Hair cortisol determinants in 11-year-old children: Environmental, social and individual factors.

INTRODUCTION: Children's exposure to chronic stress is associated with several health problems. Measuring hair cortisol concentration is particularly useful for studying chronic stress but much is unknown about hair cortisol determinants in children and adolescents, and previous research has often not considered the simultaneous exposure of multiple variables. This research is focused on investigating the relationship between environmental, social and individual factors with hair cortisol concentration in children. METHODS: The data used in this study are from the INMA prospective epidemiological cohort study. The assessment of chronic stress was made on the basis of hair samples taken at the age of 11 years in the INMA-Gipuzkoa cohort (n = 346). A metamodel summarizing the hypothesized relationships among environmental, social and individual factors and hair cortisol concentration was constructed based on previous literature. Structural Equation Modelling was performed to examine the relationships among the variables. RESULTS: In the general model higher behavioural problems were associated with higher cortisol levels and an inverse relationship between environmental noise and cortisol levels was observed, explaining 5 % of the variance in HCC. Once stratified by sex these associations were only hold in boys, while no significant effect of any of the study variables was related with cortisol levels in girls. Importantly, maternal stress was positively related to behavioural difficulties in children. Finally, higher traffic-related air pollution and lower exposure to neighborhood greenness were related to higher environmental noise. DISCUSSION: This study highlights that simultaneous exposure to different environmental, social and individual characteristics may determine the concentration of hair cortisol. More research is needed and future studies should include this complex view to better understanding of hair cortisol determinants in children.

Do Hormone Levels Influence Bullying during Childhood and Adolescence? A Systematic Review of the Literature.

(1) Background: Bullying is one of the most common forms of aggressive behavior during childhood and adolescence. Some decades ago, researchers began exploring the basis of peer victimization from a biological perspective. Specifically, the Hypothalamic-Pituitary-Adrenal (HPA) and Hypothalamic-Pituitary-Gonadal (HPG) axes have been studied in relation to status-relevant behaviors, such as bullying. (2) Methods: We conducted a systematic review following the PRISMA guide and registered the review protocol at PROSPERO (CRD42023494738). We searched for relevant studies in PubMed, Psycinfo, Scopus, and Web of Science, and assessed them using the Robins E-tool. (3) Results: Our search yielded 152 studies, of which 33 were included in the review. These studies explored the association between testosterone and cortisol levels with bullying behavior, finding diverse results. Most of the studies were rated as having a low risk of bias. (4) Conclusions: This study not only enhances our understanding of bullying, but also provides guidance for the development of prevention and management programs for it. In the future, researchers should continue exploring the joint effects of different hormones on the HPA and HPG axis, using a broader set of biomarkers.

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.

We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 µg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

Association of maternal prenatal urinary fluoride levels with ADHD symptoms in childhood.

BACKGROUND: Health concerns about the potential impact of exposure to fluoride via drinking water (DW) on neuropsychological development include behavioral outcomes such as ADHD. OBJECTIVE: We aimed to examine the association between prenatal maternal urinary fluoride and symptoms associated with attention-deficit/hyperactivity disorder (ADHD) at the age of 8 and 11 years. METHOD: Data from 255 to 236 mother-child pairs from the "Infancia y Medio Ambiente" (INMA) birth cohort (Gipuzkoa; Spain) with maternal urinary F adjusted for creatinine (MUFcr) during pregnancy (first and third trimester) and child assessments of ADHD-like symptoms reported by Conners' Rating Scales-Revised at age of 8 and 11 years was available. Clinical approach was also used: cut off criteria (T > 66). Multiple linear regression models were fitted when outcomes were analyzed as continuous, and logistic regression models when the outcomes were analyzed with a categorical clinical approach. Covariates related to maternal characteristics, birth outcomes, childhood, quality of family context and biomarkers of neuro-toxicants were used. RESULTS: No association was found between MUFcr levels during pregnancy and cognitive problems-inattention, hyperactivity or ADHD index score of symptoms at 8 or 11 years. When results were analyzed from the perspective of a clinical approach, at the age of 11 years, there were significant inverse association between MUFcr and being categorized as a cognitive problems-inattention case. ORs were also indicative of a lower risk, although not significant, for ADHD index at age 11. Sensitivity analyses, taking into consideration quality of family context or the levels of other toxicants during pregnancy showed similar results. CONCLUSIONS: Higher levels of MUFcr in pregnant women were associated with a lower risk of cognitive problems-inattention at 11 years. These findings are inconsistent with those from previous studies and indicate the need for other population-based studies to confirm or overturn these results.

