Health effects of residence near hazardous waste landfill sites: a review of epidemiologic literature.

This review evaluates current epidemiologic literature on health effects in relation to residence near landfill sites. Increases in risk of adverse health effects (low birth weight, birth defects, certain types of cancers) have been reported near individual landfill sites and in some multisite studies, and although biases and confounding factors cannot be excluded as explanations for these findings, they may indicate real risks associated with residence near certain landfill sites. A general weakness in the reviewed studies is the lack of direct exposure measurement. An increased prevalence of self-reported health symptoms such as fatigue, sleepiness, and headaches among residents near waste sites has consistently been reported in more than 10 of the reviewed papers. It is difficult to conclude whether these symptoms are an effect of direct toxicologic action of chemicals present in waste sites, an effect of stress and fears related to the waste site, or an effect of reporting bias. Although a substantial number of studies have been conducted, risks to health from landfill sites are hard to quantify. There is insufficient exposure information and effects of low-level environmental exposure in the general population are by their nature difficult to establish. More interdisciplinary research can improve levels of knowledge on risks to human health of waste disposal in landfill sites. Research needs include epidemiologic and toxicologic studies on individual chemicals and chemical mixtures, well-designed single- and multisite landfill studies, development of biomarkers, and research on risk perception and sociologic determinants of ill health

Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study

Background Maternal 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. Methods We 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. Results A 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, such as coffee consumption, vitamin D intake, and smoking, were identified as potential sources of metabolic variation during pregnancy. Conclusions Significant reproducible maternal urinary metabolic signatures of fetal growth and birth weight are identified for the first time and linked to modifiable lifestyle factors. This novel approach to prenatal screening, combining multiple risk factors, present a great opportunity to personalize pregnancy management and reduce newborn disease risk in later life

Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4years of age

There are at present very few studies of the effects of polybromodiphenyl ethers (PBDEs), used as flame retardants in consumer products, on neurodevelopment or thyroid hormone levels in humans. The present study aims to examine the association between pre and postnatal PBDE concentrations and neurodevelopment and thyroid hormone levels in children at age 4. years and isolate the effects of PBDEs from those of PCBs, DDT, DDE and HCB.A prospective birth cohort in Menorca (Spain) enrolled 482 pregnant mothers between 1997 and 1998. At 4. years, children were assessed for motor and cognitive function (McCarthy Scales of Children's Abilities), attention-deficit, hyperactivity and impulsivity (ADHD-DSM-IV) and social competence (California Preschool Social Competence Scale). PBDE concentrations were measured in cord blood (N = 88) and in serum of 4. years olds (N = 244). Among all congeners analyzed only PBDE 47 was quantified in a reasonable number of samples (LOQ = 0.002. ng/ml). Exposure to PBDE 47 was analyzed as a dichotomous variable: concentrations above the LOQ (exposed) and concentrations below (referents).Scores for cognitive and motor functions were always lower in children pre and postnatally exposed to PBDE47 than in referents, but none of these associations was statistically significant (β coefficient (95%CI) of the total cognition score: -2.7 (-7.0, 1.6) for postnatal exposure, and -1.4 (-9.2, 6.5) for prenatal exposure). Postnatal exposure to PBDE 47 was statistically significantly related to an increased risk of symptoms on the attention deficit subscale of ADHD symptoms (RR (95%CI) = 1.8 (1.0, 3.2)) but not to hyperactivity symptoms. A statistically significant higher risk of poor social competence symptoms was observed as a consequence of postnatal PBDE 47 exposure (RR (95%CI) = 2.6 (1.2, 5.9)). Adjustment for other organochlorine compounds did not influence the results. Levels of thyroid hormones were not associated to PBDE exposure.This study highlights the importance of assessing the effects of PBDE exposure not just prenatally but also during the early years of life. In the light of current evidence a precautionary approach towards PBDE exposure of both mothers and children seems warranted. © 2010 Elsevier Ltd

