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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. [ABSTRACT FROM AUTHOR]

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. [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]

Aim This study investigated whether duration of full breastfeeding is associated with child neuropsychological development and whether this association is explained by social, psychological, and nutritional factors within families. Method Participants in this study were a population-based birth cohort in the city of Sabadell ( Catalonia, Spain). Females were recruited during the first trimester of pregnancy between July 2004 and July 2006. Information about parental characteristics and breastfeeding was obtained through questionnaires. Full breastfeeding was categorized as never, short term (≤4mo), long term (4-6mo), or very long term (>6mo). A trained psychologist assessed the neuropsychological development of children at 4 years of age ( n=434) using the Mc Carthy Scales of Children's Abilities ( MSCA). Results Full breastfeeding showed an independent association with child general MSCA scores after adjusting for a range of social, psychological, and nutritional factors (>6mo, coefficient=7.4 [95% confidence interval=2.8-12.0], p=0.011). Maternal social class, education level, and IQ were also associated with child neuropsychological scores, but did not explain breastfeeding associations. Omega-3 (n3) fatty acid levels were not associated with child neuropsychological scores. Interpretation Very long-term full breastfeeding was independently associated with neuropsychological functions of children at 4 years of age. Maternal indicators of intelligence, psychopathology, and colostrum n3 fatty acids did not explain this association. [ABSTRACT FROM AUTHOR]

Abstract: There is little evidence about exposure to currently used insecticides during early life periods and adverse effects on child neuropsychological development. The aim of this study is to examine the association between residential insecticide use during pregnancy and infancy, and the development of children. Study subjects were participants in the INMA (Environment and Childhood) Project, a Spanish multicenter birth cohort study. Prenatal and postnatal use of indoor insecticides and other variables were obtained from personal interview during pregnancy and infancy. Mental and psychomotor development was assessed around 14months using the Bayley Scales of Infant Development. The associations were analyzed by linear regression models. 54% of women used indoor insecticides at home during pregnancy and 47% postnatally. 34% of women used insecticide sprays and 33% used plug-in devices during pregnancy. During infancy, the percentage of women who used insecticide sprays decreased (22%), but the use of plug-in devices was similar to the prenatal period (32%). The use of insecticide sprays during pregnancy was associated with a decrement in psychomotor development (β=−1.9; 95%CI: −3.4, −0.5) but postnatal use did not associate with mental and psychomotor development. The negative effect was enhanced according to some modifying factors, such as being female, higher levels of prenatal exposure to PCB and mercury and belonging to the lowest social class. We found certain evidence about the adverse effect of using insecticide sprays during pregnancy on the psychomotor development of children. Some socio-demographic factors and other exposures could enhance that effect. [Copyright &y& Elsevier]

Evidence suggests that iron status may be linked to symptoms of childhood attention deficit/hyperactivity disorder (ADHD), but there is little data available on the relationship between iron status in pregnancy and the risk of developing ADHD. And the data that does exist is inconsistent. Our aim here is to assess the effect of maternal serum ferritin (SF) and haemoglobin (Hb) levels during pregnancy on manifestations of ADHD in children at 7 years of age. This prospective study analysed data from 1204 mother–child pairs from three Spanish cohorts participating in the INMA project. Maternal SF and Hb levels during pregnancy and other mother and child characteristics were collected. The children's ADHD behaviours were reported by their parents using Conners' Parent Rating Scale-Revised Short Form (CPRS-R:S). In the unadjusted regression analysis, maternal SF was positively associated with children's T-scores on the subscales Cognitive problems/Inattention (β: 0.63, 95%CI 0.06–1.19; p = 0.029) and ADHD index (β: 0.72, 95%CI 0.20–1.24; p = 0.007). These associations were not present after multivariate adjustment or stratification by first and second trimester of pregnancy. The Hb levels were not related to any of the CPRS-R:S subscales in unadjusted or multivariate-adjusted models. We observed no association between maternal SF or Hb levels and the risk of ADHD symptomatology (T-score ≥ 65 for CPRS-R:S subscales). Our results suggest that neither maternal SF nor Hb levels during pregnancy are related to ADHD symptoms in 7-year-old children. [ABSTRACT FROM AUTHOR]

Background: Exposure to organochlorine compounds (OCs) can alter thyroid function in humans, and hypothyroidism during early life can adversely affect a child's neurodevelopment. Objectives: In this study we aimed to assess the relationship between developmental organochlorine exposures and thyroid function and the relationship between thyroid function and subsequent neurodevelopment. Methods: A population-based birth cohort of 182 children was followed annually up to 5.5 years of age. The assessments included OC concentrations in maternal pregnancy serum and milk, clinical thyroid parameters in maternal and cord serum, and subsequent neuropsychological outcomes of the child, along with sociodemographic cofactors. Resin triiodothyronine uptake ratio (T3RU) was also assessed as an estimate of the amount of thyroxine-binding globulin (TBG) sites unsaturated by thyroxine. The T3RU is high in hyperthyroidism and low in hypothyroidism. Results: The findings showed consistent inverse and monotonic associations between organochlorine exposure and T3RU after covariate adjustments. We observed no associations with other thyroid parameters. T3RU was positively associated with improved performance on most of the neuropsychological tests. For other thyroid parameters, the findings were less consistent. Conclusions: The results suggest that OC exposures may decrease the T3RU during early life, which is a proxy measure of the binding capacity of TBG. In addition, minor decreases of the thyroid function may be inversely associated with a child's neurodevelopment. [ABSTRACT FROM AUTHOR]

Background: Exposure to organochlorine compounds (OCs) can alter thyroid function in humans, and hypothyroidism during early life can adversely affect a child's neurodevelopment. Objectives: In this study we aimed to assess the relationship between developmental organochlorine exposures and thyroid function and the relationship between thyroid function and subsequent neurodevelopment. Methods: A population-based birth cohort of 182 children was followed annually up to 5.5 years of age. The assessments included OC concentrations in maternal pregnancy serum and milk, clinical thyroid parameters in maternal and cord serum, and subsequent neuropsychological outcomes of the child, along with sociodemographic cofactors. Resin triiodothyronine uptake ratio (T3RU) was also assessed as an estimate of the amount of thyroxine-binding globulin (TBG) sites unsaturated by thyroxine. The T3RU is high in hyperthyroidism and low in hypothyroidism. Results: The findings showed consistent inverse and monotonic associations between organochlorine exposure and T3RU after covariate adjustments. We observed no associations with other thyroid parameters. T3RU was positively associated with improved performance on most of the neuropsychological tests. For other thyroid parameters, the findings were less consistent. Conclusions: The results suggest that OC exposures may decrease the T3RU during early life, which is a proxy measure of the binding capacity of TBG. In addition, minor decreases of the thyroid function may be inversely associated with a child's neurodevelopment. [ABSTRACT FROM AUTHOR]