Hair cortisol as a biomarker of chronic stress in preadolescents: influence of school context and bullying.

Bullying has been identified as the most common form of aggression and a major source of stress among children and adolescents. The main objective of this study was to analyze the association that school context in general and bullying in particular might have with hair cortisol concentration (HCC), examining the effect of executive function and sex on this association. The study included 659 11-year-old preadolescents from the cohorts of Gipuzkoa and Sabadell of the INMA (INfancia y Medio Ambiente-Children and Environment) project. We gathered information about school-related factors (bullying, school environment, problems with peers and academic performance) and executive function (risky decision-making). Hair samples were collected to measure cortisol concentrations and Structural Equation Modeling was used to examine associations between school-related factors, executive function and HCC. Results showed that being involved as a bully/victim was related to higher HCC and, higher HCC was associated with poorer executive function. This study may contribute to a better understanding of the consequences that chronic exposure to a stressful factors may have on preadolescents' health and developmental outcomes. Besides, our results are relevant for designing programs for prevention and intervention, which could modify individual physiological responses to stress and reduce the effects of stress on the health.

Children who sleep more may have longer telomeres: evidence from a longitudinal population study in Spain.

BACKGROUND: Inadequate sleep duration has been suggested as a chronic stressor associated with changes in telomere length (TL). This study aimed to explore the association between sleep duration and TL using the INMA birth cohort study data. METHODS: A total of 1014 children were included in this study (cross-sectional: 686; longitudinal: 872). Sleep duration (h/day) was reported by caregivers at 4 years and classified into tertiles (7-10 h/day; >10-11 h/day; >11-14 h/day). Leucocyte TL at 4 and 7-9 years were measured using quantitative PCR methods. Multiple robust linear regression models, through log-level regression models, were used to report the % of difference among tertiles of sleep duration. RESULTS: In comparison to children who slept between >10 and 11 h/day, those in the highest category (more than 11 h/day) had 8.5% (95% CI: 3.56-13.6) longer telomeres at 4 years. Longitudinal analysis showed no significant association between sleep duration at 4 years and TL at 7-9 years. CONCLUSION: Children who slept more hours per day had longer TL at 4 years independently of a wide range of confounder factors. Environmental conditions, such as sleep duration, might have a major impact on TL during the first years of life. IMPACT: Telomere length was longer in children with longer sleep duration (>11 h/day) independently of a wide range of confounder factors at age 4 and remained consistent by sex. Sleep routines are encouraged to promote positive child development, like the number of hours of sleep duration. Considering the complex biology of telomere length, future studies still need to elucidate which biological pathways might explain the association between sleep duration and telomere length.

Do prepubertal hormones, 2D:4D index and psychosocial context jointly explain 11-year-old preadolescents' involvement in bullying?

BACKGROUND: Bullying is a type of aggressive behavior that occurs repeatedly and intentionally in school environments and where there is a power imbalance. The main objective of this study was to analyze the association that hormones and the psychosocial context jointly have with bullying behavior. METHOD: Participants were 302 11-year-old preadolescents from the Gipuzkoan cohort of the INMA Project. Bullying was assessed using the Olweus Bully/victim Questionnaire. Prenatal sexual hormones were assessed by calculating 2D:4D ratio and in order to measure prepubertal testosterone and cortisol levels saliva samples were collected within a week of each other. Additionally, various psychosocial factors were evaluated: executive function, family context, school environment and social context. To analyze our complex hypothesis, six metamodels were tested using structural equation modeling. RESULTS: In relation to victims, results showed that victimization was related to worse school environment' perception in boys, and higher stress and conflict in the family in girls. In the case of their involvement in bullying as a bully, lower salivary cortisol levels, worse school environment' perception and lower peers and social support was related to being more frequently involved as a bully in boys, while having more family stress and conflict was related with being a bully in girls. CONCLUSIONS: This approach makes it possible not only to explore the different biological and psychosocial factors affect bullying behavior, but also to explore associations between the predictor variables.

Urban environment and cognitive and motor function in children from four European birth cohorts.

