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Telomere length and mitochondrial DNA content are considered biomarkers of cellular aging, oxidative stress, and inflammation, but there is almost no information on their association with tobacco smoke exposure in fetal and early life. The aim of this study was to assess whether prenatal and childhood tobacco exposure were associated with leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in children. As part of a multi-centre European birth cohort study HELIX (Human Early-Life Exposome) (n = 1396) we assessed maternal smoking status during pregnancy through questionnaires, and through urinary cotinine levels that were then used to classify women as not exposed to smoking (<10 µg/L), exposed to secondhand smoke (SHS) (10-50 µg/L) and active smokers (>50 µg/L). When the children were around 8 years of age (range: 5.4-12.0 years), childhood SHS tobacco smoke exposure was assessed through an extensive questionnaire and through measurements of urinary cotinine (<3.03 µg/L non-detected, >3.03 µg/L detected). Leukocyte mtDNA content and LTL were measured in the children at 8 years employing real time polymerase chain reaction (qPCR). Effect estimates were calculated using multivariate linear regression models for prenatal and childhood exposures adjusted for potential confounders. Maternal cotinine levels indicative of SHS exposure during pregnancy were associated with a decrease of 3.90% in LTL in children (95% CI: -6.68, -0.91), compared with non-smoking, whereas the association for maternal cotinine levels indicative of active smoking did not reach statistical significance (-3.24%; 95% CI: -6.59, 0.21). Childhood SHS tobacco exposure was not associated with LTL in children. Global SHS exposure during childhood was associated with an increase of 3.51% (95% CI: 0.78, 6.27) in mtDNA content. Our findings suggest that tobacco smoke exposure during pregnancy, even at SHS levels, may accelerate telomere shortening in children and thus induce biological aging from an early age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The association between prenatal air pollution exposure and postnatal growth has hardly been explored. Mitochondrial DNA (mtDNA), as a marker of oxidative stress, and growth at birth can play an intermediate role in this association., Objective: In a subset of the Spanish birth cohort INMA we assessed first whether prenatal nitrogen dioxide (NO 2 ) exposure is associated with infant growth. Secondly, we evaluated whether growth at birth (length and weight) could play a mediating role in this association. Finally, the mediation role of placental mitochondrial DNA content in this association was assessed., Methods: In 336 INMA children, relative placental mtDNA content was measured. Land-use regression models were used to estimate prenatal NO 2 exposure. Infant growth (height and weight) was assessed at birth, at 6 months of age, and at 1 year of age. We used multiple linear regression models and performed mediation analyses. The proportion of mediation was calculated as the ratio of indirect effect to total effect., Results: Prenatal NO 2 exposure was inversely associated with all infant growth parameters. A 10µg/m³ increment in prenatal NO 2 exposure during trimester 1 of pregnancy was significantly inversely associated with height at 6 months of age (-6.6%; 95%CI: -11.4, -1.9) and weight at 1 year of age (-4.2%; 95%CI: -8.3, -0.1). These associations were mediated by birth length (31.7%; 95%CI: 34.5, 14.3) and weight (53.7%; 95%CI: 65.3, -0.3), respectively. Furthermore, 5.5% (95%CI: 10.0, -0.2) of the association between trimester 1 NO 2 exposure and length at 6 months of age could be mediated by placental mtDNA content., Conclusions: Our results suggest that impaired fetal growth caused by prenatal air pollution exposure can lead to impaired infant growth during the first year of life. Furthermore, molecular adaptations in placental mtDNA are associated with postnatal consequences of air pollution induced alterations in growth., (Copyright © 2017 Elsevier Inc. All rights reserved.)