Association between trimester-specific prenatal air pollution exposure and placental weight of twins.

INTRODUCTION: This study investigates the association between maternal exposure to particulate matter (PM10) and nitric dioxide (NO2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth. METHODS: Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression. RESULTS: In the third trimester, for each 10 µm/m3 increase in PM10 or NO2 placental weight decreased -19.7 g (95%-C.I. -35.1; -4.3) and -17.7 g (95%-C.I. -30.4; -0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a "small for gestational age placenta" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84). DISCUSSION: The association of PM10 and NO2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters.

Maternal perceived stress and green spaces during pregnancy are associated with adult offspring gene (NR3C1 and IGF2/H19) methylation patterns in adulthood: A pilot study.

BACKGROUND: Changes in NR3C1 and IGF2/H19 methylation patterns have been associated with behavioural and psychiatric outcomes. Maternal mental state has been associated with offspring NR3C1 promotor and IGF2/H19 imprinting control region (ICR) methylation patterns. However, there is a lack of prospective studies with long-term follow-up. METHODS: 52 mother-offspring pairs were studied from 12 to 22 weeks of pregnancy and offspring was followed-up until 28-29 years-of-age. During pregnancy, mothers filled in a Life Event Scale and a Daily Hassles Scale measuring perceived stress; i.e., appraisal or subjectively experienced severity of impact of important life events and of daily hassles in several life domains during pregnancy, respectively. Green space was quantified around the residence, using high-resolution (1 m2) map data. Saliva and blood samples were obtained from the adult offspring. Absolute DNA methylation levels were determined in blood and saliva on four NR3C1 amplicons, and one IGF2/H19 ICR amplicon using a bisulfite PCR and sequencing method. Linear mixed effect models were used to test the associations between perceived stress and green spaces during pregnancy, and adult offspring methylation patterns. RESULTS: We found associations between maternal perceived stress during pregnancy and methylation patterns on two out of the four NR3C1 amplicons, measured in blood, from offspring in adulthood, but not with IGF2/H19 methylation. For an interquartile-range (IQR) increase in maternal perceived life event or daily hassles stress scores, absolute methylation levels on several NR3C1 CpG sites were significantly changed (-1.62 % to +5.89 %, p<0.05). Maternal perceived stress scores were not associated with IGF2/H19 methylation, neither in blood nor in saliva. Maternal exposure to green spaces surrounding the residence during the pregnancy was associated with IGF2/H19 ICR methylation (-0.80 % to -1.04 %, p<0.05) in saliva, but not with NR3C1 promotor methylation. CONCLUSION: We observed significant long-term effects of maternal perceived stress during pregnancy on the methylation patterns of the NR3C1 promotor in offspring well into adulthood. This may imply that maternal psychological distress during pregnancy may influence the regulation of the HPA-axis well into adulthood. Additionally, maternal proximity to green spaces was associated with IGF2/H19 ICR methylation patterns, which is a novel finding.

Exploring the impact of lifestyle and environmental exposures on appetite hormone levels in children and adolescents: An observational study.

BACKGROUND: Appetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. OBJECTIVES: In this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. METHODS: A total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 µM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. RESULTS: GLP-1 was associated with air pollution exposure (NO2 ß* = -0.13, BC ß* = -0.15, PM2.5 ß* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (ß* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin ß* = -0.16; p = 0.04, total ghrelin ß* = -0.23; p = 0.0051) and happiness (active ghrelin ß* = 0.25; p < 0.001, total ghrelin ß* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (ß* = -0.22; p = 0.036). DISCUSSION: Our findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.

Exposure to Residential Green Space and Bone Mineral Density in Young Children.

