Title Participants Abstract "Household air pollution and risk of pulmonary tuberculosis in HIV-Infected adults" "Patrick D. M. C. Katoto, Dieudonne Bihehe, Amanda Brand, Raymond Mushi, Aline Kusinza, Brian W. Alwood, Richard N. van Zyl-Smit, Jacques L. Tamuzi, Nadia A. Sam-Agudu, Marcel Yotebieng, John Metcalfe, Grant Theron, Krystal J. Godri Pollitt, Maia Lesosky, Jeroen Vanoirbeek, Kevin Mortimer, Tim NAWROT, Benoit Nemery, Jean B. Nachega" "Background In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection.Methods We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 - March 2019). Cases had current or recent (3h/day and >= 2 times/day and >= 5 days/week were more likely to have PTB (aOR 136; 95%CI 106-175) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 464 (95%CI 11-207) for the highest quintile [123-762 ppm] compared to the lowest quintile [01-19 ppm].Conclusion Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women." "OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients" "Yu-Ling Yu, Qi-Fang Huang, Dewei AN, Julia Raad, Dries MARTENS, Agnieszka Latosinska, Katarzyna Stolarz-Skrzypek, Johan Van Cleemput, Ying-Qing Feng, Harald Mischak, Karel Allegaert, Peter Verhamme, Jan A. Staessen, Tim NAWROT, Stefan Janssens" "Background: Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix. Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins. Methods: A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30 % of patients. Applying statistical analysis on these, an 18- peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis. Results: In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95 % CI: 0.76–0.90), 74.3 % and 87.1 %, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6 %]), the ORs for osteoporosis increased (p < 0.0001) across OSTEO18 quartiles from 0.39 (95 % CI: 0.25–0.61) to 3.14 (2.08–4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p =0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p =0.0004) for OSTEO18 as continuously distributed classifier. Conclusion: OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic." "Folic Acid Supplementation during Pregnancy and Its Association with Telomere Length in Children at Four Years: Results from the INMA Birth Cohort Study" "Fanny Petermann-Rocha, Desirée Valera-Gran, Daniel Prieto-Botella, Dries MARTENS, Sandra Gonzalez-Palacios, Isolina Riaño-Galán, Mario Murcia, Amaia Irizar, Jordi Julvez, Loreto Santa-Marina, Adonina Tardón, Jordi Sunyer, Jesús Vioque, Tim NAWROT, Eva-María Navarrete-Muñoz" "Martens, D.S.; Gonzalez-Palacios, S.; Riaño-Galán, I.; Murcia, M.; Irizar, A.; Julvez, J.; Santa-Marina, L.; et al. Folic Acid Supplementation during Pregnancy and Its Association with Abstract: This study examined the association between folic acid supplements (FAs) during different periods of pregnancy and offspring telomere length (TL) at age four in 666 children from the INMA study. FAs were self-reported using food-structured questionnaires during three periods of pregnancy (the first three months of pregnancy, from month fourth onward, and the whole pregnancy). For each period, the average daily dosage of FAs was categorised into (i)" "Air pollution exposure and bone mineral density in young children: results from the ENVIRONAGE birth cohort" "Ana Inês BENTO FONSECA E SILVA, Hanne SLEURS, Yinthe DOCKX, Leen RASKING, Congrong WANG, Michelle PLUSQUIN, Esmee BIJNENS, Tim NAWROT" "Previous 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." "Sedentary Behaviour and Telomere Length Shortening during Early Childhood: Evidence from the Multicentre Prospective INMA Cohort Study" "Daniel Prieto-Botella, Dries MARTENS, Desiree Valera-Gran, Mikel Subiza-Pérez, Adonina Tardón, Manuel Lozano, Maribel Casas, Mariona Bustamante, Alba Jimeno-Romero, Ana Fernández-Somoano, Sabrina Llop, Martine Vrijheid, Tim NAWROT, Eva-María Navarrete-Muñoz" "Sedentary behaviour (SB) may be related to telomere length (TL) attrition due to a possible pro-inflammatory effect. This study examined the association between parent-reported sedentary behaviour (SB) and leukocyte TL at the age of 4 and telomere tracking from 4 to 8 years. In the Spanish birth cohort Infancia y Medio Ambiente (INMA) project, we analysed data from children who attended follow-up visits at age 4 (n = 669) and 8 (n = 530). Multiple robust regression models were used to explore the associations between mean daily hours of SB (screen time, other sedentary activities, and total SB) at 4 years categorised into tertiles and TL at 4 years and difference in TL rank between age 4 and 8, respectively. At the age of 4, the results showed that children with the highest screen time (1.6–5.0 h/day) had a shorter TL of −3.9% (95% CI: −7.4, −0.4; p = 0.03) compared with children in the lowest tertile (0.0–1.0 h/day). Between 4 and 8 