Abstract: Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10min, with visual targets presented at 1000ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first 2min, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6min interval (6.10 (2.18)), and the strongest during 7–10min after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times. [Copyright &y& Elsevier]

Background: The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable. Objectives: In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children's neurobehavioral functions at 6-8 years of age. Methods: We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children's current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity. Results: Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5-2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results. Conclusions: These findings support the notion that prenatal exposure to pesticides-at levels not producing adverse health outcomes in the mother-can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a "silent pandemic" of developmental neurotoxicity. [ABSTRACT FROM AUTHOR]

The use of folic acid supplements during very early pregnancy is recommended in order to reduce the incidence of neural tube defects. Little is known about the possible benefits of folic acid on child neurodevelopment. A total of 420 children (87% of those eligible) from a birth cohort had complete data for final analyses at age 4 years. Information about folic acid and other over-the-counter dietary supplements was obtained prospectively using interviewer-administered questionnaires at the end of the first trimester of pregnancy. Psychological outcomes were assessed by two psychologists and teachers 4 years later. Low maternal socio-economic status, smoking, high parity and short duration of breast feeding were associated with lower prevalence of folic acid supplement use. Verbal (b = 3.98, SE = 1.69), motor (b = 4.54, SE = 1.66) and verbal-executive function (b = 3.97, SE = 1.68) scores, social competence (b = 3.97, SE = 1.61) and inattention symptom [OR = 0.46; 95% CI 0.22, 0.95] scores were associated with reported folic acid use. Reported folic acid supplement use during pregnancy was associated with improved neurodevelopment in children after adjusting for a number of sociodemographic and behavioural factors. [ABSTRACT FROM AUTHOR]

[Display omitted] • A wide range of pre- and postnatal environmental exposures affects child behavior. • The exposome includes outdoor, indoor, chemical, lifestyle and social exposures. • Maternal tobacco smoke and car traffic increased behavioural problems in children. • Child sleep, healthy diet and higher family social capital reduced symptoms. • Child exposure to lead, copper, indoor air pollution, increased symptoms. Environmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior. We used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6–11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner's Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent's reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides. Our systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk. [ABSTRACT FROM AUTHOR]

Aim: The relation of longer duration of breast-feeding to cognitive development was been demonstrated in several previous studies, however its potential impact on behaviour is unknown. We assess which behavioural areas (executive function, social competence, attention behaviour and hyperactivity) are related to long-term breast-feeding in young children. Methods: Two prospective population-based birth cohorts, one from the island of Menorca (N = 421) and the second from Ribera d'Ebre county (N = 79) in Spain were followed up at the age of 4 years during a two year period (2001–2003). Children were assessed by three psychologists and their respective teachers for neuropsychological functions (McCarthy test), attention-hyperactivity behaviours (Attention-Deficit Hyperactivity Disorder Criteria of DSM-IV) and social behaviour (California Preschool Social Competence Scale). Results: Long-term breast-feeding was associated with executive function scores (an increase of 4.9 points after breast-feeding >20 weeks), and the improvement of social competence scores (relative risk for being in the poorest 20%, RR = 0.57; 0.52–0.66, after >12 weeks) and attention-deficit hyperactivity symptom scores (RR = 0.56; 0.37–0.85, after >12 weeks). All three outcomes remained significant when included as covariates in the regression models. Conclusion: Long-term breast-feeding was found to be associated with fewer attention and hyperactivity symptoms and an improvement in related behavioural areas (neuropsychological and socio-behavioural outcomes). [ABSTRACT FROM AUTHOR]

Chemical exposures often occur in mixtures and exposures during pregnancy may lead to adverse effects on the fetal brain, potentially reducing lower cognitive abilities and fine motor function of the child. We investigated the association of motheŕs exposure to a mixture of chemicals during pregnancy (i.e., organochlorine compounds, per- and polyfluoroalkyl substances, phenols, phthalates, organophosphate pesticides) with cognitive abilties and fine motor function in their children. We studied 1097 mother–child pairs from five European cohorts participating in the Human Early Life Exposome study (HELIX). Measurement of 26 biomarkers of exposure to chemicals was performed on urine or blood samples of pregnant women (mean age 31 years). Cognitive abilities and fine motor function were assessed in their children (mean age 8 years) with a battery of computerized tests administered in person (Raveńs Coloured Progressive Matrices, Attention Network Test, N-back Test, Trail Making Test, Finger Tapping Test). We estimated the joint effect of prenatal exposure to chemicals on cognitive abilities and fine motor function using the quantile-based g-computation method, adjusting for sociodemographic characteristics. A quartile increase in all the chemicals in the overall mixture was associated with worse fine motor function, specifically lower scores in the Finger Tapping Test [-8.5 points, 95 % confidence interval (CI) −13.6 to −3.4; −14.5 points, 95 % CI –22.4 to −6.6, and −18.0 points, 95 % CI −28.6 to −7.4) for the second, third and fourth quartile of the overal mixture, respectively, when compared to the first quartile]. Organochlorine compounds, phthalates, and per- and polyfluoroalkyl substances contributed most to this association. We did not find a relationship with cognitive abilities. We conclude that exposure to chemical mixtures during pregnancy may influence neurodevelopment, impacting fine motor function of the offspring. [ABSTRACT FROM AUTHOR]

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children's Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: − 1.27, 95% CI [− 2.22, − 0.32] / − 2.39, 95% CI [− 3.04, − 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: − 0.28, 95% CI [− 0.83, 0.27] / − 0.42, 95% CI [− 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children's later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication. [ABSTRACT FROM AUTHOR]

