Imperial College London

Professor Mireille B Toledano

Faculty of MedicineSchool of Public Health

Mohn Chair; Population Child Health & Director-Mohn Centre
 
 
 
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m.toledano Website

 
 
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525Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
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154 results found

Tao F, Abdallah MA-E, Ashworth DC, Douglas P, Toledano MB, Harrad Set al., 2017, Emerging and legacy flame retardants in UK human milk and food suggest slow response to restrictions on use of PBDEs and HBCDD, Environment International, Vol: 105, Pages: 95-104, ISSN: 0160-4120

The legacy flame retardants (LFRs) polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), together with six emerging flame retardants (EFRs) were measured in United Kingdom (UK) human milk collected in 2010 (n = 25) and 2014–15 (n = 10). These data are the first report of the presence of EFRs in UK human milk. The most abundant EFR was β-tetrabromoethylcyclohexane (DBE-DBCH) (average = 2.5 ng/g lw; geometric mean = 1.5 ng/g lw), which is comparable to the concentrations of the most abundant LFRs i.e. BDE 47 and α-HBCDD at 2.8 and 2.1 ng/g lw, respectively (geometric mean = 2.1 and 1.7). The estimated median dietary intake of ΣEFRs by UK nursing infants was 18 ng/kg bw/day. EFRs were also measured in UK foodstuffs with β-DBE-DBCH again the predominant compound detected, accounting – on average – for 64.5 ± 23.4% of ΣEFRs. Average estimated dietary intakes of ∑ EFRs in the UK were 89 and 26 ng/day (1.3 and 2.6 ng/body weight/day) for adults and toddlers, respectively. Concentrations of Σtri-hexa BDEs in our UK food samples exceeded those reported in UK samples from the same food categories collected in 2003–04 and 2006. Despite this and our recent report elsewhere of significant temporal declines in concentrations of BDE 209 in UK indoor dust (p < 0.05) and HBCDDs in UK indoor dust and air (p < 0.001), no significant temporal differences (p > 0.05) were observed between concentrations of Σtri-hexa BDEs, BDE 209 and HBCDDs in human milk sampled in 2010 and those obtained in 2014–15. UK adult body burdens for EFRs were predicted via inhalation, diet and dust ingestion using a simple pharmacokinetic model. The predicted EFR body burdens compared well with observed concentrations in human milk.

Journal article

Maitre L, Villanueva CM, Lewis M, Ibarluzea J, SantaMarina L, Vrijheid M, Sunyer J, Coen M, Toledano MBet al., 2016, Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study, BMC Medicine, Vol: 14, ISSN: 1741-7015

BackgroundMaternal metabolism during pregnancy is a major determinant of the intra-uterine environment and fetal outcomes. Herein, we characterize the maternal urinary metabolome throughout pregnancy to identify maternal metabolic signatures of fetal growth in two subcohorts and explain potential sources of variation in metabolic profiles based on lifestyle and clinical data.MethodsWe used 1H nuclear magnetic resonance (NMR) spectroscopy to characterize maternal urine samples collected in the INMA birth cohort at the first (n = 412 and n = 394, respectively, in Gipuzkoa and Sabadell cohorts) and third trimesters of gestation (n = 417 and 469). Metabolic phenotypes that reflected longitudinal intra- and inter-individual variation were used to predict measures of fetal growth and birth weight.ResultsA metabolic shift between the first and third trimesters of gestation was characterized by 1H NMR signals arising predominantly from steroid by-products. We identified 10 significant and reproducible metabolic associations in the third trimester with estimated fetal, birth, and placental weight in two independent subcohorts. These included branched-chain amino acids; isoleucine, valine, leucine, alanine and 3 hydroxyisobutyrate (metabolite of valine), which were associated with a significant fetal weight increase at week 34 of up to 2.4 % in Gipuzkoa (P < 0.005) and 1 % in Sabadell (P < 0.05). Other metabolites included pregnancy-related hormone by-products of estrogens and progesterone, and the methyl donor choline. We could explain a total of 48–53 % of the total variance in birth weight of which urine metabolites had an independent predictive power of 12 % adjusting for all other lifestyle/clinical factors. First trimester metabolic phenotypes could not predict reproducibly weight at later stages of development. Physical activity, as well as other modifiable lifestyle/clinical factors, suc

