Study Of Environmental Risk Factors Research Articles

A protocol for the study of environmental risk factors and candidate gene–environment interactions in neurodegenerative disorders in Nigeria (SERGEND): A cross-sectional descriptive study

Introduction: The risk of developing neurodegenerative disorders (NDDs) such as Alzheimer’s disease and related dementias (ADRD) and Parkinson’s disease and atypical parkinsonism (PDAP), has been alluded to arise predominantly from the interplay between environmental exposures and genetic variability. The contributions of these factors to NDD in Black sub-Saharan Africans are largely unknown. The broad aim of SERGEND is to investigate the effect of specific environmental exposures and genetic variability on the risk of developing ADRD and PDAP in our population. Methods: The SERGEND, a national, multi-center, cross-sectional, descriptive study, will be conducted in Nigeria, within academic hospitals located in all six geopolitical zones of the country. The study population will comprise 3000 consenting adult Nigerians aged 18 years and above, residing within the recruiting geopolitical zone in the preceding 12 months. Cases will be persons with ADRD or PDAP and age-matched healthy controls. Assessments will include dementia and parkinsonism-specific case ascertainment, disease severity, functional status, and environmental risk factors assessment. Genotyping for APOE and SNCA REP1 polymorphic variability will be conducted. Future analyses will be performed on biobanked samples. Ethics and Dissemination: The study protocol was approved by the National Health Research Ethics Committee in Nigeria, with institutional HREC concordant approval for all participating sites before enrollment of the study participants. Written informed consent was obtained from all study participants or identified proxies. The study results will be published in peer-reviewed journals and as conference abstracts. Trial Registration: International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry (www.isrctn.com). Trial registration number: ISRCTN10548575. Locator ID: https://doi.org/10.1186/ISRCTN10548575.

A case-control survey study of environmental risk factors for primary hypoadrenocorticism in dogs.

Primary hypoadrenocorticism in dogs is thought to be multifactorial with roles for both genetic and environmental factors. The contributions of environmental factors remain unexplored. Identify environmental and lifestyle exposures associated with primary hypoadrenocorticism in 2 dog breeds with high risk of developing the disease. Animals were not used in this study. Owners of Standard Poodles (STPDs) and Portuguese water dogs (POWDs) participated in a survey. Retrospective case-control study. Dog owners were invited to participate in an online survey through convenience sampling. Questions regarded the demographics, health histories, and indoor/outdoor environments in which their dogs live and play. Responses for dogs with primary hypoadrenocorticism were compared to those without the disease using univariate and multivariate logistic regression models. Five thousand forty-seven responses (358 cases, 4689 controls) met initial inclusion criteria. Significant associations with modest effect size were found for community type, ingestion of canned food, and use of lawn fertilizer in some analysis models. Reproductive (spay/neuter) status exhibited the strongest association with high effect size across all models with adjusted odds ratio (OR) 2.5 (95% confidence interval [CI], 1.4-4.5; P = .003) for spayed females and 6.0 (95% CI, 2.6-13.9; P < .001) for neutered males. The large effect size for reproductive status reflects its high potential clinical relevance, whereas modest effect sizes for other environmental variables suggest lower potential clinical relevance. These findings are associations and do not necessarily imply causation. Before any actionable recommendations are warranted, additional evidence regarding biological mechanisms is needed.

Modifiable and Non-Modifiable Predictors of Dupuytren’s Disease

Dupuytren's disease (DD) is a common multifactorial disease accompanied by deformity of the hand with flexion contracture of one or more fingers, limitation of their mobility and a fixed lesion. This disease refers to disorders of the connective tissue. Objective: to generalize the results of studies of environmental risk factors for DD and update existing ideas about modifiable and non-modifiable predictors of the disease in adults. Methods. We searched for full-text English-language publications in the PubMed, Springer, Scopus, Clinical Keys, Oxford Press, Google Scholar, eLIBRARY. Results. The most significant modifiable predictors of the development of DD include (top 5): occupation; hobby; lifestyle; comorbid diseases; drugs. Non-modifiable predictors include (top 5): gender; age; ethnos; race; genetics. Genetic predictors of DD are not well understood, but the number of candidate genes responsible for the development of DD is increasing and reaches the top 50 or more candidate genes with a statistically significant association with the risk of developing DD in adults. The most studied candidate genes are DUPC1, MMP2, MMP9, TIMP1, TIMP2, WNT4, WNT7B. Discussion. Primary and secondary prevention of DD requires accounting of the mutual influence of modifiable and non-modifiable predictors in the disease development, as well as a personalized approach in planning and choosing non-surgical and surgical treatment, as well as the carriage of single nucleotide variants (SNVs) candidate genes associated with the development of DD. A promising direction in the prevention of disabling complications of DD may be the development of decision-making information programs (personalized algorithms) that take into account non-genetic and genetic predictors in a particular person, and their implementation in real clinical practice. Conclusion. Large multicenteral studies of the influence and mutual influence of modifiable and non-modifiable predictors with a single design are required in the future.

