Geographical approach analysis of the impact of air pollution on newborn intrauterine growth and cord blood DNA damage in Mexico City.

BACKGROUND: Few epidemiologic studies have focused on the specific source of ambient air pollution and adverse health effects in early life. Here, we investigated whether air pollutants from different emission sources were associated with decreased birth anthropometry parameters and increased DNA adduct formation in mother-child pairs residing in the Mexico City Metropolitan Area (MCMA). METHODS: This cross-sectional study included 190 pregnant women recruited during their last trimester of pregnancy from two hospitals at MCMA, and a Modeling Emissions Inventory (MEI) to calculate exposure to ambient air pollutants from different emissions sources (area, point, mobile, and natural) for two geographical buffers 250 and 750 m radii around the participants households. RESULTS: Contaminants were positively correlated with umbilical cord blood (UCB) adducts, but not with maternal blood (MB) adducts. PM10 emissions (area and point sources, overall emissions), PM2.5 (point sources), volatile organic compounds (VOC), total organic compounds (TOC) from point sources were positively correlated with UCB adducts. Air pollutants emitted from natural sources were correlated with a decrease in MB and UCB adducts. PM10 and PM2.5 were correlated (p < 0.05) with a decrease in birth weight (BW), birth length (BL) and gestational age at term (GA). In multivariate analyses adjusted for potential confounders, PM10 was associated with an increase in UCB adducts. PM10 and PM2.5 from overall emissions were associated with a decrease in BW, BL and GA at term. IMPACT: Results suggested higher susceptibility of newborns compared to mothers to damage related to ambient air pollution. PMs are associated with birth anthropometry parameters and DNA damage in adjusted models, highlighting the need for more strict regulation of PM emissions.

Long-term exposure to ambient fine particulate matter and carotid intima media thickness at bilateral, left and right in adults from Mexico City: Results from GEA study.

BACKGROUND: PM2.5 exposure has been associated with intima-media thickness (cIMT) increase. However, very few studies distinguished between left and right cIMT in relation to PM2.5 exposure. AIM: To evaluate associations between chronic exposure to PM2.5 and cIMT at bilateral, left, and right in adults from Mexico City. METHODS: This study comprised 913 participants from the control group, participants without personal or family history of cardiovascular disease, of the Genetics of Atherosclerosis Disease Mexican study (GEA acronym in Spanish), recruited at the Instituto Nacional de Cardiología Ignacio Chávez from June 2008 to January 2013. To assess the associations between chronic exposure to PM2.5 (per 5 µg/m3 increase) at different lag years (1-4 years) and cIMT (bilateral, left, and right) we applied distributed lag non-linear models (DLNMs). RESULTS: The median and interquartile range for cIMT at bilateral, left, and right, were 630 (555, 735), 640 (550, 750), and 620 (530, 720) µm, respectively. Annual average PM2.5 exposure was 26.64 µg/m3, with median and IQR, of 24.46 (23.5-25.46) µg/m3. Results from DLNMs adjusted for age, sex, body mass index, low-density lipoproteins, and glucose, showed that PM2.5 exposure for year 1 and 2, were positively and significantly associated with right-cIMT [6.99% (95% CI: 3.67; 10.42) and 2.98% (0.03; 6.01), respectively]. Negative associations were observed for PM2.5 at year 3 and 4 and right-cIMT; however only year 3 was statistically significant [-2.83% (95% CI: 5.12; -0.50)]. Left-cIMT was not associated with PM2.5 exposure at any lag year. The increase in bilateral cIMT followed a similar pattern as that observed for right-cIMT, but with lower estimates. CONCLUSIONS: Our results suggest different susceptibility between left and right cIMT associated with PM2.5 exposure highlighting the need of measuring both, left and right cIMT, regarding ambient air pollution in epidemiological studies.

PPAR Alpha Activation by Clofibrate Alleviates Ischemia/Reperfusion Injury in Metabolic Syndrome Rats by Decreasing Cardiac Inflammation and Remodeling and by Regulating the Atrial Natriuretic Peptide Compensatory Response.

Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs' signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.

Long-Term Exposure to Ozone and Fine Particulate Matter and Risk of Premature Coronary Artery Disease: Results from Genetics of Atherosclerotic Disease Mexican Study.