Journal article

Krasner SW, Kostopoulou M, Toledano MB, Wright J, Patelarou E, Kogevinas M, Villanueva CM, Carrasco-Turigas G, Santa Marina L, Fernandez-Somoano A, Ballester F, Tardon A, Grazuleviciene R, Danileviciute A, Cordier S, Costet N, Righi E, Aggazzotti G, Stephanou EG, Kargaki S, Nieuwenhuijsen MJet al., 2016, Occurrence of DBPs in Drinking Water of European Regions for Epidemiology Studies, JOURNAL AMERICAN WATER WORKS ASSOCIATION, Vol: 108, Pages: E501-E512, ISSN: 2164-4535

Journal article

Robinson O, Toledano MB, Sands C, Beckonert O, Want EJ, Goldin R, Hauser ML, Fenwick A, Thursz MR, Coen Met al., 2016, Global metabolic changes induced by plant-derived pyrrolizidine alkaloids following a human poisoning outbreak and in a mouse model, Toxicology Research, Vol: 5, Pages: 1594-1603, ISSN: 2045-4538

Several hundred cases of Hirmi Valley Liver Disease (HVLD), an often fatal liver injury, occurred from 2001 to 2011 in a cluster of rural villages in Tigray, Ethiopia. HVLD is principally caused by contamination of the food supply with plant derived pyrrolizidine alkaloids (PAs), with high exposure to the pesticide DDT among villagers increasing their susceptibility. In an untargeted global approach we aimed to identify metabolic changes induced by PA exposure through 1H NMR spectroscopic based metabolic profiling. We analysed spectra acquired from urine collected from HVLD cases and controls and a murine model of PA exposure and PA/DDT co-exposure, using multivariate partial least squares discriminant analysis. In the human models we identified changes in urinary concentrations of tyrosine, pyruvate, bile acids, N-acetylglycoproteins, N-methylnicotinamide and formate, hippurate, p-cresol sulphate, p-hydroxybenzoate and 3-(3-hydroxyphenyl) propionic acid. Tyrosine and p-cresol sulphate were associated with both exposure and disease. Similar changes to tyrosine, one-carbon intermediates and microbial associated metabolites were observed in the mouse model, with tyrosine correlated with the extent of liver damage. These results provide mechanistic insight and implicate the gut microflora in the human response to challenge with toxins. Pathways identified here may be useful in translational research and as “exposome” signals.

Journal article

Kogevinas M, Bustamante M, Gracia-Lavedán E, Ballester F, Cordier S, Costet N, Espinosa A, Grazuleviciene R, Danileviciute A, Ibarluzea J, Karadanelli M, Krasner S, Patelarou E, Stephanou E, Tardón A, Toledano MB, Wright J, Villanueva CM, Nieuwenhuijsen Met al., 2016, Drinking water disinfection byproducts, genetic polymorphisms, and birth outcomes in a European mother-child cohort study, Epidemiology, Vol: 27, Pages: 903-911, ISSN: 1044-3983

BACKGROUND: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (HiWate). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. METHODS: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities were recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies. RESULTS: Average levels of trihalomethanes ranged from around 10μg/L to above the regulatory limits in the EU of 100 μg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (beta= 2.2 g in birth weight per 10μg/L of THM, 95%CI -3.3, 7.6). Birthweight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (OR per 10μg/L=1.02, 95%CI 0.95, 1.10), small-for-gestational age (OR=0.99, 0.94, 1.03) and preterm births (OR= 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. CONCLUSIONS: In this large European study we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups.

Journal article

Fecht D, Hansell A, Morley D, Dajnak D, Vienneau D, Beevers S, Toledano M, Kelly F, Anderson HR, Gulliver Jet al., 2016, Spatial and temporal associations of road traffic noise and air pollution in London: Implications for epidemiological studies, Environment International, Vol: 88, Pages: 235-242, ISSN: 0160-4120