A case–control study of risk of leukaemia in relation to mobile phone use

Background Mobile phone use is now ubiquitous, and scientific reviews have recommended research into its relation to leukaemia risk, but no large studies have been conducted.Methods In a case-control study in South East England to investigate the relation of acute and non-lymphocytic leukaemia risk to mobile phone use, 806 cases with leukaemia incident 2003-2009 at ages 18-59 years (50% of those identified as eligible) and 585 non-blood relatives as controls (provided by 392 cases) were interviewed about mobile phone use and other potentially aetiological variables.Results No association was found between regular mobile phone use and risk of leukaemia (odds ratio (OR)=1.06, 95% confidence interval (CI)=0.76, 1.46). Analyses of risk in relation to years since first use, lifetime years of use, cumulative number of calls and cumulative hours of use produced no significantly raised risks, and there was no evidence of any trends. A non-significantly raised risk was found in people who first used a phone 15 or more years ago (OR=1.87, 95% CI=0.96, 3.63). Separate analyses of analogue and digital phone use and leukaemia subtype produced similar results to those overall.Conclusion This study suggests that use of mobile phones does not increase leukaemia risk, although the possibility of an effect after long-term use, while biologically unlikely, remains open

Temporal trends in concentrations and total serum burdens of organochlorine compounds from birth until adolescence and the role of breastfeeding

Introduction: The aims of the present study are to assess the temporal trends of organochlorine compounds (OCs) concentrations and total serum burdens from birth until adolescence and the influence of breastfeeding in these temporal trends. Methods: In 1997 two birth cohort studies were set up in Ribera d'Ebre (N=102) and the island of Menorca (N=482), Spain. Concentrations (ng/mL) of OCs [pentachlorobenzene (PeCB), four isomers of hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (4,4'-DDT), dichlorodiphenyldichloroethylene (4,4'-DDE) and seven polychlorobiphenyl congeners (σ7PCBs)] were measured in cord blood and at the age of 4 and 14years. The total serum burdens (ng) of these compounds were estimated based on the total blood volume (mL) of children at the different ages. We compared median concentrations and total serum burdens of these OCs at the different time-points of follow-up between children of Ribera d'Ebre and Menorca and between breastfed and non-breastfed children. Results: From birth until adolescence concentrations of all OCs drastically reduced. These reductions were mainly derived from the dilution of OCs, associated to an increase in total blood volume of children at the age of 4 and 14years. Despite the reduction in OCs concentrations, the total serum burdens of 4,4'-DDE and σ7PCBs, were higher in adolescents than at birth. Increases in OCs total serum burden occurred both in breastfed and non-breastfed children, but were significantly higher in the first. Conclusions: Even after decades of banning OCs production and use, current young generations in westernized countries are still bioaccumulating these compounds. Given the potential health effects of OCs, especial attention should be paid in the control of secondary emissions in the environment and in the control of food production and contamination. In countries with endemic malaria it is important to work towards effective alternatives to the use of DDT. © 2014 Elsevier Ltd.This study was supported by grants from the Spanish Ministry of Health (FIS-97/1102, FIS 97/0588, 00/0021-2, PI061756, PS0901958 and FIS PS09/00362), the Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), Fundació La Caixa (97/009-00 and 00/077-00), and the Generalitat de Catalunya-CIRIT 1999SGR 00241. Finally, the authors would like to be grateful to the families in Flix and Menorca participating in the study, to the high school management team of Flix for their interest and collaboration, and to Rosa Maria Sabaté, the nurse of the health center of Flix, for her support and commitment.Peer reviewe

Geographic variation and localised clustering of congenital anomalies in Great Britain

