Carmen Freire

Hair mercury levels, fish consumption, and cognitive development in preschool children from Granada, Spain .

The main source of human exposure to mercury is the consumption of fish contaminated with methylmercury, which may adversely affect early neurodevelopment. This study assessed mercury levels in hair of preschoolers in Spain, where fish consumption is elevated, with the aim of investigating the influence of their fish intake and other factors on mercury exposure, and evaluating their association with cognitive development. A population-based birth cohort from Granada (Spain) was studied at the age of 4yr. Total mercury (T-Hg) levels were determined in childrens hair, and daily fish intake was assessed by a food frequency questionnaire. The McCarthy Scales of Childrens Abilities (MSCA) were used to assess childrens motor and cognitive abilities. Complete data were gathered on 72 children, and multivariate analyses were performed to evaluate the influence of mercury exposure and fish intake on MSCA outcomes. Mean concentration of T-Hg in hair was 0.96 microg/g (95% confidence interval=0.76; 1.20 microg/g). T-Hg levels were associated with higher frequency of oily fish consumption, place of residence, maternal age, and passive smoking. After adjustment for fish intake, T-Hg levels > or =1microg/g were associated with decrements in the general cognitive (-6.6 points), memory (-8.4 points), and verbal (-7.5 points) MSCA scores. Higher mercury exposure in children from this Mediterranean area was associated with cognitive development delay. Studies on the putative benefits of fish intake during early development should consider mercury exposure from different fish species.

Pesticide exposure and Parkinson's disease: epidemiological evidence of association.

It has been suggested that exposure to pesticides might be involved in the etiology of Parkinsons disease (PD). We conducted an updated systematic review of the epidemiologic literature over the past decade on the relationship between pesticide exposure and PD, using the MEDLINE database. Despite methodological differences, a significantly increased PD risk was observed in 13 out of 23 case-control studies that considered overall exposure to pesticides (risk estimates of 1.1-2.4) and in 10 out of 12 studies using other research designs (risk estimates of 2 or higher). Various studies found stronger associations in genetically susceptible individuals. Among a growing number of studies on the effects of exposure to specific pesticides (n=20), an increased PD risk has been associated with insecticides, especially chlorpyrifos and organochlorines, in six studies (odds ratios of 1.8-4.4), and with the herbicide paraquat, the fungicide maneb or the combination of both. Findings considerably strengthen the evidence that exposure to pesticides in well water may contribute to PD, whereas studies of farming and rural residence found inconsistent or little association with the disease. Taken together, this comprehensive set of results suggests that the hypothesis of an association between pesticide exposure and PD cannot be ruled out. However, inadequate data on consistent responses to exposure hinder the establishment of a causal relationship with PD. Given the extensive worldwide use of many pesticides, further studies are warranted in larger populations that include detailed quantitative data on exposure and determination of genetic polymorphisms.

Association of traffic-related air pollution with cognitive development in children

Background Air pollution from traffic has been associated with cardiorespiratory diseases in children and adults, but there is little information on its potential neurotoxic effects. This study aimed to investigate the association between exposure to nitrogen dioxide (NO2), as a marker of traffic-related air pollution, and cognitive development in children. Methods A population-based birth cohort from southern Spain was followed from the age of 4 years for 1 year. Complete data for analyses were gathered on 210 children living in urban and rural areas. NO2 exposure was predicted by means of land use regression models. A standardised version of the McCarthy Scales of Childrens Abilities (MSCA) was used to assess childrens motor and cognitive abilities. Multivariate analyses were performed to evaluate the relation between exposure to NO2 and MSCA outcomes, adjusting for potential confounders. Results A negative effect of NO2 was found across all MSCA subscales, despite low predicted NO2 exposure levels (5–36 μg/m3). Children exposed to higher NO2 (>24.75 μg/m3) showed a decrease of 4.19 points in the general cognitive score and decreases of 6.71, 7.37 and 8.61 points in quantitative, working memory and gross motor areas, respectively. However, except for gross motor function, associations were not statistically significant. Conclusion Although results were not statistically significant, the associations found between exposure to NO2 and cognitive functions suggest that traffic-related air pollution may have an adverse effect on neurodevelopment, especially early in life, even at low exposure levels.

