Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents

Apolipoprotein E; Genetic modifiers; NeurodevelopmentApolipoproteïna E; Modificadors genètics; NeurodesenvolupamentApolipoproteína E; Modificadores genéticos; NeurodesarrolloBackground Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. Objectives To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. Methods We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants’ home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. Results Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)). Discussion APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design.The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. A.N. was supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (024.001.003, Consortium on Individual Development), a grant of the Canadian Institutes of Health Research team, and by the Research Foundation Flanders (FWO). S.A. was supported by the Programa Talen_UAB-Banc de Santander. The geocodification of the addresses of the study participants and the air pollution estimations were done within the framework of a project funded by the Health Effects Institute (HEI) (Assistance Award No. R-82811201). We received funding from the Spanish Institute of Health Carlos III (CPII18/00018), the EU Commission (733,206, 824,989), and the Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (EST-18 RF-25). We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program”

Ambient air temperature exposure and foetal size and growth in three European birth cohorts

Introduction:Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. Methods: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers’ residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). Results: Weekly temperatures ranged from −5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1–28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: −1.6 SDS [95 %CI −2.0; −0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1–7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: −0.1 cm/week [-0.2; −0.04]), with a susceptibility period from weeks 4–12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. Conclusions: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.</p

Ambient air temperature exposure and foetal size and growth in three European birth cohorts

Introduction:Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. Methods: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers’ residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). Results: Weekly temperatures ranged from −5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1–28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: −1.6 SDS [95 %CI −2.0; −0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1–7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: −0.1 cm/week [-0.2; −0.04]), with a susceptibility period from weeks 4–12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. Conclusions: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.</p

Technical validity and usability of a novel smartphone-connected spirometry device for pediatric patients with asthma and cystic fibrosis

Background: Diagnosis and follow-up of respiratory diseases traditionally rely on pulmonary function tests (PFTs), which are currently performed in hospitals and require trained personnel. Smartphone-

Environmental noise exposure and emotional, aggressive, and attention-deficit/hyperactivity disorder-related symptoms in children from two European birth cohorts

Background: Environmental noise exposure is increasing but limited research has been done on the association with emotional, aggressive, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in children. Objective: To analyze the association between prenatal and childhood environmental noise exposure and emotional, aggressive, and ADHD-related symptoms in children from two European birth cohorts. Methods: We included 534 children from the Spanish INMA-Sabadell Project and 7424 from the Dutch Generation R Study. Average 24 h noise exposure at the participants’ home address during pregnancy and childhood periods were estimated using EU maps from road traffic noise and total noise (road, aircraft, railway, and industry). Symptom outcomes were assessed using validated questionnaires: Strengths and Difficulties Questionnaire, Child Behavioral Checklist, ADHD Criteria of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition List, and Conner's Parent Rating Scale-Revised at 4, 7 and 9 years (INMA-Sabadell cohort) and 18 months, 3, 5, and 9 years (Generation R Study). Adjusted linear mixed models of prenatal and repeated childhood noise exposure with repeated symptom outcomes were run separately by cohort and overall estimates were combined with random-effects meta-analysis. Results: Average prenatal and childhood road traffic noise exposure levels were 61.3 (SD 6.1) and 61.7 (SD 5.8) for INMA-Sabadell and 54.6 (SD 7.9) and 51.6 (SD 7.1) for Generation R, respectively. Prenatal and childhood road traffic noise exposure were not associated with emotional, aggressive, or ADHD-related symptoms. No heterogeneity was observed between cohorts and results were comparable for total noise exposure. Conclusions: No association was observed between prenatal or childhood road traffic or total noise exposure and symptom outcomes in children. Future studies should include a more comprehensive noise exposure assessment considering noise sensitivity and noise exposure at different settings such as work for pregnant women and school for children

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

Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents

Background: Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. Objectives: To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. Methods: We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants’ home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. Results: Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers. Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD. Discussion: APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design