Importance: Bone mass accrual is influenced by environmental and lifestyle factors. Targeted interventions at the early stages of life might decrease fracture and/or osteoporosis risk later in life. Objective: To investigate whether early-life exposure to residential surrounding green space is associated with a change in bone mineral density in young children. Design, Setting, and Participants: In this prospective birth cohort study (ENVIRONAGE [Environmental Influence on Aging in Early Life]), mother-child pairs from Flanders, Belgium, were recruited at birth and followed up for 4 to 6 years, between October 1, 2014, and July 31, 2021. Data analysis was conducted between January and February 2022. Exposures: Green space was estimated for high green (>3 m vegetation height), low green (≤3 m vegetation height ), and total green (sum of high and low) within several radii (100-3000 m) around the residence after geocoding of the addresses. Main Outcomes and Measures: Radial bone mineral density was assessed using quantitative ultrasound measurement at follow-up, measured as the mean of the axially transmitted speed of sound in meters per second. Multiple linear and logistic regression models were used while accounting for relevant covariates and potential confounders. Results: The study population comprised 327 children (180 [55.0%] female; mean [SD] age, 4.6 [0.4] years at the follow-up evaluation). Early-life exposure to residential green space was associated with increased childhood bone health. An IQR increment in total green (21.2%) and high green (19.9%) space within 500 m was associated with an increase of 27.38 m/s (95% CI, 9.63-45.13 m/s) and 25.30 m/s (95% CI, 7.93-42.68 m/s) in bone mineral density, respectively. Additionally, an IQR increase in total (25.2%) and high (23.2%) green space within 1000 m was associated with a 67% (odds ratio, 0.33; 95% CI, 0.17-0.61) and 61% (odds ratio, 0.39; 95% CI, 0.18-0.75) lower risk of having a bone density lower than the sex-specific 10th percentile (3567.6 m/s for girls and 3522.8 m/s for boys). Conclusions and Relevance: In this study of children aged 4 to 6 years, higher bone mineral density and a lower risk of having low bone density were associated with higher residential green space exposure during childhood. These findings highlight the importance of early-life exposure to residential green space on bone health during critical periods of growth and development, with long-term implications.

Birth outcomes of twins after multifetal pregnancy reduction compared with primary twins.

BACKGROUND: The introduction of assisted reproductive technology and the trend of increasing maternal age at conception have contributed to a significant rise in the incidence of multiple pregnancies. Multiple pregnancies bear several inherent risks for both mother and child. These risks increase with plurality and type of chorionicity. Multifetal pregnancy reduction is the selective abortion of ≥1 fetuses to improve the outcome of the remaining fetus(es) by decreasing the risk of premature birth and other complications. OBJECTIVE: This study aimed to compare birth outcomes of trichorionic triplets reduced to twins with those of trichorionic triplets and primary dichorionic twins. The added value of this study is the comparison with an additional control group, namely primary dichorionic twins. STUDY DESIGN: This was a retrospective cohort study. Data from January 1990 to November 2016 were collected from the East Flanders Prospective Twin Survey, one of the largest European multiple birth registries. A total of 85 trichorionic triplet pregnancies (170 neonates) undergoing multifetal pregnancy reduction to twins were compared with 5093 primary dichorionic twin pregnancies (10,186 neonates) and 104 expectantly managed trichorionic triplet pregnancies (309 neonates). The assessed outcomes were gestational age at delivery, birthweight, and small for gestational age. RESULTS: Pregnancy reduction from triplets to twins was associated with higher birthweight (+365.44 g; 95% confidence interval, 222.75-508.14 g; P<.0001) and higher gestational age (1.7 weeks; 95% confidence interval, 0.93-2.46; P<.0001) compared with ongoing trichorionic triplets after adjustment for sex, parity, method of conception, birth year, and maternal age. A trend toward lower risk of small for gestational age was observed. Reduced triplets had, on average, lower birthweight (-263.12 g; 95% confidence interval, -371.80 to -154.44 g; P<.0001) and lower gestational age (-1.13 weeks; 95% confidence interval, -1.70 to -0.56; P=.0001) compared with primary twins. No statistically significant difference was observed between primary twins and reduced triplets that reached 32 weeks of gestation. CONCLUSION: Multifetal pregnancy reduction from trichorionic triplets to twins significantly improved birth outcomes. This suggests that multifetal pregnancy reduction of trichorionic triplets to twins is medically justifiable. However, the birth outcomes of primary twins before 32 weeks of gestation are still better than those of reduced triplets. The process of multifetal pregnancy reduction includes at least 1 fetal death by definition, and thus prevention of higher-order pregnancies is preferable.