Residential exposure to outdoor air pollution during pregnancy and anthropometric measures at birth in a multicenter cohort in Spain.

Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children’s Health and Environment (INMA) mother and child cohort study. Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of –0.9 mm [95% confidence interval (CI), –1.8 to –0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (–0.16 mm; 95% CI, –0.27 to –0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, –45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.

Nonylphenol and octylphenol in adipose tissue of women in Southern Spain

Alkylphenols (APs) and AP ethoxylates are environmental contaminants with endocrine disrupting activities in wildlife and humans. They have been largely used in industrial, agricultural, and domestic applications. Despite strong concerns about the consequences of human exposure to endocrine disrupters, little information is available on the presence in humans of compounds such as APs. The aim of the present study was to determine 4-nonylphenol (NP) and 4-octylphenol (OP) residues in adipose tissue of non-occupationally exposed women living in Southern Spain. NP was detected in 100% (n=20/20) and OP in 23.5% (n=4/20) of samples, with median levels of 57 and 4.5 ng g(-1) adipose tissue, respectively. Body mass index emerged as a determinant of exposure since it was associated with NP levels (p=0.041). Adipose tissue NP and OP levels are similar to the few data previously published in other countries. This is the first report on NP and OP levels in a population in Southern Spain. Further research is needed to determine trends in human exposure to these compounds and to investigate their consequences.

Urinary 1-hydroxypyrene and PAH exposure in 4-year-old Spanish children

AIMS Exposure to polycyclic aromatic hydrocarbons (PAH), among the main compounds present in polluted urban air, is of concern for childrens health. Childhood exposure to PAH was assessed by urinary monitoring of 1-hydroxypyrene (1-OHP), a pyrene metabolite, investigating its association with exposure to air pollution and other factors related to PAH in air. METHODS A group of 174 4-year-old children were recruited and a questionnaire on their indoor and outdoor residential environment was completed by parents. At the same time, environmental measurements of traffic-related air pollution (NO2) were carried out. A urine sample was collected from each child in order to analyze 1-OHP using HPLC with fluorescence detection, correcting for creatinine concentrations. Non-parametric tests and regression analyses were used to identify environmental factors that influence 1-OHP excretion. RESULTS Mean urinary 1-OHP concentration was 0.061 micromol/mol creatinine, ranging from 0.004 to 0.314 micromol/mol. Non-parametric tests and regression analysis showed positive and significant associations (P<or=0.05) between 1-OHP and predicted residential exposure to NO2 (which was based on outdoor environmental measurements and geo-statistical analysis), self-reported residential vehicle traffic, passive smoking and cooking appliance. 1-OHP levels tended to be higher among children living in urban areas (0.062 micromol/mol vs. 0.058 micromol/mol for children living in rural areas) but differences were not significant (P=0.20). CONCLUSION In Southern Spain, concentrations of urinary 1-OHP were in the lower range of those generally reported for children living in non-polluted areas in Western Europe and the USA. Traffic-related air pollution, passive smoking and cooking appliance influenced urinary 1-OHP level in the children, which should be prevented due to the health consequences of the inadvertent exposure to PAH during development.

Pesticides, depression and suicide: a systematic review of the epidemiological evidence.