Summary: Background: Energy balance‐related behaviours (EBRBs), that is, dietary intake, screen, outdoor play and sleep, tend to combine into 'lifestyle patterns', with potential synergistic influences on health. To date, studies addressing this theme mainly focused on school children and rarely accounted for sleep, with a cross‐country perspective. Objectives: We aimed at comparing lifestyle patterns among preschool‐aged children across Europe, their associations with socio‐demographic factors and their links with body mass index (BMI). Methods: Harmonized data on 2–5‐year‐olds participating in nine European birth cohorts from the EU Child Cohort Network were used (EBRBs, socio‐demographics and anthropometrics). Principal component analysis and multivariable linear and logistic regressions were performed. Results: The most consistent pattern identified across cohorts was defined by at least three of the following EBRBs: discretionary consumption, high screen time, low outdoor play time and low sleep duration. Consistently, children from low‐income households and born to mothers with low education level had higher scores on this pattern compared to their socioeconomically advantaged counterparts. Furthermore, it was associated with higher BMI z‐scores in the Spanish and Italian cohorts (β = 0.06, 95% CI = [0.02; 0.10], both studies). Conclusion: These findings may be valuable in informing early multi‐behavioural interventions aimed at reducing social inequalities in health at a European scale. [ABSTRACT FROM AUTHOR]

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8–9 represent an alarm sign for presenting ADHD problems at ages 10–11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8–9) with the sleep items of the Child's Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner's Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10–11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10–1.19), 1.20 (1.14–1.26), 1.18 (1.11–1.25), and 1.18 (1.13–1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded. Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme. What is Known: • Sleep problems and Attention Deficit Hyperactivity Disorder (ADHD) are common problems during childhood and preadolescence, with prevalences of 20-40% and 3.0-7.5%, respectively. • Sleep problems are even more common in children with ADHD condition. What is New: • Sleep problems at ages 8-9 increased the risk of ADHD symptoms at ages 10-11. • This association remained strong even when considering child's previous (5 years) and concurrent (8-9 years) ADHD symptoms, and other clinical conditions, such as being born preterm or small for gestational age. [ABSTRACT FROM AUTHOR]

Background: Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to identify a childhood general health score and assess its association with a wide range of pre- and post-natal environmental exposures. Methods: The analysis is based on 870 children (6–12 years) from six European birth cohorts participating in the Human Early-Life Exposome project. A total of 53 prenatal and 105 childhood environmental factors were considered, including lifestyle, social, urban and chemical exposures. We built a general health score by averaging three sub-scores (cardiometabolic, respiratory/allergy and mental) built from 15 health parameters. By construct, a child with a low score has a low general health status. Penalized multivariable regression through Least Absolute Shrinkage and Selection Operator (LASSO) was fitted in order to identify exposures associated with the general health score. Findings: The results of LASSO show that a lower general health score was associated with maternal passive and active smoking during pregnancy and postnatal exposure to methylparaben, copper, indoor air pollutants, high intake of caffeinated drinks and few contacts with friends and family. Higher child's general health score was associated with prenatal exposure to a bluespace near residency and postnatal exposures to pets, cobalt, high intakes of vegetables and more physical activity. Against our hypotheses, postnatal exposure to organochlorine compounds and perfluorooctanoate were associated with a higher child's general health score. Conclusion: By using a general health score summarizing the child cardiometabolic, respiratory/allergy and mental health, this study reinforced previously suspected environmental factors associated with various child health parameters (e.g. tobacco, air pollutants) and identified new factors (e.g. pets, bluespace) warranting further investigations. [ABSTRACT FROM AUTHOR]

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 4–5 years 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 1 year of age using the Bayley Scales of Infant Development and at 4–5 years 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 30.3 μg/L, 9.4 μg/L, 11.6 μg/L, 10.5 μg/L, 2.7 μg/L, and 3.1 μg/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 4–5 years, 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 1 year did not persist at 4–5 years. Conclusions Minor associations observed between DBP exposure during gestation and child neuropsychological development at 1 year disappeared at 4–5 years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4–5 years, chance cannot be ruled out. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. OBJECTIVE: We investigated the association between prenatal and early-life exposures to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1- dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) and behaviors in children between 5 and 9 y of age. METHODS: In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother-child pairs from Greenland and Ukraine (n = 1,018), maternal serum PCB-153 and p,p'-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children's behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. RESULTS: The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p'-DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre- and postnatal p,p'-DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatalp,p'-DDE, respectively. CONCLUSION: Prenatal and early postnatal exposures to p,p'-DDE and PCB-153 were associated with a higher prevalence of abnormal scores for conduct and hyperactivity at 5-9 y of age in our study population. These findings provide further support for the importance of minimizing organochlorine exposures to young children and to women of childbearing age. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-23432-1, published online 01 December 2022 The original version of this Article contained errors in the spelling of the authors Josefa Canals-Sans and Silvia Fernandez-Barrés which were incorrectly given as Josefa Canals Sans and Silvia Fernandez-Bares. The correct affiliation is listed below: Nutrition and Mental Health Research Group (NUTRISAM), Rovira I Virgili University (URV), C/ Sant Llorenç 21, 43,201, Reus, Tarragona, Spain. [Extracted from the article]

The authors investigated the association of early-life exposure to indoor air pollution with neuropsychological development in preschoolers and assessed whether this association differs by glutathione-S-transferase gene (GSTP1) polymorphisms. A prospective, population-based birth cohort was set up in Menorca, Spain, in 1997–1999 (n = 482). Children were assessed for cognitive functioning (McCarthy Scales of Childrens Abilities) and attention-hyperactivity behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at age 4 years. During the first 3 months of life, information about gas appliances at home and indoor nitrogen dioxide concentration was collected at each participants home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding variant Ile105Val. Use of gas appliances was inversely associated with cognitive outcomes (β coefficient for general cognition = −5.10, 95% confidence interval (CI): −9.92, −0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14, 11.33), independent of social class and other confounders. Nitrogen dioxide concentrations were associated with cognitive function (a decrease of 0.27 point per 1 ppb, 95% CI: −0.48, −0.07) and inattention symptoms (odds ratio = 1.06, 95% CI: 1.01, 1.12). The deleterious effect of indoor pollution from gas appliances on neuropsychological outcomes was stronger in children with the GSTP1 Val-105 allele. Early-life exposure to air pollution from indoor gas appliances may be negatively associated with neuropsychological development through the first 4 years of life, particularly among genetically susceptible children. [ABSTRACT FROM AUTHOR]