Association of air pollution and green space with all-cause general practitioner and emergency room visits: A cross-sectional study of young people and adults living in Belgium.

BACKGROUND: Residing in areas with lower levels of air pollution and higher green space is beneficial to physical and mental health. We investigated associations of PM2.5, tree cover and grass cover with in-hours and out-of-hours GP visits and ER visits, for young people and adults. We estimated potential cost savings of GP visits attributable to high PM2.5. METHODS: We linked individual-level health insurance claims data of 315,123 young people (10-24 years) and 885,988 adults (25-64 years) with census tract-level PM2.5, tree cover and grass cover. Deploying negative binomial generalized linear mixed models, we estimated associations between quartile exposures and the three outcome measures. RESULTS: For in-hours and out-of-hours GP visits, among young people as well as adults, statistically significant pairwise differences between quartiles suggested increasing beneficial effects with lower PM2.5. The same outcomes were statistically significantly less frequent in quartiles with highest tree cover (>30.00%) compared to quartiles with lower tree cover, but otherwise pairwise differences were not statistically significant. These associations largely persisted in rural and urban areas. Among adults living in urban areas lower grass cover was associated with increased in-hours GP visits and ER visits. Assuming causality, reducing PM2.5 levels to the lowest quartile (4.91-7.49 µg/m³), among adults, 195,964 in-hours and 74,042 out-of-hours GP visits could be avoided annually. Among young people, 27,457 in-hours and 22,423 out-of-hours GP visits could be avoided annually. Nationally, this amounts to an annual potential cost saving of €43 million (€5.7 million in out-of-pocket payments and €37.2 million in compulsory health insurance). CONCLUSION: Higher ambient PM2.5 and lower tree cover show associations with higher non-urgent and urgent medical care utilization. These findings confirm the importance of reducing air pollution and fostering green zones, and that such policies may contribute positively to economic growth.

Pre-admission ambient air pollution and blood soot particles predict hospitalisation outcomes in COVID-19 patients.

BACKGROUND: Air pollution exposure is one of the major risk factors for aggravation of respiratory diseases. We investigated whether exposure to air pollution and accumulated black carbon (BC) particles in blood were associated with coronavirus disease 2019 (COVID-19) disease severity, including the risk for intensive care unit (ICU) admission and duration of hospitalisation. METHODS: From May 2020 until March 2021, 328 hospitalised COVID-19 patients (29% at intensive care) were recruited from two hospitals in Belgium. Daily exposure levels (from 2016 to 2019) for particulate matter with aerodynamic diameter <2.5 µm and <10 µm (PM2.5 and PM10, respectively), nitrogen dioxide (NO2) and BC were modelled using a high-resolution spatiotemporal model. Blood BC particles (internal exposure to nano-sized particles) were quantified using pulsed laser illumination. Primary clinical parameters and outcomes included duration of hospitalisation and risk of ICU admission. RESULTS: Independent of potential confounders, an interquartile range (IQR) increase in exposure in the week before admission was associated with increased duration of hospitalisation (PM2.5 +4.13 (95% CI 0.74-7.53) days, PM10 +4.04 (95% CI 1.24-6.83) days and NO2 +4.54 (95% CI 1.53-7.54) days); similar effects were observed for long-term NO2 and BC exposure on hospitalisation duration. These effect sizes for an IQR increase in air pollution on hospitalisation duration were equivalent to the effect of a 10-year increase in age on hospitalisation duration. Furthermore, for an IQR higher blood BC load, the OR for ICU admission was 1.33 (95% CI 1.07-1.65). CONCLUSIONS: In hospitalised COVID-19 patients, higher pre-admission ambient air pollution and blood BC levels predicted adverse outcomes. Our findings imply that air pollution exposure influences COVID-19 severity and therefore the burden on medical care systems during the COVID-19 pandemic.

