Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts.

BACKGROUND: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). OBJECTIVES: We investigated associations between urban environment exposures during pregnancy and PPD. METHODS: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686-30,716 depending on exposure; representing 26-46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3-18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. RESULTS: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results. DISCUSSION: The study findings suggest that exposure to PM10, road traffic noise and blue spaces in pregnancy may increase PPD risk, however future studies should explore this causally.

Short-term effects of air pollution and weather on physical activity in patients with chronic obstructive pulmonary disease (COPD).

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) accumulate low levels of physical activity. How environmental factors affect their physical activity in the short-term is uncertain. AIM: to assess the short-term effects of air pollution and weather on physical activity levels in COPD patients. METHODS: This multi-center panel study assessed 408 COPD patients from Catalonia (Spain). Daily physical activity (i.e., steps, time in moderate-to-vigorous physical activity (MVPA), locomotion intensity, and sedentary time) was recorded in two 7-day periods, one year apart, using the Dynaport MoveMonitor. Air pollution (nitrogen dioxide (NO2), particulate matter below 10 µm (PM10) and a marker of black carbon (absorbance of PM2.5: PM2.5ABS), and weather (average and maximum temperature, and rainfall) were estimated the same day (lag zero) and up to 5 days prior to each assessment (lags 1-5). Mixed-effect distributed lag linear regression models were adjusted for age, sex, weekday, public holidays, greenness, season, and social class, with patient and city as random effects. RESULTS: Patients (85% male) were on average (mean ± SD) 68 ± 9 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 ± 18% predicted. Higher NO2, PM10 and PM2.5ABS levels at lag four were associated with fewer steps, less time in MVPA, reduced locomotion intensity, and longer sedentary time (e.g., coefficient (95% CI) of -60 (-105, -15) steps per 10 µg/m3 increase in NO2). Higher average and maximum temperatures at lag zero were related to more steps and time in MVPA, and less sedentary time (e.g., +85 (15, 154) steps per degree Celsius). Higher rainfall at lag zero was related to fewer steps and more sedentary time. CONCLUSION: Air pollution affects the amount and intensity of physical activity performed on the following days in COPD patients, whereas weather affects the amount of physical activity performed on the same day.

Association between residential exposure to road traffic noise and cognitive and motor function outcomes in children and preadolescents.

BACKGROUND: Exposure to environmental noise is increasing in recent years but most of the previous literature in children has evaluated the effect of aircraft noise exposure at schools on cognition. OBJECTIVE: To assess whether residential exposure to road traffic noise during pregnancy and childhood is associated with cognitive and motor function in children and preadolescents. METHODS: The study involved 619 participants from the Spanish INMA-Sabadell cohort and 7,115 from the Dutch Generation R Study. We used noise maps to estimate the average day-evening-night road traffic noise levels at each participant's residential address during pregnancy and childhood periods. Validated tests were administered throughout childhood in both cohorts to assess non-verbal and verbal intelligence, memory, processing speed, attentional function, working memory, cognitive flexibility, risky decision-making, and fine and gross motor function. Linear models, linear mixed models, and negative binomial models were run depending on the outcome in cohort-specific analysis and combined with a random-effects meta-analysis. All models were adjusted for several socioeconomic and lifestyle variables and results corrected for multiple testing. RESULTS: Average road traffic noise exposure levels during pregnancy and childhood were 61.3 (SD 6.0) and 61.5 (SD 5.4) dB for the INMA-Sabadell cohort and 54.6 (SD 7.9) and 53.5 (SD 6.5) dB for the Generation R Study, respectively. Road traffic noise exposure during pregnancy and childhood was not related to any of the cognitive and motor function outcomes examined in this study (e.g. -0.92 (95 % CI -2.08; 0.24) and 0.20 (95 % CI -0.96; 1.35) in overall estimates of memory and fine motor function, respectively, when road traffic noise increases by 10 dB during childhood). CONCLUSIONS: These findings suggest that child's cognitive or motor functions are not affected by residential exposure to road traffic noise. However, more studies evaluating this association at school and home settings as well as noise events are needed.

