Abstract Background: Air pollution is a well-established risk factor for childhood asthma, yet its potential cross-generational effects remain largely unexplored. Objectives: To estimate the association between grandmaternal and maternal exposure to ambient air pollution during pregnancy and asthma in the grandchild. Methods: This nationwide register-based cohort study included 85,963 Swedish children. Childhood asthma was defined as purchase of at least two asthma medications during the first 6 years of life. Residential addresses were geocoded and high-resolution air pollution concentrations of particulate matter with a diameter of 2.5 μm or less (PM2.5), elemental carbon (EC), nitrogen oxides (NOx) and primary PM2.5 (pPM2.5) including EC, primary organic aerosols (POA) and mineral dust/ash were extracted from the coupled DEHM/UBM atmospheric model system. Grandmaternal exposure was estimated for the year the mother was born, and maternal exposure for the birth year of the child. Logistic regression was used to estimate odds ratios (ORs) for asthma by exposure quartiles, adjusting for individual, familial, and area-level socioeconomic covariates. Results: Both grandmaternal and maternal exposure to pPM2.5, EC, and NOx during pregnancy were associated with higher odds of asthma in the grandchildren. For grandmaternal exposure to pPM2.5, ORs were 1.06 (95% CI: 1.00–1.12), 1.09 (1.03–1.15), and 1.06 (1.01–1.13) for the second, third, and fourth quartiles, respectively, compared to the first. Maternal exposure showed similar patterns, with ORs for pPM2.5 in the highest quartile reaching 1.10 (1.04–1.17). No clear concentration–response relationship was observed. Associations were reduced only slightly after adjustment for maternal/grandmaternal exposure, respectively. Conclusions: Our findings indicate a cross-generational association between exposure to ambient air pollution and childhood asthma, proposing that respiratory vulnerability may begin earlier than previously recognized. Since the results did not show a clear concentration–response, further studies are needed.
Abstract In utero air pollution is a critical risk factor linked with adverse birth outcomes. Genomic alterations induced by air pollution can be precursors for the development of later-life diseases. Ribosomal DNA (rDNA) has an important role in genome stability and forms a potentially sensitive target for environmental stressors. Therefore, we studied the association between early life rDNA dynamics and prenatal and early childhood air pollution exposure. In the ENVIRONAGE birth cohort, we assessed rDNA copy number (rDNAcn) at birth and longitudinally after a mean follow-up of 4.5 years (5th–95th percentile: 4.1–5.3) using droplet digital PCR (ddPCR). Prenatal and postnatal exposures to particulate matter (PM10 and PM2.5) were estimated based on the maternal and child residential address. Distributed lag models (DLM) were applied to associate newborn rDNAcn, rDNAcn in childhood, and the longitudinal change in rDNAcn with prenatal air pollution exposures, accounting for potential confounders and covariates. A total of 171 newborns, including 84 girls (49.1%) with a mean gestational age of 39.1 weeks, had an rDNAcn of 245 (SD: 58.1) copies. After 4–6 years, the mean rDNAcn was 231 (SD: 55.7) copies. DLMs revealed sensitive windows of prenatal PM exposures during pregnancy for an inverse association with both rDNAcn at birth and in childhood, but not with the longitudinal change in rDNAcn. Newborn rDNAcn was inversely associated with PM exposure during the last trimester, with an SD-higher level in prenatal PM2.5 associated with −34.8 (95% CI: −60.0 to −9.7) lower newborn rDNAcn. In addition, an SD increment in prenatal PM2.5 during the entire pregnancy, first trimester, and last trimester was associated with −71.2 (95% CI: −117.0 to −25.3), −26.0 (95% CI: −46.3 to −5.7), and −33.0 (95% CI: −54.3 to −11.8) lower rDNAcn in childhood, respectively. Similar associations were observed for PM10. Finally, postnatal exposures were not associated with rDNAcn in childhood. Our findings show that prenatal particulate matter exposure is associated with a lower rDNAcn of newborns and that this association persists from birth to childhood. Therefore, early genomic effects on the level of rDNA that track over early child development are influenced by prenatal air pollution exposure. The long-term consequences of rDNA alterations in early life need to be elucidated in further follow-up studies.
