Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece

Background: Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. Methods: The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection: 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at age 11, respectively. BKMR results were compared using static versus percentile-based cutoffs to define elevated BP. Results: Molybdenum and lead were the mixture components most consistently associated with BP. J-shaped relationships were observed between molybdenum and both systolic and diastolic BP at age 4. Similar associations were identified for both molybdenum and lead in relation to elevated BP at age 11. For molybdenum concentrations above the inflection points (~ 40–80 μg/L), positive associations with BP at age 4 were stronger at high levels of lead. Lead was positively associated with BP measures at age 4, but only at high levels of molybdenum. Potential interactions between molybdenum and lead were also identified for BP at age 11, but were sensitive to the cutoffs used to define elevated BP. Conclusions: Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas

Влияние лечения тиотриазолином на состояние перекисного окисления липидов и уровни иммуновоспалительных и вазоактивных эндотелиальных факторов у больных с хронической сердечной недостаточностью и helicobacter pylori-негативными гастропатиями

Показано, что включение в схему патогенетического лечения больных с ХСН, hp-негативной гастропатией и умеренным или высоким риском сердечно-сосудистых осложнений (ССО) антиоксиданта тиотриазолина сопровождается достоверно более выраженными позитивными эффектами на процессы перекисного окисления липидов и содержание в крови иммуновоспалительных и вазоактивных эндотелиальных факторов по сравнению с динамикой при лечении без использования тиотриазолина, причем степень положительной динамики у больных с высоким риском ССО достоверно больше.Показано, що включення у схему патогенетичного лікування хворих із ХСН, hр-негативною гастропатією і з помірним або високим ризиком серцево-судинних ускладнень (ССУ) антиоксиданта тіотриазоліна супроводжується достовірно більш вираженими позитивними ефектами на процеси перекисного окислення ліпідів та вміст у крові імунозапальних і вазоактивних ендотеліальних факторів порівняно з динамікою при лікуванні без використання тіотриазоліну, причому ступінь позитивної динаміки у хворих із високим ризиком ССУ достовірно більший.It is shown that the use of tiotriazolin in the scheme of pathogenetic treatment of patients with chronic heart failure, Hp-negative gastropathy, and moderate or high risk of cardiovascular complications (CVC) is accompanied by significantly higher positive effect on the processes of lipid peroxidation and the amount of immune inflammation and vasoactive endothelial factors in the blood when compared with the dynamics at treatment without the use of tiotriazolin, the degree of positive dynamics in patients with a high risk of CVC being significantly higher

Determinants of the urinary and serum metabolome in children from six European populations

Background Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu). Methods Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit). Results We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum. Conclusions We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Respiratory symptoms and use of health services in relation with employment status