Ingested inorganic arsenic (iAs) is a human carcinogen that is also linked to other adverse health effects, such as respiratory outcomes. Yet, among populations consuming low-arsenic drinking water, the impact of iAs exposure on childhood respiratory health is still uncertain. For a Spanish child study cohort (INfancia y Medio Ambiente—INMA), low-arsenic drinking water is usually available and ingestion of iAs from food is considered the major source of exposure. Here, we explored the association between iAs exposure and children's respiratory outcomes assessed at 4 and 7 years of age (n = 400). The summation of 4-year-old children's urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was used as a biomarker of iAs exposure (∑As) (median of 4.92 μg/L). Children's occurrence of asthma, eczema, sneeze, wheeze, and medication for asthma and wheeze at each assessment time point (i.e., 4- and 7-year) was assessed with maternal interviewer-led questionnaires. Crude and adjusted Poisson regression models using Generalized Estimating Equation (GEE) were performed to account for the association between natural logarithm transformed (ln) urinary ∑As in μg/L at 4 years and repeated assessments of respiratory symptoms at 4 and 7 years of age. The covariates included in the models were child sex, maternal smoking status, maternal level of education, sub-cohort, and children's consumption of vegetables, fruits, and fish/seafood. The GEE—splines function using Poisson regression showed an increased trend of the overall expected counts of respiratory symptoms with high urinary ∑As. The adjusted expected counts (95% confidence intervals) at ln-transformed urinary ∑As 1.57 (average concentration) and 4.00 (99th percentile concentration) were 0.63 (0.36, 1.10) and 1.33 (0.61, 2.89), respectively. These exploratory findings suggest that even relatively low-iAs exposure levels, relevant to the Spanish and other populations, may relate to an increased number of respiratory symptoms during childhood. [ABSTRACT FROM AUTHOR]

The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence. The study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms. The geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 μg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction. Despite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted. • The Spanish INMA cohort presented elevated prenatal exposure to Hg. • No relation was found between Hg and child behaviour from ages 4 to 11. • No influence of fish, fruit, and vegetable intake, sex or prenatal PCBs was observed. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between maternal sleep duration (an important health indicator) and neonate birth weight. Methods: The study included 2536 mother‐neonate pairs of a Spanish birth cohort (2004–2006, INMA project). The exposures were questionnaire‐based measures of sleep duration before and during pregnancy. The primary outcome was neonate birth weight score (g) standardized to 40 weeks of gestation. Results: In women sleeping for <7 h/day before pregnancy, each additional hour of sleep increased birth weight score by 44.7 g (P = 0.049) in the minimally adjusted model, although findings were not statistically significant after considering other potential confounders (P > 0.05). However, increasing sleep duration for the group of mothers who slept for more than 9 h/day decreased birth weight score by 39.2 g per additional hour (P = 0.001). Findings were similar after adjusting for several sociodemographic confounders and maternal depression‐anxiety clinical history as an intermediate factor. Similar but attenuated associations were observed with sleep duration in the second trimester of pregnancy. Conclusion: The relationship between maternal sleep duration before and during pregnancy and neonate birth weight is an inverse U‐shaped curve. Excessive sleep duration may adversely affect neonate health through its impact on birth weight. We found an inverse U‐shaped association between maternal sleep duration before and during pregnancy and neonate birth weight, using data from a large cohort study. [ABSTRACT FROM AUTHOR]

Exposure to highly elevated levels of cortisol has been linked with impairments in cognitive capacities in both children and adults. By contrast, moderate levels of cortisol may engender beneficial effects. The main aim of this study was to assess the association between child cortisol levels and neuropsychological development during the second year of life. A population-based birth cohort was established in the city of Sabadell (Catalonia, Spain) as part of the INMA (Environment and Childhood) Project. We assessed the cognitive and psychomotor development at the age of 14 months using the Bayley Scales of Infant Development (BSID). We included 302 children assessed during their second year of life for whom we had information on neuropsychological assessment and measurements of cortisol in saliva. Higher levels of cortisol were associated with better scores in BSID's mental scale. There was no association between cortisol levels and psychomotor test scores. We found a small positive association between duration of breastfeeding and child cortisol levels. This association was only found in boys. The results of this study suggest that moderate levels of cortisol in children could have small beneficial effects on their early neuropsychological development. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Previous studies identified some environmental and lifestyle factors independently associated with children respiratory health, but few focused on exposure mixture effects. This study aimed at identifying, in pregnancy and in childhood, combined urban and lifestyle environment profiles associated with respiratory health in children. This study is based on the European Human Early-Life Exposome (HELIX) project, combining six birth cohorts. Associations between profiles of pregnancy (38 exposures) and childhood (84 exposures) urban and lifestyle factors, identified by clustering analysis, and respiratory health were estimated by regression models adjusted for confounders. Among the 1033 included children (mean ± standard-deviation (SD) age: 8.2 ± 1.6 years old, 47% girls) the mean ± SD forced expiratory volume in 1s (FEV 1) and forced vital capacity (FVC) were 99 ± 13% and 101 ± 14%, respectively, and 12%, 12% and 24% reported ever-asthma, wheezing and rhinitis, respectively. Four profiles of pregnancy exposures and four profiles of childhood exposures were identified. Compared to the reference childhood exposure profile (low exposures), two exposure profiles were associated with lower levels of FEV 1. One profile was characterized by few natural spaces in the surroundings and high exposure to the built environment and road traffic. The second profile was characterized by high exposure to meteorological factors and low levels of all other exposures and was also associated with an increased risk of ever-asthma and wheezing. A pregnancy exposure profile characterized by high exposure levels to all risk factors, but a healthy maternal lifestyle, was associated with a lower risk of wheezing and rhinitis in children, compared to the reference pregnancy profile (low exposures). This comprehensive approach revealed pregnancy and childhood profiles of urban and lifestyle exposures associated with lung function and/or respiratory conditions in children. Our findings highlight the need to pursue the study of combined exposures to improve prevention strategies for multifactorial diseases such as asthma. [Display omitted] • Exposome studies call for association studies considering exposure mixture effects • Four pregnancy and four childhood exposure profiles were identified • A pregnancy exposure profile was associated with lower risk of wheezing and rhinitis • Two childhood exposure profiles were associated with lower levels of lung function [ABSTRACT FROM AUTHOR]