Residential green space improves cognitive performances in primary schoolchildren independent of traffic-related air pollution exposure.

BACKGROUND: Cognitive performances of schoolchildren have been adversely associated with both recent and chronic exposure to ambient air pollution at the residence. In addition, growing evidence indicates that exposure to green space is associated with a wide range of health benefits. Therefore, we aimed to investigate if surrounding green space at the residence improves cognitive performance of primary schoolchildren while taking into account air pollution exposure. METHODS: Cognitive performance tests were administered repeatedly to a total of 307 primary schoolchildren aged 9-12y, living in Flanders, Belgium (2012-2014). These tests covered three cognitive domains: attention (Stroop and Continuous Performance Tests), short-term memory (Digit Span Forward and Backward Tests), and visual information processing speed (Digit-Symbol and Pattern Comparison Tests). Green space exposure was estimated within several radii around their current residence (50 m to 2000 m), using a aerial photo-derived high-resolution (1 m2) land cover map. Furthermore, air pollution exposure to PM2.5 and NO2 during the year before examination was modelled for the child's residence using a spatial-temporal interpolation method. RESULTS: An improvement of the children's attention was found with more residential green space exposure independent of traffic-related air pollution. For an interquartile range increment (21%) of green space within 100 m of the residence, a significantly lower mean reaction time was observed independent of NO2 for both the sustained-selective (-9.74 ms, 95% CI: -16.6 to -2.9 ms, p = 0.006) and the selective attention outcomes (-65.90 ms, 95% CI: -117.0 to -14.8 ms, p = 0.01). Moreover, green space exposure within a large radius (2000 m) around the residence was significantly associated with a better performance in short-term memory (Digit-Span Forward Test) and a higher visual information processing speed (Pattern Comparison Test), taking into account traffic-related exposure. However, all associations were attenuated after taking into account long-term residential PM2.5 exposure. CONCLUSIONS: Our panel study showed that exposure to residential surrounding green space was associated with better cognitive performances at 9-12 years of age, taking into account traffic-related air pollution exposure. These findings support the necessity to build attractive green spaces in the residential environment to promote healthy cognitive development in children.

Epigenome-wide analysis of maternal exposure to green space during gestation and cord blood DNA methylation in the ENVIRONAGE cohort.

BACKGROUND: DNA methylation programming is sensitive to prenatal life environmental influences, but the impact of maternal exposure to green space on newborns DNA methylation has not been studied yet. METHODS: We conducted a meta-epigenome-wide association study (EWAS) of maternal exposure to green space during gestation with cord blood DNA methylation in two subsets of the ENVIRONAGE cohort (N = 538). Cord blood DNA methylation was measured by Illumina HumanMethylation 450K in one subset (N = 189) and EPICarray in another (N = 349). High (vegetation height>3 m (m)), low (vegetation height<3 m) and total (including both) high-resolution green space exposures during pregnancy were estimated within 100 m and 1000 m distance around maternal residence. In each subset, we sought cytosine-phosphate-guanine (CpG) sites via linear mixed models adjusted on newborns' sex, ethnicity, gestational age, season at delivery, sampling day, maternal parity, age, smoking, education, and estimated blood cell proportions. EWASs results were meta-analysed via fixed-effects meta-analyses. Differentially methylated regions (DMRs) were identified via ENmix-combp and DMRcate algorithms. Sensitivity analyses were additionally adjusted on PM2.5, distance to major roads, urbanicity and neighborhood income. In the 450K subset, cord blood expression of differentially methylated genes was measured by Agilent microarrays and associated with green space. RESULTS: 147 DMRs were identified, 85 of which were still significant upon adjustment for PM2.5, distance to major roads, urbanicity and neighborhood income, including HLA-DRB5, RPTOR, KCNQ1DN, A1BG-AS1, HTR2A, ZNF274, COL11A1 and PRSS36 DMRs. One CpG reached genome-wide significance, while 54 CpGs were suggestive significant (p-values<1e-05). Among them, a CpG, hypermethylated with 100 m buffer total green space, was annotated to PAQR9, whose expression decreased with 1000 m buffer low green space (p-value = 1.45e-05). CONCLUSIONS: Our results demonstrate that maternal exposure to green space during pregnancy is associated with cord blood DNA methylation, mainly at loci organized in regions, in genes playing important roles in neurological development (e.g., HTR2A).