Εισαγωγή: Πληθώρα μελετών έχουν ερευνήσει με τη σχέση της αναπνευστικής υγείας με την επαγγελματική έκθεση, αλλά όχι με την ανεργία. Ταυτόχρονα, η επαγγελματική κατάσταση έχει συνδεθεί με τις ανεπιθύμητες εκβάσεις της υγείας, μέσα από τις άμεσες και έμμεσες επιπτώσεις της, όπως η φτώχεια και το άγχος. Χαρακτηρίζεται, επίσης, ως ένας καθοριστικός παράγοντας για την κακή διαχείριση ασθενειών. Σκοπός: Η παρούσα εργασία διερευνά την εμφάνιση συμπτωμάτων αναπνευστικών δυσλειτουργιών και τη χρήση υπηρεσιών φροντίδας υγείας, σε σχέση με την επαγγελματική κατάσταση. Επιμέρους στόχοι ήταν η εκτίμηση του επιπολασμού κατά τη φάση ολοκλήρωσης της μελέτης και της αθροιστικής επίπτωσης κατά την διάρκεια του follow up για τρία συμπτώματα αναπνευστικών δυσλειτουργιών (συριγμός, χρόνιος βήχας και χρόνιο φλέγμα) και δύο αναπνευστικά νοσήματα (άσθμα και χρόνια βρογχίτιδα). Μέθοδοι: Η ανάλυση βασίζεται στα δεδομένα της διεθνούς μελέτης ECRHS II. Το δείγμα αποτελείται από 10.933 συμμετέχοντες, ηλικίας 26 έως 56 ετών, οι οποίοι απάντησαν σε εκτενές ερωτηματολόγιο. Η στατιστική ανάλυση συμπεριλαμβάνει τη χρήση των μεθόδων της λογιστικής παλινδρόμησης, το λογαριθμικό – δυωνυμικό μοντέλο, την παλινδρόμηση Poisson και το μοντέλο εξάρτησης του COX. Αποτελέσματα: Η στατιστική επεξεργασία έδειξε αυξημένο επιπολασμό του συριγμού, χωρίς κρύωμα (OR=1.49, 95%CI 1.02-2.18) και του άσθματος (συμπτωματικός ορισμός: OR=2.08, 95%CI 1.25-3.45, κλινικός ορισμός: OR=2.24, 95% CI 1.11-4.53) στους άνεργους ενήλικες σε σχέση με τους εργαζόμενους. Αναφορικά με την εμφάνιση νέων περιπτώσεων αναπνευστικών δυσλειτουργιών κατά τη διάρκεια του follow-up, οι άνεργοι είχαν 91% περισσότερες πιθανότητες για αναφορά χρόνιου βήχα (RR=1.91 95% CI 1.21, 3.02). Οι άνεργοι επισκέπτονται συχνότερα το νοσοκομείο για αναπνευστικά προβλήματα, αν και δεν επαληθεύτηκε στατιστικά. Συμπεράσματα: Ο επιπολασμός του συριγμού και του άσθματος ήταν αυξημένος για τους ανέργους σε σχέση με τους εργαζόμενους. Οι άνεργοι τείνουν να απευθύνονται συχνότερα στις υπηρεσίες υγείας λόγω αναπνευστικών δυσλειτουργιών.Background: A large number of studies examine respiratory health in relation to occupational exposure, but unemployment has hardly been examined. Employment status has been connected with negative health outcomes, through its direct or indirect effects, such as poverty and stress. Unemployment is also a determinant of poor disease management. Objective: The aim of this study was to examine the respiratory health and use of healthcare services of unemployed adults in comparison with employed subjects. The prevalence of three respiratory symptoms (wheeze, chronic cough and chronic phlegm) and two diseases (asthma and chronic bronchitis) was estimated for the period of completion of the study, as well as the cumulative incidence for new onset of those symptoms and diseases during the period of follow-up. Methods: The analysis is based on data from the study ECRHS II. The sample consists of 10.933 subjects, aged 26 - 56 years, who answered an extensive questionnaire. For the statistical analysis the methods used include binary logistic regression for odds ratio estimation, Log-binomial regression and Poisson regression for cumulative incidence estimation, as well as, proportional hazards Cox regression for survival analysis. Results: The results showed an increased prevalence for wheezing without a cold (OR=1.49, 95% CI 1.02-2.18) and asthma (asthma symptoms or medication: OR=2.08, 95%CI 1.25-3.45, clinical asthma: OR=2.24, 95%CI 1.11-4.53) for unemployed subjects in relation with employed. Cumulative incidence estimation showed that unemployed had 91% higher risk of chronic cough during follow-up, (RR=1.91 95%CI 1.21, 3.02) than those who were employed. Lastly, unemployed tend to have visited a hospital due to respiratory problems, more often than employed, even though it was not statistically significant for more symptoms or diseases. Conclusion: Prevalence of wheezing and asthma was higher for unemployed subjects compared to employed. At the same time, unemployed adults contact more often healthcare services due to respiratory problems

The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother-child cohort study in Crete, Greece (Rhea study)