We aimed to investigate the association of attention-deficit hyperactivity disorder (ADHD) symptoms and social competence outcomes with cognitive status in preschool children. The study population was drawn from three birth cohorts belonging to the Spanish INMA ( Infancia y Medio Ambiente) project: Menorca ( n = 289), Ribera d'Ebre ( n = 60), and Granada ( n = 108). Children were assessed at the age of 4 years for cognitive functions (McCarthy Scales of Children's Abilities, MSCA) by psychologists and for inattention and hyperactivity symptoms (ADHD Criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ADHD-DSM-IV) and social competence (California Preschool Social Competence Scale) by their teachers. Multiple regression analyses were conducted to examine potential associations between behavioral outcomes (ADHD symptoms and social competence) and MSCA cognitive outcomes, adjusting for confounders. The presence of general ADHD symptoms (inattention, hyperactivity, or both) and poorer social competence both showed negative associations with cognitive outcomes. When we compared children according to ADHD subtypes, those with inattention symptoms alone and those with both inattention and hyperactivity symptoms showed significantly lower cognitive function scores in comparison to children with no ADHD symptoms. Behavioral dysfunctions in preschoolers may be associated with impairment of cognitive functions. [ABSTRACT FROM AUTHOR]

Objective: To analyse the relationship between maternal intakes of fish and other seafood during pregnancy and child neurodevelopment at age 4 years. Although pregnant women are advised to limit seafood intakes because of possible neurotoxin contamination, several studies suggest that overall maternal seafood intakes are associated with improved child neurodevelopment, perhaps because of higher DHA intakes. Design: The study uses data from a prospective birth cohort study. Maternal seafood intakes were assessed using a semi-quantitative FFQ administered shortly after delivery. Multivariate linear regression was used to estimate associations between seafood consumption and scores on the McCarthy Scales of Children's Abilities (MCSA). Analyses were stratified by breast-feeding duration as breast milk is a source of DHA during the postnatal phase of the brain growth spurt. Setting: Menorca, Spain, 1997-2001. Subjects: Full-term children (n 392) with data on maternal diet in pregnancy, breast-feeding duration and neurodevelopment at age 4 years. Results: Among children breast-fed for <6 months, maternal fish intakes of >2-3 times/week were associated with significantly higher scores on several MCSA subscales compared with intakes ≤1 time/week. There was no association among children breast-fed for longer periods. Maternal intakes of other seafood (shellfish/squid) were, however, inversely associated with scores on several subscales, regardless of breast-feeding duration. Conclusions: The study suggests that moderately high intakes of fish, but not other seafood, during pregnancy may be beneficial for neurodevelopment among children breast-fed for <6 months. Further research in other populations with high seafood intakes and data on additional potential confounders are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Mental disorders among children and adolescents pose a significant global challenge. The exposome framework covering the totality of internal, social and physical exposures over a lifetime provides opportunities to better understand the causes of and processes related to mental health, and cognitive functioning. The paper presents a conceptual framework on exposome, mental health, and cognitive development in children and adolescents, with potential mediating pathways, providing a possibility for interventions along the life course. The paper underscores the significance of adopting a child perspective to the exposome, acknowledging children's specific vulnerability, including differential exposures, susceptibility of effects and capacity to respond; their susceptibility during development and growth, highlighting neurodevelopmental processes from conception to young adulthood that are highly sensitive to external exposures. Further, critical periods when exposures may have significant effects on a child's development and future health are addressed. The paper stresses that children's behaviour, physiology, activity pattern and place for activities make them differently vulnerable to environmental pollutants, and calls for child-specific assessment methods, currently lacking within today's health frameworks. The importance of understanding the interplay between structure and agency is emphasized, where agency is guided by social structures and practices and vice-versa. An intersectional approach that acknowledges the interplay of social and physical exposures as well as a global and rural perspective on exposome is further pointed out. To advance the exposome field, interdisciplinary efforts that involve multiple scientific disciplines are crucial. By adopting a child perspective and incorporating an exposome approach, we can gain a comprehensive understanding of how exposures impact children's mental health and cognitive development leading to better outcomes. • Conceptual framework of a child perspective for the exposome and mental health. • Framework combines child development, life-course perspective and vulnerability. • Social practice theory integrates multiple exposures articulating relevant concepts. • Mediating pathways provides the base for interventions. • Framework based on interdisciplinary efforts for comprehensive understanding. [ABSTRACT FROM AUTHOR]

[Display omitted] • Outcome-wide analysis is a promising approach for the study of the exposome and its multiple effects on human health. • Advanced statistical multivariate techniques, well-suited for outcome-wide exposome analysis, have recently been developed. • An overview of methods for outcome-wide exposome analysis is provided along with guidelines and codes for their implementation. Outcome-wide analysis can offer several benefits, including increased power to detect weak signals and the ability to identify exposures with multiple effects on health, which may be good targets for preventive measures. Recently, advanced statistical multivariate techniques for outcome-wide analysis have been developed, but they have been rarely applied to exposome analysis. In this work, we provide an overview of a selection of methods that are well-suited for outcome-wide exposome analysis and are implemented in the R statistical software. Our work brings together six different methods presenting innovative solutions for typical problems arising from outcome-wide approaches in the context of the exposome, including dependencies among outcomes, high dimensionality, mixed-type outcomes, missing data records, and confounding effects. The identified methods can be grouped into four main categories: regularized multivariate regression techniques, multi-task learning approaches, dimensionality reduction approaches, and bayesian extensions of the multivariate regression framework. Here, we compare each technique presenting its main rationale, strengths, and limitations, and provide codes and guidelines for their application to exposome data. Additionally, we apply all selected methods to a real exposome dataset from the Human Early-Life Exposome (HELIX) project, demonstrating their suitability for exposome research. Although the choice of the best method will always depend on the challenges to be faced in each application, for an exposome-like analysis we find dimensionality reduction and bayesian methods such as reduced rank regression (RRR) or multivariate bayesian shrinkage priors (MBSP) particularly useful, given their ability to deal with critical issues such as collinearity, high-dimensionality, missing data or quantification of uncertainty. [ABSTRACT FROM AUTHOR]

