Níveis de poluentes orgânicos persistentes e de metais pesados no sangue e os efeitos no desenvolvimento neuro-psicológico na primeira infância e em coortes mães-filhos INMA (INfância e Meio Ambiente)

Introduction: The INMA project is a multicenter study based on prospective monitoring of mother-child cohorts in different Spanish geographical areas. Objective: To study the relationship between major environmental pollutants and child development in the pre-and postnatal phases. Material and Methods: The cohort groups share data collection methodology and tools (environmental exposure, biological samples, physical and neuropsychological examinations, diet questionnaires etc.) during intrauterine growth and monitored childhood development. Results: The levels of Persistent Organic Pollutants (POPs) in serum during the first trimester of pregnancy are reported, together with those for lead (Pb) and total mercury (Hg-T) in the umbilical cord, which are associated with the neuropsychological development analyzed to date. The POPs most frequently found were p, p’-DDE (99%) and PCB 153 (95%) with geometric mean in serum (ng / g-lipid) of 110.0 (p, p’-DDE) and 38.9 (PCB 153). The geometric mean and the maximum Pb level were 1.06 mg/dL and 19 mg/dL, respectively. The geometric mean Hg-T was 8.2 mg/L, with fish consumption being the main predictor. The Hg-T reference levels set by USEPA (6.4 mg/L) were exceeded in 64% of the samples. Conclusion: T The levels of POPs and Pb observed in the study areas were within the range of values previously described in earlier studies. The Hg levels require more in-depth assessment, as well as study of the possible associations with neuropsychological development.Introducción: El proyecto INMA es un estudio multicéntrico basado en el seguimiento prospectivo de cohortes de madres-hijos en distintas áreas de la geografía española. Objetivo: Estudiar la relación entre los principales contaminantes ambientales y el desarrollo de los niños y niñas en las fases pre y postnatales. Material y Métodos: El conjunto de las cohortes comparten metodología e instrumentos de recogida de información (exposición ambiental, muestras biológicas, exámenes del desarrollo físico y neuropsicológico, cuestionarios de dieta etc.) durante el crecimiento intrauterino y en las fases de seguimiento en la infancia. Resultados: Se presentan los niveles de Compuestos Orgánicos Persistentes (COP) en suero del primer trimestre de embarazo y de plomo (Pb) y mercurio total (Hg-T) de cordón umbilical y las asociaciones con el desarrollo neuropsicológico analizadas hasta la fecha. Los COP más frecuentemente encontrados fueron el p,p ́-DDE (99%) y el PCB 153 (95%) con medias geométricas en suero (ng/g-lípido) de 110,0 (p,p ́-DDE) y 38,9 (PCB 153). La media geométrica y el nivel máximo de Pb fueron 1,06 μg/dL y 19 μg/dL, respectivamente. La media geométrica de Hg-T fue de 8,2 μg/L, siendo el consumo de pescado el principal predictor. Un 64% de las muestras superan los niveles de referencia de Hg-T establecidos por la USEPA (6,4 μg/L). Conclusión: Los niveles de COP y Pb observados en las áreas de estudio se encuentran en el rango de valores ya descritos en estudios anteriores. Los niveles de Hg requieren una valoración más profunda, así como el estudio de las posibles asociaciones con el desarrollo neuropsicológico. Introdução: O projeto INMA é um estudo multicêntrico, que consiste no acompanhamento prospetivo de coortes mães-filhos em diferentes regiões de Espanha. Objetivo: Estudar a relação entre os principais poluentes ambientais e desenvolvimento da criança nas fases pré e pós-natal. Material e Métodos: Em todas as coortes é utilizada a mesma metodologia e instrumentos de recolha de dados (exposição ambiental, amostras biológicas, exames de desenvolvimento físico e neuro-psicológico, questionários de dieta, etc.) durante o crescimento intrauterino e nas fases de seguimento da infância. Resultados: Apresentam-se os níveis de poluentes orgânicos persistentes (POP) no soro do primeiro trimestre de gravidez, os valores de chumbo (Pb) e de mercúrio total (Hg-T) no cordão umbilical, e as associações com o desenvolvimento neuro-psicológico analisadas até à data. Os POP encontrados com maior frequência foram p,p ́-DDE (99%) e PCB 153 (95%) com uma média no soro (ng/g-lípido) de 110,0 (p,p ́-DDE) e 38,9 (PCB 153). A média e o nível máximo de Pb foram 1,06 μg/dL e 19 μg/dL, respetivamente. A média de Hg-T foi de 8,2 μg/L, sendo o consumo de peixe o principal responsável. Os níveis de Hg-T de referência estabelecidos pela USEPA (6,4 μg/L) foram ultrapassados em 64% das amostras. Conclusão: Os níveis de POP e Pb observados nas áreas de estudo apresentaram-se dentro dos valores descritos em estudos anteriores. Os teores de Hg requerem uma avaliação mais aprofundada, assim como o estudo das possíveis associações com o desenvolvimento neuro-psicológico

Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort

Background: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. Methods: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. Results: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (β 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). Conclusions: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations

Prenatal exposure to mercury and neuropsychological development in young children: the role of fish consumption

BACKGROUND: Vulnerability of the central nervous system to mercury exposure is increased during early development. The aim of this study is to evaluate the association between prenatal exposure to mercury and child neuropsychological development in high-fish-intake areas in Spain. METHODS: Study subjects were 1362 children, participants in the INMA (Environment and Childhood) birth cohort study. Cord blood total mercury (CB-Hg) and cord polyunsaturated fatty acids (PUFA) concentrations were analysed in samples collected between 2004 and 2008. Child neuropsychological development was assessed at age 4-5 years by the McCarthy Scales of Children's Abilities (MSCA). Socio-demographic, lifestyle and dietary information was obtained by questionnaires administered during pregnancy and childhood. RESULTS: The geometric mean of CB-Hg was 8.8 µg/L [95% confidence interval (CI) 8.4, 9.2]. A doubling in CB-Hg was associated with higher scores in most of the MSCA scales (β=1.29; 95% CI 0.28, 2.31 for the general cognitive scale). The association between CB-Hg and the scores obtained on the scales was inverse among children whose mothers consumed fewer than three weekly servings of fish during the first trimester of pregnancy, although confidence intervals did not exclude the null (β=-1.20; 95% CI -2.62, 0.22 for the perceptive-manipulative scale and β=-3.06; 95% CI -6.37, 0.24 for the general cognitive scale). An inverse association between CB-Hg and the scores on the motor scale was also suggested for children with an n-6/n-3 PUFA ratio above the median (β=-0.23; 95% CI -0.87, 0.40, interaction p-value=0.03). CONCLUSION: The relationship between CB-Hg concentrations and child neuropsychological development was influenced by maternal nutritional factors, such as fish consumption and the PUFA statu

Dietary and Household Sources of Prenatal Exposure to Polybrominated Diphenyl Ethers (PBDEs) in the INMA Birth Cohort (Spain)

This study looked at predictors of exposure to polybrominated diphenyl ethers (PBDEs) with a focus on dietary and household-level factors. Concentrations of BDE-47, -99, -153, and -209 and their sum (∑PBDEs) were measured in cord serum. Spanish women (<i>n</i> = 541) completed two semiquantitative food frequency questionnaires during the first and third trimesters of pregnancy. The daily mean intake (grams) of eggs, dairy products, meat, cereals and pasta, vegetables and pulses, fruits, shellfish and cephalopods, and fish, and the weekly mean intake (servings) of lean, large oily, other oily, and other fish from both questionnaires were averaged. Information on house size, curtains and carpets at home, mattress type, housekeeping frequency, and television use was also collected later in gestation. Multivariate censored regression was used to assess the association between PBDE concentration (log₂ transformed) and potential predictors. BDE-47, -99, -209 and ∑PBDE concentrations increased by 13.6%(95% CI:0.0, 29.0%), 21.1%(2.3, 43.5%), 21.7%(0.4, 47.5%) and 11.5%(2.2, 21.7%), respectively, per interquartile range increment in daily intake of shellfish and cephalopods. Fish intake was associated with BDE-99 (20.8%[1.7, 43.4%]). When fish was disaggregated by types, BDE-99 and ∑PBDEs increased by 13.8%(4.0, 24.7%) and 5.7%(0.8, 10.8%), respectively, per 1-serving/week increment in large oily fish intake. BDE-153 was associated with higher housekeeping frequency (35.9%[0.4, 83.9%]) and BDE-209 with foam mattress use (48.9%[5.8, 109.7%]). In conclusion, seafood consumption, higher housekeeping frequency, and foam mattress were associated with prenatal PBDE exposure

Second-hand smoke exposure in 4-year-old children in Spain: Sources, associated factors and urinary cotinine

