PFAS Concentrations and Cardiometabolic Traits in Highly Exposed Children and Adolescents.

BACKGROUND: Residents of a large area of north-eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations that were quantifiable in at least 40% of samples and lipid profile, blood pressure (BP) and body mass index (BMI) in highly exposed adolescents and children. METHODS: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic BP were measured, and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. The weighted quantile sum regression approach was used to assess PFAS-mixture effects for each outcome. Analyses were stratified by gender and adjusted for potential confounders. RESULTS: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a lesser extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Higher serum concentrations of PFAS, particularly PFOS, were associated with lower BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. These results were confirmed by the multi-pollutant analysis. CONCLUSIONS: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI

Migrant status disparities in blood pressure: a multiple mediation analysis of modifiable factors

BackgroundWe examined differences in blood pressure (BP) levels between first-generation immigrants and natives in adult residents in Northeast Italy, and investigated the role of lifestyle behaviors, body mass index (BMI), and education as potentially modifiable mediating factors.MethodsWe included 20-69-year-old participants from the Health Surveillance Program of the Veneto Region (n = 37,710). Immigrants born in a high migratory pressure country (HMPC) were further grouped into geographical macro-areas. The outcomes were systolic BP (SBP) and hypertension. Multiple mediation analyses were performed to determine the contribution of each mediator of the SBP/migrant status association.ResultsOf the 37,380 subjects included, 8.7% were born in an HMPC. BMI, education, alcohol, sweets and meat consumption were included as potential mediators. A small advantage in SBP was seen for immigrants compared to natives (& beta; = - 0.71,95%CI - 1.30; - 0.10). The direct effect (net of the covariates) of immigrant status on SBP was a reduction of 1.62 mmHg (95%CI - 2.25; - 0.98). BMI played the highest suppressive role (& beta; = 1.14,95%CI 0.99; 1.35), followed by education. Alcohol consumption amplified the health advantage of immigrants. The suppressing effect of BMI was particularly evident among women and North Africans compared to natives. Similar results were seen for hypertension rates.ConclusionsAlthough causation cannot be proven given the cross-sectional design, our findings identify BMI as the most effective target to preserve the health advantage of immigrants with respect to BP levels

Estimation of per- and polyfluoroalkyl substances (PFAS) half-lives in human studies: A systematic review and meta-analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) constitute a heterogeneous group of synthetic compounds widely used in industrial applications. The estimation of PFAS half-life (t1/2) is essential to quantify their persistence, their toxicity and mechanism of action in humans. OBJECTIVES: The purpose of this review is to summarize the evidence on PFAS half-lives in humans from the available literature, and to investigate the limitations and uncertainties characterizing half-life estimation. METHODS: The search was conducted on PubMed, Scopus, and Embase databases up to July 03, 2023 and was aimed at identifying all papers that estimated PFAS half-life in human populations. We excluded studies on temporal trends or providing estimates of half-life based solely on renal clearance. As persistent and ongoing exposures can influence half-life estimation, we decided to include only studies that were conducted after the main source of exposure to PFAS had ceased. A random-effects meta-analysis was conducted on studies that reported perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) or perfluorohexanesulfonic acid (PFHxS) half-life estimation. Risk of bias was evaluated using the OHAT tool. RESULTS: A total of 13 articles were included in the review, with 5 studies conducted in exposed general populations and 8 studies conducted in exposed workers; the estimated mean half-life ranged from 1.48 to 5.1 years for PFOA, from 3.4 to 5.7 years for total PFOS, and from 2.84 to 8.5 years for PFHxS. High heterogeneity among studies was observed; potential reasons include the variability among the investigated populations, discrepancies in considering ongoing exposures, variability in PFAS isomeric compositions, accounting for background exposure, time since exposure stopped and methods used for half-life estimation. DISCUSSION: Despite the efforts made to better understand PFAS toxicokinetics, further studies are needed to identify important characteristics of these persistent chemicals. Biomonitoring studies should focus on persistent and unaccounted sources of exposure to PFAS and on individual characteristics potentially determining half-life, to ensure accurate estimates

Association of pediatric COVID-19 vaccination and socioeconomic position: a nested case-control study from the Pedianet Veneto cohort

Background: The success of pediatric COVID-19 vaccination strongly depends on parents' willingness to vaccinate their children. To date, the role of socioeconomic position (SEP) in pediatric COVID-19 vaccination has not been thoroughly examined. Objective: To evaluate the association between COVID-19 vaccination and SEP in a large pediatric cohort. Methods: A case-control study design nested into a pediatric cohort of children born between 2007-2017 living in the Veneto Region and followed-up to at least January 1st, 2022, was adopted. Data on children was collected from the Pedianet database and linked with the regional COVID-19 registry. Each child vaccinated with at least one dose of any COVID-19 vaccine between July 1st, 2021 and March 31st, 2022, was matched by sex, year of birth, and family pediatrician to up to five unvaccinated children. Unvaccinated children with a positive swab within 180 days before the index date were excluded from the analyses. Children were georeferenced to determine their area deprivation index (ADI), a social and material deprivation measure calculated at the census block level and consisting of 5 socioeconomic items. The index was then categorized in quintiles based on the regional ADI level. The association between ADI quintiles and vaccination status was measured by conditioned logistic regression models to estimate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CI). Quantile-g-computation-regression models were applied to develop a weighted combination of the individual items (WDI) to estimate how much each component influenced the likelihood of vaccination. All analyses were stratified by age at vaccination (5-11, 12-14 years). Results: The study population consisted of 6,475 vaccinated children, matched with 32,124 non-vaccinated children. Increasing area deprivation was associated with a lower probability of being vaccinated, with approximately a linear dose-response relationship. Children in the highest deprivation quintile were 36% less likely to receive a COVID-19 vaccine compared to children with the lowest deprivation (95%CI: 0.59-0.70). The results were similar in the two age groups, with a slightly stronger association in 5-11-year-old children. When assessing the effects of the WDI, a quintile increase was associated with a 17% decrease in the probability of being vaccinated (95%CI: 0.80-0.86). The conditions that influenced the probability of vaccination the most were living on rent, unemployment and single-parent families. Conclusions: This study has shown a significant reduction in the likelihood of receiving a COVID-19 vaccination among children living in areas characterized by a lower socioeconomic position. Findings were robust among multiple analyses and definitions of the deprivation index. These findings suggest that SEP plays an important role in vaccination coverage, emphasizing the need to promote targeted public health efforts to ensure global vaccine equity