Higher proportion of agricultural land use around the residence is associated with higher urinary concentrations of AMPA, a glyphosate metabolite.

INTRODUCTION: Pesticides, including herbicides, are widely used for agricultural and sanitary reasons and concerns have been raised about their various health effects. Little research has been done into the extent to which agricultural land use in the residential surroundings contributes to (internal) exposure of pesticides. OBJECTIVES: We investigated the associations between the proportion of agricultural land use around the residence and the exposure to pesticides in adolescents in Flanders (Belgium). MATERIAL AND METHODS: We included 424 adolescents participating in the fourth Flemish Environment and Health Study (FLEHS IV) between 2016 and 2020. The residential address of all participants was geocoded and the proportion of agricultural land use around the residence was estimated in several buffers (300 m, 500 m, 1000 m and 2000 m). The concentrations of the following biomarkers of pesticides were measured in urine and adjusted for the specific gravity: glyphosate and its metabolite, aminomethyl-phosphonic acid (AMPA); 3-phenoxybenzoic acid (3-PBA); 3,5,6-trichloro-2-pyridinol (TCPy) and 2,4-dichlophenoxy-acetic acid (2,4-D). We categorized the pesticide biomarkers in three categories according to the exposure levels and used ordinal logistic regression models adjusted for sex, season and household education to estimate the odds ratio for an increase in an interquartile range (IQR) of proportion of agricultural land use. We also used binary logistic regression models in which the category of highest exposure was compared to the category of lowest exposure. In addition, we explored potential effect modification by sex and season. RESULTS: We found a significant association between the proportion of agricultural land use in a buffer of 2000 m around the residence and the levels of urinary AMPA divided into three categories (OR = 1.35 for an IQR increase in the proportion of agricultural land use around residence; 95% CI: 1.00-1.83). This association was less pronounced and not statistically significant for the other studied pesticides (OR ranging between 0.95 and 1.16). Stratified analysis showed the strongest association of the proportion of agricultural land use within 2000 m buffers for AMPA among boys (OR = 1.89; 95% CI: 1.19-3.04). Results using smaller buffers were comparable, but did not reach statistical significance. CONCLUSION: Our findings suggest that a higher proportion of agricultural land use around the residence might increase exposure to AMPA.

A multi-exposure approach to study telomere dynamics in childhood: A role for residential green space and waist circumference.

BACKGROUND: Telomeres are vulnerable to various environmental exposures and lifestyle factors, encompassed in the exposome. Recent research shows that telomere length is substantially determined early in life and that exposures in childhood may have important consequences in setting later life telomere length. OBJECTIVES: We explore in a child population the associations of 17 exposures with telomere length and longitudinal telomere change. METHODS: Children (2.8-10.3y at baseline, 51.3% boys) were followed-up for five to seven years. Relative telomere length was measured at baseline and follow-up using quantitative real-time PCR. Exposures and lifestyle factors included: body composition (body mass index and waist circumference), dietary habits (sugar- and fat-rich food intake, vegetables and fruit intake), psychosocial stress (events, emotions, behaviour), sleep duration, physical activity, and residential environmental quality (longterm black carbon, particulate matter exposure, and residential green space). Cross-sectional (n=182) and longitudinal (n=150) analyses were assessed using linear regression models, adjusting for age, sex, socioeconomic status and multiple testing. RESULTS: Our longitudinal analyses showed that higher residential green space at baseline was associated with (ß=0.261, p=0.002) lower telomere attrition and that children with a higher waist circumference at baseline showed a higher telomere attrition (ß=-0.287, p=0.001). These two predictors were confirmed via LASSO variable selection and correction for multiple testing. In addition, children with more unhealthy exposures at baseline had a significantly higher telomere attrition over the follow-up period compared to children with more healthy exposures (ß=-0.200, p=0.017). DISCUSSION: Waist circumference and residential green space were identified as predictors associated with telomere attrition in childhood. These results further support the advantages of a healthy lifestyle from early age onwards and the importance of a green environment to promote molecular longevity from childhood onwards.

