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Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6-12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS-IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: -8.8%; 95% CI: -16.7, -0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Assigned female at birth with anorgasmia possess a smaller clitoral glans and clitoral components farther from the vagina lumen than women with normal orgasmic function. There are no studies evaluating this correlation in operated transgender women. We evaluated whether differences in MRI measurements of neoclitoris volume and distance between the neoclitoris and the neovagina were correlated with differences in sexual function. We recruited for a prospective survey study 40 operated male to female patients (oMtF) who had undergone genital gender affirming surgery and postoperative pelvic MRI. Individual pelvic MRIs were reviewed by two blinded investigators, the three axes of the neoclitoris were measured and the volume was calculated using the ellipsoid formula. The distance between the neoclitoris and the neovagina was also measured. Sexual functioning was assessed using the Female Sexual Function Index (FSFI) and the operated Male to Female Sexual Function Index (oMtFSFI). Mean scores differences in FSFI, oMtFSFI were examined; associations with clitoral size, location, sexual functioning and demographical variables were investigated as well. The response rate was 55%, 11 MtFs operated with pubic neoclitoris technique (PNT) and 11 with neo-urethroclitoroplasty according to Petrović (NCP). The NCP group presented a neoclitoris mean volume of 1.04 (SD 0.39) cc vs 1.31 (SD 0.78) cc of the other group (p = 0.55). The mean distance between neoclitoris and neovagina was 4.20 (SD 0.57) cm in the PNT group and 2.55 (SD 0.45) in the NCP group (p < 0.001). Patients who had undergone NCP achieved a higher FSFI and oMtFSFI mean Total Score than those operated with the previous technique (FSFI 25.81 SD 3.02 vs 18.62 SD 9.92 p = 0.08; oMtFSFI 37.63 SD 8.28 vs 43.36 SD 13.02 p = 0.23). According to pelvic MRI measurements, this study suggests a correlation between neoclitoral location and oMtF sexual satisfaction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear., Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents., Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6-12 years, 2014-2021) and 2499 adolescents (10 studies, 12-18 years, 2014-2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects., Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: -0.19, -0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: -0.14, -0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: -0.25, 0.03, per joint exposure quantile)., Conclusion: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: A rise in affective and anxiety disorders and in antidepressant (AD) treatment during the COVID-19 pandemic has been extensively described, but few studies were provided at the individual level, further considering COVID-19 severity and vaccination status., Methods: Case-control study evaluating the association between the new use of ADs and a previous COVID-19 infection, in Friuli Venezia Giulia Region, Italy, from March 1, 2020, to July 19, 2022. Multiple conditional logistic regressions assess the association between a new AD use and a COVID-19 infection previous to the index date, stratified by gender, age and anti-COVID-19 vaccination status. Odds Ratios (OR) and 95% confidence intervals were reported., Results: COVID-19 was associated with AD treatment after the infection. The disease severity was positively associated with a growing risk of being dispensed an AD, with the highest risk in unvaccinated subjects previously hospitalised in ICU (OR = 28.77). The risk of using ADs after COVID-19 infection was higher in unvaccinated subjects aged 65 years and older, both females and males. The association between COVID-19 infection and AD dispensation in vaccinated subjects was not significant, with the exception of females aged 65 years and over., Conclusions: Anti-COVID-19 vaccination, especially among the elderly, might prevent post-COVID AD treatment. Clinicians should be aware that COVID-19 patients requiring hospitalisation are more likely to experience these symptoms, given their higher risk of being dispensed ADs. Future studies may benefit by analysing the incidence of both mental disorders and psychotropic treatment in post-COVID patients, considering socioeconomic factors and vaccination status., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID., Methods: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions., Results: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38)., Conclusions: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

Background: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers., Methods: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period., Results: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter., Conclusions: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time., (© 2023 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Background: Vaccine effectiveness (VE) studies consolidate knowledge of real-world effectiveness in different contexts. However, methodological issues may undermine their conclusions: to assess the VE against COVID-19 within the Italian population, a specific threat to validity is related to the consequences of divergent compliance to the Green Pass policy., Methods: To address this challenge we conducted a test negative case-control (TNCC) study and multiple sensitivity analysis among residents aged ≥ 12 in Friuli Venezia Giulia Region (FVG), North-east Italy, from February 1, 2021 to March 31, 2022. Information regarding 211,437 cases of COVID-19 infection and 845,748 matched controls was obtained from the regional computerized health database. The investigation considered: COVID-19 infection, hospitalization, and death. Multiple conditional logistic regressions adjusted for covariates were performed and VE was estimated as (1-OR COVID-19 vaccinated vs. unvaccinated )x100. Mediation analyses were carried out to offset potential collider variables, particularly, the number of swabs performed after the introduction of pandemic restrictions., Results: Full-cycle VE against infection decreased from 96% (95% CI: 96, 97) in the Alpha period to 43% (95% CI: 42, 45) in the Omicron period. Booster dose raised the protection in Omicron period to 67% (95% CI: 66, 67). Against the evasive Omicron variant, the protection of the booster dose was 87% (95% CI: 83, 90) for hospitalization and 90% (95% CI: 82, 95) for death. The number of swabs performed was included as a covariate in the adjustments, and the mediation analysis confirmed that it was a strong mediator between vaccination and COVID-19-related outcomes., Conclusions: The study suggests that, under similar TNCC settings, mediation analysis and adjustment for number of diagnostic tests should be included, as an effective approach to the challenge of differential testing behavior that may determine substantial selection bias. This correction allowed us to align with results from other studies that show how full-cycle VE against infection was initially high but decreased over time by variant circulation, counterbalanced by booster dose that raised protection across variants and outcome severity., (© 2023. The Author(s).)

Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (β coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:β =  - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: β =  - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:β =  - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:β =  - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:β =  - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:β =  - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries., (© 2023. The Author(s).)

