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Bibliography Tag: epidemiological studies

Tiegs et al., 2018

Tiegs, A. W., Landis, J., Garrido, N., Scott, R., & Hotaling, J., “Total motile sperm count trend over time across two continents: evaluation of semen analyses from 119,972 infertile men,” Fertility and Sterility, 2018, 110(4). DOI: 10.1016/j.fertnstert.2018.07.093.


OBJECTIVE: While previous reports of declining sperm counts in the fertile and unselected population are concerning, the most reliable indicator of male fertility, the total motile sperm count (TMSC), has not been previously evaluated (1,2). Furthermore, the TMSC trend in the subfertile population remains unknown. We sought to characterize the TMSC trend over time in a large sample of men from infertile couples in two large fertility centers on separate continents to determine if TMSC was declining over time.

DESIGN: Retrospective cohort

MATERIALS AND METHODS: The first semen analysis (SA) of male patients from Reproductive Medicine Associates of New Jersey (RMANJ) and Instituto Valenciano de Infertilidad (IVI) were identified; SAs from 2002-2017 and 2011-2017, respectively, were included due to robust sample size (n>2000). SAs were excluded if collected retrograde, post-vasectomy, or if TMSC not available. SAs were categorized into 3 clinically relevant groups based on treatment strategy: TMSC >15 million (M) (Group 1), TMSC 5-15M (Group 2), and TMSC 0-5M (Group 3). Linear and logistic regression were used where appropriate to assess the impact of age and estimate TMSC group as a function of collection year. RESULTS: A total of 41809 SAs from RMANJ and 78163 from IVI (129 countries of origin; 74% Spanish) were included. Analyses were performed on RMANJ and IVI data separately. In the RMANJ cohort, linear regression demonstrated TMSC decreased by 1.8% per year in Group 1 (p¼2.2e-16), and the odds of belonging to Group 1 decreased over time (OR ¼ 0.979; 95% CI ¼ 0.974 – 0.985; p¼2.8e-14). Age was associated with TMSC in Group 1: For every 1 yr increase in age, TMSC decreased by 1.1% (p¼2.2e-16), and the odds of belonging to Group 1 decreased with age (OR ¼ 0.977; 95% CI ¼ 0.973 – 0.981; p¼2.2e-16). Similar trends in groups were found in the IVI cohort.

CONCLUSIONS: Although TMSCwas found to marginally decrease over time, the clinical significance of this finding is unclear. This trend may reflect a selection bias, in that more infertile men are presenting for treatment each year, or adverse effects of environmental factors. Whatever the underlying etiology, the shift in groups over time is clinically relevant, as treatment strategies differ by categorization. Longer follow up is necessary to confirm TMSC trends in the infertile population.

Roberts et al., 2019

Roberts, J. R., Dawley, E. H., & Reigart, J. R., “Children’s low-level pesticide exposure and associations with autism and ADHD: a review,” Pediatric Research, 2019, 85(2), 234-241. DOI: 10.1038/s41390-018-0200-z.


Pesticides are chemicals that are designed specifically for the purpose of killing or suppressing another living organism. Human toxicity is possible with any pesticide, and a growing body of literature has investigated possible associations with neurodevelopmental disorders. Attention deficit disorder with or without hyperactivity (ADHD) and autism spectrum disorder (ASD) are two of these specific disorders that have garnered particular interest. Exposure to toxic chemicals during critical windows of brain development is a biologically plausible mechanism. This review describes the basic laboratory science including controlled pesticide dosing experiments in animals that supports a mechanistic relationship in the development of ADHD and/or ASD. Epidemiological relationships are also described for low-level pesticide exposure and ADHD and/or ASD. The available evidence supports the hypothesis that pesticide exposure at levels that do not cause acute toxicity may be among the multifactorial causes of ADHD and ASD, though further study is needed, especially for some of the newer pesticides. FULL TEXT

Presutti et al., 2016

Presutti, R., Harris, S. A., Kachuri, L., Spinelli, J. J., Pahwa, M., Blair, A., Zahm, S. H., Cantor, K. P., Weisenburger, D. D., Pahwa, P., McLaughlin, J. R., Dosman, J. A., & Freeman, L. B., “Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project,” International Journal of Cancer, 2016, 139(8), 1703-1714. DOI: 10.1002/ijc.30218.


Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled x years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40-7.23) for </=10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend = 0.01). For captan, </=17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend = 0.01). An increasing trend (ptrend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT. FULL TEXT

Pembrey et al., 2015

Pembrey, M., Saffery, R., Bygren, L. O., & Network in Epigenetic Epidemiology, “Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research,” Journal of Medical Genetics, 2014, 51(9), 563-572. DOI: 10.1136/jmedgenet-2014-102577.