Road traffic gives rise to noise and air pollution exposures, both of which are associated with adverse health effects especially for cardiovascular disease, but mechanisms may differ. Understanding the variability in correlations between these pollutants is essential to understand better their separate and joint effects on human health.We explored associations between modelled noise and air pollutants using different spatial units and area characteristics in London in 2003–2010.We modelled annual average exposures to road traffic noise (LAeq,24 h, Lden, LAeq,16 h, Lnight) for ~ 190,000 postcode centroids in London using the UK Calculation of Road Traffic Noise (CRTN) method. We used a dispersion model (KCLurban) to model nitrogen dioxide, nitrogen oxide, ozone, total and the traffic-only component of particulate matter ≤ 2.5 μm and ≤ 10 μm. We analysed noise and air pollution correlations at the postcode level (~ 50 people), postcodes stratified by London Boroughs (~ 240,000 people), neighbourhoods (Lower layer Super Output Areas) (~ 1600 people), 1 km grid squares, air pollution tertiles, 50 m, 100 m and 200 m in distance from major roads and by deprivation tertiles.Across all London postcodes, we observed overall moderate correlations between modelled noise and air pollution that were stable over time (Spearman's rho range: | 0.34–0.55 |). Correlations, however, varied considerably depending on the spatial unit: largest ranges were seen in neighbourhoods and 1 km grid squares (both Spearman's rho range: | 0.01–0.87 |) and was less for Boroughs (Spearman's rho range: | 0.21–0.78 |). There was little difference in correlations between exposure tertiles, distance from road or deprivation tertiles.Associations between noise and air pollution at the relevant geographical unit of analysis need to be carefully considered in any epidemiological analysis, in particular in complex urban areas. Low correlations near roads, however, sugges

Journal article

Ghosh RE, Ashworth DC, Hansell AL, Garwood K, Elliott P, Toledano MBet al., 2016, Routinely collected English birth data sets: comparisons and recommendations for reproductive epidemiology., Archives of Disease in Childhood: Fetal and Neonatal edition, Vol: 101, Pages: F451-F457, ISSN: 1359-2998

BACKGROUND: In England there are four national routinely collected data sets on births: Office for National Statistics (ONS) births based on birth registrations; Hospital Episode Statistics (HES) deliveries (mothers' information); HES births (babies' information); and NHS Numbers for Babies (NN4B) based on ONS births plus gestational age and ethnicity information. This study describes and compares these data, with the aim of recommending the most appropriate data set(s) for use in epidemiological research and surveillance. METHODS: We assessed the completeness and quality of the data sets in relation to use in epidemiological research and surveillance and produced detailed descriptive statistics on common reproductive outcomes for each data set including temporal and spatial trends. RESULTS: ONS births is a high quality complete data set but lacks interpretive and clinical information. HES deliveries showed good agreement with ONS births but HES births showed larger amounts of missing or unavailable data. Both HES data sets had improved quality from 2003 onwards, but showed some local spatial variability. NN4B showed excellent agreement with ONS and HES deliveries for the years available (2006-2010). Annual number of births increased by 17.6% comparing 2002 with 2010 (ONS births). Approximately 6% of births were of low birth weight (2.6% term low birth weight) and 0.5% were stillbirths. CONCLUSIONS: Routinely collected data on births provide a valuable resource for researchers. ONS and NN4B offer the most complete and accurate record of births. Where more detailed clinical information is required, HES deliveries offers a high quality data set that captures the majority of English births.

Journal article

Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, Landström A, Villanueva CM, Merlo DF, Fthenou E, Gracia-Lavedan E, van Schooten FJ, Hoek G, Brunborg G, Meltzer HM, Alexander J, Nielsen JK, Sunyer J, Wright J, Kovács K, de Hoogh K, Gutzkow KB, Hardie LJ, Chatzi L, Knudsen LE, Anna L, Ketzel M, Haugen M, Botsivali M, Nieuwenhuijsen MJ, Cirach M, Toledano MB, Smith RB, Fleming S, Agramunt S, Kyrtopoulos SA, Lukács V, Kleinjans JC, Segerbäck D, Kogevinas Met al., 2016, Erratum: “Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood: A European Mother–Child Study (NewGeneris)”, Environmental Health Perspectives, Vol: 124, Pages: A12-A12, ISSN: 1552-9924

Journal article

Halonen JI, Blangiardo M, Toledano MB, Fecht D, Gulliver J, Anderson HR, Beevers SD, Dajnak D, Kelly F, Tonne Cet al., 2016, Long-term exposure to traffic pollution and hospital admissions in London, Environmental pollution, Vol: 208, Pages: 48-57, ISSN: 1873-6424

