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The objective of this study was to describe the postnatal exposure to Hg and to evaluate its association with neuropsychological development among preschool children. The study population are 4-5 years old children (n = 1252) participant in the Spanish INMA Project. Total Hg was measured in cord blood and in hair samples taken at 4 years of age (2008-2012). Neuropsychological development was assessed using the McCarthy Scales of Children's Abilities (MSCA). Information on covariates and possible confounders was obtained by questionnaires during pregnancy and childhood. Generalized additive and linear regression models were built in order to assess the relationship between MSCA scores and Hg exposure. We also evaluated the magnitude of the possible bias generated from measurement error in seafood intake estimate from questionnaire and Hg determination. The geometric mean of hair Hg was 0.98 µg/g [95% confidence interval (CI) 0.94, 1.03]. In the regression analysis, the association between Hg and the MSCA scores was positive for all the scales and statistically significant for the verbal (β = 0.89; 95%CI 0.38, 1.39), memory (β = 0.42; 95%CI 0.09, 0.76) and general cognitive scales (β = 1.35; 95%CI 0.45, 2.25). However, these associations were clearly attenuated when we adjusted by the children's fish intake variables or when took into account theoretical scenarios of low precision in fish intake and Hg measurements. Hg levels in this Spanish population were high in comparison with other European countries; however, we did not observe adverse effects on child neuropsychological development associated with this postnatal exposure to Hg.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Early neuropsychological assessment provides important information for clinical practice and research. As previously no tool for neuropsychological assessment has been developed in or adapted to Basque, the aim of this study was to adapt and validate the McCarthy Scales of Children's Abilities for 4 years old children. The adaptation and validation of the original instrument followed the methodological steps established by the International Test Commission. We examined the psychometric properties of the adapted instrument in 273 Basque preschool children (aged between 4 years and 4 months and 4 years and 11 months; 52.2% boys). Confirmatory factor analysis showed satisfactory fit indexes except for the General Cognitive and Memory scales. Most scales presented adequate internal consistency (Reliability coefficients ranged between .55 and .81). The Basque version also showed evidence of validity based on the relationship between neuropsychological development and sex, parental education, attention deficit hyperactivity disorder-like behaviours and early neurodevelopment (p < .05; effect sizes ranged between Cohen's d = .26 and .52 and r = .15 and 39). The Basque MSCA can be regarded as a useful tool to evaluate cognitive and psychomotor development in preschool children.

Stress system activity in early life can have long-term effects on neurodevelopment. The main aim of this study was to assess the association of child evening salivary cortisol and alpha-amylase basal levels at 14months of age with longer-term neuropsychological development at 4years in a low-risk population-based birth cohort derived from the INMA (Environment and Childhood) project in Spain. We included 186 parent-children pairs with information on both stress system activity and neurodevelopment. Both stress markers at 14months of age showed an association with neuropsychological development at 4years. Salivary cortisol showed a sex-specific pattern of association. In girls, cortisol levels at 14months were negatively associated with cognitive development [long-term declarative memory (β=-17.8, p=0.028; 95% CI=-33.2 to -2.5); executive function (β=-9.8, p=0.08; 95% CI=-21 to 1)] and gross motor development (β=-13; p=0.022; 95% CI=-24 to -2), whereas in boys cortisol levels were negatively associated with socioemotional development [autistic-like behaviours: Incidence Rate Ratio (IRR)=1.6, p=0.039; 95% CI=1.01 to 2.41]. Salivary alpha-amylase was positively associated with socioemotional development in boys only [social competence (β=2.11, p=0.013; 95% CI=0.47 to 3.72), autistic-like behaviours (IRR=0.93, p=0.042; 95% CI=0.87 to 0.99) and hyperactivity symptoms (IRR=0.81, p=0.021; 95% CI=0.69 to 0.97)]. These results suggest that stress system activity in early life is associated with longer-term neurodevelopment and that sex is an important factor in this relationship., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age., Methods: This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner's Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities., Results: Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38)., Conclusions: Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

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 status. [ABSTRACT FROM AUTHOR]

Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype. We evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004-2008. Bayley and McCarthy scales and the Childhood Asperger Syndrome Test were used to assess neuropsychological development. Results from multivariate linear regression models were adjusted for sociodemographic characteristics and further adjusted for umbilical cord blood mercury or long-chain polyunsaturated fatty acid concentrations. Overall, consumption of seafood above the recommended limit of 340 g/week was associated with 10-g/week increments in neuropsychological scores. By subtype, in addition to lean fish, consumption of large fatty fish showed a positive association; offspring of persons within the highest quantile (>238 g/week) had an adjusted increase of 2.29 points in McCarthy general cognitive score (95% confidence interval: 0.42, 4.16). Similar findings were observed for the Childhood Asperger Syndrome Test. Beta coefficients diminished 15%-30% after adjustment for mercury or long-chain polyunsaturated fatty acid concentrations. Consumption of large fatty fish during pregnancy presents moderate child neuropsychological benefits, including improvements in cognitive functioning and some protection from autism-spectrum traits. [ABSTRACT FROM AUTHOR]

Background Prenatal and postnatal exposure to air pollution has been linked to cognitive impairment in children, but very few studies have assessed its association with attentional function. Objectives To evaluate the association between prenatal and postnatal exposure to nitrogen dioxide (NO 2 ) and attentional function in children at 4–5 years of age. Methods We used data from four regions of the Spanish INMA—Environment and Childhood—Project, a population-based birth cohort. Using land-use regression models (LUR), we estimated prenatal and postnatal NO 2 levels in all of these regions at the participants' residential addresses. We assessed attentional function using the Kiddie-Conners Continuous Performance Test (K-CPT). We combined the region-specific adjusted effect estimates using random-effects meta-analysis. Results We included 1298 children with complete data. Prenatal exposure to NO 2 was associated with an impaired standard error of the hit reaction time (HRT(SE)) (increase of 1.12 ms [95% CI; 0.22 a 2.02] per 10 μg/m 3 increase in prenatal NO 2 ) and increased omission errors (6% [95% CI; 1.01 to 1.11] per 10 μg/m 3 increase in prenatal NO 2 ). Postnatal exposure to NO 2 resulted in a similar but borderline significant increase of omission errors (5% [95% CI; = 0.99 to 1.11] per 10 μg/m 3 increase in postnatal NO 2 ). These associations did not vary markedly between regions, and were mainly observed in girls. Commission errors and lower detectability were associated with prenatal and postnatal exposure to NO 2 only in some regions. Conclusions This study indicates that higher exposure to ambient NO 2 , mainly during pregnancy and to a lesser extent postnatally, is associated with impaired attentional function in children at 4–5 years of age. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) have been related to neurodevelopmental toxicity in animals. However, human studies are inconclusive. To evaluate the association between prenatal PFAS exposure and neuropsychological development during childhood. 1240 mother–child pairs from the Spanish INMA Project were analyzed. Perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) were measured in first-trimester maternal plasma. Neuropsychological development was assessed at 14 months, 4–5 and 7 years covering four domains: general cognitive, general motor, attention, and working memory. Associations were studied by means of multivariable regression analyses. PFHxS, PFOA, PFOS, and PFNA medians were: 0.6, 2.4, 6.1, and 0.7 ng/mL. Higher PFAS prenatal exposure was associated with worse motor development at 14 months, especially in the case of PFHxS (β[95%CI]: −1.49[−2.73, −0.24]) and to a lesser extent PFOS (−1.25[−2.62, 0.12]). There was also a marginal positive association between general cognitive development at 4–5 years and PFOS (1.17[−0.10, 2.43]) and PFNA (0.99[−0.13, 2.12]). No clear associations for other neuropsychological outcomes or any sex differences were found. This study shows no clear-cut evidence of an association between prenatal PFAS exposure and adverse neuropsychological development in children up to the age of 7 years. [Display omitted] • Study on prenatal PFASs and neurodevelopment up to 7 years (n = 1240, Spain). • Negative pattern between PFASs and 14-month motor development, p < 0.05 for PFHxS. • Some marginal positive associations with 4–5-year-old cognitive development. • No consistent sex modifying effects. [ABSTRACT FROM AUTHOR]