BACKGROUND: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. METHODS: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-exposure models using the Deletion-Substitution-Addition algorithm. RESULTS: Higher greenness exposure within 300 m during pregnancy was associated with higher verbal abilities (1.5 points (95% confidence interval 0.4, 2.7) per 0.20 unit increase in greenness). Higher connectivity density within 100 m and land use diversity during pregnancy were related to lower verbal abilities. Childhood exposure to PM2.5 mediated 74% of the association between greenness during childhood and verbal abilities. Higher exposure to PM2.5 during pregnancy was related to lower fine motor function (-1.2 points (-2.1, -0.4) per 3.2 µg/m3 increase in PM2.5). No associations were found with non-verbal abilities and gross motor function. DISCUSSION: This study suggests that built environment, greenness, and air pollution may impact child cognitive and motor function at five years old. This study adds evidence that well-designed urban planning may benefit children's cognitive and motor development.

Is Brief Exposure to Green Space in School the Best Option to Improve Attention in Children?

The positive effects of Green Spaces on health are thought to be achieved through the mechanisms of mitigation, instoration and restoration. One of the benefits of Green Spaces may be the restoration of attention and so the objective of this research is testing empirically whether exposure to a green environment improves attention in school children. For so doing, we first used a split-unit statistical design in each of four schools, then combined the primary results via meta-analysis. The Attention Network Test (ANT) was used to measure attention before and after exposure and a total of 167 seven-year-old students participated in the experiments. Overall, our experimental results do not support the hypothesis that students' exposure to activities in green vs. grey spaces affected their performance in ANT. This was so despite the fact that neither age nor gender biases have been detected and despite that our experiments have been proved to be sufficiently statistically powerful. It would be advisable to consider air pollution and noise. We also recommend that participants attend the experiment with mental exhaustion to maximize the ability to detect significant changes.

Correction: Santa-Marina et al. Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA-INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study. Int. J. Environ. Res. Public Health 2020, 17, 7704.

In the original article [...].

Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

Prenatal manganese serum levels and neurodevelopment at 4 years of age.

BACKGROUND: The excess of manganese (Mn) causes severe deleterious effects in the central nervous system, and the developing brain is especially sensitive to Mn overload. However, results of prospective studies regarding Mn neurodevelopmental effects remain inconclusive. The present study aims at studying the association of prenatal Mn exposure and neurodevelopment at 4-5 years of age. METHODS: Mn serum concentration was measured in 1465 pregnant women from the INMA (INfancia y MedioAmbiente, Environment and Childhood) Project. Neurodevelopment was assessed using a standardized version of the McCarthy Scales of Children's Abilities (MSCA). Multivariate regression models were used for data analysis. RESULTS: No association was found between Mn levels in serum and any of the McCarthy scales. However, the stratification by sex showed a positive and beneficial association of prenatal Mn levels and the verbal, quantitative and general-cognitive scales in girls (ß (95%CI): 4 (0.03, 7.96), 4.5 (0.43, 8.57) and 4.32 (0.6, 8.05), respectively). CONCLUSIONS: A beneficial association was found for the first time between prenatal Mn levels measured in serum and neurodevelopment of female offspring at 4 years of age, which could have implications on public health policies, specifically on the establishment of policies promoting prenatal health related to dietary deficits of micronutrients such as Mn.

Prenatal perfluoroalkyl substance exposure and neuropsychological development throughout childhood: The INMA Project.

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

Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA-INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study.

Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children's ADHD-like symptoms at ages 4-5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, ß = -0.19 (-0.32, -0.07), for boys. Comparing ferritin level by tertiles, significant differences were observed between the first tertile ([1.98, 20.92]) and the second ([20.92, 38.79]) and third tertiles ([38.79, 216.5]) (mg/L).The number of symptoms was lower for those in the third tertile, ß = -0.3 (-0.55, -0.5), and for those in the second one, ß = -0.37 (-0.6, -0.14). The model stratification by sex also showed this inverse association for boys only, ß = -0.21 (-0.34, -0.08). No associations were found between ferritin level and hyperactivity or total ADHD symptoms. High ferritin levels during pregnancy show a protective association with child inattentive-type ADHD symptoms.

Risk and Protective Factors for Bullying at 11 Years of Age in a Spanish Birth Cohort Study.