Background: The geothermal power plants for electricity production currently active in Italy are all located in Mt. Amiata area in the Tuscany region. A cross-sectional survey was conducted in the framework of the regional project "InVETTA-Biomonitoring Survey and Epidemiological Evaluations for the Protection of Health in the Amiata Territories", using objective measures of lung function to investigate the role of hydrogen sulphide (H2S) in affecting the respiratory health of the population living in this area., Methods: 2018 adults aged 18-70 were enrolled during 2017-2019. Home and workplace addresses of participants were geocoded. Dispersion modelling was used to evaluate the spatial variability of exposure to H2S from the geothermal power plants' emissions. We estimated average long-term historical exposure to H2S and more recent exposure indicators. Chronic Obstructive Pulmonary Disease (COPD) was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Multivariable logistic regressions were performed to investigate associations between outcome and exposure., Results: Our findings did not showed any evidence of an association between increasing H2S exposure and lung function impairments. Some risk reductions were observed: a -32.8% (p = 0.003) for FEV1<80% and a -51.7% (p = 0.001) risk decrease for FVC<80% were associated with interquartile increase (13.8 μg/m3) of H2S levels., Conclusion: Our study provides no evidence that chronic exposure to low levels of H2S is associated with decrements in pulmonary function, suggesting that ambient H2S exposure may benefit lung function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stoppa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The knowledge of the effects of organophosphate flame retardants on children's neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children's neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children's urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt ( β = -1.30; 95%CI = -2.72; 0.11; p -value = 0.07) and no clear association with DPHP standardized by crt ( β = -0.98; 95%CI = -2.96; 0.99; p -value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP ( β = -1.42; 95% CI = -2.70; -0.06; p -value = 0.04) and no clear association with DPHP ( β = -1.09; 95% CI = -2.87; 0.68; p -value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was -0.49 (95%CI = -1.85; 0.87; p -value = 0.48), and with DPHP standardized by crt it was -0.35 (95%CI = -1.90; 1.20; p -value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

Objectives: To estimate the incidence and describe the spectrum of inflammatory and autoimmune diseases linked to SARS-CoV-2 infection and COVID-19 vaccination in children from two neighbouring south central European countries., Methods: We performed a multi-centre prospective cohort study of children under 18 years diagnosed with inflammatory/autoimmune diseases linked to SARS-CoV-2 infection or COVID-19 vaccination, who were admitted to the paediatric tertiary care hospitals in Slovenia and Friuli Venezia Giulia, Italy, from January 1, 2020, to December 31, 2021. Disease incidence was calculated based on laboratory-confirmed cases only., Results: Inflammatory and autoimmune diseases linked to SARS-CoV-2 were diagnosed in 192 children (127 laboratory-confirmed), of whom 112 had multisystem inflammatory syndrome (MIS-C), followed by vasculitis, neurological and cardiac diseases. Calculated risk of MIS-C was 1 in 860 children after SARS-CoV-2 infection and cumulative incidence of MIS-C was 18.3/100,000 of all children. Fifteen children had severe COVID-19. Two patients with MIS-C and a patient with myositis presented after COVID-19 vaccination. All 3 had at presentation also a serologically proven recent SARS-CoV-2 infection. After MIS-C, nine patients were vaccinated against COVID-19 and 25 patients had a SARS-CoV-2 reinfection, without recurrence of MIS-C., Conclusions: Autoimmune diseases following SARS-CoV-2 infection in children were 8.5 times as common as severe COVID-19. MIS-C was the most common manifestation and its incidence in this predominantly white population was higher than previously reported. MIS-C does not seem to recur after SARS-CoV-2 reinfection or COVID-19 vaccination. Autoimmune diseases were much more common after SARS-CoV-2 infection than after COVID-19 vaccination.

Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes ∼5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for ∑DEHP metabolites (33.6 μg/L), MiBP (26.6 μg/L), and MEP (24.4 μg/L) and lowest for∑DiDP metabolites (1.91 μg/L) and ∑DINCH metabolites (3.57 μg/L). In adolescents highest GMs were found for MEP (43.3 μg/L), ∑DEHP metabolites (28.8 μg/L), and MiBP (25.6 μg/L) and lowest for ∑DiDP metabolites (= 2.02 μg/L) and ∑DINCH metabolites (2.51 μg/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest related to this work., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures., Competing Interests: Declarations of competing interest The authors declare no conflict of interest. José V. Tarazona is employed by the European Food Safety Authority (EFSA). The views expressed in this publication are those of the authors and should not be interpreted as representing the official position of EFSA., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Natural sources and anthropogenic activities are responsible for the widespread presence of heavy metals in the environment in the volcanic and geothermal area of Mt. Amiata (Tuscany, Italy). This study evaluates the extent of the population exposure to metals and describes the major individual and environmental determinants. A human biomonitoring survey was carried out to determine the concentrations of arsenic (As), mercury (Hg), thallium (Tl), antimony (Sb), cadmium (Cd), nickel (Ni), chromium (Cr), cobalt (Co), vanadium (V), and manganese (Mn). The associations between socio-demographics, lifestyle, diet, environmental exposure, and metal concentrations were evaluated using multiple log-linear regression models, adjusted for urinary creatinine. A total of 2034 urine and blood samples were collected. Adjusted geometric averages were higher in women (except for blood Hg) and younger subjects (except for Tl and Cd). Smoking was associated with Cd, As, and V. Some dietary habits (rice, fish, and wine consumption) were associated with As, Hg, Co, and Ni. Amalgam dental fillings and contact lenses were associated with Hg levels, piercing with As, Co, and Ni. Among environmental determinants, urinary As levels were higher in subjects using the aqueduct water for drinking/cooking. The consumption of locally grown fruits and vegetables was associated with Hg, Tl, and Co. Exposure to geothermal plant emissions was associated only with Tl., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The impacts of single-nucleotide polymorphisms (SNPs) in ALAD and VDR genes on Pb health effects and/or kinetics are inconclusive at low exposure levels, while studies including APOE SNPs are rare. In this study, we examined the associations of ALAD, VDR and APOE SNPs with exposure biomarkers of Pb and other trace elements (TEs) in Italian pregnant women (N = 873, aged 18-44 years) and their newborns (N = 619) with low-level mixed-element exposure through diet, the environment or endogenously. DNA from maternal peripheral venous blood (mB), sampled during the second and third trimesters, was genotyped for ALAD (rs1800435, rs1805313, rs1139488, rs818708), VDR (rs2228570, rs1544410, rs7975232, rs731236) and APOE (rs429358, rs7421) using TaqMan SNP assays. Personal and lifestyle data and TE levels (mB, maternal plasma, hair and mixed umbilical cord blood [CB]) from the PHIME project were used. Multiple linear regression models, controlling for confounding variables, were performed to test the associations between SNPs and TEs. The geometric means of mB-Pb, mB-Hg, mB-As and mB-Cd (11.0 ng/g, 2.16 ng/g, 1.38 ng/g and 0.31 ng/g, respectively) indicated low exposure levels, whereas maternal plasma Zn and Se (0.72 μg/mL and 78.6 ng/g, respectively) indicated adequate micronutritional status. Variant alleles of ALAD rs1800435 and rs1805313 were negatively associated with mB-Pb levels, whereas a positive association was observed for rs1139488. None of the VDR SNPs or their haplotypes had any association with Pb levels. Regarding APOE, the ϵ4 allele was associated with lower mB-Hg and CB-Hg, while a positive association was found with the ϵ2 allele and CB-Pb when the model included only newborn girls. The observed associations indicate possible modification effects of ALAD and APOE SNPs on Pb or Hg kinetics in women and their newborns with low exposure to non-essential TEs, as well as an adequate nutritional status of Zn and Se., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Research from different sources supports a link between nutrition and neurodevelopment, but evidence is still sparse regarding the relationship between a posteriori dietary patterns (DPs) and cognitive performance in school-aged children. Within the Northern Adriatic Cohort II, Friuli Venezia Giulia, Italy, 379 7-year-old children were cross-sectionally evaluated. Dietary patterns were identified through a principal component factor analysis based on 37 nutrients from children's 3-day dietary records. The Wechsler Intelligence Scale of Children (WISC-IV) test provided measures of cognitive performance, including the full-scale intelligence quotient (FSIQ) and single index scores. Each DP was related to FSIQ or single index scores through multiple robust linear regression models. We identified five DPs named "Dairy Products", "Plant-based Foods", "Fats", "Meat and Potatoes", and "Seafood" (63% of variance explained). After adjustment, no significant relationship was observed with the FSIQ score; positive associations were found between the "Seafood" DP and Verbal Comprehension Index or Perceptual Reasoning Index. The "Meat and Potatoes" and "Dairy Products" DPs were inversely associated with the Verbal Comprehension Index and Processing Speed Index scores, respectively. In the absence of a relation with the overall FSIQ score, single DPs might influence specific cognitive functions, including verbal and reasoning abilities, as targeted by single indexes, in the expected direction.

Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL ® DINCH) on children's neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL ® DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children's urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL ® DINCH biomarkers. The relation between phthalates/HEXAMOLL ® DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 ± 11 (NAC-II), 98 ± 12 (OCC), and 81 ± 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP's biomarkers were found: 5OH-MEHP+5oxo-MEHP (β = 2.56; 95% CI 0.58-4.55; N = 270), 5OH-MEHP+5cx-MEPP (β = 2.48; 95% CI 0.47-4.49; N = 270) and 5OH-MEHP (β = 2.58; 95% CI 0.65-4.51; N = 270). On the contrary, in the OCC the relation between DEHP's biomarkers and FSIQ tended to be inverse but imprecise ( p -value ≥ 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL ® DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children.

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014-2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000-2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.

Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL ® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll ® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

Few Italian and European studies have assessed adherence to dietary recommendations in primary school children using dietary records. No Italian studies have provided an index-based nutritional adequacy assessment. We provided a comprehensive overview of dietary intake in 381 7-year-old children from NAC-II cohort study, Friuli Venezia Giulia (Italy). Energy, macro-, and micronutrient intakes were derived from 3-day dietary records. Standard (median and percentage) and index-based (Nutrient Adequacy Ratio (NAR) and Mean Adequacy Ratio (MAR)) approaches were used to evaluate adequacy to Italian dietary reference values at nutrient- and overall-diet-level. Percentage contribution of macronutrients to energy intake (%En) was unbalanced towards total fats and protein. In 25% of children, total fats intake exceeded the reference intake upper limit. In ~63% of children, protein intake was at least doubled in their child-specific population reference intake. Median intakes of sodium (1.7 g/day), saturated fatty acids (12.2 %En), and soluble carbohydrates (19.4 %En) exceeded the suggested dietary target in most (65-84%) children. Inadequacy was also observed for micronutrients, with median NARs ranging from 0.11 (vitamin D) to 0.90 (zinc). The median MAR was 0.75 (0.69-0.79), with 1 indicating optimal overall dietary intake. In conclusion, the enrolled children showed suboptimal intakes of several macro- and micronutrients, in line with Italian and European studies on primary school children. Based on the current findings, public health interventions may be targeted to specific nutrients or subpopulations.

Background: During major epidemic outbreaks, the preparedness of public health systems is challenged and -healthcare workers (HCWs) are at the frontline. Italy was among the first- and worst-hit countries by COVID-19., Aim: To analyze the prevalence and incidence of infection among HCWs in Friuli Venezia Giulia region (north-eastern Italy) from March 1 to the end of the Italian lock-down, May 10, 2020., Methods: HCWs exposed to COVID-19 patients were actively surveyed and all HCWs were routinely tested with nasopharyngeal and oropharyngeal swab for RNA virus detection (n. 54,670)., Results: Infected HCWs (n. 595) represented the 32.3% of all COVID-19 cases in the region under 65 years of age, and incidence of infection was 11.4 cases/1000 workers. HCWs accounted for a significant proportion of coronavirus infection and experienced high infection incidence after unprotected contact., Conclusions: HCWs' knowledge of SARS-CoV-2 epidemiology and proper infection control practices are critical to the control of the disease.

Unhealthy dietary habits established in early infancy may lead to under or over nutrition later in life. This paper describes the energy, nutrients and food-type intake of 18-month-old infants belonging to the Italian PHIME cohort ( n = 389) and evaluates adherence to the Italian dietary reference values (DRVs). Infant dietary data were collected using 7-day dietary records. Mean energy, macro and micronutrient intakes were estimated and compared with the DRVs. The percentage contribution of 19 selected food groups to total energy and macro- and micronutrient intake was determined with the aim of establishing the main food sources. Most infants' diet shared common characteristics: poor variety, excessive intake of proteins (16.5 E% vs. 8-12 E% DRV) and saturated fatty acids (SFAs) (13.8 E% vs. <10 E% DRV), mainly derived from milk and dairy products, and low intake of total fats (33.2 E% vs. 35-40 E% DRV), polyunsaturated fatty acids (PUFAs) (3.1 E% vs. 5-10 E% DRV), vitamin D (1.1 vs. 15 µg/day DRV) and iron (4.5 vs. 8 mg/day DRV). The unbalanced distribution of macronutrients was reflected in energy intakes outside DRV ranges for more than half the infants. Public health interventions promoting healthy eating habits from early on, even from pregnancy, could yield significant short- and long-term health benefits.