Background: Environmental pollution as a cause of congenital anomalies is sometimes suspected because of clustering of anomalies in areas of higher exposure. This highlights questions around spatial heterogeneity (clustering) in congenital anomaly rates. If spatial variation is endemic, then any one specific cluster is less remarkable, though the presence of uncontrolled geographically clustered risk factors is suggested. If rates are relatively homogeneous across space other than around specific hazards, then evidence for these hazards causing the clusters is strengthened. We sought to estimate the extent of spatial heterogeneity in congenital anomaly rates in the United Kingdom. Methods: The study population covered about one million births from five registers in Britain from 1991–1999. We estimated heterogeneity across four geographical levels: register area, hospital catchment, electoral ward, and enumeration district, using a negative binomial regression model. We also sought clusters using a circular scan statistic. Results: Congenital anomaly rates clearly varied across register areas and hospital catchments (p 0.2). Adjusting for socioeconomic deprivation and maternal age made little difference to the extent of geographical variation for most congenital anomaly subtypes. The two most significant circular clusters (of four ano-rectal atresias and six congenital heart diseases) contained two or more siblings. Conclusion: The variation in rates between registers and hospital catchment area may have resulted in part from differences in case ascertainment, and this should be taken into account in geographical epidemiological studies of environmental exposures. The absence of evidence for variation below this level should be interpreted cautiously in view of the low power of general heterogeneity tests. Nevertheless, the data suggest that strong localised clusters in congenital anomalies are uncommon, so clusters around specific putative environmental hazards are remarkable when observed. Negative binomial models applied at successive hierarchical levels provide an approach of intermediate complexity to characterising geographical heterogeneity

Prenatal Concentrations of Polychlorinated Biphenyls, DDE, and DDT and Overweight in Children: A Prospective Birth Cohort Study

Background: Recent experimental evidence suggests that prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase postnatal obesity risk and that these effects may be sex or diet dependent

Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers

Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a ‘healthy worker effect'. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2–3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards

Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth

BACKGROUND: Rapid postnatal growth may result from exposure in utero or early life to adverse conditions and has been associated with diseases later in life and, in particular, with childhood obesity. DNA methylation, interfacing early-life exposures and subsequent diseases, is a possible mechanism underlying early-life programming. METHODS: Here, a meta-analysis of Illumina HumanMethylation 450K/EPIC-array associations of cord blood DNA methylation at single CpG sites and CpG genomic regions with rapid weight growth at 1 year of age (defined with reference to WHO growth charts) was conducted in six European-based child cohorts (ALSPAC, ENVIRONAGE, Generation XXI, INMA, Piccolipiù, and RHEA, N = 2003). The association of gestational age acceleration (calculated using the Bohlin epigenetic clock) with rapid weight growth was also explored via meta-analysis. Follow-up analyses of identified DNA methylation signals included prediction of rapid weight growth, mediation of the effect of conventional risk factors on rapid weight growth, integration with transcriptomics and metabolomics, association with overweight in childhood (between 4 and 8 years), and comparison with previous findings. RESULTS: Forty-seven CpGs were associated with rapid weight growth at suggestive p-value <1e-05 and, among them, three CpGs (cg14459032, cg25953130 annotated to ARID5B, and cg00049440 annotated to KLF9) passed the genome-wide significance level (p-value <1.25e-07). Sixteen differentially methylated regions (DMRs) were identified as associated with rapid weight growth at false discovery rate (FDR)-adjusted/Siddak p-values < 0.01. Gestational age acceleration was associated with decreasing risk of rapid weight growth (p-value = 9.75e-04). Identified DNA methylation signals slightly increased the prediction of rapid weight growth in addition to conventional risk factors. Among the identified signals, three CpGs partially mediated the effect of gestational age on rapid weight growth. Both CpGs (N=3) and DMRs (N=3) were associated with differential expression of transcripts (N=10 and 7, respectively), including long non-coding RNAs. An AURKC DMR was associated with childhood overweight. We observed enrichment of CpGs previously reported associated with birthweight. CONCLUSIONS: Our findings provide evidence of the association between cord blood DNA methylation and rapid weight growth and suggest links with prenatal exposures and association with childhood obesity providing opportunities for early prevention