Mammalian experiments provide clear evidence of male line transgenerational effects on health and development from paternal or ancestral early-life exposures such as diet or stress. The few human observational studies to date suggest (male line) transgenerational effects exist that cannot easily be attributed to cultural and/or genetic inheritance. Here we summarise relevant studies, drawing attention to exposure sensitive periods in early life and sex differences in transmission and offspring outcomes. Thus, variation, or changes, in the parental/ancestral environment may influence phenotypic variation for better or worse in the next generation(s), and so contribute to common, non-communicable disease risk including sex differences. We argue that life-course epidemiology should be reframed to include exposures from previous generations, keeping an open mind as to the mechanisms that transmit this information to offspring. Finally, we discuss animal experiments, including the role of epigenetic inheritance and non-coding RNAs, in terms of what lessons can be learnt for designing and interpreting human studies. This review was developed initially as a position paper by the multidisciplinary Network in Epigenetic Epidemiology to encourage transgenerational research in human cohorts. FULL TEXT

Olsson and Brandt, 1988

Olsson, H., & Brandt, L., “Risk of non-Hodgkin’s lymphoma among men occupationally exposed to organic solvents,” Scandinavian Journal of Work and Environmental Health, 1988, 14(4), 246-251.


An occupational history of exposure to organic solvents, defined as daily occupational exposure for at least one year, was more common among 167 men with newly diagnosed non-Hodgkin’s lymphoma than among 130 healthy referents from the general population (38 versus 14%). Categorization in five-year age groups gave 3.3 as a Mantel-Haenszel estimate of the odds ratio (95% CI 1.9-5.8). The odds ratio was 6.5 (95% CI 3.2-13.3) for localized supradiaphragmatic tumors and 2.3 (95% CI 1.3-4.3) for other lymphoma presentations. In a logistic model including age and organic solvent, phenoxy acid, and chlorophenol exposure, it could be shown that solvent exposure was an independent risk factor and that no important interaction occurred between the risk factors. With increasing duration of exposure there was a significantly increased risk of lymphoma, a finding implying a dose-response relationship. There was no significant difference in tumor histology between the exposed and unexposed patients. These findings support the concept that occupational exposure to organic solvents is a risk factor for non-Hodgkin’s lymphoma. The results also confirm a strong association between such exposure and an initial supradiaphragmatic location of the lymphomas.


Nougadère et al., 2012

Nougadère, Alexandre, Sirot, Véronique, Kadar, Ali, Fastier, Antony, Truchot, Eric, Vergnet, Claude, Hommet, Frédéric, Baylé, Joëlle, Gros, Philippe, & Leblanc, Jean-Charles, “Total diet study on pesticide residues in France: Levels in food as consumed and chronic dietary risk to consumers,” Environment International, 2012, 45, 135-150. DOI: 10.1016/j.envint.2012.02.001.


Chronic dietary exposure to pesticide residues was assessed for the French population using a total diet study (TDS) to take into account realistic levels in foods as consumed at home (table-ready). Three hundred and twenty-five pesticides and their transformation products, grouped into 283 pesticides according to their residue definition, were sought in 1235 composite samples corresponding to 194 individual food items that cover 90% of the adult and child diet. To make up the composite samples, about 19,000 food products were bought during different seasons from 2007 to 2009 in 36 French cities and prepared according to the food preparation practices recorded in the individual and national consumption survey (INCA2). The results showed that 37% of the samples contained one or more residues. Seventy-three pesticides were detected and 55 quantified at levels ranging from 0.003 to 8.7mg/kg. The most frequently detected pesticides, identified as monitoring priorities in 2006, were the post-harvest insecticides pirimiphos-methyl and chlorpyrifos-methyl—particularly in wheat-based products—together with chlorpyrifos, iprodione, carbendazim and imazalil, mainly in fruit and fruit juices. Dietary intakes were estimated for each subject of INCA2 survey, under two contamination scenarios to handle left-censored data: lower-bound scenario (LB) where undetected results were set to zero, and upper-bound (UB) scenario where undetected results were set to the detection limit. For 90% of the pesticides, exposure levels were below the acceptable daily intake (ADI) under the two scenarios. Under the LB scenario, which tends to underestimate exposure levels, only dimethoate intakes exceeded the ADI for high level consumers of cherry (0.6% of children and 0.4% of adults). This pesticide, authorised in Europe, and its metabolite were detected in both cherries and endives. Under the UB scenario, that overestimates exposure, a chronic risk could not be excluded for nine other pesticides (dithiocarbamates, ethoprophos, carbofuran, diazinon, methamidophos, disulfoton, dieldrin, endrin and heptachlor). For these pesticides, more sensitive analyses of the main food contributors are needed in order to refine exposure assessment.

Nordstrom et al., 1998

Nordstrom, M., Hardell, L., Magnuson, A., Hagberg, H., & Rask-Anderson, A., “Occupational exposures, animal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study,” British Journal of Cancer, 1998, 77(11), 2048-2052.