Background: Diagnosis of endometriosis and evaluation of incidence data are complex tasks because the disease is identified laparoscopically and confirmed histologically. Incidence estimates reported in literature are widely inconsistent, presumably reflecting geographical variability of risk and the difficulty of obtaining reliable data., Methods: We retrieved incident cases of endometriosis in women aged 15-50 years using hospital discharge records and pathology databases of the Friuli Venezia Giulia region in the calendar period 2004-2017. We studied the spatial pattern of endometriosis incidence applying Bayesian approaches to Disease Mapping, and profiled municipalities at higher risk controlling for multiple comparisons using both q-values and a fully Bayesian approach., Results: 4125 new cases of endometriosis were identified in the age range 15 to 50 years in the period 2004-2017. The incidence rate (x100 000) is 111 (95% CI 110-112), with a maximum of 160 in the age group 31-35 years. The geographical distribution of endometriosis incidence showed a very strong north-south spatial gradient. We consistently identified a group of five neighboring municipalities at higher risk (RR 1.31 95% CI 1.13; 1.52), even accounting for ascertainment bias., Conclusions: The cluster of 5 municipalities in the industrialized and polluted south-east part of the region is suggestive. However, due to the ecologic nature of the present study, information on the patients' characteristics and exposure histories are limited. Individual studies, including biomonitoring, and life-course studies are necessary to better evaluate our findings.

Background: The aim of this study was to analyze the incidence, preoperative findings, pathological features and prognosis in patients with incidental prostate cancer (iPCa) detected at radical cystectomy (RC) for bladder cancer (BCa)., Methods: We retrospectively reviewed data of patients who underwent RC for BCa at our Institution between January 2005 and March 2018. Data regarding patient's history, preoperative digital rectal examination (DRE), total serum PSA level were collected from the chart review. Univariable and multivariable Cox regression models addressed the association of iPCa with recurrence-free survival (RFS) and overall survival (OS)., Results: We obtained a final study cohort of 177 patients. Median age was 69 years (IQR 42-89) and 80(45.2%) patients had iPCa. Patients with iPCa had higher age, preoperative PSA levels and a significant rate of suspicious DRE (all P<0.05). Four patients had BCR during a median follow-up of 28 months (IQR 6-159) and none died for prostate cancer. In multivariable analyses adjusted for age, bladder cancer BCa pT and pN stage and LVI the ten-years RFS and OS rates were not impacted by iPCa regardless of whether it is a clinically significant cancer or not (HR=1.25, 95% CI: 0.65-2.38, P=0.51 vs. HR=1.37, 95% CI: 0.71-2.64, P=0.35) (HR=1.04, 95% CI: 0.53-1.86, P=0.89 vs. HR=1.20, 95% CI: 0.22-6.72, P=0.83)., Conclusions: iPCa is quite common in our study group and most of cases are organ-confined and well differentiated. Regardless of clinical relevance, iPCa does not have an impact on survival outcomes as BCa is driving the prognosis of these patients.

Few studies provide a detailed description of dietary habits during pregnancy, despite the central role of nutrition for the health of the mother and offspring. This paper describes the dietary habits, energy and nutrient intake in pregnant women from four countries belonging to the Mediterranean PHIME cohort (Croatia, Greece, Italy and Slovenia) and evaluates their adherence to the European Food Safety Authority (EFSA) recommendations. A total of 1436 women were included in the present analysis. Maternal diet was assessed using a food frequency questionnaire (FFQ). The mean macro and micronutrient intakes were estimated and compared with the dietary reference values (DRVs). The percentage distribution of the 16 food groups in the total intake of each macronutrient was estimated. All women shared a similar diet during pregnancy; almost all the women in the four countries exceeded the DRV for sugars, and the total fat intake was above the DRV in most women in all the countries, as was the contribution of saturated fatty acids (SFAs) to the total energy intake. In all four countries, we observed an increased risk of micronutrient deficiency for iron, folate and vitamin D. Shared guidelines, implemented at both the national and European level, are essential to improve the maternal nutritional status during pregnancy.

Background: Increasing efforts toward quality improvement (QI) are necessary in low- and middle-income countries (LMICs) to reduce maternal and perinatal mortality and morbidity and to promote respectful care. In Brazil, perinatal health indicators are below targets in several states despite universal access to perinatal services and very high rates of institutional births, indicating poor quality of care (QoC) as a key issue to be addressed. However, research efforts to develop and test QoC improvement interventions are scarce., Objectives: We assessed the effects of a 1-year comprehensive QI cycle using a World Health Organization (WHO) assessment and quality tool on maternal and newborn care at hospital level and documented QIs obtained after a 1-year comprehensive QI cycle., Methods: Uncontrolled, unblinded, pre-post study carried out in six maternity hospitals in Pernambuco, Brazil, accounting for 29 128 live births in 2014. A standards-based and participatory approach based on a WHO quality assessment and improvement tool for maternal and neonatal care at hospital level was used. A national team of assessors supervised by international experts carried out baseline and final assessments. An action plan was developed and implemented to address key quality gaps emerging from the baseline assessment and from two supportive supervision visits., Results: At baseline, hospitals presented a variety of quality gaps, the majority common to all participating centers. Gaps in case management of normal and complicated deliveries and in respectful and holistic care were predominant, in both teaching/tertiary and secondary care hospitals. After one year, several improvements were observed, particularly in respectful care during labor and at delivery, in case management of normal labor and delivery and in neonatal care., Conclusions: A systematic participatory approach based on a WHO tool produced important QIs in a relatively short time and should be considered for use for large-scale QI programs in Brazil and other LMICs. Its comprehensive, peer-to-peer and action-oriented nature and its capability to document QI over time and to build a QI culture represent important comparative advantages over other QI interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: to assess the changes in prevalence, incidence and hospitalisation rates during the first four months of 2020, compared to the same period of 2019, in Friuli Venezia Giulia Mental Health Departments (MHDs); to analyse the features of MHDs patients tested for Sars-Cov-2, and to monitor whether MHDs applied and adhered to regional recommendations., Methods: Observational study using MHDs' administrative data and individual data on suspected and positive cases of Sars-Cov-2. Adherence to recommentations was assessed using 21 indicators. Changes in rates were calculated by Poisson regression analysis, while the Fisher exact test was used for assessing differences between suspected and positive cases., Results: The decrease in voluntary admission rates on 100,000 inhabitants in hospital services was significantly larger from January to April 2020, compared to the same period of 2019 ( P <0.001), while no other data showed a significant decrease. Among the 82 cases tested for Sars-Cov-2, five were positive, and they significantly differ from suspected cases only in that they were at home or in supported housing facilities prior to the test. The MHDs mostly complied with the indicators in the month after the publication of recommendations., Conclusions: Outpatient services continued to work normally during the emergency, while hospital services decreased their activities. A low number of positive cases was found among MHDs' users, which might be linked to a rapid reconversion of services, with an extensive use of home visits and telepsychiatry. These preliminary data should be interpreted with caution, due to the small size and the limited period of observation., (© 2021 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved.)