We examined whether high doses of folic acid and iron supplementation in early-to-mid pregnancy affect the risk of preterm birth, low birth weight, and small for gestational age neonates, in the mother-child cohort in Crete, Greece (Rhea study). We included 1,279 women with singleton pregnancies with complete data on supplements use in early-to-mid pregnancy and birth outcomes. Anthropometric measurements at birth were obtained from medical records. Red blood cell folate concentrations in cord blood were measured in a subsample of the study population (n = 58). Sixty-six percent of the study participants reported high doses of supplemental folic acid use (5 mg/day), while 21 % reported excessive doses of folic acid use (> 5 mg/day) in early-to-mid pregnancy. Daily intake of 5-mg supplemental folic acid was associated with a 31 % decrease in the risk of preterm birth (RR, 0.69; 95 % CI, 0.44, 0.99), 60 % decrease in the risk of delivering a low birth weight neonate (RR, 0.40; 95 % CI, 0.21, 0.76), and 66 % decrease in the risk of delivering a small for gestational age (SGA) neonate (RR, 0.34; 95 % CI, 0.16, 0.73). Daily doses of iron supplementation more than 100 mg were associated with a twofold increased risk for SGA neonates (RR, 2.14; 95 % CI, 0.99, 5.97). These findings suggest that high daily doses of supplementary folic acid in early-to-mid pregnancy may be protective for preterm birth, low birth weight, and small for gestational age neonates, while high daily doses of supplementary iron may be harmful for fetal growth

Sleep Patterns in Late Pregnancy and Risk of Preterm Birth and Fetal Growth Restriction

Background: During pregnancy, women are at particular risk for sleep deprivation and snoring because of the physiologic and hormonal changes of pregnancy. There is limited evidence for the association between sleep patterns in pregnancy and adverse birth outcomes. We examined the association of sleep duration and snoring in late pregnancy with the risk of preterm birth and fetal growth restriction. Methods: We used data from the prospective mother-child cohort “Rhea” study in Crete, Greece 2007-2009. The analysis included 1091 women with singleton pregnancies, providing complete data on sleeping habits at the third trimester of gestation and birth outcomes. Fetal growth restriction was based on a customized model, and multivariate log-binomial regression models were used to adjust for confounders. Results: Women with severe snoring were at high risk for low birth weight (relative risk = 2.6 [95% confidence interval = 1.2-5.4]), and fetal-growth-restricted neonates (2.0 [1.0-3.9]) after adjusting for maternal age, education, smoking during pregnancy, and prepregnancy body mass index (BMI). Women with sleep deprivation (<= 5 hours sleep) were at high risk for preterm births (1.7 [1.1-2.8]), with the highest risk observed for medically indicated preterm births (2.4 [1.0-6.4]) after adjusting for maternal age, education, parity, smoking during pregnancy, and prepregnancy BMI. Conclusions: These findings suggest that women with severe snoring in late pregnancy have a higher risk for fetal-growth-restricted neonates; and women with sleep deprivation have a higher risk for preterm births. The mechanisms underlying these associations remain unclear. (Epidemiology 2011; 22: 738-744

Dietary patterns during pregnancy and the risk of postpartum depression: the mother-child `Rhea' cohort in Crete, Greece

Objective: To identify and describe dietary patterns in a cohort of pregnant women, and investigate whether dietary patterns during pregnancy are related to postpartum depression (PPD). Design: The study uses data from the prospective mother-child cohort ‘Rhea’ study. Pregnant women completed an FFQ in mid-pregnancy and the Edinburg Postpartum Depression Scale (EPDS) at 8-10 weeks postpartum. Dietary patterns during pregnancy (’health conscious’, ‘Western’) were identified using principal component analysis. Associations between dietary patterns categorized in tertiles and PPD symptoms were investigated by multivariable regression models after adjusting for confounders. Setting: Heraklion, Crete, Greece, 2007-2010. Subjects: A total of 529 women, participating in the ‘Rhea’ cohort. Results: High adherence to a ‘health conscious’ diet, characterized by vegetables, fruit, pulses, nuts, dairy products, fish and olive oil, was associated with lower EPDS scores (highest v. lowest tertile: beta-coefficient = -1.75, P = 0.02). Women in the second (relative risk (RR) = 0.52, 95% CI 0.30, 0.92) or third tertile (RR = 0.51, 95% CI 0.25, 1.05) of the ‘health conscious’ dietary pattern were about 50% less likely to have high levels of PPD symptoms (EPDS >= 13) compared with those in the lowest tertile. Conclusions: This is the first prospective study showing that a healthy diet during pregnancy is associated with reduced risk for PPD. Additional longitudinal studies and trials are needed to confirm these findings