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BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. OBJECTIVES: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. METHODS: Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR)< 0.05 and differentially methylated regions (DMRs) were identified using comb-p (Å idák-adjusted 푝< 0.05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. RESULTS: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (?= 0.28-0.76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR < 0.05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR < 0.1). DISCUSSION: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. [ABSTRACT FROM AUTHOR]

Prenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth. Among 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM 2.5) and ozone (O 3), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010–2014). We calculated average PM 2.5 and O 3 in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O 3 exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood. We identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM 2.5 (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O 3 on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant. Differentially methylated regions in cord blood were identified in association with maternal exposure to PM 2.5 and O 3. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O 3 exposure and 5-month infant adiposity. • Air pollution during pregnancy was associated with DNA methylation in cord blood. • Associated genes were linked to cardiometabolic, immune, and neurologic diseases. • Limited support for mediation by methylation of associations with infant adiposity. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates the correlation between inhalation of organic dust and adverse pulmonary disorders of agricultural workers in the U.S. Researchers quantified the exposures of workers and the changes of pulmonary functions of dairy, feedlot and corn farm employees. They found response exposure on smokers and workers who reported asthma, allergies and pesticides.

Few studies have demonstrated associations between maternal dietary inflammatory index (DII) during pregnancy and offspring asthma and/or wheeze. The study aimed to assess associations between maternal DII during pregnancy and 1) offspring cord sera pro-inflammatory cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-10, tumor necrosis factor-α) and chemokines (IL-8, monocyte chemoattractant protein-1) at birth and 2) offspring asthma and/or wheeze at age 4 years. The Healthy Start study is a prospective prebirth longitudinal study that recruited pregnant women in Denver, Colorado and tracked their offspring. This study used data from 1228 mother-child dyads enrolled in the Healthy Start study. Pregnant women were recruited in Denver, Colorado, between 2009 and 2014, and offspring tracked until age 4 years. Cord sera cytokines and chemokines were analyzed with multiplex panel immunoassays. Offspring diagnosis of asthma and/or wheeze by age 4 years was extracted from electronic medical records. Unadjusted and adjusted linear and logistic regression models were used to assess associations. Covariates included factors such as nulliparity, race/ethnicity, gestational smoking, and maternal history of asthma. Unadjusted analysis showed that increasing maternal DII scores were associated with increased odds of child asthma and/or wheeze by 4 years (odds ratio = 1.17; 95% CI: 1.07-1.27), but the association was attenuated and no longer statistically significant in the adjusted model (odds ratio = 1.15; 95% CI: 0.99-1.33). There were no significant associations between DII scores and cord sera cytokine or chemokine levels. The study showed that the inflammatory profile of the maternal diet was not associated with cytokines and chemokine levels at birth. The results suggested that a more inflammatory maternal diet was associated with increased odds of offspring asthma and/or wheeze by age 4 years, which could be considered of clinical relevance but the finding was not statistically significant at the.05 level. [ABSTRACT FROM AUTHOR]

Objective: Our hypothesis was that the activity of placental nutrient-sensing pathways is associated with adiposity and metabolic health in childhood., Research Design and Methods: Using placental villus samples from healthy mothers from the Healthy Start Study, we measured the abundance and phosphorylation of key intermediates in the mTOR, insulin, AMPK, and ER stress signaling pathways. Using multivariate multiple regression models, we tested the association between placental proteins and offspring adiposity (%fat mass) at birth (n = 109), 4-6 months (n = 104), and 4-6 years old (n = 64), adjusted for offspring sex and age., Results: Placental mTORC1 phosphorylation was positively associated with adiposity at birth (R 2  = 0.13, P = 0.009) and 4-6 years (R 2  = 0.15, P = 0.046). The mTORC2 target PKCα was positively associated with systolic blood pressure at 4-6 years (β = 2.90, P = 0.005). AMPK phosphorylation was positively associated with adiposity at birth (β = 2.32, P = 0.023), but the ratio of phosphorylated to total AMPK was negatively associated with skinfold thickness (β = -2.37, P = 0.022) and body weight (β = -2.92, P = 0.005) at 4-6 years., Conclusions: This is the first report of associations between key placental protein activity measures and longitudinal child outcomes at various life stages. Our data indicate that AMPK and mTOR signaling are linked to cardiometabolic measures at birth and 4-6 years, providing novel insight into potential mechanisms underpinning how metabolic signaling in the placenta is associated with future risk of cardiovascular disease.

Background: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT., Methods: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed., Findings: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex., Interpretation: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities., Competing Interests: Competing interests: DAS is the founder and chief scientific officer of Eleven P15, a company focused on the early diagnosis and treatment of pulmonary fibrosis. DAS has an awarded patent (US patent no: 8,673,565) for the treatment and diagnosis of fibrotic lung disease. DAL and SMH have a pending patent (application US20170330320A1) for image analysis; SMH reports a consulting agreement with Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)