Background: The extent to which prenatal low-level mercury (Hg) exposure through maternal fish intake and heavy metals exposure affect children's neurodevelopment is controversial and may appear in the long term. In 2007, a prospective cohort, the Northern Adriatic Cohort II (NAC-II), was established to investigate the association between prenatal Hg exposure from maternal fish consumption and child neurodevelopment. The study enrolled 900 pregnant women, and 632 and 470 children underwent neurodevelopmental evaluation at 18 and 40 months of age, respectively. The NAC-II cohort is a part of the Mediterranean cohort in the "Public health impact of long-term, low-level, mixed element exposure in susceptible population strata" project., Methods: This protocol describes the follow-up assessment of the effects of prenatal low level Hg and other heavy metals exposure on the developing nervous system of the children born within the NAC-II who reached the age of 7 years. Child diet components are estimated through a Diet Diary. Child hair and urine are collected for determination of Hg level. In addition, levels of other potentially neurotoxic metals, namely Manganese, Cadmium, Lead, Arsenic, and Selenium, are also measured in the same matrices., Discussion: This protocol extends to the first years of schooling age the evaluation of the neurotoxicant effect of Mercury and of the other heavy metals on children's neurodevelopment, adjusting for the potential confounders, such as the lifestyles and social economic status of children's families. Longitudinal analysis of neurodevelopment, assessed in different ages (18 months, 40 months, and 7 years), are performed.

Environmental studies have identified mercury pollution in the Northern Adriatic Sea (Italy). High- level methyl mercury exposure is a known cause of neurodevelopmental disorders. However, the exposure-effect relation at levels <10ppm is controversial. To assess the possible health effects of prenatal methyl mercury exposure through maternal fish consumption, we conducted an epidemiologic cohort study in a mercury polluted area of the Adriatic Sea. We identified all the children born between 1999 and 2001 to women who were resident in two coastal fishing towns. A comparison group was identified inland. A total of 243 children were enrolled. Their mothers were interviewed approximately two months after delivery to determine a variety of covariates and the type, quantity and origin of fish consumed during pregnancy. Total mercury (THg) and methyl mercury (MeHg) were assessed in maternal hair and breast milk and in the child's hair. The children were evaluated after age 18 months with a physical examination and the Denver Developmental Screening Test II (DDST II). Statistical analyses matched by residential area are not presented since they were not associated with fresh fish consumption, THg or MeHg exposure level or neurodevelopmental outcomes. To date 52 children have been evaluated. After adjustment for a number of potential confounders, preliminary results indicate that the fine motor adaptive score on the Denver Developmental test is inversely related to maternal hair THg. These pilot findings are suggestive of an association between children's fine motor skills and their prenatal methyl mercury exposure from maternal fish consumption. However, only a small number of the cohort have been tested and more extensive testing with more sensitive and specific tests is needed to determine if these findings persist., (Copyright © 2021. Published by Elsevier B.V.)