The association between urban land use and depressive symptoms in young adulthood: a FinnTwin12 cohort study.

BACKGROUND: Depressive symptoms lead to a serious public health burden and are considerably affected by the environment. Land use, describing the urban living environment, influences mental health, but complex relationship assessment is rare. OBJECTIVE: We aimed to examine the complicated association between urban land use and depressive symptoms among young adults with differential land use environments, by applying multiple models. METHODS: We included 1804 individual twins from the FinnTwin12 cohort, living in urban areas in 2012. There were eight types of land use exposures in three buffer radii. The depressive symptoms were assessed through the General Behavior Inventory (GBI) in young adulthood (mean age: 24.1). First, K-means clustering was performed to distinguish participants with differential land use environments. Then, linear elastic net penalized regression and eXtreme Gradient Boosting (XGBoost) were used to reduce dimensions or prioritize for importance and examine the linear and nonlinear relationships. RESULTS: Two clusters were identified: one is more typical of city centers and another of suburban areas. A heterogeneous pattern in results was detected from the linear elastic net penalized regression model among the overall sample and the two separated clusters. Agricultural residential land use in a 100 m buffer contributed to GBI most (coefficient: 0.097) in the "suburban" cluster among 11 selected exposures after adjustment with demographic covariates. In the "city center" cluster, none of the land use exposures was associated with GBI, even after further adjustment with social indicators. From the XGBoost models, we observed that ranks of the importance of land use exposures on GBI and their nonlinear relationships are also heterogeneous in the two clusters. IMPACT: This study examined the complex relationship between urban land use and depressive symptoms among young adults in Finland. Based on the FinnTwin12 cohort, two distinct clusters of participants were identified with different urban land use environments at first. We then employed two pluralistic models, elastic net penalized regression and XGBoost, and revealed both linear and nonlinear relationships between urban land use and depressive symptoms, which also varied in the two clusters. The findings suggest that analyses, involving land use and the broader environmental profile, should consider aspects such as population heterogeneity and linearity for comprehensive assessment in the future.

Adopting a child perspective for exposome research on mental health and cognitive development - Conceptualisation and opportunities.

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.

Protective effect of restorative possibilities on cognitive function and mental health in children and adolescents: A scoping review including the role of physical activity.

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.

Sub-anesthetic doses of ketamine increase single cell entrainment in the rat auditory cortex during auditory steady-state response.

BACKGROUND: Understanding the effects of the N-methyl-D-aspartate receptor (NMDA-R) antagonist ketamine on brain function is of considerable interest due to the discovery of its fast-acting antidepressant properties. It is well known that gamma oscillations are increased when ketamine is administered to rodents and humans, and increases in the auditory steady-state response (ASSR) have also been observed. AIMS: To elucidate the cellular substrate of the increase in network activity and synchrony observed by sub-anesthetic doses of ketamine, the aim was to investigate spike timing and regularity and determine how this is affected by the animal's motor state. METHODS: Single unit activity and local field potentials from the auditory cortex of awake, freely moving rats were recorded with microelectrode arrays during an ASSR paradigm. RESULTS: Ketamine administration yielded a significant increase in ASSR power and phase locking, both significantly modulated by motor activity. Before drug administration, putative fast-spiking interneurons (FSIs) were significantly more entrained to the stimulus than putative pyramidal neurons (PYRs). The degree of entrainment significantly increased at lower doses of ketamine (3 and 10 mg/kg for FSIs, 10 mg/kg for PYRs). At the highest dose (30 mg/kg), a strong increase in tonic firing of PYRs was observed. CONCLUSIONS: These findings suggest an involvement of FSIs in the increased network synchrony and provide a possible cellular explanation for the well-documented effects of ketamine-induced increase in power and synchronicity during ASSR. The results support the importance to evaluate different motor states separately for more translational preclinical research.