Residential green space in association with the methylation status in a CpG site within the promoter region of the placental serotonin receptor HTR2A.

Green space could influence adult cognition and childhood neurodevelopment , and is hypothesized to be partly driven by epigenetic modifications. However, it remains unknown whether some of these associations are already evident during foetal development. Similar biological signals shape the developmental processes in the foetal brain and placenta.Therefore, we hypothesize that green space can modify epigenetic processes of cognition-related pathways in placental tissue, such as DNA-methylation of the serotonin receptor HTR2A. HTR2A-methylation was determined within 327 placentas from the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort using bisulphite-PCR-pyrosequencing. Total green space exposure was calculated using high-resolution land cover data derived from the Green Map of Flanders in seven buffers (50 m-3 km) and stratified into low (<3 m) and high (≥3 m) vegetation. Residential nature was calculated using the Land use Map of Flanders. We performed multivariate regression models adjusted for several a priori chosen covariables. For an IQR increment in total green space within a 1,000 m, 2,000 m and 3,000 m buffer the methylation of HTR2A increased with 1.47% (95%CI:0.17;2.78), 1.52% (95%CI:0.21;2.83) and 1.42% (95%CI:0.15;2.69), respectively. Additionally,, we found 3.00% (95%CI:1.09;4.91) and 1.98% (95%CI:0.28;3.68) higher HTR2A-methylation when comparing residences with and without the presence of nature in a 50 m and 100 m buffer, respectively. The methylation status of HTR2A in placental tissue is positively associated with maternal green space exposure. Future research is needed to understand better how these epigenetic changes are related to functional modifications in the placenta and the consequent implications for foetal development.

Higher buccal mtDNA content is associated with residential surrounding green in a panel study of primary school children.

BACKGROUND: Mitochondria are known to respond to environmental stressors but whether green space is associated with mitochondrial abundance is unexplored. Furthermore, as exposures may affect health from early life onwards, we here evaluate if residential green space is associated with mitochondria DNA content (mtDNAc) in children. METHODS: In primary schoolchildren (COGNAC study), between 2012 and 2014, buccal mtDNAc was repeatedly (three times) assessed using qPCR. Surrounding low (<3m), high (≥3m) and total (sum of low and high) green space within different radii (100m-1000m) from the residence and distance to the nearest large green space (>0.5ha) were estimated using a remote sensing derived map. Given the repeated measures design, we applied a mixed-effects model with school and subject as random effect while adjusting for a priori chosen fixed covariates. RESULTS: mtDNAc was assessed in 246 children with a total of 436 measurements (mean age 10.3 years). Within a 1000m radius around the residential address, an IQR increment in low (11.0%), high (9.5%), and total (13.9%) green space was associated with a respectively 15.2% (95% CI: 7.2%-23.7%), 10.8% (95% CI: 4.5%-17.5%), and 13.4% (95% CI: 7.4%-19.7%) higher mtDNAc. Conversely, an IQR increment (11.6%) in agricultural area in the same radius was associated with a -3.4% (95% CI: 6.7% to -0.1%) lower mtDNAc. Finally, a doubling in distance to large green space was associated with a -5.2% (95% CI: 7.9 to -2.4%) lower mtDNAc. CONCLUSION: To our knowledge, this is the first study evaluating associations between residential surrounding green space and mtDNAc in children. Our results showed that green space was associated with a higher mtDNAc in children, which indicates the importance of the early life environment. To what extent these findings contribute to later life health effects should be further examined.

