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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]

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]

Green spaces may have beneficial impacts on children's cognition. However, few studies explored the exposure to green spaces beyond residential areas, and their availability, accessibility and uses at the same time. The aim of the present study was to describe patterns of availability, accessibility, and uses of green spaces among primary school children and to explore how these exposure dimensions are associated with cognitive development. Exposures to green space near home, school, commuting route, and other daily activity locations were assessed for 1607 children aged 6–11 years from six birth cohorts across Europe, and included variables related to: availability (NDVI buffers: 100, 300, 500 m), potential accessibility (proximity to a major green space: linear distance; within 300 m), and use (play time in green spaces: hours/year), and the number of visits to green spaces (times/previous week). Cognition measured as fluid intelligence, inattention, and working memory was assessed by computerized tests. We performed multiple linear regression analyses on pooled and imputed data adjusted for individual and area-level confounders. Availability, accessibility, and uses of green spaces showed a social gradient that was unfavorable in more vulnerable socioeconomic groups. NDVI was associated with more playing time in green spaces, but proximity to a major green space was not. Associations between green space exposures and cognitive function outcomes were not statistically significant in our overall study population. Stratification by socioeconomic variables showed that living within 300 m of a major green space was associated with improved working memory only in children in less deprived residential areas (β = 0.30, CI: 0.09,0.51), and that more time playing in green spaces was associated with better working memory only in children of highly educated mothers (β per IQR increase in hour/year = 0.10; 95% CI: 0.01, 0.19). However, studying within 300 m of a major green space increased inattention scores in children in more deprived areas (β = 15.45, 95% CI: 3.50, 27.40). [Display omitted] • Green space availability, accessibility and use are unequal across socioeconomic groups. • Availability more than accessibility seems to foster play time in green spaces. • Accessibility improved working memory in children of higher socioeconomic areas. • Play time in green spaces improved working memory in children of higher educated mothers. • Accessibility increased inattention in children studying in more deprived areas. [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]

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: Prospective longitudinal studies are essential in characterizing cognitive trajectories, yet few of them have been reported on the development of attention processes in children. We aimed to explore attention development in normal children and children with attention deficit and hyperactivity disorder (ADHD) symptoms in a repeated measures design using the attention network test (ANT). Methods: The population sample included 2,835 children (49.6% girls) aged 7-11 years from 39 schools in Barcelona (Catalonia, Spain) who performed the ANT four times from January 2012 to March 2013. According to teacher ratings, 10.5% of the children presented ADHD symptoms. We performed multilevel mixed-effects linear regression models, adjusting for school and individual, to test the effects of age-related growth on the ANT networks: alerting, orienting and executive attention, and three measurements related to attentiveness: median of hit reaction time (HRT), hit reaction time standard error (HRT-SE) and variability. Results: We observed age-related growth in all the outcomes, except orienting. The curves were steeper at the younger groups, although for alertness the improvement was further at the oldest ages. Gender and ADHD symptoms interacted with age in executive attention, HRT and variability. Girls performed better in executive attention at young ages although boys reached females at around 10 years of age. For HRT, males showed faster HRT. However, girls had a more pronounced improvement and reached the levels of boys at age 11. Children with ADHD symptoms had significant differences in executive attention, HRT and variability compared to children without ADHD symptoms. Conclusions: We detected an ongoing development of some aspects of attention in primary school children, differentiating patterns by gender and ADHD symptoms. Our findings support the ANT for assessing attention processes in children in large epidemiological studies. [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: 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]

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]

Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child's neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children's Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings. [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]

[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]

Objective: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age.Study Design: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates.Results: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria.Conclusions: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring. [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 Air pollution from traffic has been associated with cardiorespiratory diseases in children and adults, but there is little information on its potential neurotoxic effects. This study aimed to investigate the association between exposure to nitrogen dioxide (NO2), as a marker of traffic-related air pollution, and cognitive development in children. Methods A population-based birth cohort from southern Spain was followed from the age of 4 years for 1 year. Complete data for analyses were gathered on 210 children living in urban and rural areas. NO2 exposure was predicted by means of land use regression models. A standardised version of the McCarthy Scales of Children's Abilities (MSCA) was used to assess children's motor and cognitive abilities. Multivariate analyses were performed to evaluate the relation between exposure to NO2 and MSCA outcomes, adjusting for potential confounders. Results A negative effect of NO2 was found across all MSCA subscales, despite low predicted NO2 exposure levels (5-36μm3). Children exposed to higher NO2 (>24.75μg/m3) showed a decrease of 4.19 points in the general cognitive score and decreases of 6.71, 7.37 and 8.61 points in quantitative, working memory and gross motor areas, respectively. However, except for gross motor function, associations were not statistically significant. Conclusion Although results were not statistically significant, the associations found between exposure to NO2 and cognitive functions suggest that traffic-related air pollution may have an adverse effect on neurodevelopment, especially early in life, even at low exposure levels. [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]

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]