Abstract Environmental exposures to radioactive and stable iodine and predisposing germline genetic variants contribute to the development of papillary thyroid carcinoma (PTC) after the Chernobyl accident, but their joint effects and interaction effects remain unknown. A retrospective observational case-control study enrolled 945 PTC patients and 1040 healthy control individuals from Belarus aged 0–18 years old at the time of exposure. Clinicopathological data, individual radiation doses to the thyroid, extent of stable iodine consumption, and genotypes for six predisposing genetic variants were used in the multiplicative and additive statistical models to address the individual environmental (E) and genetic factor (G) effects, and those of E×E, G×G, and G×E interactions. The radiation dose and soil iodine level were statistically significantly associated with PTC and displayed a negative interaction. Out of six, four genetic variants displayed significant association signals with a positive interaction between two of them. Importantly, one of these variants negatively interacts with the radiation dose. The soil iodine level did not interact with genetic components. The impact of radiation exposure was stronger than that of genetic variants. The findings show that environmental and genetic factors demonstrate complex nonindependent effects on the development of thyroid cancer after childhood radiation exposure and point at the absence of radiation risk augmentation by the major cancer-associated genetic variants. These observations can be used for radiation risk communication with the public.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous pollutants with potential neurodevelopmental toxicity. However, epidemiological evidence on prenatal exposure to PFAS particularly emerging PFAS and PFAS isomers in relation to children’s intellectual development remain limited. This study aimed to examine associations of prenatal exposure to a variety of PFAS, including legacy, emerging, and branched PFAS, with children’s intellectual development, and to evaluate early metabolic pathway changes potentially linking prenatal PFAS exposure to these outcomes. In 1,062 mother–child pairs from a prospective cohort in Wuhan, we quantified 32 PFAS in cord sera and conducted metabolomic profiling of cord plasma. At 6 years of age, children’s intellectual development was assessed using the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition, a standardized and clinically validated instrument capturing multiple intellectual domains. Generalized linear models (GLM) and weighted quantile sum regression models were used to assess the association of individual PFAS and PFAS mixtures with children’s intellectual development. A metabolome-wide association study (MWAS) using GLM was conducted to examine associations between PFAS exposure, individual metabolites, and children’s intellectual development. Then, the meet-in-the-middle framework was applied to evaluate metabolic signatures as potential intermediary biomarkers. After adjusting for confounders, each doubling in 3,4,5m-PFOS concentration was associated with a decreased Full Scale Intelligence Quotient (FSIQ) of 0.92 (95% CI = −1.68, −0.17) points, with similar associations observed for the Cognitive Proficiency Index (CPI), Processing Speed Index (PSI), and Working Memory Index (WMI). Similarly, each doubling in 6m-PFOS was associated with decreased scores of 1.22 (95% CI = −2.02, −0.42) for CPI, 1.05 (95% CI = −1.82, −0.27) for PSI, and 0.89 (95% CI = −1.76, −0.01) for WMI. Furthermore, significant mixture effects of multiple PFAS on CPI and WMI were observed, with 6m-PFOS and 3,4,5m-PFOS identified as the primary contributors, respectively. Metabolomic analyses revealed that prenatal PFAS exposure was linked to changes in lipid metabolism pathways, potential serving as candidate intermediary biomarkers in linkages between prenatal PFAS and childhood intellectual development. In conclusion, prenatal PFAS exposure, particularly to branched PFOS isomers, was associated with lower domain-specific intellectual performance in childhood. Integrative analyses combining exposure and metabolomic data may advance the understanding of PFAS-related neurodevelopmental risk.