Methylome-wide analysis of IVF neonates that underwent embryo culture in different media revealed no significant differences.

A growing number of children born are conceived through in vitro fertilisation (IVF), which has been linked to an increased risk of adverse perinatal outcomes, as well as altered growth profiles and cardiometabolic differences in the resultant individuals. Some of these outcomes have also been shown to be influenced by the use of different IVF culture media and this effect is hypothesised to be mediated epigenetically, e.g. through the methylome. As such, we profiled the umbilical cord blood methylome of IVF neonates that underwent preimplantation embryo development in two different IVF culture media (G5 or HTF), using the Infinium Human Methylation EPIC BeadChip. We found no significant methylation differences between the two groups in terms of: (i) systematic differences at CpG sites or regions, (ii) imprinted sites/genes or birth weight-associated sites, (iii) stochastic differences presenting as DNA methylation outliers or differentially variable sites, and (iv) epigenetic gestational age acceleration.

Indoor green can modify the indoor dust microbial communities.

Little is known about the potential role of indoor plants in shaping the indoor microbiota. Within the ENVIRONAGE birth cohort, we collected settled dust and performed 16S and ITS amplicon sequencing and qPCR measurements to characterize the indoor microbiota, including bacterial and fungal loads and Chao1 richness, Shannon, and Simpson diversity indices. For 155 households, we obtained information on the number of indoor plants. We performed linear regression models adjusted for several a priori chosen covariables. Overall, an increase in indoor plants and density was associated with increased microbial diversity, but not load. For example, we found an increase of 64 (95%CI:3;125) and 26 (95%CI:4;48) units of bacterial and fungal taxa richness, respectively, in households with more than three plants compared to no plants. Our results support the hypothesis that indoor plants can enrich indoor microbial diversity, while impacts on microbial loads are not obvious.

Residential green space is associated with a buffering effect on stress responses during the COVID-19 pandemic in mothers of young children, a prospective study.

Green spaces are associated with increased well-being and reduced risk of developing psychiatric disorders. In this study, we aimed to investigate how residential proximity to green spaces was associated with stress response buffering during the COVID-19 pandemic in a prospective cohort of young mothers. We collected information on stress in 766 mothers (mean age: 36.6 years) from the ENVIRONAGE birth cohort at baseline of the study (from 2010 onwards), and during the COVID-19 pandemic (from December 2020 until May 2021). Self-reported stress responses due to the COVID-19 pandemic were the outcome measure. Green space was quantified in several radiuses around the residence based on high-resolution (1 m2) data. Using ordinal logistic regression, we estimated the odds of better resistance to reported stress, while controlling for age, socio-economic status, stress related to care for children, urbanicity, and household change in income during the pandemic. In sensitivity analyses we corrected for pre-pandemic stress levels, BMI, physical activity, and changes in health-related habits during the pandemic. We found that for an inter-quartile range contrast in residential green space 300 m and 500 m around the residence, participants were respectively 24% (OR = 1.24, 95%CI: 1.03 to 1.51) and 29% (OR = 1.29, 95%CI: 1.04 to 1.60) more likely to be in a more resistant category, independent of the aforementioned factors. These results remained robust after additionally controlling for pre-pandemic stress levels, BMI, physical activity, smoking status, urbanicity, psychological disorders, and changes in health-related habits during the pandemic. This prospective study in young mothers highlights the importance of proximity to green spaces, especially during challenging times.

Early life exposure to residential green space impacts cognitive functioning in children aged 4 to 6 years.

