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Residential green as a determinant of the indoor microbiota and the link with early-life cognition
No full textIt is well established that exposure to greener environments is associated with an
improved mental wellbeing and with cognitive developmental processes. Of
particular interest are the vulnerable windows of fetal and childhood development,
characterized by neuronal networks that are highly susceptible to environmental
exposures and in which changes to cognitive-related outcomes are proven to have
profound effects in later-life. However, the underlying biological mechanisms
through which green space can exert its influence on cognition are still being
investigated. Considering the fact that surrounding green space accommodates
highly diverse microbial communities, one of the proposed explanations is through
the exposure to environmental microbial agents.
Within this PhD project the main objective was to investigate the associations
between early life exposure to residential green and cognitive and behavioral
development in the first years of life. In addition, within this PhD project we
wanted to elucidate the underlying mechanisms interconnecting residential green
and early-life cognition, with a specific focus on the role of the indoor dust
microbiota. The work for this thesis was conducted within the Environmental
Influences on Early Ageing (ENVIRONAGE) birth cohort through which detailed
data on exposure information and clinical outcomes from newborns and children
could be obtained. In addition, we performed visits to the homes of four to six
year old children to characterize the indoor settled dust microbiota.
This dissertation starts with a general introduction, followed by the research
outputs and ends with a general discussion and conclusions. The research outputs
are divided in three parts and five chapters. Part I includes the research on the
influence of green space exposures on cognition-related outcomes, and includes
two chapters (Chapter one and two) In Chapter one, we investigated the
association between green space exposure and behavior and cognitive function of
children aged four to six years. In Chapter two, we investigated the relationship
between maternal green space exposure during pregnancy and DNA methylation
of the placental serotonin receptor, HTR2A, which is involved in infant
neurobehavioral outcomes.
A proposed underlying mechanism through which green space may influence
cognition is through exposure to environmental microbial communities. Therefore, in part II, we first investigated green space (Chapter three) and indoor green,
as represented by indoor plants (Chapter four) as potential determinants of
indoor dust microbial communities. Finally, in part III consisting of Chapter five,
we investigated the association between exposure to indoor dust microbiota and
behavioral and cognitive function of children. A summary of each chapter is shown
in Table 1.Het is algemeen bekend dat blootstelling aan groenere omgevingen kan worden
gelinkt aan een verbeterd mentaal welzijn en dat deze betrokken is bij cognitieve
ontwikkelingsprocessen. Van bijzonder belang zijn de kwetsbare
ontwikkelingsfasen, namelijk de prenatale periode en de kindertijd, die
gekenmerkt zijn door neuronale netwerken die zeer gevoelig zijn voor
blootstelling aan de omgeving en waarvan is aangetoond dat cognitiegerelateerde veranderingen ingrijpende effecten kunnen hebben op het latere
leven. Er is echter nog onderzoek nodig naar de onderliggende biologische
mechanismen waardoor groene ruimte van invloed is op cognitie. Aangezien de
omliggende groene ruimte zeer diverse microbiële gemeenschappen bevat, wordt
de blootstelling aan microbiota in de natuurlijk omgeving voorgesteld als één van
de mogelijke verklaringen.
Binnen dit doctoraatsproject was het hoofddoel het onderzoeken van de
associaties tussen de blootstelling van residentieel groen op jonge leeftijd en de
ontwikkeling van gedrag en cognitie in de eerste levensjaren. Daarboven, wilden
we de relaties en onderliggende mechanismen die residentieel groen en cognitie
op jonge leeftijd met elkaar verbinden ophelderen, met een specifieke focus op
de rol van microbiota in binnenhuisstof. Het werk voor dit proefschrift is
uitgevoerd binnen het geboortecohort Environmental Influences on Early Aging
(ENVIRONAGE), waarmee gedetailleerde blootstellingsinformatie en klinische
uitkomsten van de prenatale periode en de kindertijd konden worden verkregen.
Daarnaast hebben we huisbezoeken uitgevoerd bij vier tot zesjarige kinderen om
de microbiota in huisstof te karakteriseren.
Dit proefschrift start met een algemene introductie, gevolgd door de
onderzoeksoutput en eindigt met een algemene discussie en conclusie. De
onderzoeksoutput is opgedeeld in drie delen en vijf hoofdstukken die zijn
onderverdeeld in drie delen. Deel I omvat het onderzoek naar de invloed van de
blootstelling aan groene ruimte en cognitie-gerelateerde gezondheidsuitkomsten
(Hoofdstuk één en twee). In Hoofdstuk één onderzochten we de associatie
tussen blootstelling aan groene ruimte en gedrag en cognitieve functie van
kinderen van vier tot zes jaar. In Hoofdstuk twee hebben we de relatie
onderzocht tussen blootstelling van de moeder aan groene ruimte tijdens de zwangerschap en DNA-methylatie van de placenta serotoninereceptor, HTR2A, die
betrokken is bij neurologische gedragsuitkomsten bij pasgeborenen.