Journal article

Halonen JI, Blangiardo M, Toledano MB, Fecht D, Gulliver J, Ghosh R, Anderson HR, Beevers S, Dajnak D, Kelly F, Wilkinson P, Tonne Cet al., 2016, Is long-term exposure to traffic pollution associated with mortality? A small-area study in London, Environmental Pollution, Vol: 208, Pages: 25-32, ISSN: 0269-7491

Journal article

Toledano MB, Smith RB, Chang I, Douglass M, Elliott Pet al., 2015, Cohort profile: UK COSMOS – a UK cohort for study of environment and health, International Journal of Epidemiology, Vol: 46, Pages: 775-787, ISSN: 1464-3685

Journal article

Halonen JI, Hansell AL, Gulliver J, Morley D, Blangiardo M, Fecht D, Toledano MB, Beevers S, Anderson HR, Kelly F, Tonne Cet al., 2015, Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London, European Heart Journal, Vol: 36, Pages: 2653-2661, ISSN: 0195-668X

AimsRoad traffic noise has been associated with hypertension but evidence for the long-term effects on hospital admissions and mortality is limited. We examined the effects of long-term exposure to road traffic noise on hospital admissions and mortality in the general population.Methods and resultsThe study population consisted of 8.6 million inhabitants of London, one of Europe's largest cities. We assessed small-area-level associations of day- (7:00–22:59) and nighttime (23:00–06:59) road traffic noise with cardiovascular hospital admissions and all-cause and cardiovascular mortality in all adults (≥25 years) and elderly (≥75 years) through Poisson regression models. We adjusted models for age, sex, area-level socioeconomic deprivation, ethnicity, smoking, air pollution, and neighbourhood spatial structure. Median daytime exposure to road traffic noise was 55.6 dB. Daytime road traffic noise increased the risk of hospital admission for stroke with relative risk (RR) 1.05 [95% confidence interval (CI): 1.02–1.09] in adults, and 1.09 (95% CI: 1.04–1.14) in the elderly in areas >60 vs. <55 dB. Nighttime noise was associated with stroke admissions only among the elderly. Daytime noise was significantly associated with all-cause mortality in adults [RR 1.04 (95% CI: 1.00–1.07) in areas >60 vs. <55 dB]. Positive but non-significant associations were seen with mortality for cardiovascular and ischaemic heart disease, and stroke. Results were similar for the elderly.ConclusionsLong-term exposure to road traffic noise was associated with small increased risks of all-cause mortality and cardiovascular mortality and morbidity in the general population, particularly for stroke in the elderly.

Journal article

Smith RB, Edwards SC, Best N, Wright J, Nieuwenhuijsen MJ, Toledano MBet al., 2015, Birth Weight, Ethnicity, and Exposure to Trihalomethanes and Haloacetic Acids in Drinking Water during Pregnancy in the Born in Bradford Cohort., Environmental Health Perspectives, Vol: 124, Pages: 681-689, ISSN: 1552-9924

BACKGROUND: Evidence for a relationship between trihalomethane (THM) or haloacetic acid (HAA) exposure and adverse fetal growth is inconsistent. Disinfection by-products exist as complex mixtures in water supplies, but THMs and HAAs have typically been examined separately. OBJECTIVES: We investigated joint exposure at the individual level to THMs and HAAs in relation to birth weight in the multi-ethnic Born in Bradford birth cohort. METHODS: Pregnant women reported their water consumption and activities via questionnaire. These data were combined with area-level THM and HAA concentrations to estimate integrated uptake of THMs into blood and HAA ingestion, accounting for boiling/filtering. We examined the relationship between THM and HAA exposures and birth weight of up to 7,438 singleton term babies using multiple linear regression, stratified by ethnicity. RESULTS: Among Pakistani-origin infants, mean birth weight was significantly lower in association with the highest versus lowest tertiles of integrated THM uptake (e.g., -53.7 g; 95% CI: -89.9, -17.5 for ≥ 1.82 vs. < 1.05 μg/day of total THM) and there were significant trends (p < 0.01) across increasing tertiles, but there were no associations among white British infants. Neither ingestion of HAAs alone or jointly with THMs was associated with birth weight. Estimated THM uptake via showering, bathing, and swimming was significantly associated with lower birth weight in Pakistani-origin infants, when adjusting for THM and HAA ingestion via water consumption. CONCLUSIONS: To our knowledge, this is the largest DBP and fetal growth study to date with individual water use data, and the first to examine individual-level estimates of joint THM-HAA exposure. Our findings demonstrate associations between THM, but not HAA, exposure during pregnancy and reduced birth weight, but suggest this differs by ethnicity. This study suggests that THMs are not acting as a proxy for HAAs, or vice-versa. CITATION: Smith RB