To evaluate occupational exposures as risk factors for hairy cell leukaemia (HCL), a population-based case-control study on 121 male HCL patients and 484 controls matched for age and sex was conducted. Elevated odds ratio (OR) was found for exposure to farm animals in general: OR 2.0, 95% confidence interval (Cl) 1.2-3.2. The ORs were elevated for exposure to cattle, horse, hog, poultry and sheep. Exposure to herbicides (OR 2.9, Cl 1.4-5.9), insecticides (OR 2.0, Cl 1.1-3.5), fungicides (OR 3.8, Cl 1.4-9.9) and impregnating agents (OR 2.4, Cl 1.3-4.6) also showed increased risk. Certain findings suggested that recall bias may have affected the results for farm animals, herbicides and insecticides. Exposure to organic solvents yielded elevated risk (OR 1.5, Cl 0.99-2.3), as did exposure to exhaust fumes (OR 2.1, Cl 1.3-3.3). In an additional multivariate model, the ORs remained elevated for all these exposures with the exception of insecticides. We found a reduced risk for smokers with OR 0.6 (Cl 0.4-1.1) because of an effect among non-farmers.  FULL TEXT

Nevison, 2014

Nevison, C. D., “A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors,” Environmental Health, 2014, 13, 73. DOI: 10.1186/1476-069X-13-73.


BACKGROUND: The prevalence of diagnosed autism has increased rapidly over the last several decades among U.S. children. Environmental factors are thought to be driving this increase and a list of the top ten suspected environmental toxins was published recently.

METHODS: Temporal trends in autism for birth years 1970–2005 were derived from a combination of data from the California Department of Developmental Services (CDDS) and the United States Individuals with Disabilities Education Act (IDEA). Temporal trends in suspected toxins were derived from data compiled during an extensive literature survey. Toxin and autism trends were compared by visual inspection and computed correlation coefficients. Using IDEA data, autism prevalence vs. birth year trends were calculated independently from snapshots of data from the most recent annual report, and by tracking prevalence at a constant age over many years of reports. The ratio of the snapshot:tracking trend slopes was used to estimate the “real” fraction of the increase in autism.

RESULTS: The CDDS and IDEA data sets are qualitatively consistent in suggesting a strong increase in autism prevalence over recent decades. The quantitative comparison of IDEA snapshot and constant-age tracking trend slopes suggests that ~75-80% of the tracked increase in autism since 1988 is due to an actual increase in the disorder rather than to changing diagnostic criteria. Most of the suspected environmental toxins examined have flat or decreasing temporal trends that correlate poorly to the rise in autism. Some, including lead, organochlorine pesticides and vehicular emissions, have strongly decreasing trends. Among the suspected toxins surveyed, polybrominated diphenyl ethers, aluminum adjuvants, and the herbicide glyphosate have increasing trends that correlate positively to the rise in autism.

CONCLUSIONS: Diagnosed autism prevalence has risen dramatically in the U.S over the last several decades and continued to trend upward as of birth year 2005. The increase is mainly real and has occurred mostly since the late 1980s. In contrast, children’s exposure to most of the top ten toxic compounds has remained flat or decreased over this same time frame. Environmental factors with increasing temporal trends can help suggest hypotheses for drivers of autism that merit further investigation. FULL TEXT

Lang and Nuevo-Chiquero, 2012

Lang, K., & Nuevo-Chiquero, A., “Trends in self-reported spontaneous abortions: 1970-2000,” Demography, 2012, 49(3), 989-1009. DOI: 10.1007/s13524-012-0113-0.


Little is known about how the miscarriage rate has changed over the past few decades in the United States. Data from Cycles IV to VI of the National Survey of Family Growth (NSFG) were used to examine trends from 1970 to 2000. After accounting for abortion availability and the characteristics of pregnant women, the rate of reported miscarriages increased by about 1.0% per year. This upward trend is strongest in the first seven weeks and absent after 12 weeks of pregnancy. African American and Hispanic women report lower rates of early miscarriage than do whites. The probability of reporting a miscarriage rises by about 5% per year of completed schooling. The upward trend, especially in early miscarriages, suggests awareness of pregnancy rather than prenatal care to be a key factor in explaining the evolution of self-reported miscarriages. Any beneficial effects of prenatal care on early miscarriage are obscured by this factor. Differences in adoption of early-awareness technology, such as home pregnancy tests, should be taken into account when analyzing results from self-reports or clinical trials relying on awareness of pregnancy in its early weeks. FULL TEXT

Lamure et al., 2019

Lamure, S., Carles, C., Aquereburu, Q., Quittet, P., Tchernonog, E., Paul, F., Jourdan, E., Waultier, A., Defez, C., Belhadj, I., Sanhes, L., Burcheri, S., Donadio, D., Exbrayat, C., Saad, A., Labourey, J. L., Baldi, I., Cartron, G., & Fabbro-Peray, P., “Association of Occupational Pesticide Exposure With Immunochemotherapy Response and Survival Among Patients With Diffuse Large B-Cell Lymphoma,” JAMA Network Open, 2019, 2(4), e192093. DOI: 10.1001/ jamanetworkopen.2019.2093.


IMPORTANCE: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma.

OBJECTIVE: To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018.

MAIN OUTCOMES AND MEASURES: Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors.

RESULTS: A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0).

CONCLUSIONS AND RELEVANCE: This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma. FULL TEXT

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