Een voorgesteld onderliggend mechanisme waardoor groene ruimte een invloed
kan hebben op cognitie, is via de blootstelling aan microbiële gemeenschappen.
Daarom hebben we in deel II eerst groene ruimte onderzocht (in Hoofdstuk drie)
en groen binnenshuis, vertegenwoordigd door kamerplanten, (in Hoofdstuk
vier) als potentiële determinanten van microbiële gemeenschappen in huisstof.
Ten slotte, in deel III, bestaande uit Hoofdstuk vijf, onderzochten we de
associatie tussen de blootstelling aan microbiota in huisstof en cognitie van
kinderen. Een samenvatting van elk hoofdstuk wordt getoond in Tabel 1
Residential green space can shape the indoor microbial environment
No full textBACKGROUND: The influence of outdoor green space on microbial communities indoors has scarcely been investigated. Here, we study the associations between nearby residential green space and residential indoor microbiota. METHODS: We collected settled dust from 176 living rooms of participants of the ENVIRONAGE birth cohort. We performed 16S and ITS amplicon sequencing, and quantitative PCR measurements of total bacterial and fungal loads to calculate bacterial and fungal diversity measures (Chao1 richness, Shannon and Simpson diversity indices) and relative abundance of individual taxa. Green spaces were estimated within 50m and 100m buffers around the residential address. We defined total residential green space using high-resolution land-cover data, further stratified in low-growing (height3m). We used land-use data to calculate the residential nature. We ran linear regression models, adjusting for confounders and other potential determinants. Results are expressed as units change for an interquartile range (IQR) increase in residential green space and their 95% confidence intervals (CI). RESULTS: After adjustment, we observed statistically significant associations between the indoor microbial diversity indices and nearby residential green space. For bacteria, the Shannon index was directly associated with residential nature (e.g. 0.08 units increase (CI:0.02,0.13) per IQR increase in nature within a 50m buffer). Fungal diversity was directly associated with high-growing residential green and inversely with low-growing green. For example, an IQR increase in high-growing green within a 50m buffer was associated with increases in 0.14 (CI:0.01,0.27) and 0.02 (CI:0.008,0.04) units in the Shannon and Simpson indices, respectively. CONCLUSIONS: Nearby green space determines the diversity of indoor environment microbiota, and the type of green differently impacts bacterial and fungal diversity. Further research is needed to investigate in more detail possible microbial taxa compositions underlying the observed changes in indoor microbiota diversity and to explore their contribution to beneficial health effects associated with green space exposure.sponsorship: This investigation is supported by the EU research council "project ENVIRONAGE" (ERC-2012-StG 310,890) and Flemish Scientific Fund (G073315N/G048420N) . These measurements are done within the research projects of the Research Foundation Flanders (FWO) , grant number 1518019N, the BELSPO Brain project and Science and Technology in childhood Obesity Policy (STOP) that is part of the HORIZON2020. Lidia Casas is recipient of a post-doctoral fellowship a of the Research Foundation Flanders (FWO) , grant number 12I1517N. Esmee M Bijnens holds a fellowship from the Marguerite-Marie Delacroix foundation. The work at the Finnish Institute for Health and Welfare was supported by the Academy of Finland grant 296817. (EU research council "project ENVIRONAGE" (ERC-2012-StG)|310,890, Flemish Scientific Fund|G073315N/G048420N, Research Foundation Flanders (FWO)|1518019N, Research Foundation Flanders (FWO)|12I1517N, Marguerite-Marie Delacroix foundation, Academy of Finland|296817)status: Publishe
Air pollution exposure and bone mineral density in young children: results from the ENVIRONAGE birth cohort
No full textPrevious epidemiological studies have suggested that air pollution exposure has an adverse effect on bone health in older individuals. However , no studies on early life exposure to air pollution and childhood bone mineral density have been reported. Therefore, this study aims to investigate whether long-term exposure to air pollution is associated with a change in bone mineral density in young children. Within the ongoing prospective birth cohort ENVIRONAGE (Envi-ronmental Influence on Ageing in Early Life), a total of 478 children aged 4-6 were followed-up. Radial bone mineral density (m/s) was assessed using a quantitative ultrasound method. The residential air pollution exposure (μg/m 3) one year before the follow-up was estimated using a high-resolution spatial-temporal interpolation method. Multiple linear regression models were used after adjusting for relevant covariates and potential confounders. Radial bone mineral density was on average (SD) 3680.84 (112.39) m/s. An interquartile (IQR) increment in long-term exposure to PM 2.5 (2.54 μg/m 3) and PM 10 (3.65 μg/m 3) was associated with a decrease of 24.81 m/s (95% CI:-42.55% to-7.07%, p=0.006) and 26.24 m/s (95% CI:-41.95% to 10.54%, p=0.001) in bone mineral density, respectively. On the other hand, no significant associations were observed for long-term exposure to nitrogen dioxide and black carbon. These findings provide evidence that long-term exposure to particulate matter has a relevant effect on childhood bone mineral density. Moreover, this study reinforces the need for increased public health policies and awareness campaigns on air quality improvement with long-term implications on bone health.Flemish Scientific Fund [G073315N/G048420N/G026222P]; European Unio