The aim of this study was to provide urinary levels of total arsenic (TAs) and As species as arsenobetaine (AsB), arsenocholine (AsC), inorganic As (i.e., [As(III)+As(V)]), methylarsonic acid (MMA) and dimethylarsinic acid (DMA) in 7 year-old-children (n = 200) enrolled in the Northern Adriatic Cohort II (NACII), a prospective cohort in a coastal area of Northeast Italy. TAs was determined by sector field-inductively coupled plasma mass spectrometry (SF-ICP-MS) and AsB, AsC, As(III), As(V), MMA and DMA by ion chromatography coupled to ICP-MS (IC-ICP-MS). The geometric mean (GM) for TAs was 12.9 μg/L and for [iAs + MMA + DMA] was 4.26 μg/L. The species AsB (GM of 5.09 μg/L) and DMA (GM of 3.20 μg/L) had the greatest percentage contribution to TAs levels; a greater percentage contribution from AsB is seen at TAs >10 μg/L and from DMA at TAs <10 μg/L. Urinary [iAs + MMA] levels were positively associated with [iAs + MMA + DMA] and DMA with AsB levels. Fish, shellfish and crustaceans consumption increased the AsB and TAs levels, while rice intake, mothers' education level and selenium (Se) concentration influenced the DMA concentration. Children have a high capacity to metabolize and detoxify the iAs because of the higher secondary methylation index (ratio DMA/MMA) with respect to primary methylation index (ratio MMA/iAs). In addition, the median level of [iAs + MMA + DMA] in the whole population of children was lower than the Biomonitoring Equivalent (BE) value for non-cancer endpoints. Also the Margin of Safety (MOS) value based on the population median was greater than 1, thus the exposure to the toxicologically relevant As species was not likely to be of concern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: to investigate the role of gender, age, province of residence, and nursing home residency on the risk of death for residents in the Friuli Venezia Giulia (FVG) Region (Northern Italy) tested positive for Covid-19, considering recovery as a competing event. The secondary objective is to describe the impact of the Covid-19 epidemic in FVG and in the Regions of Northern and Central Italy in terms of incidence and mortality compared to the national data., Design: retrospective cohort study., Setting and Participants: resident population in FVG in the period between 29 February and 25 June 2020., Main Outcome Measures: in order to describe the impact of the Covid-19 outbreak in FVG, in terms of incidence and mortality compared to the national data, the standardized incidence (SIR) and mortality (SMR) ratios and their respective 95% confidence intervals (95%CI) were calculated compared to the Italian population for the northern and central Regions of Italy and the autonomous Provinces (PA) of Trento and Bolzano. A retrospective cohort study was conducted on subjects residing in FVG to whom at least one naso-oropharyngeal swab (hereafter, named swab) resulted positive for Covid-19. For each subject included in the cohort, the observation period started with the first positive swab and ended with the first of the following events: death, recovery or censored, which means that at the end of the observation period the subject was still alive and positive. The cause of death was assigned to Covid-19 if a subject had not yet recovered at the time when the event occurred. Cohort members were considered recovered after two negative consecutive swabs. The sub-hazard ratio (SHR) was estimated by applying the regression model of competing risks by Fine and Gray, in which the event of interest was the death caused by Covid-19 and the competing event was recovery. The explanatory variables included in the multiple models are: gender, age at the beginning of the observation period, the Province of residence, and nursing home residency. The cause-specific hazard was estimated using Cox proportional hazard regression., Results: during the observation period, 3,305 cases and 345 deaths were recorded in FVG; SIR and SMR resulted, respectively, equal to 0.64 (95%CI 0.61-0.68) and 0.43 (95%CI 0.37-0.50). The FVG was the Northern Region one with the lowest incidence and mortality. The cohort consisted of 3,121 residents in FVG with at least one swab with a positive Covid-19 result during the study period. The SHR of dying for Covid-19 is equal to 16.13 (95%CI 9.73-26.74) for people with age 70-79 years and 35.58 (95%CI 21.77-58.15) with age >=80 years respect those with age <70 years. It is higher in males (SHR 1.71; 95%CI 1.34-2.17). There is no evidence that being resident in a nursing home affects the SHR (SHR 0.91 and 95%CI 0.69-1.20). As regards the province as an explanatory variable, the sub-hazard of death in the province of Trieste appears to overlap to the sub-hazard of Pordenone used as a reference; for the provinces of Udine and Gorizia the sub-hazards seem lower than the reference., Conclusions: while other Northern Regions and autonomous Provinces show higher standardized incidence and mortality compared with Italy, FVG and Veneto do not. In FVG, male gender and age are important determinants of death while there is no evidence that the condition of guest in a nursing home increases the sub-hazard of death.

Despite a 15-year long effort to define the "safety" of fish intake during pregnancy, there remains still uncertainty on this important public health issue. The evaluation of the toxic effects of contaminants, particularly mercury (Hg) in fish-eating populations is complicated by the fact that sea-food is also rich in beneficial nutrients, such as selenium (Se). There is toxicological plausibility of an antagonistic effects between Se and Hg, and some theoretical support for the inclusion of the Se-Hg interaction to better assess the risk linked with fish intake. To assess the effects of exposure to low-level Hg through fish consumption on the developing brain and the interaction between Hg and Se, we conducted an analysis at age 40 months in Italian children, enrolled in a prospective mother-child cohort, comparing additive and multiplicative models. Participant subjects were the 470 children born within the Northern Adriatic Cohort II (NAC-II) cohort who were tested by using the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) (BSID-III) at age 40. Family demographic and socioeconomic information, pregnancy and delivery history, parental and child medical history and food consumption were assessed through questionnaires. Maternal blood samples were collected during pregnancy, cord blood at birth and maternal milk 1 month after delivery. As other exposures of interest, we considered the level of Se in maternal and cord blood and in breast milk and the potential Se-Hg antagonism. Se and inverse of THg (1:THg) concentrations were categorized according to the tertiles of their distributions, in low, medium and high levels of exposure. The lower end of the composite cognitive score distribution closest to 20% was defined as suboptimal development. Multiple logistic regression were applied to assess the association between the dichotomized composite cognitive score and the categorized exposure to Se and 1:THg, and the antagonism between Se and 1:THg. In the recruiting period, 900 pregnant women were enrolled in the cohort; 767 of these remained in the study at delivery and 470 children at 40 months. After excluding preterm births, 456 children were used in the final analyses. The larger difference in risk for suboptimal neurodevelopment was observed for the category with High THg and Low Se with OR = 2.55 (90% CI 1.02; 6.41) under the multiplicative and OR = 1.33 (90% CI 0.80; 1.87) under the additive model. The category High THg and High Se showed a very slightly better fit of the additive model (OR = 1.07, 90% CI 0.65; 1.50) versus the multiplicative (OR = 1.66, 90% CI 0.73; 1.77). A negative - antagonistic - interaction term for this category was estimated under the multiplicative model giving an OR = 1.17 (90% CI 0.42; 3.28). Although this evidence of the effects of the Se-Hg antagonism on the children neuro-development needs to be confirmed, if Se can counterbalance Hg toxicity, the evaluation of the effect on human health of fish consumption, should also consider the diverse ratios between Se and Hg concentration in different fish species., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: the first confirmed cases of COVID-19 in WHO European Region was reported at the end of January 2020 and, from that moment, the epidemic has been speeding up and rapidly spreading across Europe. The health, social, and economic consequences of the pandemic are difficult to evaluate, since there are many scientific uncertainties and unknowns., Objectives: the main focus of this paper is on statistical methods for profiling municipalities by excess mortality, directly or indirectly caused by COVID-19., Methods: the use of excess mortality for all causes has been advocated as a measure of impact less vulnerable to biases. In this paper, observed mortality for all causes at municipality level in Italy in the period January-April 2020 was compared to the mortality observed in the corresponding period in the previous 5 years (2015-2019). Mortality data were made available by the Ministry of Internal Affairs Italian National Resident Population Demographic Archive and the Italian National Institute of Statistics (Istat). For each municipality, the posterior predictive distribution under a hierarchical null model was obtained. From the posterior predictive distribution, we obtained excess death counts, attributable community rates and q-values. Full Bayesian models implemented via MCMC simulations were used., Results: absolute number of excess deaths highlights the burden paid by major cities to the pandemic. The Attributable Community Rate provides a detailed picture of the spread of the pandemic among the municipalities of Lombardy, Piedmont, and Emilia-Romagna Regions. Using Q-values, it is clearly recognizable evidence of an excess of mortality from late February to April 2020 in a very geographically scattered number of municipalities. A trade-off between false discoveries and false non-discoveries shows the different values of public health actions., Conclusions: despite the variety of approaches to calculate excess mortality, this study provides an original methodological approach to profile municipalities with excess deaths accounting for spatial and temporal uncertainty.