It has been suggested that high exposure to pesticides, including poisoning, experienced by agriculture workers and rural residents may result in an elevated risk of psychiatric disorders and suicidal behavior. Epidemiological data supporting this hypothesis are very limited. An updated systematic review was conducted in epidemiologic literature on the relationship of pesticide exposure with depression and suicide published over the last 15 years by using MEDLINE database. A total of 11 studies on depression and 14 studies on suicide met inclusion criteria. Depression or other psychiatric disorders have shown increased risks associated with previous pesticide poisoning in 5 studies, with statistically significant odds ratios (OR) ranging from 2.08 to 5.95. Lower risk estimates have been found for chronic pesticide exposure. Among studies on suicide, 4 reports found increased suicide rates in areas with intensive pesticide use (OR between 1.60 and 2.61) compared to areas with lower pesticide use. Occupation in agriculture has shown a significant association with higher suicide risk than other occupational groups in 4 studies (OR between 1.30 and 4.13), but not in one recent report. Regarding specific pesticides, lifetime use of chlorpyrifos was related with increased suicide mortality (OR=2.37) in one study. Scientific evidence of association between pesticide exposure and either depression or suicide has been shown in some populations, in studies using varying epidemiological approaches, but is still very limited and inconclusive. Review of the literature warrants further research to explore such relationships, in particular prospective studies among large samples of high- and low-dose-exposed workers, using detailed exposure assessments, and evaluating other potential sources of psychological stress.

Newborn TSH concentration and its association with cognitive development in healthy boys

OBJECTIVE An association between thyroid function during pregnancy or infancy and neurodevelopment in children has been demonstrated. We aimed to investigate whether newborn TSH concentrations are related to subsequent neurocognitive development. DESIGN We conducted a longitudinal study on 178 children from a general population birth cohort in Granada (Spain) born in 2000-2002. METHODS TSH concentrations were measured in umbilical cord blood, and cognitive functions were assessed at 4 years of age using the McCarthys scales of childrens abilities (MSCA). Organochlorine (OC) compound concentrations and the combined oestrogenicity (total effective xeno-oestrogenic burden (TEXB)) were also determined in the placentae. RESULTS Mean newborn TSH was 3.55  mU/l (range=0.24-17 mU/l). In multivariate regression analyses, adjusting for maternal and child characteristics, higher newborn TSH concentrations showed a decrease of 3.51 and 3.15 points on the MSCA general cognitive and executive function scores respectively and were associated with a higher risk of scoring below the 20th percentile (P20) on the quantitative score (odds ratio (OR)=2.64). Children with TSH in the upper quartile (4.19-17.0 mU/l) were at higher risk of scoring <P20 on span memory (OR=5.73), whereas children with TSH in the second quartile (2.05-2.95 mU/l) were at lower risk of scoring <P20 on the verbal scale (OR=0.24). Neonatal TSH status was also associated with general cognitive and executive function outcomes when controlling for prenatal exposure to OCs or placental TEXB. CONCLUSIONS Newborn thyroid hormone status expressed by TSH in cord blood may adversely affect later cognitive function. A more thorough screening for neonatal thyroid deficiency is warranted.

Exposure to Trihalomethanes through Different Water Uses and Birth Weight, Small for Gestational Age, and Preterm Delivery in Spain

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

Prenatal exposure to mirex impairs neurodevelopment at age of 4 years.

BACKGROUND Some studies have suggested that certain organochlorine (OC) compounds may impair neurodevelopment in animals and humans. The objective of this study was to investigate the association between prenatal exposure to an OC pesticide, mirex, and cognitive development in children at age of 4 years. METHODS A population-based birth cohort in Granada (Spain) recruited between 2000 and 2002 was studied between 2005 and 2006, when the children were 4 years old. Complete data for analyses, including mirex determination in placentas, were gathered on a random sample of 104 children. A standardized version of the McCarthy Scales of Childrens Abilities (MSCA) was used to assess childrens motor and cognitive abilities. Multivariate analyses were performed to evaluate the relation between MSCA scores and prenatal exposure to mirex, adjusting for potential confounders. RESULTS The presence of mirex in placenta was inversely associated with cognitive development at 4 years of age: children with prenatal exposure to mirex (>or=limit of quantification: 26%; median: 1.4 ng/g placenta) showed a decrease of 5.15 points in working memory and of 7.33 points in the quantitative area with respect to children of the same age not prenatally exposed to mirex. CONCLUSION The deficit found in intellectual function during early childhood suggests that prenatal exposure to mirex may have a significant impact on school performance.