Air pollution exposure and bone mineral density in young children: results from the ENVIRONAGE birth cohort
No full textPrevious epidemiological studies have suggested that air pollution exposure has an adverse effect on bone health in older individuals. However , no studies on early life exposure to air pollution and childhood bone mineral density have been reported. Therefore, this study aims to investigate whether long-term exposure to air pollution is associated with a change in bone mineral density in young children. Within the ongoing prospective birth cohort ENVIRONAGE (Envi-ronmental Influence on Ageing in Early Life), a total of 478 children aged 4-6 were followed-up. Radial bone mineral density (m/s) was assessed using a quantitative ultrasound method. The residential air pollution exposure (μg/m 3) one year before the follow-up was estimated using a high-resolution spatial-temporal interpolation method. Multiple linear regression models were used after adjusting for relevant covariates and potential confounders. Radial bone mineral density was on average (SD) 3680.84 (112.39) m/s. An interquartile (IQR) increment in long-term exposure to PM 2.5 (2.54 μg/m 3) and PM 10 (3.65 μg/m 3) was associated with a decrease of 24.81 m/s (95% CI:-42.55% to-7.07%, p=0.006) and 26.24 m/s (95% CI:-41.95% to 10.54%, p=0.001) in bone mineral density, respectively. On the other hand, no significant associations were observed for long-term exposure to nitrogen dioxide and black carbon. These findings provide evidence that long-term exposure to particulate matter has a relevant effect on childhood bone mineral density. Moreover, this study reinforces the need for increased public health policies and awareness campaigns on air quality improvement with long-term implications on bone health.Flemish Scientific Fund [G073315N/G048420N/G026222P]; European Unio
Association of Newborn Telomere Length With Blood Pressure in Childhood
No full textIMPORTANCE: Adult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease. OBJECTIVE: To evaluate whether newborn TL is associated with early life blood pressure differences in childhood. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was part of the ENVIRONAGE (Environmental Influence on Aging in Early Life) study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021. MAIN OUTCOMES AND MEASURES: Cord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure (standardized for child age, sex, and height) was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood. RESULTS: This study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a –1.54 mm Hg (95% CI, –2.36 to –0.72 mm Hg) lower diastolic blood pressure and –1.18 mm Hg (95% CI, –1.89 to –0.46 mm Hg) lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years (adjusted OR, 0.72; 95% CI, 0.53 to 0.98). In placenta, a 1-IQR increase in TL was associated with a –0.96 mm Hg (95% CI, –1.72 to –0.21 mm Hg) lower diastolic, –0.88 mm Hg (95% CI, –1.54 to –0.22 mm Hg) lower MAP, and a lower adjusted OR of 0.69 (95% CI, 0.52 to 0.92) for having a high blood pressure in childhood. CONCLUSIONS AND RELEVANCE: In this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming
Associations between urinary paraben concentrations and measures of cardiometabolic risk in pre-school children of the ENVIRONAGE birth cohort
No full textBackground and Aim: Parabens are widely used as antimicrobial preservatives in personal care products. Endocrine-disrupting effects have been described previously, but studies investigating obesogenic or cardiovascular effects have shown discordant results. Cardiometabolic changes associated with paraben exposure and predictive for later life health conditions may already be visible in early life. Methods: Paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples from 4-6-year-old children of the ENVIRONAGE birth cohort. Values below the limit of quantification (LOQ) were imputed by censored likelihood multiple imputations. The association with anthropometric and cardiovascular measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) was analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. Results: The geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the (LOQ) were 32.60 (6.64), 1.26 (3.50), and 4.82 (4.11) µg/L respectively. For BuP 97% of all measurements were below the LOQ. In adjusted models with log-transformed paraben values MeP was associated with central retinal venular equivalent (β = 1.33, p = 0.029) and inversely associated with BMI z-scores (β =-0.065, p = 0.019). PrP was associated with the retinal tortuosity index (β = 0.0018, p = 0.0034). Additionally, EtP was significantly associated with BMI z-scores in boys (β = 0.12, p = 0.012). Conclusions: The inverse association between MeP and BMI z-scores could illustrate underlying biological mechanisms related to endocrine-disrupting properties of parabens. Associations between parabens and retinal microvasculature in preschool children may indicate adverse effects on cardiometabolic health even at a young age and provide a starting point for further research on paraben-related modes of action
Exposure to Residential Green Space and Bone Mineral Density in Young Children
No full textImportance: 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..</p
Exposure to endocrine disrupters and cardiometabolic health effects in preschool children: Urinary parabens are associated with wider retinal venular vessels.