INTRODUCTION: During early childhood, neuronal networks are highly susceptible to environmental factors. Previous research suggests that green space exposure is beneficial for cognitive functioning. Here, we investigate the associations between residential green space exposure and behavioral problems and cognitive development in children aged four to six years. METHOD: We included children participating in the ENVIRONAGE birth cohort. Residential green spaces were calculated based on high-resolution land cover data within several buffers (50-1,000 m) around the residence. The children's behavior was assessed with the Strengths and Difficulties Questionnaire (SDQ) among 411 children. In addition, to evaluate cognitive function, 456 children completed four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We used multivariate logistic and linear regression models while accounting for potential confounders and covariables. RESULTS: An interquartile (IQR) increase of residential green space within 50 m was associated with a 38% (95% CI: 56;14) lower odds of a child having hyperactivity problems. Additionally, we found a beneficial influence of residential green space in close proximity (50-100 m) on the attention and psychomotor speed, represented by the Motor Screening Task. For example, we found a decrease of 0.45 (95% CI: -0.82;-0.09) pixel units from target center with an IQR increase of residential green space in a 50 m buffer. In addition, we observed an improved visual recognition/working memory, represented by the Delayed Matching to Sample Task within all included buffers (50-1000 m). For example, we observed a decrease of 4.91% (95 %CI: -7.46;-2.36) probability of an error occurring if the previous trial was correct and a 2.02% (95 %CI: 0.08; 3.97) increase of correct trials with an IQR increase of green space within a 100 m buffer. CONCLUSION: This study provides additional indications for a beneficial influence of green space exposure on the development of behavioral problems and cognitive function as young as four years of age.

Higher surrounding green space is associated with better attention in Flemish adolescents.

INTRODUCTION: Previous studies suggested that green space is beneficial for the cognitive development in children. However, evidence in adolescents is limited. Therefore, we aim to investigate green space exposure in association with attention and behaviour in adolescents. METHODS: This study includes 596 Flemish adolescents between 13 and 17 years old. Attention was assessed with Stroop Test (selective attention) and Continuous Performance Test (sustained and selective attention). Behaviour was determined based on the Strengths and Difficulties Questionnaire. Green space was estimated in several radius distances around their current residence and school based on high-resolution land cover data. Multilevel regression analyses were used adjusting for participant's age, sex, education level of the mother, and area deprivation index. RESULTS: Surrounding green space in a 2000 m radius is associated with a faster reaction time in adolescents. An IQR (13%) increment in total green space within 2000 m of the residence and school combined, is associated with a 32.7 ms (95% CI: -58.9 to -6.5; p = 0.02) and a 7.28 ms (95% CI: -11.7 to -2.8; p = 0.001) shorter mean reaction time between the presentation of a stimulus and the response based on the Stroop Test and the Continuous Performance Test. Subdividing green space based on vegetation height, shows that green space higher than 3 m is associated with a faster reaction time of the Continuous Performance Test (-6.50 ms; 95% CI: -10.9 to -2.2; p = 0.004), while low green is not. We did not find an association between green space and behavioural development in adolescents. CONCLUSIONS: Our study shows that green space, especially trees, surrounding the residence and school combined is associated with better sustained and selected attention in adolescents. These findings indicate that the availability of green is important for adolescents that are growing up in a rapidly urbanizing world.

Determinants of Chronic Biological Stress, Measured as Hair Cortisol Concentration, in a General Population of Adolescents: From Individual and Household Characteristics to Neighborhood Urbanicity.

Chronic biological stress may adversely affect adolescents' physical and mental health, but insight in the personal and environmental factors that determine chronic stress is limited. We measured 3-month cumulative hair cortisol concentration (HCC) in 419 adolescents, participating in the Flemish Environment and Health Study. Adolescents' health and lifestyle characteristics, household and neighborhood socio-economic status as well as neighborhood urbanicity were assessed as potential determinants of HCC, using multiple linear regression models. We additionally explored heterogeneity of our results by sex. HCC were significantly higher in boys from densely populated neighborhoods, the association was not significant in girls. Accordingly, boys living outside cities had significantly lower HCC than boys, living in cities. HCC was significantly lower in adolescents with an optimal vitality, a measure of a positive mental health status. In adolescent girls, menarcheal status (pre-/postmenarche) was a significant determinant of HCC. Our findings are the first to suggest that residential urbanicity may have an impact on chronic biological stress in a general population of adolescent boys.