Introduction Second-hand smoke exposure (SHS) in children remains as a major pollution problem, with important consequences for children's health. This study aimed to identify the sources of exposure to SHS among 4-year-old children, comparing self-reports to a urinary biomarker of exposure, and characterize the most important variables related to SHS exposure in this population. Methods 4-year-old children's exposure to SHS was assessed by a parental-reported questionnaire and by urinary cotinine (UC) measurements in 1757 participants from 4 different areas of the Spanish INMA (INfancia y Medio Ambiente – Environment and Childhood) Project. The questionnaire about SHS included information about smoking habits at home by household members, and about exposure to SHS in other places including other homes, bars, restaurants or transportation. The association between quantified UC levels (>4 ng/ml) and sociodemographic variables and the different sources of SHS exposure was examined using logistic regression. Results Based on parental reports, 21.6% of the children were exposed to SHS at home and 47.1% elsewhere; making a total 55.9% of the children exposed to SHS. In addition, 28.2% of the children whose parents reported being not regularly exposed to SHS had quantified UC values. Children from younger mothers (<34 vs. ≥39.4 y) had a higher odds of exposure to SHS [OR (95% CI): 2.28 (1.70–3.05) per year], as well as from families with a lower educational level [OR secondary: 2.12 (1.69–2.65); primary or less: 2.91 (2.19–3.88)]. The odds of quantifiable UC in children dropped after the smoking ban in public places [OR=0.59 (0.42–0.83)]. Regarding the sources of SHS exposure we observed that quantifiable UC odds was increased in children whose parents smoked at home in their presence [OR mother occasionally: 13.39 (7.03–25.50); mother often: 18.48 (8.40–40.66); father occasionally: 10.98 (6.52–18.49); father often: 11.50 (5.96–22.20)] or in children attending other confined places, mainly other houses where people smoked [OR: 2.23 (1.78–2.80)]. Conclusions Children's SHS exposure is nowadays an unresolved major public health problem in Spain. After the ban of smoking in public places health care professionals should put more emphasis to the parents on the importance of controlling the exposure of their children in private spaces.INMA project is funded by grants by the Carlos III Instituto de Salud (Red INMA G03/176 and CB06/02/0041) and Fundación Roger Torné. The studies in the specific regions were funded by the Spanish Ministry of Health (FIS-FEDER 03/1615, 04/1436, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/0867, 06/1213, 07/0314, 08/1151, 09/02647, 04/2018, 09/02311, 11/02591, 11/02038, 13/02032, 13/02429, 14/0891, 14/1687, and MS13/00054), the Generalitat de Catalunya (CIRIT 1999SGR00241), the Diputación Foral de Gipuzkoa (DFG06/004), the Department of Health of the Basque Government (2005111093), the Regional Government of Andalucía (SAS 07/183), and support of Obra Social Cajastur/Fundación Liberbank, University of Oviedo and the Conselleria de Sanitat Generalitat Valenciana. http://www.proyectoinma.org/instituciones-participantes/en_entidades-colaboradoras/. The authors are grateful to all fieldworkers for their assistance in administering the questionnaires. A full listing of the INMA project researchers can be found at http://www.proyectoinma.org/presentacioninma/listado-investigadores/en_listado-investigadores.htm

Maternal Smoking During Pregnancy and Fetal Biometry: The INMA Mother and Child Cohort Study

In utero tobacco exposure has been associated with fetal growth restriction, but uncertainty remains about critical windows of exposure and specific effects on body segments. In the present study, we aimed to examine the association of maternal smoking with fetal biometry in different stages of pregnancy. The study population comprised 2,478 fetuses from a Spanish birth cohort study that was established between 2003 and 2008. Biparietal diameter, femur length, abdominal circumference, and estimated fetal weight were evaluated at 12, 20, and 34 weeks of gestation. Fetal size and growth were assessed by standard deviation scores adjusted by maternal and fetal characteristics. Maternal smoking was assessed using questionnaire and a sample of urinary cotinine at week 32 of gestation. Associations were estimated using multiple regression analysis. Smokers at week 12 of gestation showed decreased fetal growth as reflected by all growth parameters at 20-34 weeks, leading to a reduced fetal size at week 34. The reduction was greatest in femur length, at -9.4% (95% confidence interval -13.4, -5.4) and least in abdominal circumference, at -4.4% (95% CI: -8.7, -0.1). Fetuses of smokers who quit smoking before week 12 showed reduced growth only in femur length (-5.5; 95% CI: -10.1, -0.9). Dose-response curves for smoking versus fetal growth parameters (abscissa: log2 cotinine) were linear for biparietal diameter and femur length