(1) Background: Epidemiological studies have identified associations between fine particulate matter (PM2.5) and ozone exposure with cardiovascular disease; however, studies linking ambient air pollution and premature coronary artery disease (pCAD) in Latin America are non-existing. (2) Methods: Our study was a case−control analysis nested in the Genetics of Atherosclerotic Disease (GEA) Mexican study. We included 1615 participants (869 controls and 746 patients with pCAD), recruited at the Instituto Nacional de Cardiología Ignacio Chávez from June 2008 to January 2013. We defined pCAD as history of myocardial infarction, angioplasty, revascularization surgery or coronary stenosis > 50% diagnosed before age 55 in men and age 65 in women. Controls were healthy individuals without personal or family history of pCAD and with coronary artery calcification equal to zero. Hourly measurements of ozone and PM2.5 from the Atmospheric Monitoring System in Mexico City (SIMAT in Spanish; Sistema de Monitero Atmosférico de la Ciudad de México) were used to calculate annual exposure to ozone and PM2.5 in the study participants. (3) Results: Each ppb increase in ozone at 1-year, 2-year, 3-year and 5-year averages was significantly associated with increased odds (OR = 1.10; 95% CI: 1.03−1.18; OR = 1.17; 95% CI: 1.05−1.30; OR = 1.18; 95% CI: 1.05−1.33, and OR = 1.13; 95% CI: 1.04−1.23, respectively) of pCAD. We observed higher risk of pCAD for each 5 µg/m3 increase only for the 5-year average of PM2.5 exposure (OR = 2.75; 95% CI: 1.47−5.16), compared to controls. (4) Conclusions: Ozone exposure at different time points and PM2.5 exposure at 5 years were associated with increased odds of pCAD. Our results highlight the importance of reducing long-term exposure to ambient air pollution levels to reduce the burden of cardiovascular disease in Mexico City and other metropolitan areas.

Maternal urinary fluoride during pregnancy and birth weight and length: Results from ELEMENT cohort study.

Epidemiological studies assessing prenatal fluoride exposure and anthropometry at birth are scarce, inconsistent and with methodological limitations. The aim of this study was to evaluate associations between maternal urinary fluoride (MUF) at each trimester of pregnancy and birth weight and length in 536 mother-child pairs in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort study. MUF (mg/L) was measured using microdiffusion/fluoride-specific electrode from at least one trimester of pregnancy. Non-linear associations were assessed through segmented regression models (MUF and birth weight Z-score) and we used linear regression models for MUF and birth length Z-score. Models were adjusted for potential confounders including urinary creatinine concentrations as a covariate. Non-creatinine adjusted MUF levels at each trimester of pregnancy were 0.81, 0.86, and 0.82 mg/L, mean concentrations for first, second and third trimester, respectively. For birth weight, we identified a MUF breakpoint at 0.99, 0.68 and 0.58 mg/L, for first, second and third trimester of pregnancy, respectively. In the first trimester, an increase of 1 mg/L in MUF concentrations ≥0.99 mg/L was associated with an increase in weight Z-score at birth (ß = 0.79; 95% CI: 0.10, 1.48; p = 0.02). Second trimester MUF (≥0.68 mg/L) was marginally associated with birth weight decrease (ß = -0.25; 95% CI: -0.55, 0.04; p = 0.09) and third trimester MUF (≥0.58 mg/L) was significantly associated with birth weight decrease (ß = -0.33; 95% CI: -0.63, -0.03; p = 0.03). We observed a linear and significant association between MUF and Z-score of length at birth only for the first trimester of pregnancy (ß = 0.55; 95% CI: 0.07, 1.04; p < 0.02). Prenatal fluoride exposure was associated with birthweight z-score with different susceptibility windows. Our findings reinforce the hypothesis that maternal fluoride exposure may affect birth anthropometry.

Prenatal Particulate Matter (PM) Exposure and Natriuretic Peptides in Newborns from Mexico City.

(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.

The rs12617336 and rs17574 Dipeptidyl Peptidase-4 Polymorphisms Are Associated With Hypoalphalipoproteinemia and Dipeptidyl Peptidase-4 Serum Levels: A Case-Control Study of the Genetics of Atherosclerotic Disease (GEA) Cohort.