Long-term exposure to air pollution and severe COVID-19 in Catalonia: a population-based cohort study.

The association between long-term exposure to ambient air pollutants and severe COVID-19 is uncertain. We followed 4,660,502 adults from the general population in 2020 in Catalonia, Spain. Cox proportional models were fit to evaluate the association between annual averages of PM2.5, NO2, BC, and O3 at each participant's residential address and severe COVID-19. Higher exposure to PM2.5, NO2, and BC was associated with an increased risk of COVID-19 hospitalization, ICU admission, death, and hospital length of stay. An increase of 3.2 µg/m3 of PM2.5 was associated with a 19% (95% CI, 16-21) increase in hospitalizations. An increase of 16.1 µg/m3 of NO2 was associated with a 42% (95% CI, 30-55) increase in ICU admissions. An increase of 0.7 µg/m3 of BC was associated with a 6% (95% CI, 0-13) increase in deaths. O3 was positively associated with severe outcomes when adjusted by NO2. Our study contributes robust evidence that long-term exposure to air pollutants is associated with severe COVID-19.

The Interaction between Circulating Cell-Free Mitochondrial DNA and Inflammatory Cytokines in Predicting Human Mental Health Issue Risk in Adolescents: An Explorative Study.

Adolescence is often a challenging time in which psychiatric issues have a strong connection to mental health disorders later in life. The early identification of the problems can reduce the burden of disease. To date, the effective identification of adolescents at risk of developing mental health problems remains understudied. Altogether, the interaction between circulating cell-free mtDNA (ccf-mtDNA) and inflammatory cytokines in adolescents is insufficiently understood regarding experienced mental health difficulties. Our study selected the participants based on the Strength and Difficulty Questionnaire (SDQ) score using the cut-off points of 3 and 18 for the low and the high score groups, respectively. The answers of the SDQ at the age of 12.2-15.7 years contributed to the investigation of (i) whether ccf-mtDNA units are associated with cytokines, and (ii) if an interaction model for predicting risk of mental health issues is observed. We discovered a sex-specific correlation between the screened markers associated with mental health problems in the low and high SDQ score groups among the male participants and in the low SDQ score group among the female participants. The mitochondrial MT-ND4 and MT-CO1 genes correlated significantly with interleukin-12p70 (IL-12p70) in males and with monocyte chemoattractant protein-1 (MCP-1) in females. Due to the nature of the explorative study, the studied markers alone did not indicate statistical significance for the prediction of mental health problems. Our analysis provided new insight into potential plasma-based biomarkers to predict mental health issues.

Outdoor residential noise exposure and sleep in preadolescents from two European birth cohorts.

OBJECTIVE: To examine whether outdoor residential exposure to annual average road traffic and multiple (i.e., road traffic, railway, aircraft, industry) noise levels is related with preadolescents' sleep using maternal-reported and wrist-actigraphy data in two European birth cohorts. METHODS: This cross-sectional study used data of 1245 preadolescents from the Dutch Generation R Study and 232 from the Spanish INMA-Sabadell cohort with a mean age of 12.3 years old. We used noise maps to assess average outdoor road traffic and multiple noise levels (day-evening-night noise indicator, LDEN) at each child's residential address for the year before the sleep assessment. Sleep disturbances were reported by mothers through the Sleep Disturbance Scale for Children and objectively recorded using GeneActiv wrist-actigraphy during seven subsequent days. Linear and Poisson regression models adjusted for several potential confounding variables were performed. RESULTS: The mean (SD) exposure to road traffic noise was 53.2 dB (7.3) in the Generation R Study and 61.3 dB (5.9) in the INMA-Sabadell cohort. Exposure to road traffic was related with reduced total sleep time and longer wake after sleep onset (e.g. -3.62 min (95%CI -6.87; -0.37) and 6.88 min (95%CI 1.15; 12.61) per an increase of 10 dB in road traffic noise, respectively) collected by wrist-actigraphy. We observed no association between road traffic exposure and maternal-reported sleep disturbances. Results were similar for multiple noise exposure. CONCLUSIONS: These findings indicate that sleep may be compromised for preadolescents living in areas highly exposed to outdoor residential noise. Future studies using longitudinal designs to further explore these associations during the different stages of sleep development across childhood and adolescence are warranted. Also, wrist-actigraphy measurements which provide more accurate information and may be complementary to the parental- and self-reported data should be considered.