Journal article

Toledano MB, Smith RB, Brook JP, Douglass M, Elliott Pet al., 2015, How to Establish and Follow up a Large Prospective Cohort Study in the 21st Century - Lessons from UK COSMOS., PLOS One, ISSN: 1932-6203

Journal article

Smith RB, Bennett JE, Rantakokko P, Martinez D, Nieuwenhuijsen MJ, Toledano MBet al., 2015, The relationship between MX [3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone], routinely monitored trihalomethanes, and other characteristics in drinking water in a long-term survey, Environmental Science & Technology, Vol: 49, Pages: 6485-6493, ISSN: 1520-5851

MX (3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) is a drinking water disinfection byproduct (DBP). It is a potent mutagen and is of concern to public health. Data on MX levels in drinking water, especially in the UK, are limited. Our aim was to investigate factors associated with variability of MX concentrations at the tap, and to evaluate if routinely measured trihalomethanes (THMs) are an appropriate proxy measure for MX. We conducted quarterly water sampling at consumers’ taps in eight water supply zones in and around Bradford, UK, between 2007 and 2010. We collected 79 samples which were analyzed for MX using GC-HRMS. Other parameters such as pH, temperature, UV-absorbance and free chlorine were measured concurrently, and total THMs were modeled from regulatory monitoring data. To our knowledge this is the longest MX measurement survey undertaken to date. Concentrations of MX varied between 8.9 and 45.5 ng/L with a median of 21.3 ng/L. MX demonstrated clear seasonality with concentrations peaking in late summer/early fall. Multivariate regression showed that MX levels were associated with total trihalomethanes, UV-absorbance and pH. However, the relationship between TTHM and MX may not be sufficiently consistent across time and location for TTHM to be used as a proxy measure for MX in exposure assessment.

Journal article

Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, Landstrom A, Villanueva CM, Merlo DF, Fthenou E, Gracia-Lavedan E, van Schooten F-J, Hoek G, Brunborg G, Meltzer HM, Alexander J, Nielsen JK, Sunyer J, Wright J, Kovacs K, de Hoogh K, Gutzkow KB, Hardie LJ, Chatzi L, Knudsen LE, Anna L, Ketzel M, Haugen M, Botsivali M, Nieuwenhuijsen MJ, Cirach M, Toledano MB, Smith RB, Fleming S, Agramunt S, Kyrtopoulos SA, Lukacs V, Kleinjans JC, Segerback D, Kogevinas Met al., 2015, Environmental, dietary, maternal, and fetal predictors of bulky DNA adducts in cord blood: a European mother-child study (NewGeneris), Environmental Health Perspectives, Vol: 123, Pages: 374-380, ISSN: 0091-6765

Background: Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk.oBjective: We selected factors known or hypothesized to affect inutero adduct formation and repair and examined their associations with adduct levels in neonates.Methods: Pregnant women from Greece, Spain, England, Denmark, and Norway were recruited in 2006–2010. Cord blood bulky DNA adduct levels were measured by the 32P-postlabeling technique (n=511). Diet and maternal characteristics were assessed via questionnaires. Modeled exposures to air pollutants and drinking-water disinfection by-products, mainly trihalomethanes (THMs), were available for a large proportion of the study population.results: Greek and Spanish neonates had higher adduct levels than the northern European neonates [median, 12.1 (n=179) vs. 6.8 (n=332) adducts per 108 nucleotides, p<0.001].Residence in southern European countries, higher maternal body mass index, delivery by cesarean section, male infant sex, low maternal intake of fruits rich in vitaminC, high intake of dairyproducts, and low adherence to healthy diet score were statistically significantly associated with higher adduct levels in adjusted models. Exposure to fine particulate matter and nitrogen dioxide was associated with significantly higher adducts in the Danish subsample only. Overall, the pooled results for THMs in water show no evidence of association with adduct levels; however, there are country-specific differences in results with a suggestion of an association in England.conclusion: These findings suggest that a combination of factors, including unknown country-specific factors, influence the bulky DNA adduct levels in neonates.citation: Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, LandströmA, Villanueva