Dipeptidyl peptidase-4 (DPP4) can influence lipid homeostasis and atherosclerosis progression. We aimed to assess the association of DPP4 gene polymorphisms with hypoalphalipoproteinemia and DPP4 serum levels, in a cohort of Mexican individuals. Five DPP4 polymorphisms (rs12617336, rs12617656, rs1558957, and rs3788979, and rs17574) were genotyped in 748 participants with and 745 without hypoalphalipoproteinemia. The associations were evaluated using logistic regression analyses. Under inheritance models adjusted for confounding variables, the rs12617336 (OR = 0.22, P heterozygote = 0.001) and rs17574 (OR = 0.78, P additive = 0.022; OR = 0.73, P dominant = 0.012; OR = 0.73, P heterozygote = 0.017; OR = 0.72, P codominant 1 = 0.014) minor alleles were associated with a low risk of hypoalphalipoproteinemia. After the correction for multiple comparisons, the associations were marginal except the association of the rs12617336 that remaining significant. Additionally, both DPP4 minor alleles were associated with protection for the presence of insulin resistance (IR) (OR = 0.17, P heterozygote = 0.019 for rs12617336 and OR = 0.75, P additive = 0.049 for rs17574). The rs12617336 minor allele was also associated with a low risk of hyperinsulinemia (OR = 0.11, P heterozygote = 0.006). Differences in DPP4 levels were observed in individuals with rs17574 genotypes, the rs17574 GG genotype individuals had the lowest levels. Our data suggest that rs12617336 and rs17574 DPP4 minor alleles could be envisaged as protective genetic markers for hypoalphalipoproteinemia, IR, and hyperinsulinemia. The rs17574 GG genotype was associated with the lowest DPP4 levels.

Metal exposure and bone remodeling during pregnancy: Results from the PROGRESS cohort study.

Pregnancy is characterized by high bone remodeling and might be a window of susceptibility to the toxic effects of metals on bone tissue. The aim of this study was to assess associations between metals in blood [lead (Pb), cadmium (Cd)and arsenic (As)] and bone remodeling during pregnancy. We studied pregnant woman from the PROGRESS Cohort (Programming Research in Obesity, Growth, and Environment and Social Stress). We measured concentrations of metals in blood and obtained measures of bone remodeling by quantitative ultrasound (QUS) at the radius in the second and third trimester of pregnancy. To account for chronic lead exposure, we measured lead in tibia and patella one-month postpartum with K-shell X-ray fluorescence. We assessed cross-sectional and longitudinal associations between multiple-metal concentrations and QUS z-scores using linear regression models and linear mixed models adjusted for potential confounders. Third trimester blood Cd concentrations were marginal associated with lower QUS z-scores [-0.16 (95% CI: -0.33, 0.007); P-Value = 0.06]. Mixed models showed that blood Cd was longitudinally and marginally associated with an average of -0.10 z-score (95% CI: -0.21, 0.002; P-Value = 0.06) over the course of pregnancy. Associations for Pb and As were all inverse however none reached significance. Additionally, bone Pb concentrations in patella, an index of cumulative exposure, were significantly associated with -0.06 z-score at radius (95% CI: -0.10, -0.01; P-Value = 0.03) during pregnancy. Pb and Cd blood levels are associated with lower QUS distal radius z-scores in pregnant women. Bone Pb concentrations in patella were negatively associated with z-score at radius showing the long-term effects of Pb on bone tissue. However, we cannot exclude the possibility of reverse causality for patella Pb and radius z-score associations. Our results support the importance of reducing women's metal exposure during pregnancy, as metals exposure during pregnancy may have consequences for bone strength later in life. The main finding of our study is the association between Cd blood levels and radius z-score during pregnancy. Bone lead in patella was also negatively associated with radius z-scores.

Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification. METHODS AND RESULTS: This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13-14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11-400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes. CONCLUSIONS: Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.

Prenatal PM2.5 exposure and the risk of adverse births outcomes: Results from Project ELEFANT.