Objective: Thirty-four geothermal power plants for the production of electricity are currently active in the geothermal areas in Tuscany. The present study aimed to investigate the association between short-term exposure to hydrogen sulfide (H 2 S) and acute health outcomes., Methods: This study used individual data on non-accidental, cardiovascular and respiratory mortality, urgent hospital admissions (HA) and emergency department (ED) visits for cardiorespiratory diseases occurring from 2000 to 2017. All cases were georeferenced and matched to daily H 2 S data, derived from 18 monitoring sites. A case-crossover design following the matched pair interval approach was applied and conditional logistic regression models were fitted to estimate odds ratios and their 90% confidence intervals, adjusting for a set of time-dependent variables, such as influenza epidemics, holidays and temperature., Results: A total of 8054 deaths, 30,527 HA and 15,263 ED visits occurred. Mortality for non-accidental (OR = 1.11, 90% CI 1.02-1.22) and cardiovascular causes (OR = 1.22, 90% CI 1.03-1.44) were associated with an increase of 10 µg/m 3 of H 2 S daily levels only among men. Hospital admissions for respiratory diseases were positively associated with H 2 S exposure: OR = 1.11 (90% CI 1.00-1.22) among women. No associations were observed in ED visits analyses., Conclusions: In this case-crossover study in the Tuscan geothermal areas, short-term exposure to H 2 S was weakly associated with some mortality and morbidity outcomes. Our findings did not show a clear pattern as the results were not homogeneous between mortality and morbidity data or between men and women.

Objectives: Poor social conditions are strong determinants of poor health but positive health and healthcare changes caused by social interventions are difficult to demonstrate. In 2006, in Trieste (Italy), a social intervention known as 'Habitat Microaree' (HM) project was implemented in eight deprived neighbourhoods. In 2016, an observational study was launched to assess the impact of the HM project on healthcare., Design: Retrospective cohort study., Setting: The eight geographically defined neighbourhoods of Trieste involved in the 2006 HM project, accounting for a total of 11 380 residents., Participants: Participants were all residents in the intervention areas. By means of a propensity score based on deprivation index, age, sex, Charlson index and drug utilisation, a non-participating, comparison group was defined., Intervention: The community-based intervention consisted of facilitating access to social services and outpatient healthcare facilities, coordinating intersectoral public services and specifically planning hospital discharge. These services were not provided in other areas of the city., Outcome Measures: Hospital admissions and emergency department access., Results: We followed 16 256 subjects between 2008 and 2015. Living in microareas was associated with an HR for first hospital admission, for all causes, of 0.95 (95% CI 0.91 to 0.99); while the HR for urgent admissions in females was 0.92 (95% CI 0.85 to 1.00). The HR for psychiatric disorders, in females, was 0.39 (95%CI 0.18 to 0.82); in particular, the HR for psychosis was 0.15 (95% CI 0.05 to 0.51). The HR for acute respiratory diseases in females was 0.44 (95% CI 0.21 to 0.95). In males, the HR for genitourinary diseases and heart diseases were 0.65 (95% CI 0.42 to 1.01) and 0.72 (95% CI 0.54 to 0.97), respectively. Concerning urgent multiple admissions, the OR for fractures in females was 0.75 (95% CI 0.58 to 0.97)., Conclusion: In the study period, the effects on healthcare appear evident, especially in females., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available., Methods: Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks., Results: The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks., Conclusion: The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