Journal article

Iszatt N, Nieuwenhuijsen MJ, Bennett JE, Toledano MBet al., 2014, Trihalomethanes in public drinking water and stillbirth and low birth weight rates: an intervention study, ENVIRONMENT INTERNATIONAL, Vol: 73, Pages: 434-439, ISSN: 0160-4120

Journal article

Mukherjee S, Khan SA, Toledano MB, Bilton D, Simmonds NJet al., 2014, THE BURDEN OF CYSTIC FIBROSIS ASSOCIATED LIVER DISEASE IN THE UNITED KINGDOM: A NATIONAL REGISTRY REVIEW, 2008-2012, PEDIATRIC PULMONOLOGY, Vol: 49, Pages: 414-415, ISSN: 8755-6863

Journal article

Ashworth DC, Elliott P, Toledano MB, 2014, Waste incineration and adverse birth and neonatal outcomes: a systematic review, ENVIRONMENT INTERNATIONAL, Vol: 69, Pages: 120-132, ISSN: 0160-4120

Journal article

Maitre L, 2014, Urinary metabolic profiles in early pregnancy are associated with preterm birth and fetal growth restriction in the Rhea mother–child cohort study, BMC Medicine, Vol: 12, ISSN: 1741-7015

BackgroundPreterm birth (PB) and fetal growth restriction (FGR) convey the highest risk of perinatal mortality and morbidity, as well as increasing the chance of developing chronic disease in later life. Identifying early in pregnancy the unfavourable maternal conditions that can predict poor birth outcomes could help their prevention and management. Here we used an exploratory metabolic profiling approach (metabolomics) to investigate the association between birth outcomes and metabolites in maternal urine collected early in pregnancy as part of the prospective mother–child cohort Rhea study. Metabolomic techniques can simultaneously capture information about genotype and its interaction with the accumulated exposures experienced by an individual from their diet, environment, physical activity or disease (the exposome). As metabolic syndrome has previously been shown to be associated with PB in this cohort, we sought to gain further insight into PB-linked metabolic phenotypes and to define new predictive biomarkers.MethodsOur study was a case–control study nested within the Rhea cohort. Major metabolites (n = 34) in maternal urine samples collected at the end of the first trimester (n = 438) were measured using proton nuclear magnetic resonance spectroscopy. In addition to PB, we used FGR in weight and small for gestational age as study endpoints.ResultsWe observed significant associations between FGR and decreased urinary acetate (interquartile odds ratio (IOR) = 0.18 CI 0.04 to 0.60), formate (IOR = 0.24 CI 0.07 to 0.71), tyrosine (IOR = 0.27 CI 0.08 to 0.81) and trimethylamine (IOR = 0.14 CI 0.04 to 0.40) adjusting for maternal education, maternal age, parity, and smoking during pregnancy. These metabolites were inversely correlated with blood insulin. Women with clinically induced PB (IPB) had a significant increase in a glycoprotein N-acetyl resonance (IOR =&

Journal article

Ladep NG, Khan SA, Crossey MME, Thillainayagam AV, Taylor-Robinson SD, Toledano MBet al., 2014, Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 20, Pages: 1544-1553, ISSN: 1007-9327

Journal article

Goslan EH, Krasner SW, Villanueva CM, Carrasco Turigas G, Toledano MB, Kogevinas M, Stephanou EG, Cordier S, Grazuleviciene R, Parsons SA, Nieuwenhuijsen MJet al., 2014, Disinfection by-product occurrence in selected European waters, JOURNAL OF WATER SUPPLY RESEARCH AND TECHNOLOGY-AQUA, Vol: 63, Pages: 379-390, ISSN: 0003-7214

Journal article

Robinson O, Want E, Coen M, Kennedy R, van den Bosch C, Gebrehawaria Y, Kudo H, Sadiq F, Goldin RD, Hauser ML, Fenwick A, Toledano MB, Thursz MRet al., 2014, Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT, J Hepatol, Vol: 60, Pages: 96-102, ISSN: 0168-8278