BACKGROUND: Studies investigating the impact of fine particulate matter (PM2.5) exposure during pregnancy upon adverse birth outcomes have primarily been performed in Western nations with low ambient PM2.5 levels. We examined associations between high levels of PM2.5 exposure during pregnancy and risk of adverse birth outcomes by timing and level of exposure in a Chinese population. METHODS: We analysed data from 10,738 live births within the Project ELEFANT study based in Tianjin, China. Personal mean daily PM2.5 exposures were estimated using data from 25 local monitoring sites across the city, used to compute the days exceeding 50, 100, 150, 200 and 250 µg/m3. Relative risk of pre-term birth (<37 weeks) and low birthweight (<2500 g) were estimated by generalized additive distributed lag models, adjusted for maternal age, sex, region, paternal smoking, parity, maternal occupation, season, temperature and dew point. RESULTS: A dose-response was exhibited for PM2.5 exposure and relative risk (RR) of adverse birth outcomes, with exposure in the second and third trimesters of pregnancy associated with greatest risk of adverse birth outcomes. The RRs of pre-term birth with exposures of >50, >150 and > 250 µg/m3 PM2.5 in the third trimester were 1.09 (95%CI: 1.03-1.16), 1.30 (1.09-1.54) and 2.73 (2.03-3.66) respectively. For low birthweight, exposures of >50, >150 and > 250 µg/m3 PM2.5 in the third trimester were associated with RRs of 0.99 (0.88-1.11), 1.37 (1.04-1.81) and 3.03 (1.75-5.23) respectively. CONCLUSIONS: Exposure to high levels of PM2.5 from the second trimester onwards was most strongly associated with increased risk of pre-term birth and low birthweight, with a dose-response relationship. Our data demonstrates the need to account for both level and timing of exposure in analysis of PM2.5-associated birth outcomes.

Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

BACKGROUND: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic. OBJECTIVE: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. METHODS: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. RESULTS: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UAs tertiles (<47 ng/mL: reference, 47-72 ng/mL: 48.7 pg/mL, >72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT-proBNP were significantly related to arsenic exposure or echocardiographic parameters. CONCLUSIONS: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life.

IL-12B Polymorphisms Are Associated with the Presence of Premature Coronary Artery Disease and with Cardiovascular Risk Factors: The Genetics of Atherosclerotic Disease Mexican Study.

The aim of this study was to evaluate the association of the IL-12B polymorphisms with the presence of premature coronary artery disease (pCAD) and with cardiovascular risk factors. The study included 2163 individuals (1133 patients with pCAD and 1030 healthy controls). Seven IL-12B polymorphisms (rs1363670, rs3212220, rs3212227, rs6887695, rs1433048, rs2853694, and rs1368439) were determined by TaqMan assays. The associations were evaluated by logistic regression using inheritance models adjusted for confounding variables. The rs1363670 was associated with a low risk of pCAD (odds ratio [OR] 0.718, pdominant = 0.034; OR 0.701, pheterozygote = 0.024; OR 0.702, pcodominant1 = 0.025). The association of the polymorphisms with cardiovascular risk factors was evaluated independently in each group. In controls, the rs3212227, rs3212220, and rs6887695 polymorphisms were associated with subcutaneous abdominal fat > p75, whereas the rs6887695 was associated with a high risk of central obesity. In pCAD patients, the rs2853694 was associated with a low risk of insulin resistance; and association of rs3212227 and rs3212220 with a low risk of metabolic syndrome was found, and the rs6887695 polymorphism was nominally associated with a high risk of hyperuricemia. In conclusion, the IL-12B rs1363670 polymorphism was associated with a low risk of pCAD, and in both pCAD patients and healthy controls, some IL-12B polymorphisms were associated with cardiovascular risk factors.

Fine particulate matter exposure and lipid levels among children in Mexico city.