The effects of exposure to road traffic noise at school on central auditory pathway functional connectivity.

As the world becomes more urbanized, more people become exposed to traffic and the risks associated with a higher exposure to road traffic noise increase. Excessive exposure to environmental noise could potentially interfere with functional maturation of the auditory brain in developing individuals. The aim of the present study was to assess the association between exposure to annual average road traffic noise (LAeq) in schools and functional connectivity of key elements of the central auditory pathway in schoolchildren. A total of 229 children from 34 representative schools in the city of Barcelona with ages between 8 and 12 years (49.2% girls) were evaluated. LAeq was obtained as the mean of 2-consecutive day measurements inside classrooms before lessons started following standard procedures to obtain an indicator of long-term road traffic noise levels. A region-of-interest functional connectivity Magnetic Resonance Imaging (MRI) approach was adopted. Functional connectivity maps were generated for the inferior colliculus, medial geniculate body of the thalamus and primary auditory cortex as key levels of the central auditory pathway. Road traffic noise in schools was significantly associated with stronger connectivity between the inferior colliculus and a bilateral thalamic region adjacent to the medial geniculate body, and with stronger connectivity between the medial geniculate body and a bilateral brainstem region adjacent to the inferior colliculus. Such a functional connectivity strengthening effect did not extend to the cerebral cortex. The anatomy of the association implicating subcortical relays suggests that prolonged road traffic noise exposure in developing individuals may accelerate maturation in the basic elements of the auditory pathway. Future research is warranted to establish whether such a faster maturation in early pathway levels may ultimately reduce the developing potential in the whole auditory system.

Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles.

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins' exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders.

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Associations of residential greenspace exposure and fetal growth across four areas in Spain.

An accumulating body of evidence has associated exposure to greenspace with improved birth outcomes, including higher birth weight and lower risk of low birth weight; however, evidence on such association with in-utero fetal growth is scarce. We explored the influence of maternal exposure to residential greenspace and fetal growth in four INMA (Infancia y Medio Ambiente) Spanish birth cohorts (2003-2008), with 2,465 participants. Residential greenspace was characterised by the Normalised Difference Vegetation Index (NDVI) average across 100 m, 300 m, and 500 m buffers around the residence. Repeated ultrasound measurements of the abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW) were used. We created customised-generalised least squares models to evaluate associations of residential greenspace exposure on each fetal growth parameter, controlled for the relevant confounders. There were associations between the 500 m buffer and BPD, FL, and AC. We also found associations in the 300 m buffer and FL and AC. The associations in the 100 m buffer were null. Estimates were higher among participants with lower socioeconomic status. Mediation analyses found that air pollution might explain 15-37% of our associations. Mediation by physical activity was not observed. Greenspace exposure may be beneficial for fetal growth.

