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Introduction: Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. Methods: In newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. Results: We observed lower cord plasma TSH (−10.2% [95% CI: −15.0, −4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of −2.9% (95% CI: −5.7, −0.1) and −3.9% (95% CI: −6.2, −1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (−11.2% [95% CI: −19.5, −0.1]).Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. Conclusions: A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

Background: Studies investigating short-term exposure to ambient air pollution and heart rate variability (HRV) suggest that particulate matter (PM) exposure is associated with reductions in measures of HRV. Mitochondria are sensitive to PM exposure and may represent a biologically relevant underlying mechanism. However, evidence in children is lacking. Objectives: Here we examine whether PM has an influence on children's HRV and evaluate whether mitochondrial DNA content (mtDNAc) reflects individual susceptibility. Methods: Within a panel study in primary school children (aged 9–12 years), we measured HRV in a subset of 60 children on three different days during school-time using four indicators: normal-to-normal intervals (SDNN), square root of mean squared difference of normal-to-normal intervals (rMSSD), high frequency (HF), and low frequency (LF). This resulted in a total number of 150 visits (median number of visits per child: 2.5/child). MtDNAc was measured using qPCR in buccal cells. We measured recent PM exposure at the school. Residential 24-hour mean exposure to PM was modelled with a high resolution spatial temporal model. Mixed-effects models were used to estimate the association between HRV and recent PM exposure and potential effect-modification by mtDNAc. Results: Children were on average [SD] 9.9 [1.2] years and comprised 39 girls. Median [25th–75th] recent outdoor PM2.5 and PM10 exposure at school was 6.20 [2.8–12.8] μg/m3 and 29.3 [24.7–42.0] μg/m3, respectively. In children with low mtDNAc (25th percentile), we observed for each 10 μg/m3 increment in recent PM2.5 exposure a lowering in the LF parameter with 9.76% (95% CI: −16.9 to −1.99%, p = 0.02; pint = 0.007). Children with high mtDNAc did not show this association. For PM10 exposure, we observed an inverse association with three HRV indicators in children with low mtDNAc: −2.24% (95% CI: −4.27 to −0.16%; p = 0.04; pint = 0.02) for SDNN, −5.67% (95% CI: −10.5 to −0.59%; p = 0.03; pint = 0.04) for HF and −6.64% (95% CI: −10.7 to −2.38%; p = 0.003; pint = 0.005) for LF. Conclusions: HRV is inversely associated with recent PM air pollution, especially in children with low mtDNAc. Our data revealed that mtDNAc determines susceptibility to adverse autonomic effects of recent PM exposure in children. Keywords: Air pollution, Mitochondria, Heart rate variability

Background: Pro-inflammatory conditions such as air pollution might induce biological ageing. However, the available evidence on such an impact in children is still very scarce. We studied in primary schoolchildren the association of ambient residential air pollution exposure with telomere length (TL) and mitochondrial DNA content (mtDNAc), two important targets of the core axis of ageing. Methods: Between 2012 and 2014, buccal TL and mtDNAc were repeatedly assessed using qPCR in 197 Belgian primary schoolchildren (mean age 10.3 years) as part of the COGNAC study. At the child’s residence, recent (week), sub-chronic (month) and chronic (year) exposure to nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5) and black carbon (BC) were estimated using a high resolution spatiotemporal model. A mixed-effects model with school and subject as random effect was used while adjusting for a priori chosen covariates. Results: An interquartile range (IQR) increment (1.9 µg/m3) in chronic PM2.5 exposure was associated with a 8.9% (95% CI: −15.4 to −1.9%) shorter TL. In contrast to PM2.5, chronic exposure to BC and NO2 was not associated with TL but recent exposure to BC and NO2 showed significant inverse associations with TL: an IQR increment in recent exposure to BC (0.9 µg/m3) and NO2 (10.2 µg/m3) was associated with a 6.2% (95% CI: −10.6 to −1.6%) and 6.4% (95% CI: −11.8 to −0.7%) shorter TL, respectively. Finally, an IQR increment in chronic PM2.5 exposure was associated with a 12.7% (95% CI: −21.7 to −2.6%) lower mtDNAc. However, no significant associations were seen for NO2 and BC or for other exposure windows. Conclusion: Chronic exposure to PM2.5 below the EU threshold was associated with child’s shorter buccal TL and lower mtDNAc, while traffic-related pollutants (BC and NO2) showed recent effects on telomere biology. Our data add to the literature on air pollution-induced effects of TL and mtDNAc, two measures part of the core axis of cellular ageing, from early life onwards.

Summary: Background: Exposure to particulate air pollution has been linked with risk of carcinogenesis. Damage to repair pathways might have long-term adverse health effects. We aimed to investigate the association of prenatal exposure to air pollution with placental mutation rate and the DNA methylation of key placental DNA repair genes. Methods: This cohort study used data from the ongoing ENVironmental Influence ON early AGEing (ENVIRONAGE) birth cohort, which enrols pairs of mothers and neonates (singleton births only) at the East-Limburg Hospital (Genk, Belgium). Placental DNA samples were collected after birth. We used bisulfite-PCR-pyrosequencing to investigate the mutation rate of Alu (a marker for overall DNA mutation) and DNA methylation in the promoter genes of key DNA repair and tumour suppressor genes (APEX1, OGG1, PARP1, ERCC1, ERCC4, p53, and DAPK1). We used a high-resolution air pollution model to estimate exposure to particulate matter with a diameter less than 2·5 μm (PM2·5), black carbon, and NO2 over the entire pregnancy on the basis of maternal address. Alu mutation was analysed with a linear regression model, and methylation values of the selected genes were analysed in mixed-effects models. Effect estimates are presented as the relative percentage change in methylation for an ambient air pollution increment of one IQR (ie, the difference between the first and third quartiles of exposure in the entire cohort). Findings: 500 biobanked placental DNA samples were randomly selected from 814 pairs of mothers and neonates who were recruited to the cohort between Feb 1, 2010, and Dec 31, 2014, of which 463 samples met the pyrosequencing quality control criteria. IQR exposure increments were 3·84 μg/m3 for PM2·5, 0·36 μg/m3 for black carbon, and 5·34 μg/m3 for NO2. Among these samples, increased Alu mutation rate was associated with greater exposure to PM2·5 (r=0·26, p