BACKGROUND & AIMS: Hirmi Valley liver disease was first reported in 2001 in Tigray, Ethiopia. 591 cases, including 228 deaths, were reported up to December 2009. The pyrrolizidine alkaloid acetyllycopsamine was detected in stored grain and residents reported adding the pesticide DDT (dichlorodiphenyldichloroethylene) directly to their food stores. We aimed to characterise the clinical features of the disease, and explore the role of these chemicals in its aetiology. METHODS: 32 cases were examined and full clinical histories taken. Nine cases underwent liver biopsy in hospitals. Serum and urine samples were collected from cases and controls. Urine was analysed for acetyllycopsamine by UPLC-MS. Total DDT in serum was measured by ELISA. Hepatotoxicity of DDT and acetyllycopsamine alone or in combination was explored in C57BL/6J mice. RESULTS: Clinical presentation included epigastric pain, abdominal swelling, bloody diarrhoea, hepatomegaly, splenomegaly, and ascites. Histology revealed acute injury characterised by centrilobular necrosis or chronic injury with bile ductular reaction, cytomegaly and fibrosis but no hepatic vein occlusion. Acetyllycopsamine was detected in urine samples taken in the affected area with significantly greater concentrations in 45 cases than in 43 controls (p=0.02). High levels of DDT (>125 ppb) were detected in 78% of serum samples. In mice, DDT (3 x 75 mg/kg) significantly increased the hepatotoxicity (plasma ALT, p=0.0065) of acetyllycopsamine (750 mg/kg), and in combination induced liver pathology similar to Hirmi Valley liver disease including centrilobular necrosis and cytomegaly. CONCLUSIONS: This novel form of disease appears to be caused by co-exposure to acetyllycopsamine and DDT.

Journal article

Iszatt N, Nieuwenhuijsen MJ, Bennett J, Best N, Povey AC, Pacey AA, Moore H, Cherry N, Toledano MBet al., 2013, Chlorination by-products in tap water and semen quality in England and Wales, OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, Vol: 70, Pages: 754-760, ISSN: 1351-0711

Journal article

Smith RB, Nieuwenhuijsen MJ, Wright J, Raynor P, Cocker J, Jones K, Kostopoulou-Karadanelli M, Toledano MBet al., 2013, Validation of trichloroacetic acid exposure via drinking water during pregnancy using a urinary TCAA biomarker, ENVIRONMENTAL RESEARCH, Vol: 126, Pages: 145-151, ISSN: 0013-9351

Journal article

Elliott P, Toledano MB, 2013, Adult Cancers Near High-voltage Power Lines <i>response</i>, EPIDEMIOLOGY, Vol: 24, Pages: 783-784, ISSN: 1044-3983

Journal article

Dean S, Rudan I, Althabe F, Girard AW, Howson C, Langer A, Lawn J, Reeve M-E, Teela KC, Toledano M, Venkatraman C-M, Belizan JM, Car J, Chan KY, Chatterjee S, Chitekwe S, Doherty T, Donnay F, Ezzati M, Humayun K, Jack B, Lassi ZS, Martorell R, Poortman Y, Bhutta ZAet al., 2013, Setting Research Priorities for Preconception Care in Low- and Middle-Income Countries: Aiming to Reduce Maternal and Child Mortality and Morbidity, PLOS MEDICINE, Vol: 10, ISSN: 1549-1277

Journal article

Geneletti S, Best N, Toledano MB, Elliott P, Richardson Set al., 2013, Uncovering selection bias in case-control studies using Bayesian post-stratification, STATISTICS IN MEDICINE, Vol: 32, Pages: 2555-2570, ISSN: 0277-6715

Journal article

Elliott P, Shaddick G, Douglass M, de Hoogh K, Briggs DJ, Toledano MBet al., 2013, Adult Cancers Near High-voltage Overhead Power Lines, EPIDEMIOLOGY, Vol: 24, Pages: 184-190, ISSN: 1044-3983

Journal article

Elliott P, Toledano MB, 2013, Adult Cancers and Magnetic Fields from Overhead Power Lines <i>Epidemiologic Investigation</i>, <i>Not Speculation</i>, EPIDEMIOLOGY, Vol: 24, Pages: 193-194, ISSN: 1044-3983

Journal article

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