Adult first-generation immigrants and cardiovascular risk factors in the Veneto Region, Northeast Italy

Introduction: The health condition of immigrants traditionally follows a transition from a low disease occurrence to the epidemiological profile of the deprived groups in the host country. In the Europe, studies examining differences in biochemical and clinical outcomes among immigrants and natives are lacking. We examined differences in cardiovascular risk factors between first-generation immigrants and Italians, and how migration pattern variables could affect health outcomes. Material and methods: We included participants between 20 and 69 years recruited from a Health Surveillance Program of the Veneto Region. Blood pressure (BP), total cholesterol (TC) and LDL cholesterol levels were measured. Immigrant status was defined by being born in a high migratory pressure country (HMPC) and subdivided by geographical macro-areas. We used generalized linear regression models to investigate differences between these outcomes among immigrants compared to native-born, adjusting for age, sex, education, BMI, alcohol consumption, smoking status, food consumption, salt consumption in the BP analysis and the laboratory in charge for cholesterol analysis. Within immigrant subjects, the results were stratified by variables of the migration pattern: age at immigration and length of residence in Italy. Results: Thirty seven thousand three hundred and eighty subjects were included in the analysis, 8.6% were born in an HMPC. Heterogeneous results were seen by the macro-areas of origin and sex, with male immigrants from CE Europe (β = 8.77 mg/dl) and Asia (β = 6.56 mg/dl) showing higher levels of TC than native-born, while female immigrants from Northern Africa showed lower levels of TC (β = -8.64 mg/dl). BP levels were generally lower among immigrants. Immigrants residing in Italy for more than 20 years had lower levels of TC (β = -2.9 mg/dl) than native-born. In contrast, immigrants who arrived <20 years ago or arrived older than 18 years had higher levels of TC. This trend was confirmed for CE Europeans and was inverted for Northern Africans. Conclusions: The large heterogeneity in the results depending on sex and macro-area of origin indicates the need for targeted intervention in each specific immigrant group. The results confirm that acculturation leads to a convergence toward the epidemiological profile of the host population that depends on the starting condition of the immigrant group

Associations between Mixture of Perfluoroalkyl Substances and Lipid Profile in a Highly Exposed Adult Community in the Veneto Region.

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters. Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20-64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals. Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (beta: 4.09, 95% CI: 3.47-4.71), HDL-C (beta: 1.13, 95% CI: 0.92-1.33) and LDL-C (beta: 3.14, 95% CI: 2.65-3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (psi: 4.04, 95% CI 3.5-4.58), HDL-C (psi: 1.07, 95% CI 20.87-1.27) and LDL-C (psi: 2.71, 95% CI 2.23-3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender. Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS

Perfluoroalkyl substance mixtures and cardio-metabolic outcomes in highly exposed male workers in the Veneto Region: A mixture-based approach

Background: Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits. Occupational exposures to multiple PFAS with health outcomes have been poorly investigated. The aim of the present study was to examine these associations among former workers involved in PFAS production.Methods: We considered 232 male ex-employees who had worked in a factory (Trissino, Veneto Region, Italy), which produced PFAS and other chemicals during 1968-2018. Out of twelve serum PFAS, only four (PFOA, PFOS, PFHxS, and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between serum PFAS mixture and considered outcomes were assessed through linear regression mixed models and Weighted Quantile Sum (WQS) regression, adjusting for potential confounders.Results: PFOA was detected at the highest level, with a median concentration (in ng/mL) of 80.8 (min-max: 0.35-13,033), followed by PFOS (median: 8.55, min-max: 0.35-343), PFHxS (median: 6.8, min-max: 0.35-597) and PFNA (median: 0.8, min-max: 0.35-5). We observed that each A quartile increase in the WQS index was positively associated with the levels of TC (beta: 8.41, 95% IC: 0.78-16.0), LDL-C (beta: 8.02, 95% IC: 1-15.0) and SBP (beta: 3.21, 95% IC: 0.82-5.60). No association of serum PFAS concentration on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although PFOA reported the highest concentration. PFOA and PFOS emerged as chemicals of concern regarding the association with SBP.Conclusions: The results showed a clear association between serum PFAS levels and markers of cardiovascular risk and support the importance of clinical surveillance of cardiovascular risk factors in population with a high exposure to PFAS, especially in the occupational setting

Avoidable Hospitalization for Heart Failure Among a Cohort of 18- to 64-Year-Old Italian Citizens and Immigrants: Results From the Italian Network for Longitudinal Metropolitan Studies

Heart failure (HF) represents a severe public health burden. In Europe, differences in hospitalizations for HF have been found between immigrants and native individuals, with inconsistent results. Immigrants face many barriers in their access to health services, and their needs may be poorly met. We aimed to compare the rates of avoidable hospitalization for HF among immigrants and native individuals in Italy