Background: Pollen exposure in early life is shown to be associated with allergy and asthma. DNA methylation (DNAm), an epigenetic marker, potentially reacts to pollen. However, the role of at-birth DNAm between prenatal pollen grain (PPG) exposure and childhood asthma and allergic rhinitis is unknown. Methods: Data in a birth cohort study on the Isle of Wight, UK, were analyzed (n = 236). Newborn DNAm was measured in cord blood or blood spots on Guthrie cards and screened for potential association with PPG exposure using the R package ttScreening. CpGs that passed screening were further assessed for such associations via linear regressions with adjusting covariates included. Finally, DNAm at PPG-associated CpGs were evaluated for their association with asthma and allergic rhinitis using logistic regressions, adjusting for covariates. The impact of cell heterogeneity on the findings was assessed. Statistical significance was set at p < 0.05. Results: In total, 42 CpGs passed screening, with 41 remaining statistically significant after adjusting for covariates and cell types (p < 0.05). High PPG exposure was associated with lower DNAm at cg12318501 (ZNF99, β = −0.029, p = 0.032) and cg00929606 (ADM2, β = −0.023, p = 0.008), which subsequently was associated with decreased odds of asthma (OR = 0.11, 95% CI 0.02–0.53, p = 0.006; OR = 0.14, 95% CI 0.02–1.00, p = 0.049). For rhinitis, cg15790214 (HCG11) was shown to play such a role as a mediator (β = −0.027, p ≤ 0.0001; OR = 0.22, 95% CI 0.07–0.72, p = 0.01). Conclusions: The association of PPG exposure with childhood asthma and allergic rhinitis incidence is potentially mediated by DNAm at birth.

Introduction: While the phenotypic diversity of childhood wheezing is well described, the subsequent life course of such phenotypes and their adult outcomes remain poorly understood. We hypothesized that different childhood wheezing phenotypes have varying longitudinal outcomes at age 26. We sought to identify factors associated with wheezing persistence, clinical remission, and new onset in adulthood. Methods: Participants were seen at birth and at 1, 2, 4, 10, 18, and 26 years in the Isle of Wight Birth Cohort (n = 1456). Information was collected prospectively on wheeze prevalence and phenotypic characteristics at each assessment. Wheeze phenotypes at 10 years were defined as participants wheezing (CW10) or not wheezing at 10 (CNW10). Multivariable regression analyses were undertaken to identify factors associated with wheezing persistence/remission in CW10 and wheeze development in CNW10 at age 26 years. Results: Childhood wheezing phenotypes showed different subsequent outcomes and associated risk factors. Adult wheeze developed in 17.8% of CNW10. Factors independently associated with adult wheeze development in CNW10 included eczema at age 4 years, family history of rhinitis, and parental smoking at birth. Conversely, 56.1% of CW10 had remission of wheeze by 26 years. Factors predicting adult wheezing remission in CW10 included absence of both atopy at age 4 years and family history of rhinitis. Conclusion: Early-life factors influence adult outcomes for childhood wheezing phenotypes, both with respect to later development of adult wheezing in asymptomatic participants and of wheeze remission in childhood wheezers. This suggests potential areas that could be targeted by early-life interventions to alleviate adult disease burden.

Background/Objectives: The experience of pregnancy and parturition has been associated with long-term health effects in mothers, imparting protective effects against some diseases while the risk of other diseases is increased. The mechanisms that drive these altered disease risks are unknown. This study examined DNA methylation (DNAm) changes from pre-pregnancy to several years after giving birth in parous women compared to nulliparous controls over the same time interval. Methods: Using 180 parous-associated CpGs, three analyses were carried out to test DNAm changes from pre-pregnancy at age 18 years to gestation; from gestation to post-pregnancy at age 26 years in parous women; and from 18 to 26 years in nulliparous women using linear mixed models with repeated measures. Results: The directions of DNAm changes were the same between the parous and nulliparous groups. Most CpG dinucleotides (67%, 121 of 180) had a decreasing trend while a small number (7%, 13 of 180) had an increasing trend. Of the CpGs showing increasing or decreasing DNAm, approximately half had DNAm change to a smaller extent in parous women and the other half changed more in parous women than nulliparous controls. 9% (17 of 180) changed significantly in nulliparous women only, leading to a significant difference in DNAm levels in parous women at the post-pregnancy 26 years time point. Conclusions: Pregnancy and parturition may accelerate methylation changes in some CpGs, but slow down or halt methylation changes over time in other CpGs.

Community water fluoridation is a key public health intervention, yet ongoing debates about systemic risks call for evidence on fluoride exposure. We analyzed NHANES 2013–2016 biomonitoring data to assess fluoride exposure in children and adolescents aged 0–19 years. We calculated the proportion of children with fluoride levels in relation to guidelines from the United States Environmental Protection Agency (USEPA), World Health Organization (WHO), and Centers for Disease Control and Prevention (CDC). Biomonitoring data was obtained from the National Health and Nutrition Examination Survey (NHANES). Median water fluoride concentration was 0.50 (95% CI: 0.35, 0.64) mg/L for males, 0.49 (95% CI: 0.35, 0.63) mg/L for girls, 0.49 (95% CI: 0.35, 0.63) for the <3 age group, and 0.50 (95% CI: 0.36, 0.64) for the 18–19 age group. Median urine fluoride concentration was 0.56 (95% CI: 0.51, 0.62) mg/L for males, 0.46 (95% CI: 0.41, 0.50) for girls, 0.59 (95% CI: 0.50, 0.62) for the age group 6–8, and 0.51 (95% CI: 0.42, 0.60) for the 18–19 age group. Of the children, 99.96% were below the EPA’s enforceable 4.0 mg/L limit, 99.05% below the EPA’s 2.0 mg/L limit, and 98.6% below the WHO 1.5 mg/L standard. For urinary fluoride, 88.1% were within the CDC reference range of 0.2–<3.2 mg/L. We found that water fluoride levels did not vary across age and sex groups, but urine fluoride levels changed. Results indicate that most children remain within regulatory agencies’ guidelines.