(1) Background: Bullying affects a large number of children worldwide. This study has two objectives, to provide data on the prevalence of bullying in Spain, and to identify risk and protective factors associated with bullying. (2) Methods: Participants were 858 eleven-year-old children. Bullying was assessed using a short version of the Olweus Bully Victim Questionnaire, and the following data were gathered to explore potential predictors: individual (inattention, behavior problems, attention deficit hyperactivity disorder symptomatology, traumatic life events), family-related (sociodemographic characteristics, family context, child-parent relations), school-related (school characteristics, peer and social support, school environment) and community-related data. (3) Results: 9.3% of the children were victims, 1.4% bullies and 1.6% bully-victims. Results showed that a higher level of attention deficit hyperactivity disorder symptomatology increased the risk of victimization, whereas having better relationships with parents and stronger social support were associated with a lower risk of victimization. Children having strong peer relationships and social support was also associated with less risk of perpetrating bullying. Finally, having behavior problems at 8 years of age was associated with being a bully-victim. (4) Conclusions: The findings emphasize the importance of studying all bullying predictors together, regarding three of the roles children may take in bullying situations.

Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies.

INTRODUCTION: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. OBJECTIVE: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. METHODS: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. RESULTS: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. CONCLUSION: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444.

Prenatal Manganese Exposure and Long-Term Neuropsychological Development at 4 Years of Age in a Population-Based Birth Cohort.

Background: Manganese (Mn) is an essential micronutrient for humans, the diet being the main source of exposure. Some epidemiological studies describe a negative association between prenatal Mn and later neuropsychological development, but results are inconsistent. The aim of this study was to explore the association between prenatal Mn exposure and neuropsychological development assessed at 4 years of age. Methods: Study subjects were 304 mother-child pairs from the Gipuzkoa cohort of the INMA (Environment and Childhood) Project. Mn was measured in newborns' hair. Children's neuropsychological development was assessed at 4 years of age using the McCarthy Scales of Children's Abilities. Multivariate linear regression models were built. Stratified analysis by sex was performed. Generalized additive models were used to assess the shape of the relation. Results: The median Mn concentration in newborns' hair was 0.42 µg/g (95% CI = 0.38, 0.46). The association between Mn levels and the neuropsychological development was not statistically significant for the general cognitive scale (ß [95% CI] = 0.36 [-5.23, 5.95]), motor scale (ß [95% CI] = 1.9 [-3.74, 7.55]) or any of the other outcomes. No sex-specific pattern was found. The best shape describing the relationship was linear for all the scales. Conclusion: Our results suggest that prenatal Mn concentrations measured in newborns' hair do not affect cognitive or motor development at 4 years of age in boys or in girls at the observed Mn levels.

Postnatal exposure to mercury and neuropsychological development among preschooler children.

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

Prenatal exposure to PM2.5 and NO2 and sex-dependent infant cognitive and motor development.

BACKGROUND: Prenatal exposure to air pollutants including particulate matter (<2.5 µm of diameter,PM2.5)and nitrogen dioxide (NO2) has been identified as a potential risk factor for neuropsychological developmental and mental health disorders. OBJECTIVE: This study aimed to analyze the associations between prenatal PM2.5 and NO2 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. DESIGN: 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 PM2.5 and NO2 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. RESULTS: The majority of coefficients for the different cognitive domains were negative either for PM2.5 and NO2, 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 PM2.5 and NO2), and global cognition and verbal for NO2. Duration of predominant breastfeeding was not found to have a modifying effect. CONCLUSIONS: 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 During Pregnancy and Symptoms of Attention Deficit and Hyperactivity Disorder in Children in Europe.

BACKGROUND: Exposure to air pollution during pregnancy may increase attention-deficit/hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs. METHODS: Air pollution concentrations (nitrogen dioxide [NO2] and particulate matter [PM]) were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified children as having ADHD symptoms within the borderline/clinical range and within the clinical range using validated cutoffs. We combined all adjusted area-specific effect estimates using random-effects meta-analysis and multiple imputations and applied inverse probability-weighting methods to correct for loss to follow-up. RESULTS: We classified a total of 2,801 children as having ADHD symptoms within the borderline/clinical range, and 1,590 within the clinical range. Exposure to air pollution during pregnancy was not associated with a higher odds of ADHD symptoms within the borderline/clinical range (e.g., adjusted odds ratio [OR] for ADHD symptoms of 0.95, 95% confidence interval [CI] = 0.89, 1.01 per 10 µg/m increase in NO2 and 0.98, 95% CI = 0.80, 1.19 per 5 µg/m increase in PM2.5). We observed similar associations for ADHD within the clinical range. CONCLUSIONS: There was no evidence for an increase in risk of ADHD symptoms with increasing prenatal air pollution levels in children aged 3-10 years. See video abstract at, http://links.lww.com/EDE/B379.