BACKGROUND: Studies have identified associations between air pollution and lipid levels in adults, suggesting a mechanism by which air pollution contributes to cardiovascular disease. However, little is known about the association between early life air pollution exposure and lipid levels in children. METHODS: Participants included 465 mother-child pairs from a prospective birth cohort in Mexico City. Daily particulate matter <2.5 µm in diameter (PM2.5) predictions were estimated using a satellite-based exposure model and averaged over trimesters, the entire pregnancy, and the first year of life. We assessed associations with several lipid measures at 4-6 years of age, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Linear regression models were used to estimate change in lipid levels with each interquartile range increase in PM2.5. We additionally assessed if associations between PM2.5 and lipid levels varied across lipid quantiles using quantile regression. Models were adjusted for maternal education, body mass index, and age, child's age at study visit, prenatal environmental tobacco smoke, and season of conception. RESULTS: PM2.5 exposure during the third trimester was associated with increases in childhood total cholesterol, LDL-C, and non-HDL-C, and decreases in HDL-C and triglycerides. There was additionally an increasing trend in the effect estimate across higher quantiles of total cholesterol, LDL-C, and non-HDL-C during the third trimester and entire pregnancy period. There were no consistent associations for first year of life exposures. CONCLUSION: In this longitudinal birth cohort in Mexico City, associations between prenatal PM2.5 and childhood lipid (total cholesterol, LDL-C, non-HDL-C) levels were greater for children at higher lipid quantiles.

Dietary characteristics associated with plasma concentrations of per- and polyfluoroalkyl substances among adults with pre-diabetes: Cross-sectional results from the Diabetes Prevention Program Trial.

Diet is assumed to be the main source of exposure to per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations, but studies on the diet-PFAS relationship in the United States are scarce. We extracted multiple dietary variables, including daily intakes of food group, diet scores, and dietary patterns, from self-reported dietary data collected at baseline (1996-1999) from adults with pre-diabetes enrolled in the Diabetes Prevention Program, and used linear regression models to evaluate relationships of each dietary variable with plasma concentrations of six PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), perfluorononanoic acid (PFNA) adjusting for covariates. Participants (N = 941, 65% female, 58% Caucasian, 68% married, 75% with higher education, 95% nonsmoker) had similar PFAS concentrations compared to the general U.S. population during 1999-2000. Using a single food group approach, fried fish, other fish/shellfish, meat and poultry had positive associations with most PFAS plasma concentrations. The strongest effect estimate detected was between fried fish and PFNA [13.6% (95% CI: 7.7, 19.9) increase in median concentration per SD increase]. Low-carbohydrate and high protein diet score had positive association with plasma PFHxS. Some food groups, mostly vegetables and fruits, and the Dietary Approaches to Stop Hypertension diet score had inverse associations with PFOS and MeFOSAA. A vegetable diet pattern was associated with lower plasma concentrations of MeFOSAA, while high-fat meat and low-fiber and high-fat grains diet patterns were associated with higher plasma concentrations of PFOS, PFHxS, MeFOSAA and PFNA. We summarized four major dietary characteristics associated with variations in PFAS plasma concentrations in this population. Specifically, consuming more meat/fish/shellfish (especially fried fish, and excluding Omega3-rich fish), low-fiber and high-fat bread/cereal/rice/pasta, and coffee/tea was associated with higher plasma concentrations while dietary patterns of vegetables, fruits and Omega-3 rich fish were associated with lower plasma concentrations of some PFAS.

Early life tobacco exposure and children's telomere length: The HELIX project.

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.

Association between fluoride exposure and cardiometabolic risk in peripubertal Mexican children.

BACKGROUND: Several animal studies have suggested that fluoride exposure may increase the levels of cardiometabolic risk factors, but little is known about whether fluoride exposure is associated with such risk in humans. OBJECTIVES: We examined the cross-sectional association between peripubertal exposure to fluoride and markers of cardiometabolic risk in 280 girls and 256 boys at age 10-18 years living in Mexico City. METHODS: We measured plasma fluoride concentration using a microdiffusion method. We collected data on anthropometry including BMI, waist circumference (WC) and trunk fat percentage. We measured serum markers of cardiometabolic risk, including fasting glucose, insulin and lipids. All the indicators of outcome were converted to age- and sex-specific z-scores. We also calculated a summary cardiometabolic risk score for each participant. Multivariable linear regression models were used to examine these associations. RESULTS: The geometric mean (95% confidence interval (CI)) of plasma fluoride was 0.21 µmol/L (0.20, 0.23 µmol/L) in the total sample. In girls, plasma fluoride concentrations were associated with higher z-scores for all the individual markers (except for lipids) and for the combined cardiometabolic risk score (risk score: ß = 1.28, 95% CI: 0.57-2.00, p-sex interaction = 0.02)), adjusting for covariates. No associations were found in boys. CONCLUSIONS: We found that higher peripubertal fluoride exposure at the levels observed in this study population was significantly associated with increased levels of cardiometabolic risk factors in Mexican girls but not boys. Future studies with a longitudinal design are needed to confirm our findings and further elucidate the role of fluoride in cardiometabolic risk.