Background The exposome approach can be a powerful tool for understanding the intertwining of social, physical, and internal influences that shape mental health and cognitive development throughout childhood. To distil conceptual models for subsequent analyses, the EU-funded project Early Environmental quality and Life-course mental health effects (Equal-Life) has conducted literature reviews on potential mediators linking the exposome to these outcomes. We report on a scoping review and a conceptual model of the role of restorative possibilities and physical activity. Methods Peer-reviewed studies published since the year 2000 in English, on the association between the exposome and mental health/cognition in children/adolescents, and quantitatively investigating restoration/restorative quality as a mediating variable were considered. Database searches were last updated in December 2022. We used an unstructured expert-driven approach to fill in gaps in the reviewed literature. Results Five records of three distinct studies were identified, indicating a scarcity of empirical evidence in this newly developing research area. Not only were these studies few in numbers, but also cross-sectional, lending only tentative support to the idea that perceived restorative quality of adolescent's living environment might mediate the association between greenspace and mental health. Physical activity emerged as a mediator leading to better psychological outcomes in restorative environments. We provide a critical discussion of potential caveats when investigating the restoration mechanism in children and propose a hierarchical model including restoration, physical activity, and relational dynamics between children and their environment, including social context, as well as restorative environments other than nature. Conclusions It is justified to further explore the role of restoration and physical activity as mediators in the association between early-life exposome and mental health/cognitive development. It is important to consider the child perspective and specific methodological caveats. Given the evolving conceptual definitions/operationalizations, Equal-Life will attempt to fill in a critical gap in the literature. • We report on a review of children/adolescent mental health/cognition. • This paper was produced in the Equal-Life exposome project. • We investigate restoration and physical activity as mechanistic pathways. • Limited body of evidence suggesting that exploring these mediators is justified. • We propose a conceptual model for empirical testing in the project. [ABSTRACT FROM AUTHOR]

Prenatal exposure to air pollutants including particulate matter (<2.5 μm of diameter,PM 2.5)and nitrogen dioxide (NO 2) has been identified as a potential risk factor for neuropsychological developmental and mental health disorders. This study aimed to analyze the associations between prenatal PM 2.5 and NO 2 exposure and cognitive functions in children at 4–6 years of age, including sex differences, and the modification effect of the duration predominant breastfeeding these associations. This study was conducted as part of the INMA project, a population-based birth cohort study in Spain (n = 1119). Each of the pregnant mothers was assigned a prenatal exposure to PM 2.5 and NO 2 for their whole pregnancy based on their place of residence. At the 4-6 year-old follow-up, infants' neuropsychological development was assessed using McCarthy scales: Verbal, Perceptive-Manipulative, Numeric, General Cognitive, Memory and Motor (gross and fine). Between 6 and 14 months of age, information concerning breastfeeding was gathered with a questionnaire. Regression analyses were performed to estimate the associations between exposure and outcomes, accounting for potential confounders. The analyses were stratified by child sex and breastfeeding duration. The majority of coefficients for the different cognitive domains were negative either for PM 2.5 and NO 2 , though none was statistically significant. After stratifying by sex, the associations become even more negative for boys, with some of the associations becoming statistically significant (memory both for PM 2.5 and NO 2), and global cognition and verbal for NO 2. Duration of predominant breastfeeding was not found to have a modifying effect. These findings suggest a sex-dependent effects on neuropsychological development at 4–6 years of age, with a greater vulnerability in boys, specifically in domains related to memory, verbal and general cognition. No modifying effect was observed for duration of predominant breastfeeding. • Air pollution exposure in pregnancy shows sex-dependent neuropsychological effects. • Boys show a greater vulnerability in cognitive functions. • Duration of breastfeeding did not modify the effect of air pollutants. [ABSTRACT FROM AUTHOR]

The aim of this study is to understand the association between prenatal, newborn and postnatal head circumference (HC) and preschool neurodevelopment in a large population-based birth cohort. The INMA project followed 1795 children from 12 weeks of pregnancy to preschool years. HC measurements were carried out prospectively, and following a standardized protocol during pregnancy (12, 20 and 34 weeks), birth, and child ages of 1-1.5 and 4 years old; and z-scores were further estimated. Prenatal head growth was assessed using conditional z-scores between weeks 12-20 and 20-34. Several neuropsychological tests [MSCA (cognition), CPT (attention)] and behavioral rating scales [DSM-IV-ADHD, CAST (autism), CPSCS (social competence)] were carried out during the last follow-up (5 years old). Multivariable models adjusted for family and child characteristics were applied to analyze associations between HC and neurodevelopment. In fully adjusted models, prenatal HC and head growth showed little or no associations with the neurodevelopment outcomes. Independent associations were observed between HC z-scores at birth, 1-1.5 years and 4 years and MSCA global cognitive scores and DSM-IV inattention symptoms. Specifically, z-score at birth was positively associated with general cognitive scores [β 1.22, 95% confidence interval (CI) 0.59, 1.85], and we observed a protective association with ADHD-DSM-IV total symptoms, mean ratio (MR) 0.85 (0.75, 0.96). Prenatal HC and head growth measurements gave little information about child cognitive abilities and behavior at preschool years. However, HC at birth and early childhood was positively associated with a range of neuropsychological outcomes, including protective associations with ADHD symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Median urinary iodine concentration (UIC) is used to describe the iodine status of a population. However, the link between UIC and iodine intake may vary during pregnancy. The aim of this study was to compare UIC during and after pregnancy, adjusting for factors that affect iodine intake.Methods: Two repeated measures of UIC and data on maternal iodine intake estimated through questionnaires were collected during pregnancy and 1-4 years after pregnancy in a subsample of women (n = 598) from a mother and child cohort study in Spain. Random-effects interval regression was used to assess the changes in UIC according to pregnancy status.Results: Median UIC was similar during (133 μg/L) and after pregnancy (139 μg/L). After adjusting for iodised salt, iodine supplement consumption, and socio-demographic related variables, UIC was 24.0% (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was maintained in a subsample of women with exhaustive information on diet (n = 291): 26.2%, 95% CI 10.3, 44.4.Conclusions: In an iodine sufficient area for the general population, iodine excretion was lower during than after pregnancy when factors affecting iodine intake were controlled for. Current recommendations of median UIC during pregnancy are based on the equivalence between iodine intake and UIC estimated from studies in non-pregnant populations, which might lead to overestimation of iodine deficiency during gestation. Further studies should evaluate the equivalence between iodine intake and its urinary excretion during pregnancy. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to identify factors associated with non-initiation and cessation of predominant breastfeeding (PBF) in a mother-child cohort from Spain. Materials and Methods The analysis included 2195 mother-infant from birth to 14 months post- delivery recruited between 2004 and 2008. Maternal characteristics were collected during the pregnancy. Lactation data were obtained at 6 and 14 months after delivery. PBF was defined as intake of breast milk plus liquids like juices or water. The PBF cessation was calculated using the date that women started PBF and the date that she reported to start giving infant formula and/or food. The relationship between maternal variables and PBF initiation and cessation was modeled using logistic and Cox proportional hazards regression analysis. Results The prevalence of PBF at hospital discharge was 85.3, 53.4% at 3 months, 46.1% at 4 months and 7.2% at 6 month. Only two women continued PBF at 12 months and none at 14 months. The initiating of PBF was associated with higher levels of maternal education, being a first-time mother and worked in a non-manual occupation. Higher level of physical activity, not smoking and having a healthy BMI, were also positively associated with PBF initiation. PBF cessation was higher in young, obese women, who had had complications during the pregnancy, and who had lower levels of education and smoked. The employment status of women, in week 32 of pregnancy and also in month 14 post-delivery, determined likelihood of PBF cessation. Conclusions Healthier habits and education positively influenced PBF initiation and duration. Decrease in PBF duration rates in Spain can be interpreted in part as a consequence of women returning to work. [ABSTRACT FROM AUTHOR]