years, a higher screen time (highest tertile group vs. lowest tertile) was associated with a decrease in the LTL rank of −1.9% (95% CI: −3.8, −0.1; p = 0.03) from 4 to 8 years. Children exposed to a higher screen time at 4 years were more prone to have shorter TL at 4 and between 4 and 8 years of age. This study supports the potential negative effect of SB during childhood on cellular longevity." "Association of urinary and ambient black carbon, and other ambient air pollutants with risk of prediabetes and metabolic syndrome in children and adolescents" "Rajini Nagrani, Manuela Marron, Eva BONGAERTS, Tim NAWROT, Marcel AMELOOT, Kees de Hoogh, Danielle Vienneau, Emeline Lequy, Benedicte Jacquemin, Kathrin Guenther, Thais DE RUYTER, Kirsten Mehlig, Denes Molnar, Luis A. Moreno, Paola Russo, Toomas Veidebaum, Wolfgang Ahrens, Christoph Buck" "The effects of exposure to black carbon (BC) on various diseases remains unclear, one reason being potential exposure misclassification following modelling of ambient air pollution levels. Urinary BC particles may be a more precise measure to analyze the health effects of BC. We aimed to assess the risk of prediabetes and metabolic syndrome (MetS) in relation to urinary BC particles and ambient BC and to compare their associations in 5453 children from IDEFICS/I. Family cohort. We determined the amount of BC particles in urine using label-free white-light generation under femtosecond pulsed laser illumination. We assessed annual exposure to ambient air pollutants (BC, PM2.5 and NO2) at the place of residence using land use regression models for Europe, and we calculated the residential distance to major roads (" "Associations of four biological age markers with child development: a multi-omic analysis in the European HELIX cohort" "Oliver Robinson, Chung-Ho E Lau, Sungyeon Joo, Sandra Andrusaityte, Eva Borras, Paula de Prado-Bert, Lida Chatzi, Hector C Keun, Regina Grazuleviciene, Kristine Bjerve Gutzkow, Lea Maitre, Dries MARTENS, Eduard Sabido, Valérie Siroux, Jose Urquiza, Marina Vafeiadi, John Wright, Mariona Bustamante, Tim NAWROT, Martine Vrijheid" "Background: While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators , to child developmental outcomes, including growth and adiposity, cognition, behaviour, lung function and onset of puberty, among European school-age children participating in the HELIX exposome cohort. Methods: The study population included up to 1,173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece. Telomere length was measured through qPCR, blood DNA methylation and gene expression was measured using microarray, and proteins and metabolites were measured by a range of targeted assays. DNA methylation age was assessed using Horvath's skin and blood clock, while novel blood transcriptome and 'immunometabolic' (based on plasma protein and urinary and serum metabolite data) clocks were derived and tested in a subset of children assessed six months after the main follow-up visit. Associations between biological age indicators with child developmental measures as well as health risk factors were estimated using linear regression, adjusted for chronological age, sex, ethnicity and study centre. The clock derived markers were expressed as Δ age (i.e., predicted minus chronological age). Results: Transcriptome and immunometabolic clocks predicted chronological age well in the test set (r= 0.93 and r= 0.84 respectively). Generally, weak correlations were observed, after adjustment for chronological age, between the biological age indicators. Among associations with health risk factors, higher birthweight was associated with greater immunometabolic Δ age, smoke exposure with greater DNA methylation Δ age and high family affluence with longer telomere length. Among associations with child developmental measures, all biological age markers were associated with greater BMI and fat mass, and all markers except telomere length were associated with greater height, at least at nominal significance (p" "Association of indoor dust microbiota with cognitive function and behavior in preschool-aged children" "Yinthe DOCKX, Martin Taeubel, Janneke HOGERVORST, Leen LUYTEN, Martien PEUSENS, Hanne SLEURS, Katrien WITTERS, Michelle PLUSQUIN, Maria Valkonen, Tim NAWROT, Lidia CASAS RUIZ" "Background: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." "Accumulation of Black Carbon Particles in Placenta, Cord Blood, and Childhood Urine in Association with the Intestinal Microbiome Diversity and Composition in Four- to Six-Year-Old Children int he ENVIRONAGE Birth Cohort" "Thessa VAN PEE, Janneke HOGERVORST, Yinthe DOCKX, Katrien WITTERS, Sofie THIJS, Congrong WANG, Eva BONGAERTS, Jonathan D. Van Hamme, Jaco VANGRONSVELD, Marcel AMELOOT, Jeroen Raes, Tim NAWROT" "BACKGROUND: The gut microbiome plays an