Objectives: Prenatal exposure of long chain polyunsaturated fatty acids (LCPUFA) are essential for normal fetal growth and neurodevelopment. Availability of LCPUFA depends mostly on maternal fish consumption. Fish consumption also exposes the fetus to mercury which is well known neurotoxicant. We analyzed the associations of combined LCPUFA and mercury from fish consumption during pregnancy on newborn's brain measures and child neurodevelopment in a northern Adriatic coastal area., Patients and Methods: The prospective cohort study included 257 mother - infant pairs enrolled in a susceptible population of the Public Health Impact on long-term, low-level, Mixed Element exposure (PHIME) EU Sixth Framework Programme from 2 recruitment areas of the northern part of the Adriatic coast. Umbilical cord blood taken at delivery was used for measuring concentration of total mercury (THg) and specific LCPUFA - docosahexaenoic acid (DHA) and arachidonic acid (ARA). Neonatal cranial sonography was performed at the age of 3 days in 57 newborns. Neurodevelopmental assessment of cognitive, motor and language skills were conducted at 257 children at the age of 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition. The participants were divided into two groups depending on the THg concentration in the umbilical cord blood (exposed > 5.8 μg/L and unexposed < 5.8 μg/L). Dietary habits and exposures to environmental and social factors were assessed through questionnaires., Results: There is a statistically significant difference in the cerebellum length (p = 0.032) and the superior frontal gyrus width (p = 0.023) between the exposed and the unexposed group. In combined analysis, including possible protective variables as DHA and ARA (R 2  = 0.22, p = 0.001), the negative contribution of THg on cerebellum length (beta = -0.16, p = 0.001) persisted. We found no correlation between THg concentration in umbilical cord blood and child neurodevelopment scores at the age of 18 months. Language score with receptive and expressive subscores was significantly associated with fish consumption (p < 0.05)., Conclusion: This analysis demonstrates the existence of morphological brain changes in newborns that are prenatally exposed at mercury concentrations what was diminished in combined analyse including LCPUFA. Our results emphasizes the importance of LCPUFA's and mercury common influence as a predictor of developmental outcome. Fish consumption, not solely LCPUFA contributes to better language development of children at the age of 18 months., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In recent years, several studies have addressed the issue of prenatal exposure to methylmercury (MeHg); however, few have actually analysed MeHg blood concentrations. Our study population included mothers and their new-borns from Slovenia (central region; N = 584) and Croatia (coastal region; N = 234). We have measurements of total Hg (THg) and MeHg in maternal hair, maternal peripheral blood, and cord blood. Cord blood Hg concentrations were low to moderate (median THg = 1.84 ng/g and MeHg = 1.69 ng/g). The proportion of THg as MeHg (%MeHg) in maternal and cord blood varied between 4% and 100% (coefficient of variation, CV = 32%) and between 8% and 100% (CV = 20%), respectively. Our data shows that variability of %MeHg was higher at lower blood THg levels. Concentrations of MeHg in maternal blood and cord blood were highly correlated (R s  = 0.943), in the case of inorganic Hg correlation was significant but weaker (R s  = 0.198). MeHg levels in maternal blood and cord blood were positively associated with seafood intake, maternal age, and negatively associated with pre-pregnancy BMI. Additionally, MeHg in maternal blood was positively associated with plasma selenium levels, and cord blood MeHg was negatively associated with parity. The results of multiple linear regression models showed that speciation analysis provides more defined estimation of prenatal exposure in association modelling. Associations between Hg exposure and cognitive performance of children (assessed using Bayley Scales of Infant and Toddler development) adjusted for maternal or child Apolipoprotein E genotypes showed higher model R 2 and lower p-values when adjusted for MeHg compared to THg. This study demonstrates that Hg speciation improves the association between exposure and possible negative health effects., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Urinary metabolites of organophosphate (OP) and pyrethroid (PYR) pesticides from seven years old children of a birth cohort study (n=199; PHIME cohort of Trieste, Italy) have been measured. Six OP and two PYR metabolites have been investigated, 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY, pirimiphos metabolite) was the one found at higher concentrations, median 3.4 ng/mL specific gravity adjusted (SG adjusted), followed by 4-nitrophenol (PNP, median 1.4 ng/mL SG adjusted) and 3,5,6-trichloro-2-pyridinol (TCPY, median 0.36 ng/mL SG adjusted), parathion and chlorpyriphos metabolites, respectively. TCPY concentrations were low in comparison to other distributions of OP metabolites in children from other studies. Accordingly, the PHIME cohort showed a distinct OP metabolite distribution with high concentrations of pirimiphos and parathion. Another specific characteristic of this cohort was the high concentration of 3-phenoxybenzoic acid (3-BPA, median 0.36 ng/mL SG adjusted), a general metabolite of PYR pesticides. Evaluation of anthropometric and socio-demographic characteristics of children and families only showed a positive association between family educational level and urinary concentrations of DEAMPY metabolite (p<0.05), which could reflect distinct dietary habits depending on the educational level. Estimated daily intakes were evaluated, all studied metabolites were found within safe levels., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To determine the acute effects on respiratory function of children exposed to sulphur dioxide (SO₂), we conducted two population-based longitudinal investigations near a major oil refinery. We enrolled 233 children, age 8⁻14, in Sarroch (Italy). The first study entailed five monthly spirometric visits (Panel 5). In a subgroup, children positive for history of respiratory symptoms were tested weekly (20 times) with spirometry and fractional exhaled nitric oxide (FeNO) measurement (Panel 20). Baseline questionnaires and daily diaries were recorded. SO₂, NO₂, PM 10 and O₃ were measured by monitoring stations. Multiple regression models were fitted. Using a multipollutant model, we found that a 10 µg/m³ SO₂ increase at lag0⁻2 days determined a percent variation (PV) of -3.37 (90% confidence interval, CI: -5.39; -1.30) for forced expiratory volume after one second (FEV1) in Panel 5 and a PV = -3.51 (90% CI: -4.77; -2.23) in Panel 20. We found a strong dose-response relation: 1-h SO₂ peaks >200 µg/m³ at lag2 days = FEV1 PV -2.49. For FeNO, we found a PV = 38.12 (90% CI: 12.88; 69.01) for each 10 µg/m³ SO₂ increase at 8-h time lag and a strong dose-response relation. Exposure to SO₂ is strongly associated with reduction of lung function and an increase in airway inflammation. This new evidence of harmful effects of SO₂ peaks should induce regulatory intervention.

Background: Births by cesarean section (CS) usually require longer recovery time, and as a result women remain hospitalized longer following CS than vaginal delivery (VD). A number of strategies have been proposed to reduce avoidable health care costs associated with childbirth. Among these, the containment of length of hospital stay (LoS) has been identified as an important quality indicator of obstetric care and performance efficiency of maternity centres. Since improvement of obstetric care at hospital level needs quantitative evidence, we compared the maternity services of an Italian region on LoS post CS., Methods: We conducted a population-based study in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from all its 12 maternity centres (coded from A to K) during 2005-2015. We fitted a multivariable logistic regression using LoS as a binary outcome, higher/lower than the international early discharge (ED) cutoffs for CS (4 days), controlling for hospitals as well as several factors related to the clinical conditions of the mothers and the newborn, the obstetric history and socio-demographic background. Results were expressed as adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Population attributable risks (PARs) were also calculated as proportional variation of LoS>ED for each hospital in the ideal scenario of having the same performance as centre J (the reference) during calendar year 2015. Results were expressed as PAR with 95%CI. Differences in mean LoS were also investigated with a multivariable linear regression model including the same explanatory factors of the above multiple logistic regression. Results were expressed as adjusted regression coefficients (aRC) with 95%CI., Results: Although decreasing over the years (5.0 ± 1.7 days in 2005 vs. 4.4 ± 1.7 days in 2015), the pooled mean LoS in the whole FVG during these 11 years was still 4.7 ± 1.7 days, higher than respective international ED benchmark. The significant decreasing trend of LoS>ED over time in FVG (aOR = 0.89; 95%CI: 0.88; 0.90) was marginal as compared to the variability of LoS>ED observed among the various maternity services. Regardless it was expressed as aRC or aOR, LoS after CS was lowest in hospital C, highest in hospital D and intermediate in centres I, K, G, F, A, H, E, B and J (in descending order). The aOR of LoS being longer than ED ranged from 1.63 (95%CI:1.46; 1.81) in hospital B up to 32.09 (95%CI: 25.68; 40.10) in facility D. When hospitals were ranked by PAR the same pattern was found, even if restricting the analysis to low risk pregnancies., Conclusions: Although significantly decreasing over time, the mean LoS in FVG during 2005-2015 was 4.7 days, higher than the international threshold recommended for CS. There was substantial variability in LoS by facility centre, suggesting that internal organizational processes of single hospitals should be improved by enforcing standardized guidelines and using audits, economic incentives and penalties if need be., Competing Interests: The authors have declared that no competing interests exist.