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

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]

Background Urban residents may experience cognitive fatigue and little opportunity for mental restoration due to a lack of access to nature. Natural outdoor environments (NOE) are thought to be beneficial for cognitive functioning, but underlying mechanisms are not clear. Objectives To investigate the long-term association between NOE and cognitive function, and its potential mediators. Methods This cross-sectional study was based on adult participants of the Positive Health Effects of the Natural Outdoor Environment in Typical Populations in Different Regions in Europe (PHENOTYPE) project. Data were collected in Barcelona, Spain; Doetinchem, the Netherlands; and Stoke-on-Trent, United Kingdom. We assessed residential distance to NOE, residential surrounding greenness, perceived amount of neighborhood NOE, and engagement with NOE. Cognitive function was assessed with the Color Trails Test (CTT). Mediation analysis was undertaken following Baron and Kenny. Results Each 100 m increase in residential distance to NOE was associated with a longer CTT completion time of 1.50% (95% CI 0.13, 2.89). No associations were found for other NOE indicators and cognitive function. Neighborhood social cohesion was (marginally) significantly associated with both residential distance to NOE and CTT completion time, but no evidence for mediation was found. Nor were there indications for mediation by physical activity, social interaction with neighbors, loneliness, mental health, air pollution worries, or noise annoyance. Conclusions Our findings provide some indication that proximity to nature may benefit cognitive function. We could not establish which mechanisms may explain this relationship. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to traffic noise has been associated with adverse effects on neuro-psychological outcomes in children, but findings with regard to behavioral problems are inconsistent. OBJECTIVE: We investigated whether residential road traffic noise exposure is associated with behavioral problems in 7-year-old children. METHODS: We identified 46,940 children from the Danish National Birth Cohort with complete information on behavioral problems at 7 years of age and complete address history from conception to 7 years of age. Road traffic noise (Lden) was modeled at all present and historical addresses. Behavioral problems were assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Associations between pregnancy and childhood exposure to noise and behavioral problems were analyzed by multinomial or logistic regression and adjusted for potential confounders. RESULTS: A 10-dB increase in average time-weighted road traffic noise exposure from birth to 7 years of age was associated with a 7% increase (95% CI: 1.00, 1.14) in abnormal versus normal total difficulties scores; 5% (95% CI: 1.00, 1.10) and 9% (95% CI: 1.03, 1.18) increases in borderline and abnormal hyperactivity/inattention subscale scores, respectively; and 5% (95% CI: 0.98, 1.14) and 6% (95% CI: 0.99, 1.12) increases in abnormal conduct problem and peer relationship problem subscale scores, respectively. Exposure to road traffic noise during pregnancy was not associated with child behavioral problems at 7 years of age. CONCLUSIONS: Residential road traffic noise in early childhood may be associated with behavioral problems, particularly hyperactivity/inattention symptoms. [ABSTRACT FROM AUTHOR]

Background Bisphenol A (BPA) may be a neurodevelopmental toxicant, but evidence is not consistent in terms of the sex-specific patterns of the associations and the specific behavioral or cognitive domains most affected. Objective To examine the effects of prenatal BPA exposure on cognitive, psychomotor, and behavioral development in 438 children at 1, 4 and 7 years of age. Methods BPA was measured in spot urine samples collected in trimester 1 and 3 of pregnancy from women participating in the INMA-Sabadell birth cohort study. Cognitive and psychomotor development was assessed at 1 and 4 years using psychologist-based scales. Attention deficit hyperactivity disorder (ADHD) symptoms and other behavioral problems were assessed at 4 years by teachers and at 7 years by parents using questionnaire-based rating scales. Results Geometric mean creatinine-adjusted BPA concentration of the averaged samples was 2.6 μg/g creatinine. BPA exposure was not associated with the cognitive scores or their subscales at 1 and 4 years of age. At 1 year of age, exposure in the highest tertile of BPA concentrations was associated with a reduction of psychomotor scores (T3 vs T1 β =−4.28 points, 95% CI: −8.15, −0.41), but there was no association with psychomotor outcomes at 4 years. At 4 years, BPA exposure was associated with an increased risk of ADHD-hyperactivity symptoms (Incidence Rate Ratio (IRR) per log 10 μg BPA/g creatinine increase=1.72; 1.08, 2.73) and this association was stronger in boys than in girls. Further, boys had an increased risk of ADHD-inattention symptoms whereas girls showed a reduced risk ( p for interaction <0.1). At 7 years, these associations were not statistically significant nor were any other behavioral problems. Conclusions These results suggest that prenatal BPA exposure does not affect cognitive development up to age 4 years. Associations are observed with psychomotor development and ADHD-related symptoms at early ages, but these do not appear to persist until later ages. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. Methods The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. Results The geometric means of TSH, TT3, FT4 and mercury were 1.1 μU/L, 2.4 nmol/L, 10.5 pmol/L and 7.7 μg/L, respectively. Mercury levels were marginally significantly associated with TT3 ( β : −0.05; 95%CI: −0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (−0.08; 95%CI: −0.15, −0.02, interaction p -value=0.07). The association with FT4 followed the same pattern, albeit not significant. Conclusion Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed. [ABSTRACT FROM AUTHOR]