Urban environment and physical activity and capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity and exercise capacity are key prognostic factors in chronic obstructive pulmonary disease (COPD) but their environmental determinants are unknown. OBJECTIVES: To test the association between urban environment and objective physical activity, physical activity experience and exercise capacity in COPD. METHODS: We studied 404 patients with mild-to-very severe COPD from a multi-city study in Catalonia, Spain. We measured objective physical activity (step count and sedentary time) by the Dynaport MoveMonitor, physical activity experience (difficulty with physical activity) by the Clinical visit-PROactive (C-PPAC) instrument, and exercise capacity by the 6-min walk distance (6MWD). We estimated individually (geocoded to the residential address) population density, pedestrian street length, slope of terrain, and long-term (i.e., annual) exposure to road traffic noise, nitrogen dioxide (NO2) and particulate matter (PM2.5). We built single- and multi-exposure mixed-effects linear regressions with a random intercept for city, adjusting for confounders. RESULTS: Patients were 85% male, had mean (SD) age 69 (9) years and walked 7524 (4045) steps/day. In multi-exposure models, higher population density was associated with fewer steps, more sedentary time and worse exercise capacity (-507 [95% CI: 1135, 121] steps, +0.2 [0.0, 0.4] h/day and -13 [-25, 0] m per IQR). Pedestrian street length related with more steps and less sedentary time (156 [9, 304] steps and -0.1 [-0.1, 0.0] h/day per IQR). Steeper slope was associated with better exercise capacity (15 [3, 27] m per IQR). Higher NO2 levels related with more sedentary time and more difficulty in physical activity. PM2.5 and noise were not associated with physical activity or exercise capacity. DISCUSSION: Population density, pedestrian street length, slope and NO2 exposure relate to physical activity and capacity of COPD patients living in highly populated areas. These findings support the consideration of neighbourhood environmental factors during COPD management and the attention to patients with chronic diseases when developing urban and transport planning policies.

Exposure to road traffic noise and cognitive development in schoolchildren in Barcelona, Spain: A population-based cohort study.

BACKGROUND: Road traffic noise is a prevalent and known health hazard. However, little is known yet about its effect on children's cognition. We aimed to study the association between exposure to road traffic noise and the development of working memory and attention in primary school children, considering school-outdoor and school-indoor annual average noise levels and noise fluctuation characteristics, as well as home-outdoor noise exposure. METHODS AND FINDINGS: We followed up a population-based sample of 2,680 children aged 7 to 10 years from 38 schools in Barcelona (Catalonia, Spain) between January 2012 to March 2013. Children underwent computerised cognitive tests 4 times (n = 10,112), for working memory (2-back task, detectability), complex working memory (3-back task, detectability), and inattentiveness (Attention Network Task, hit reaction time standard error, in milliseconds). Road traffic noise was measured indoors and outdoors at schools, at the start of the school year, using standard protocols to obtain A-weighted equivalent sound pressure levels, i.e., annual average levels scaled to human hearing, for the daytime (daytime LAeq, in dB). We also derived fluctuation indicators out of the measurements (noise intermittency ratio, %; and number of noise events) and obtained individual estimated indoor noise levels (LAeq) correcting for classroom orientation and classroom change between years. Home-outdoor noise exposure at home (Lden, i.e., EU indicator for the 24-hour annual average levels) was estimated using Barcelona's noise map for year 2012, according to the European Noise Directive (2002). We used linear mixed models to evaluate the association between exposure to noise and cognitive development adjusting for age, sex, maternal education, socioeconomical vulnerability index at home, indoor or outdoor traffic-related air pollution (TRAP) for corresponding school models or outdoor nitrogen dioxide (NO2) for home models. Child and school were included as nested random effects. The median age (percentile 25, percentile 75) of children in visit 1 was 8.5 (7.8; 9.3) years, 49.9% were girls, and 50% of the schools were public. School-outdoor exposure to road traffic noise was associated with a slower development in working memory (2-back and 3-back) and greater inattentiveness over 1 year in children, both for the average noise level (e.g., ‒4.83 points [95% CI: ‒7.21, ‒2.45], p-value < 0.001, in 2-back detectability per 5 dB in street levels) and noise fluctuation (e.g., ‒4.38 [‒7.08, ‒1.67], p-value = 0.002, per 50 noise events at street level). Individual exposure to the road traffic average noise level in classrooms was only associated with inattentiveness (2.49 ms [0, 4.81], p-value = 0.050, per 5 dB), whereas indoor noise fluctuation was consistently associated with all outcomes. Home-outdoor noise exposure was not associated with the outcomes. Study limitations include a potential lack of generalizability (58% of mothers with university degree in our study versus 50% in the region) and the lack of past noise exposure assessment. CONCLUSIONS: We observed that exposure to road traffic noise at school, but not at home, was associated with slower development of working memory, complex working memory, and attention in schoolchildren over 1 year. Associations with noise fluctuation indicators were more evident than with average noise levels in classrooms.

