and slightly increased gestational age (0.35 weeks, 95%CI = -0.07; 0.77, p-trend = 0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome. CONCLUSIONS: Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30519915

RESUMO

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 30th 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.

8.
Environ Res ; 166: 215-222, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29890426

RESUMO

BACKGROUND: The relationship between maternal selenium (Se) status and child neurodevelopment has been scarcely assessed. In a previous study we observed an inverse U-shaped association between maternal Se concentrations and infant neurodevelopment at 12 months of age. In this study, this non-linear association was explored at preschool age. The effect modification by breastfeeding, child's sex and cord blood mercury was also evaluated. METHODS: Study subjects were 490 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2012). Child neuropsychological development was assessed at around 5 years of age by the McCarthy Scales of Children's Abilities (MSCA). Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation and at 5 years of age. Se was measured in serum samples by ICP-MS at the end of the first trimester of pregnancy (mean ±â€¯standard deviation (SD) = 12.4 ±â€¯0.6 weeks of gestation). RESULTS: The mean ±â€¯SD of maternal serum Se concentrations was 79.9 ±â€¯8.1 µg/L. In multivariate analysis, no linear association was found between Se concentrations and the nine MSCA scales. Generalized additive models indicated inverted U-shaped relationships between Se concentrations and the verbal and global memory scales. When assessing the influence of effect modifiers, breastfeeding played a role: the association between Se and neuropsychological development was inverted U-shaped for the quantitative, general cognitive, working memory, fine motor, global motor and executive function scales only for non-breastfed children. CONCLUSION: Low and high maternal Se concentrations seem to be harmful for child neuropsychological development, however further studies should explore this non-linear relationship.

9.
Lancet Respir Med ; 6(5): 379-388, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29496485

RESUMO

BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. FINDINGS: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p<1·14 × 10-7) after meta-analysis. Consistently lower methylation levels were observed at all associated loci across childhood from age 4 to 16 years in participants with asthma, but not in cord blood at birth. All 14 CpG sites were significantly associated with asthma in the second replication study using whole-blood DNA, and were strongly associated with asthma in purified eosinophils. Whole-blood transcriptional signatures associated with these CpG sites indicated increased activation of eosinophils, effector and memory CD8 T cells and natural killer cells, and reduced number of naive T cells. Five of the 14 CpG sites were associated with asthma in respiratory epithelial cells, indicating cross-tissue epigenetic effects. INTERPRETATION: Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context. FUNDING: EU and the Seventh Framework Programme (the MeDALL project).


Assuntos
Asma/genética , Ilhas de CpG , Metilação de DNA , Eosinófilos/imunologia , Epigênese Genética , Asma/sangue , Criança , Pré-Escolar , DNA/sangue , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Linfócitos T Citotóxicos
10.
Environ Int ; 110: 113-122, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29107351

RESUMO

BACKGROUND: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. OBJECTIVES: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4-5years of age. METHODS: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003-2008). Neuropsychological development was measured at 1year of age using the Bayley Scales of Infant Development and at 4-5years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalomethanes (THM) were combined with personal ingestion, showering and bathing habits to estimate exposure as ingestion uptake, all route (showering, bathing, ingestion) uptake (µg/day) and crude levels (µg/l) in the residence. Chloroform, brominated THMs (bromodichloromethane, dibromochloromethane, bromoform) and total THMs (chloroform and brominated THMs) were analysed separately. Nine haloacetic acids levels were available in one of the areas. Linear regression was used to estimate associations in 1855 subjects adjusting for covariables. RESULTS: The median concentration of total THMs, chloroform, brominated THMs, total haloacetic acids, dichloroacetic acid, and trichloroacetic acid were, respectively 30.3µg/L, 9.4µg/L, 11.6µg/L, 10.5µg/L, 2.7µg/L, and 3.1µg/L. The associations between THM exposure and neuropsychological outcomes were null, except for total and brominated THM uptake though all routes and the general cognitive score at 4-5years, with a decrease in -0.54 points (95%CI -1.03, -0.05) and -0.64 (95%CI -1.16, -0.12), respectively, for doubling total and brominated THM uptake. A positive association found between dichloroacetic acid and the mental score at 1year did not persist at 4-5years. CONCLUSIONS: Minor associations observed between DBP exposure during gestation and child neuropsychological development at 1year disappeared at 4-5years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4-5years, chance cannot be ruled out.