Background: Green spaces have been associated with improved mental health in children; however, available epidemiological evidence on their impact on child behavioral development is scarce. Objectives: We investigated the impact of contact with green spaces and blue spaces (beaches) on indicators of behavioral development and symptoms of attention deficit/hyperactivity disorder (ADHD) in schoolchildren. Methods: This study was based on a sample of 2,111 schoolchildren (7–10 years of age) from 36 schools in Barcelona in 2012. We obtained data on time spent in green spaces and beaches and Strengths and Difficulties Questionnaires (SDQ) from parents, and ADHD/DSM-IV questionnaires from teachers. Surrounding greenness was abstracted as the average Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, and 500 m around each home address. Proximity to green spaces was defined as living within 300 m of a major green space (≥ 0.05 km2). We applied quasi-Poisson mixed-effects models (with school random effect) to separately estimate associations between indicators of contact with green spaces and SDQ and ADHD total and subscale scores. Results: We generally estimated beneficial associations between behavioral indicators and longer time spent in green spaces and beaches, and with residential surrounding greenness. Specifically, we found statistically significant inverse associations between green space playing time and SDQ total difficulties, emotional symptoms, and peer relationship problems; between residential surrounding greenness and SDQ total difficulties and hyperactivity/inattention and ADHD/DSM-IV total and inattention scores; and between annual beach attendance and SDQ total difficulties, peer relationship problems, and prosocial behavior. For proximity to major green spaces, the results were not conclusive. Conclusion: Our findings support beneficial impacts of contact with green and blue spaces on behavioral development in schoolchildren. [ABSTRACT FROM AUTHOR]

Highlights: [•] Concentrations of seven metals (cobalt, copper, arsenic, cadmium, antimony, thallium and lead) were measured at 1st and 3rd trimester of pregnancy. [•] No statistically significant associations were found between metals and general cognitive scale or executive function of the MSCA. [•] Prenatal exposure to metals was not associated to ADHD symptomatology at the age of 4 years. [Copyright &y& Elsevier]

Iodine supplementation during pregnancy is a common practice in developed countries. However, scant evidence is available regarding the safety and effectiveness of maternal iodine supplementation with regard to child neuropsychological development. We previously reported an inverse association between iodine supplementation and the psychomotor development of infants in a birth cohort from Valencia, Spain. In the present study, we assessed this association in a wider sample of mother and child pairs from 3 other regions in Spain. Neuropsychological development was assessed using the Bayley Scales of Infant Development in 1,519 infants (median age, 16 months) between 2006 and 2009. In multivariate analyses, maternal consumption of 150 μg/day or more of iodine from supplements was related to a 1.5-fold increase in the odds of a psychomotor score less than 85 (95% confidence interval: 0.8, 2.9) and to a 1.7-fold increase in the odds of a mental score less than 85 (95% confidence interval: 0.9, 3.0). Findings previously reported in the Valencia cohort were only partially verified. The results of the present study suggest that, at least in these regions, iodine supplementation does not improve infant neuropsychological development at 1 year of age. Further research is needed on the risks and benefits of supplementary iodine for both maternal thyroid function and child neurodevelopment. [ABSTRACT FROM AUTHOR]

Abstract: Polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), and dichlorodiphenyl dichloroethylene (pp′DDE) are persistent, bioaccumulative, and toxic environmental pollutants with potential neurotoxic effects. Despite a growing body of studies investigating the health effects associated with these compounds, their specific effects on early neuropsychological development remain unclear. We investigated such neuropsychological effects in a population-based birth cohort based in three regions in Spain (Sabadell, Gipuzkoa, and Valencia) derived from the INMA [Environment and Childhood] Project. The main analyses in this report were based on 1391 mother–child pairs with complete information on maternal levels of organochlorine compounds and child neuropsychological assessment (Bayley Scales of Infant Development) at age 14months. We found that prenatal PCB exposure, particularly to congeners 138 and 153, resulted in impairment of psychomotor development (coefficient=−1.24, 95% confidence interval=−2.41, −0.07), but found no evidence for effects on cognitive development. Prenatal exposure to pp′DDE or HCB was not associated with early neuropsychological development. The negative effects of exposure to PCBs on early psychomotor development suggest that the potential neurotoxic effects of these compounds may be evident even at low doses. [Copyright &y& Elsevier]

Abstract: Polychlorinated biphenyls (PCB) are synthetic organochlorine compounds with potential neurotoxic effects. Although negative effects on neuropsychological development have been observed in previous studies on PCB exposure, there are inconsistencies in these effects at current exposure levels of these compounds which are much lower than for previous generations. This study aimed to disentangle the effects of prenatal and postnatal PCB exposure on neuropsychological development at 4years of age. This study is based on a population-based birth cohort design established in Menorca (Spain) as part of the INMA [Environment and Childhood] Project. We assessed general neuropsychological development using the McCarthy Scales of Children''s Abilities (MCSA). A total of 422 4-year old children were assessed with the MCSA. Levels of PCBs were measured in cord blood (n=405) and in blood samples taken at 4years (n=285). We found no statistically significant effects of the sum of prenatal PCBs on MCSA scores. Nevertheless, individual congener analyses yielded significant detrimental effects of prenatal PCB153 on the majority of MCSA scores, while no effects were reported for other congeners. The levels of PCBs at 4years of age were not associated with neuropsychological development. Thus, prenatal exposure to low-level concentrations of PCBs, particularly PCB153, was associated with an overall deleterious effect on neuropsychological development at 4years of age, including negative effects on executive function, verbal functions and visuospatial abilities, but not on motor development. [Copyright &y& Elsevier]

Prenatal and early-life exposures can affect the course of children's neuropsychological development well into pre-adolescence, given the vulnerability of the developing brain. However, it is unknown which socio-environmental factors at early childhood can influence specific cognitive processes like attention at a later age. In this study, we aim to determine social and environmental exposures in early childhood that may be associated with attention function of 11-year-olds. We measured attention function using the continuous performance test-II (CPT-II) on 393 11-year old children from the Menorca's birth-cohort within the INMA-project (Spain), and pre-selected a list of socio-environmental observations taken when they were up to 4 years of age. We found that earlier socio-environmental characteristics, such as parental social class, educational level and maternal mental health are associated with later inattentive and impulsive symptomatology through a higher rate of omission and commission errors. In addition, omission errors were higher in children with atopy and lower in those whose mothers took dietary supplementation with folic acid and vitamins during pregnancy. Breastfeeding played a protective role against commission errors, while higher DDE and PCBs levels at age 4 were associated with slow speed response. Our findings suggest that a number of life socio-environmental factors during prenatal life and early childhood, such as socio-demographic characteristics, breastfeeding, maternal nutritional supplementation with folic acid and vitamins and exposure to some organochlorine compounds may influence inattentive and hyperactive/impulsive symptomatology during pre-adolescence. [Copyright &y& Elsevier]