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

BACKGROUND: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. METHODS: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). RESULTS: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. CONCLUSIONS: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.

A study on exposure to greenspace during pregnancy and lipid profile in cord blood samples.

Although evidence reporting the beneficial associations of prenatal greenspace exposure with pregnancy outcomes is increasing, there is still a lack of evidence on the potential association of such exposure to greenspace on fetal lipid profile. We aimed to first-time investigate the associations between prenatal exposure to greenspace and lipid levels in the cord blood. The present study was based on data from 150 expectant mothers, residents of Sabzevar city in Iran (2018). For each participant, we identified exposure to greenspace in residential surroundings, residential accessibility to green space, use of green spaces, and the number of plant pots inside the home. Measures of levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C and TG/HDL-C ratios in samples of cord blood were applied to identify the lipid profile. We developed adjusted linear regression models to estimate the associations of each indicator of greenspace exposure with each cord blood lipid. We found increased greenspace in residential surroundings across a 100 m buffer, higher residential accessibility to green space, and more use of green spaces were associated with decreased cord blood lipid levels. The remainder findings regarding the greenspace in residential surroundings across 300 m and 500 m buffers and the number of plant pots were null. Some suggestions were observed for a potential mediatory role of air pollution. This study suggests that greenspace exposure during pregnancy may influence positively fetal lipid levels in the cord blood.

Exposure to traffic-related air pollution and noise during pregnancy and childhood, and functional brain connectivity in preadolescents.

BACKGROUND: The amount of people affected by traffic-related air pollution and noise is continuously increasing, but limited research has been conducted on the association between these environmental exposures and functional brain connectivity in children. OBJECTIVE: This exploratory study aimed to analyze the associations between the exposure to traffic-related air pollution and noise during pregnancy and childhood, and functional brain connectivity amongst a wide-swath of brain areas in preadolescents from 9 to 12 years of age. METHODS: We used data of 2,197 children from the Generation R Study. Land use regression models were applied to estimate nitrogen oxides and particulate matter levels at participant's homes for several time periods: pregnancy, birth to 3 years, 3 to 6 years, and 6 years of age to the age at magnetic resonance imaging (MRI) assessment. Existing noise maps were used to estimate road traffic noise exposure at participant's homes for the same time periods. Resting-state functional MRI was obtained at 9-12 years of age. Pair-wise correlation coefficients of the blood-oxygen-level-dependent signals between 380 brain areas were calculated. Linear regressions were run and corrected for multiple testing. RESULTS: Preadolescents exposed to higher levels of NO2, NOx, and PM2.5 absorbance, from birth to 3 years, and from 3 to 6 years of age showed higher correlation coefficients among several brain regions (e.g. from 0.16 to 0.19 higher correlation coefficient related to PM2.5 absorbance exposure, depending on the brain connection). Overall, most identified associations were between brain regions of the task positive and task negative networks, and were mainly inter-network (20 of 26). Slightly more than half of the connections were intra-hemispheric (14 of 26), predominantly in the right hemisphere. Road traffic noise was not associated with functional brain connectivity. CONCLUSIONS: This exploratory study found that exposure to traffic-related air pollution during the first years of life was related to higher functional brain connectivity predominantly in brain areas located in the task positive and task negative networks, in preadolescents from 9 to 12 years of age. These results could be an indicator of differential functional connectivity in children exposed to higher levels of air pollution.