Altered cord blood mitochondrial DNA content and pregnancy lead exposure in the PROGRESS cohort.

INTRODUCTION: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. MATERIALS AND METHODS: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. RESULTS: Maternal blood Pb measured in the second (mean 3.79 µg/dL, SD 2.63; ß = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 µg/dL; SD 2.84; ß = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 µg/dL, SD 2.59; ß = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). CONCLUSION: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead.

Dietary intake and urinary metals among pregnant women in the Pacific Northwest.

Pregnancy is a period when the mother and her offspring are susceptible to the toxic effects of metals. We investigated associations of intake of frequently consumed foods with urinary metals concentrations among pregnant women in the Pacific Northwest. We measured urinary cadmium (U-Cd), arsenic (U-As) and molybdenum (U-Mo) concentrations from spot urine samples in early pregnancy (15 weeks of gestation, on average) among 558 women from Seattle and Tacoma, Washington. We assessed periconceptional dietary intake using a semi-quantitative food frequency questionnaire (FFQ). We also determined early pregnancy zinc concentrations in serum. Statistical analyses involved multivariable linear regression models, adjusted for smoking status, age, race/ethnicity, multivitamin and supplement use, education, estimated total energy intake, and gravidity. The geometric mean and range in µg/g creatinine for U-Cd, U-As and U-Mo were 0.29 (0.1-8.2), 18.95 (3-550), and 72.1 (15-467), respectively. U-Cd was positively associated with dietary zinc intake (P-value = 0.004) and serum zinc (P-value<0.001) while it was negatively associated with coffee intake (P-value = 0.03). U-As was positively associated with dietary fish [(Lean fish, fatty fish, shellfish and non-fried fish) (P-values<0.01)], selenium (P-value = 0.004), zinc (P-value = 0.017), vegetables (P-value = 0.004), and low-fat yogurt (P-value = 0.03). Women who reported higher intake of dietary magnesium (Mg)(P-value = 0.04), insoluble fiber (P-value = 0.03), and low-fat yogurt (P-value = 0.04) had higher U-Mo concentrations. Our study suggests that vegetables, fish, fiber and yogurt might be significant dietary sources of metals. Future studies aimed at investigating the risk of exposure to metals from other various food sources among reproductive-age and pregnant women are needed.

Maternal intake of fried foods and risk of gestational diabetes mellitus.

PURPOSE: We examined the relationship of maternal periconceptional (i.e., before conception and early pregnancy) intake of fried foods with gestational diabetes mellitus (GDM) risk. METHODS: In a prospective birth cohort in Seattle and Tacoma, Washington State, USA, we assessed maternal periconceptional fried food intake using a food frequency questionnaire among 3414 participants. We used multivariable generalized linear regression models to derive estimates of relative risks (RRs; and 95% confidence intervals, 95% CIs) of GDM in relation to the intake of different types of fried foods (i.e., fried fish, fried chicken, fried potatoes, chips, and donuts). RESULTS: A total of 169 GDM incident cases were identified in this cohort (4.96%). Compared with no fried fish intake, fried fish intake >1 servings/month was associated with 68% higher GDM risk (adjusted RR and 95% CI; 1.68 [1.16, 2.45]; Ptrend = .019). After adjusting for confounders, the RRs (95% CI) of GDM relative to fried chicken intake were 1.0, 1.44 (0.98, 2.09), and 1.81 (1.22, 2.70) for none, ≤1 and > 1 servings/month intake of fried chicken, respectively (Ptrend = .002). Dietary intake of fried potatoes, snack chips or donuts was not significantly associated with higher GDM risk. Limitations of our study include the lack of information about frying methods and the intake of fried foods at home and away from home. CONCLUSIONS: Regular intake of fried fish and fried chicken are associated with elevated GDM risk.