essential role in human health. Despite the link between air pollution exposure and various diseases, its association with the gut microbiome during susceptible life periods remains scarce. OBJECTIVES: In this study, we examined the association between black carbon particles quantified in prenatal and postnatal biological matrices and bacterial richness and diversity measures, and bacterial families. METHODS: A total of 85 stool samples were collected from 4-to 6-y-old children enrolled in the ENVIRonmental influence ON early AGEing birth cohort. We performed 16S rRNA gene sequencing to calculate bacterial richness and diversity indices (Chao1 richness, Shannon diversity, and Simpson diversity) and the relative abundance of bacterial families. Black carbon particles were quantified via white light generation under femtosecond pulsed laser illumination in placental tissue and cord blood, employed as prenatal exposure biomarkers, and in urine, used as a post-natal exposure biomarker. We used robust multivariable-adjusted linear models to examine the associations between quantified black carbon loads and measures of richness (Chao1 index) and diversity (Shannon and Simpson indices), adjusting for parity, season of delivery, sequencing batch, age, sex, weight and height of the child, and maternal education. Additionally, we performed a differential relative abundance analysis of bacterial families with a correction for sampling fraction bias. Results are expressed as percentage difference for a doubling in black carbon loads with 95% confidence interval (CI). RESULTS: Two diversity indices were negatively associated with placental black carbon [Shannon: −4:38% (95% CI: −8:31%, −0:28%); Simpson: −0:90% (95% CI: −1:76%, −0:04%)], cord blood black carbon [Shannon: −3:38% (95% CI: −5:66%, −0:84%); Simpson: −0:91 (95% CI: −1:66%, −0:16%)], and urinary black carbon [Shannon: −3:39% (95% CI: −5:77%, −0:94%); Simpson: −0:89% (95% CI: −1:37%, −0:40%)]. The explained variance of black carbon on the above indices varied from 6.1% to 16.6%. No statistically significant associations were found between black carbon load and the Chao1 richness index. After multiple testing correction, placental black carbon was negatively associated with relative abundance of the bacterial families Defluviitaleaceae and Marinifilaceae, and urinary black carbon with Christensenellaceae and Coriobacteriaceae; associations with cord blood black carbon were not statistically significant after correction. CONCLUSION: Black carbon particles quantified in prenatal and postnatal biological matrices were associated with the composition and diversity of the childhood intestinal microbiome. These findings address the influential role of exposure to air pollution during pregnancy and early life in human health. https://doi." "Transplacental transfer of cobalt: Evidence from a study of mothers and their neonates in the African Copperbelt" "Tony Kayembe-Kitenge, Celestin Banza Lubaba Nkulu, Sebastien Mbuyi Musanzayi, Toni Lubala Kasole, Leon Kabamba Ngombe, Paul Musa Obadia, Daan Van Brusselen, Daniel Kyanika Wa Mukoma, Taty Muta Musambo, Augustin Mutombo Mulangu, Patient Nkulu Banza, P. D. M. C. Katoto, Erik Smolders, Benoit Nemery, Tim NAWROT" "Background: Transfer of the trace metal cobalt (Co) from mother to foetus has not been documented in pop-ulations with high environmental exposure to Co, as is the case in the African Copperbelt mining region. We analysed data obtained from 246 mother-infant pairs included (at delivery) in a previously published case -control study on birth defects, done in Lubumbashi (Democratic Republic of Congo) between March 1, 2013, and Feb 28, 2015.Methods: Co was measured by Inductively Coupled Plasma Mass Spectrometry in maternal blood, maternal urine, umbilical cord blood and placental tissue, as available.Results: The Co concentrations [geometric mean (GM) with interquartile range (IQR)] in maternal blood (GM 1.77 mu g/L, IQR 1.07-2.93) and urine (GM 7.42 mu g/g creatinine, IQR 4.41-11.0) were highly correlated (Spearman r = 0.71, n = 166; p < 0.001) and considerably higher than reference values determined for general populations elsewhere in the world. The concentrations of Co in umbilical cord blood (GM 2.41 mu g/L) were higher (Wilcoxon test, p < 0.001) than in maternal blood (GM 1.37 mu g/L), with a correlation between both values (Spearman r = 0.34; n = 127, p < 0.001). Co concentrations in placental tissue (geometric mean 0.02 mu g/g wet weight) correlated with concentrations in maternal blood (Spearman r = 0.50, n = 86, p < 0.001) and in neonatal blood (Spearman r = 0.23, n = 83, p = 0.039).Conclusion: This first study of maternal and neonatal Co concentrations in the African Copperbelt provides strong evidence of a high transfer of Co from mother to foetus."