Exposure to outdoor residential noise during pregnancy, embryonic size, fetal growth, and birth outcomes

INTRODUCTION: Previous literature suggested that noise exposure during pregnancy was not associated with adverse birth outcomes. However, no studies evaluated the association between noise exposure and embryonic and fetal growth, or mutually assessed other urban environmental exposures such as traffic-related air pollution or natural spaces. METHODS: We included 7947 pregnant women from the Generation R Study, the Netherlands. We estimated total (road traffic, aircraft, railway, and industry), road traffic, and railway noise at the participants' home addresses during pregnancy using environmental noise maps. We estimated traffic-related air pollution using land-use regression models, greenness within a 300 m buffer using the normalized difference vegetation index, and distance to blue spaces using topographical maps at the home addresses. Embryonic size (crown-rump length) and fetal growth parameters (head circumference, femur length, and estimated fetal weight) were measured by ultrasound at several gestational ages. Information on neonatal anthropometrics at birth (head circumference, length, and weight) and adverse birth outcomes (preterm birth, low birth weight, and small for gestational age) were retrieved from medical records. RESULTS: Higher total noise exposure during pregnancy was associated with larger crown-rump length (0.07 SDS [95%CI 0.00 to 0.14]). No association was found with fetal growth parameters, neonatal anthropometrics, and adverse birth outcomes. Similar results were observed for road traffic noise exposure, while railway noise exposure was not associated with any of the outcomes. Traffic-related air pollution was not associated with crown-rump length. Total noise exposure mediated 15% of the association between exposure to greenness and smaller crown-rump length. No association was observed between distance to blue spaces and total noise exposure. CONCLUSION: Exposure to outdoor residential noise during pregnancy was associated with larger embryonic size. Moreover, a reduction of total noise exposure during pregnancy partially mediated the association between exposure to greenness and smaller embryonic size. Additional research is warranted to confirm and further understand these novel findings

Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents

Background: Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. Objectives: To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. Methods: We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants' home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9-12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. Results: Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)). Discussion: APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design

Air pollution exposure during pregnancy and childhood, cognitive function, and emotional and behavioral problems in adolescents

Background: Exposure to air pollution may impact neurodevelopment during childhood, but current evidence on the association with cognitive function and mental health is inconclusive and primarily focusses on young children. Therefore, we aim to study the association of exposure to air pollution during pregnancy and childhood, with cognitive function and emotional and behavioral problems in adolescents. Methods: We used data from 5170 participants of a birth cohort in Rotterdam, the Netherlands. Concentrations of fourteen air pollutants at participant's home addresses were estimated during pregnancy and childhood, using land use regression models. We included four cognitive domains (processing speed, working memory, fluid reasoning and verbal intelligence quotient (IQ)) and an estimated full-scale IQ. Internalizing, externalizing, and attention problems were self- and parent-reported. We used linear regression models to assess the association of each air pollutant, with cognitive function and emotional and behavioral problems, adjusting for socioeconomic status and lifestyle characteristics. Then, we performed multipollutant analyses using the Deletion/Substitution/Addition (DSA) algorithm. Results: Air pollution exposure was not associated with full-scale IQ, working memory, or processing speed. Higher exposure to few air pollutants was associated with higher fluid reasoning and verbal IQ scores (e.g. 0.22 points of fluid reasoning (95%CI 0.00; 0.44) per 1 μg/m3 increase in organic carbon during pregnancy). Higher exposure to some air pollutants was also associated with less internalizing, externalizing, and attention problems (e.g. -0.27 internalizing problems (95% CI -0.52; -0.02) per each 5 ng/m3 increase in copper during pregnancy). Conclusions: Higher exposure to air pollution during pregnancy and childhood was not associated with lower cognitive function or more emotional and behavioral problems in adolescents. Based on previous literature and biological plausibility, the observed protective associations are probably explained by negative residual confounding, selection bias, or chance and do not represent a causal relationship