Full text linkpeer reviewed[en] BACKGROUND AND AIM: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life.
METHODS: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms.
RESULTS: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) μg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (β = 1.23, p = 0.039) and PrP with the retinal tortuosity index (β = 0.0018, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (β = -0.067, p = 0.015 and β = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (β = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (β = 0.10, p = 0.060).
CONCLUSIONS: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature
Association of indoor dust microbiota with cognitive function and behavior in preschool-aged children
No full textBACKGROUND: Childhood cognitive development depends on neuroimmune interactions. Immunomodulation by early-life microbial exposure may influence neuropsychological function. In this study, we investigate the association between residential indoor microbiota and cognition and behavior among preschoolers. RESULTS: Indoor-settled dust bacterial and fungal characteristics were assessed using 16S and ITS amplicon sequencing (microbial diversity) and qPCR measurements (microbial loads). Child behavior was assessed using four scales: peer relationship, emotional, conduct, and hyperactivity was assessed by the Strengths and Difficulties Questionnaire (SDQ). Cognitive function was assessed using four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB) software. The first two tasks were designed to assess attention and psychomotor speed (Motor Screening (MOT) and Big/Little Circle (BLC)) and the last two to evaluate the child’s visual recognition/working memory (Spatial Span (SSP) and Delayed Matching to Sample (DMS)). Among the 172 included children (age 4–6 years), we observed a 51% (95%CI;75%;9%) lower odds of children scoring not normal for hyperactivity and a decrease of 3.20% (95%CI, −6.01%; −0.30%) in BLC response time, for every IQR increase in fungal Shannon diversity. Contrarily, microbial loads were directly associated with SDQ scales and response time. For example, a 2-fold increase in Gram-positive bacterial load was associated with 70% (95%CI 18%; 156%) higher odds of scoring not normal for hyperactivity and an increase of 5.17% (95%CI 0.87%; 9.65%) in DMS response time. CONCLUSIONS: Our findings show that early-life exposure to diverse indoor fungal communities is associated with better behavioral and cognitive outcomes, whereas higher indoor microbial load was associated with worse outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01406-9
Dynamics of skin microvascular blood flow in 4–6-year-old children in association with pre- and postnatal black carbon and particulate air pollution exposure
No full textBackground: A growing body of evidence indicates that cardiovascular health in adulthood, particularly that of the microcirculation, could find its roots during prenatal development. In this study, we investigated the association between pre- and postnatal air pollution exposure on heat-induced skin hyperemia as a dynamic marker of the microvasculature. Methods: In 139 children between the ages of 4 and 6 who are followed longitudinally within the ENVIRONAGE birth cohort, we measured skin perfusion by Laser Doppler probes using the Periflux6000. Residential black carbon (BC), particulate (PM10 and PM2.5) air pollution, and nitrogen dioxide (NO2) levels were modelled for each participant's home address using a high-resolution spatiotemporal model for multiple time windows. We assessed the association between skin hyperemia and pre- and postnatal air pollution using multiple regression models while adjusting for relevant covariates. Results: Residential BC exposure during the whole pregnancy averaged (IQR) 1.42 (1.22–1.58) µg/m3, PM10 18.88 (16.64 – 21.13) µg/m3, PM2.5 13.67 (11.5 – 15.56) µg/m3 and NO2 18.39 (15.52 – 20.31) µg/m3. An IQR increment in BC exposure during the third trimester of pregnancy was associated with an 11.5 % (95% CI: −20.1 to −1.9; p = 0.020) lower skin hyperemia. Similar effect estimates were retrieved for PM10, PM2.5 and NO2 (respectively 13.9 % [95% CI: −21.9 to −3.0; p = 0.003], 17.0 % [95% CI: −26.7 to −6.1; p = 0.004] and 12.7% [95 % CI: –22.2 to −1.9; p = 0.023] lower skin hyperemia). In multipollutant models, PM2.5 showed the strongest inverse association with skin hyperemia. Postnatal exposure to BC, PM10, PM2.5 or NO2, was not associated with skin hyperemia at the age of 4 to 6, and did not alter the previous reported prenatal associations when taken into account. Conclusion: Our findings support that BC, particulate air pollution, and NO2 exposure, even at low concentrations, during prenatal life, can have long-lasting consequences for the microvasculature. This proposes a role of prenatal air pollution exposures over and beyond postnatal exposure in the microvascular alterations which were persistent into childhood
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