Assuntos
Desinfetantes/toxicidade , Água Potável/análise , Exposição Materna/efeitos adversos , Doenças do Sistema Nervoso/epidemiologia , Poluentes Químicos da Água/toxicidade , Abastecimento de Água , Adulto , Desenvolvimento Infantil , Pré-Escolar , Estudos de Coortes , Desinfetantes/análise , Feminino , Humanos , Lactente , Masculino , Doenças do Sistema Nervoso/etiologia , Gravidez , Espanha/epidemiologia , Poluentes Químicos da Água/análise
11.
J Epidemiol Community Health ; 72(3): 216-222, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29279360

RESUMO

BACKGROUND: The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4-5 years. METHODS: We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4-5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children's Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC~Cr). RESULTS: Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC~Cr <100 µg/L had 3.93 (95% CI -6.18 to -1.69) general cognitive scores lower than the reference (150-249 µg/L). Dietary iodine was inversely associated with motor scores and milk but not other dairy products or seafood consumption accounted for this association (beta: -1.36; 95% CI -2.12 to -0.61; per one daily milk serving). CONCLUSIONS: We found an association between low maternal urinary iodine and lower cognitive scores in childhood, although only when corrected for creatinine, adding to the evidence that iodine deficiency may have potential harmful effects on neurodevelopment. Iodine supplementation does not appear to improve child's neurodevelopment at 4-5 years.

12.
Sci Total Environ ; 610-611: 741-749, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28822941

RESUMO

Selenium (Se) has been positively associated with neurodevelopment in early life. However, its margin of safety is rather narrow, and few prospective studies have evaluated its potential neurotoxic effects at intermediate levels. We aimed to explore the association between maternal Se concentrations and child neuropsychological development, including the genetic effect modification of the Se metabolizing gene INMT. Study subjects were 650 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2005). Infant neuropsychological development was assessed around 12months of age by the Bayley Scales of Infant Development. Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation. Se was measured in serum samples at the first trimester. The mean serum Se concentration was 79.7 (standard deviation=7.9) µg/L. In multivariate analysis, nonsignificant inverse linear associations were found between Se concentrations and standardized mental and psychomotor development scores (ß (95% CI)=-0.13 (-0.29, 0.03) and ß (95% CI)=-0.08 (-0.24, 0.07), respectively). Generalized additive models indicated inverted U-shaped relationships between Se concentrations and both scales. Using segmented regression, the turning point for the associations was estimated at 86µg/L for both scales. The association between Se and neuropsychological development was inverted U-shaped for children with the AG+AA genotype for rs6970396 INMT but a descending curve was suggested for the GG genotype. Further studies would be necessary in order to disentangle the complex equilibrium between the toxicity and benefits of Se exposure during the prenatal period.


Assuntos
Desenvolvimento Infantil , Metiltransferases/genética , Gravidez/sangue , Selênio/sangue , Adulto , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , Efeitos Tardios da Exposição Pré-Natal , Estudos Prospectivos , Compostos de Selênio
13.
Environ Res ; 160: 97-106, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968527

RESUMO

BACKGROUND: Prenatal mercury exposure has been related to reductions in anthropometry at birth. Levels of mercury have been reported as being relatively elevated in the Spanish population. OBJECTIVE: To investigate the relation between prenatal exposure to mercury and fetal growth. METHODS: Study subjects were pregnant women and their newborns (n:1867) participating in a population-based birth cohort study set up in four Spanish regions from the INMA Project. Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were measured by ultrasounds at 12, 20, and 34 weeks of gestation. Size at and growth between these points were assessed by standard deviation (SD) scores adjusted for constitutional characteristics. Total mercury (T-Hg) was determined in cord blood. Associations were investigated by linear regression models, adjusted by sociodemographic, environmental, nutritional - including four seafood groups - and lifestyle-related variables in each sub-cohort. Final estimates were obtained using meta-analysis. Effect modification by sex, seafood intake and polychlorinated biphenyl (PCB) congener 153 concentration was assessed. RESULTS: Geometric mean of cord blood T-Hg was 8.2µg/L. All the estimates of the association between prenatal Hg and growth from 0 to 12 weeks showed reductions in SD-scores, which were only statistically significant for BPD. A doubling of cord blood T-Hg was associated with a 0.58% reduction in size of BPD at week 12 (95% confidence interval -CI-: - 1.10, - 0.07). Size at week 34 showed estimates suggestive of a small reduction in EFW, i.e., a doubling of T-Hg levels was associated with a reduction of 0.38% (95% CI: - 0.91, 0.15). An interaction between PCB153 and T-Hg was found, with statistically significant negative associations of T-Hg with AC and EFW in late pregnancy among participants with PCB153 below the median. CONCLUSIONS: Exposure to mercury during pregnancy was associated with early reductions in BPD. Moreover, an antagonism with PCB 153 was observed with noteworthy reductions late in pregnancy in AC and EFW in the group with lower PCB153.


Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Exposição Materna/efeitos adversos , Mercúrio/toxicidade , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Gravidez , Adulto Jovem
14.
Sci Total Environ ; 621: 340-351, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29190557

RESUMO

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 4-5years. 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.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Metais Pesados/efeitos adversos , Placenta/química , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Arsênico/efeitos adversos , Cádmio/efeitos adversos , Pré-Escolar , Feminino , Humanos , Chumbo/efeitos adversos , Manganês/efeitos adversos , Mercúrio/efeitos adversos , Testes Neuropsicológicos , Gravidez , Espanha
15.
Environ Health Perspect ; 125(9): 097016, 2017 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-28934095

RESUMO

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.


Assuntos
Atenção , Exposição Ambiental/análise , Criança , Pré-Escolar , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Estudos Prospectivos
16.
Environ Res ; 159: 69-75, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28772151

RESUMO

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.


Assuntos
Arsênico/urina , Dieta , Exposição Ambiental , Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Oryza/química , Alimentos Marinhos/análise , Criança , Pré-Escolar , Monitoramento Ambiental , Feminino , Humanos , Masculino , Espanha , Inquéritos e Questionários
17.
Expo Health ; 9(2): 105-111, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28553665

RESUMO

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 µg/l (arsenobetaine-AsB), 3.97 µg/l (dimethylarsinic acid-DMA), 0.44 µg/l (monomethylarsonic acid-MMA) and 0.35 µg/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.

18.
Environ Health ; 16(1): 46, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28514952

RESUMO

BACKGROUND: Prenatal exposure to organophosphate pesticides (OPs) has been associated with impaired child development. Pesticide exposure determinants need to be studied in order to identify sources and pathways of pesticide exposure. The aim of this paper is to describe prenatal exposure to OPs and evaluate the associated factors in pregnant women. METHODS: The study population consisted of pregnant women (n = 573) who participated in the INMA birth cohort study in Valencia (Spain, 2003-2006). OP metabolites were analyzed in maternal urine at the 32nd week of gestation using a liquid chromatography-high resolution mass spectrometry method. The analysis included non-specific (diethyl phosphate [DEP], diethyl thiophosphate [DETP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP]) and specific metabolites (2-diethylamino-6-methyl-4-pyrimidinol [DEAMPY], 2-isopropyl-4-methyl-6-hydroxypyrimidine [IMPY], para-nitrophenol [PNP], and 3,5,6-trichloro-2-pyridinol [TCPY]). Information about the sociodemographic, environmental, and dietary characteristics was obtained by questionnaire. The association between log-transformed OPs and covariates was analyzed using multivariable interval censored regression. RESULTS: The detection frequencies were low, DMTP and TCPY being the most frequently detected metabolites (53.8% and 39.1%, respectively). All the OP metabolites were positively associated with maternal intake of fruits and vegetables. Other maternal characteristics related to the OPs were body mass index (BMI) before pregnancy and smoking habit during pregnancy. Women with lower BMI and those who did not smoke presented higher OP concentrations. Moreover, mothers who had a yard or garden with plants at home or who lived in an urban area were also more exposed to OPs. CONCLUSIONS: The OP detection frequencies and the concentrations observed in our study population were low, compared with most of the previously published studies. Given the high vulnerability of the fetus to neurotoxicant exposure, further research on the determinants of the body burden of OPs during pregnancy would be necessary. The knowledge gained from such studies would enhance the effectiveness of public health control and future recommendations in order to reduce the risk to both the health of pregnant women and the health and development of their children.


Assuntos
Poluentes Ambientais/urina , Inseticidas/urina , Compostos Organofosforados/urina , Gravidez/urina , Adulto , Estudos de Coortes , Dieta , Feminino , Humanos , Exposição Materna , Espanha
19.
Environ Res ; 157: 96-102, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28535425

RESUMO

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 10µg/m³ 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.


Assuntos
Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , DNA Mitocondrial/análise , Crescimento/efeitos dos fármacos , Exposição Materna , Dióxido de Nitrogênio/efeitos adversos , Placenta/química , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Espanha
20.
Environ Int ; 105: 34-42, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28500872

RESUMO

BACKGROUND: Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. OBJECTIVES: We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. METHODS: The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age, 2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). RESULTS: There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (ß[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only. CONCLUSIONS: Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Citocromo P-450 CYP3A/genética , Compostos de Metilmercúrio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/genética , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Sangue Fetal/química , Genótipo , Grécia , Humanos , Lactente , Itália , Masculino , Mercúrio/sangue , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/genética , Testes Neuropsicológicos , Polimorfismo Genético , Gravidez , Seicheles , Espanha
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