P339 A study of environmental risk factors in chronic rhinosinusitis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesChronic rhinosinusitis (CRS) is a complex disease that incorporates many different conditions. Our aim is to determine the role of environmental risk factors in chronic rhinosinusitis.MethodsThis was a case-control study where forty cases of CRS in the age group of 18-62 years were recruited from the ENT-OPD of UCMS and GTB Hospital, Delhi, a tertiary care hospital, along with 40 age-appropriate healthy controls. Informed and written consent was obtained from all the subjects. Detailed history and examination along with routine blood and radiological investigations were done. Subjective assessment of disease was done using visual analog scales of SNOT 22 questionnaire, environmental questionnaire, and saccharine test. Objective assessment was done using endoscopic grading according to Lund and Kennedy scoring. CT scores were also obtained using Lund and Mackay staging system. Passive air sampling was done by the settle plate method and Anderson six-stage cascade impactor was used for active air sampling. Blood agar and Sabouraud dextrose agar plates were inserted on the six stages of the cascade impactor, which were later incubated at 35°C and 25°C respectively, for 18-24 hours. Bioaerosol concentrations were calculated and MicroScan WalkAway system was used to identify bacterial and fungal growth. The correlation between total bioaerosol concentration and the symptom score was done by spearman's correlation coefficient; a comparison of mean total bioaerosol concentration between the case and control groups was done by Mann-Whitney U-test.ResultsThe mean total bio-aerosol concentration from active air sampling in the case group was 458.52 CFU/m3 and 437.63 CFU/m3 in control, which was not significant. It was found to be negatively correlated, but not significant with various parameters in case groups like SNOT 22 score, environmental exposure score, saccharine test, smoking, and endoscopic score. A positive but insignificant correlation was found between total bioaerosol concentration and absolute eosinophilic count and CT score. The mean CFU/100 mm3 counted after passive air sampling between case and control group was 34.03 and 30.88 CFU/100mm3 which was not significant. Fungal growths were mostly Aspergillus flavus and A. Niger followed by Cladosporium spp.ConclusionThe fungal burden was high in all the households of the case as well as control groups, although, a significant correlation could not be established. The environmental conditions found in this study were found to be conducive to future risk of exacerbation of preexisting fungal infections for which, indoor air quality needs to be monitored.

Dietary risk factors of primary progressive multiple sclerosis: A population-based case-control study

ObjectivesThere are growing evidences on the role of nutritional factors in multiple sclerosis (MS) occurrence. But dietary data are limited in primary progressive type of MS (PPMS). We assessed the role of dietary factors during adolescence in PPMS risk. MethodsAn incident case-control study on 143 PPMS cases with definite diagnosis and 400 controls were conducted in Sina hospital, Tehran, Iran. Demographic data were collected. Data on nutritional habits during adolescence were obtained using questionnaire designed for multinational case–control studies of environmental risk factors for multiple sclerosis (EnvIMS-Q). Logistic regression models were run to evaluate the role of diet in PPMS risk. ResultsA significant association was founded between higher intake of dairy, seafood, red meat, poultry, vegetable, fruit and nut and lower risk of PPMS (P< 00.5). This association was dose dependent for all mentioned food groups except fruit. In the fully adjusted model, more intake of dairy (OR: 0.27; 95%CI: 0.14-0.53), seafood (OR: 0.21; 95%CI: 0.10-0.44), red meat (OR:0.44; 95%CI: 0.22-0.90), vegetable (OR: 0.19; 95%CI: 0.09-0.39), fruit (OR: 0.47; 95%CI: 0.22-0.99) and nut (OR: 0.29; 95%CI: 0.15-0.56) in the third tertiles resulted in significant reduction in PPMS risk. In case of poultry consumption, the association was meaningful just in the third tertile of crude model (OR: 0.54; 95%CI: 0.30-0.95). Nutrient supplementation with calcium, iron, folic acid, vitamin B12 and C were also related with more than 84% lower risk of PPMS. ConclusionOur data proposed that adequate intake of food groups and nutrient supplementation during adolescence may be effective in reducing adult-onset PPMS risk.

Abstract IA11: Timing of environmental contributions to cancer in a multigenerational cohort

Abstract Transdisciplinary studies of environmental risk factors for cancer can discover paths to prevention. Using breast cancer as a case study, we review findings on the relation of a ubiquitous legacy environmental chemical, DDT, to breast cancer in three generations in the Child Health and Development Studies cohort. Although banned in the U.S. and in many places worldwide in the 1970s, the DDT story illustrates the potential role of legacy environmental chemicals in current cancer etiology. We demonstrate the importance of accounting for windows of susceptibility and induction time to cancer and provide evidence for multigenerational and transgenerational effects relevant to breast cancer risk in current generations. Findings provide proof of concept that the current environment may have lasting effects 60 years in the future. Findings support prudent management of current environmental exposures with known biologic toxicity. Waiting 60 years to understand human effects is too late to protect the public health and prevent cancer. The Child Health and Development Studies (CHDS) is a 60-year, prospective follow-up of 20,000 pregnancies that occurred in the 1960s and the resultant generations. The CHDS provides unique and valuable data to characterize how pregnancy and in utero exposures and responses contribute to disease risk in multiple generations. Maternal perinatal blood samples simultaneously provide the opportunity to measure the pregnancy exposome for Generation 1 mothers, the in utero exposome for Generation 2, and the germline exposome for Generation 3. In the CHDS we are also able to study the grandpaternal exposome in relation to granddaughters’ breast cancer risk factors, a design that estimates transgenerational effects via the paternal line. CHDS generations are tracked for place of residence, cancer risk factors, and cancer incidence to provide high quality of evidence avoiding errors of recall and accurate exposure assessment. We review breast cancer findings for Generation 1 (cohort mothers), Generation 2 (cohort daughters), and Generation 3 (cohort granddaughters). We describe perinatal DDT associations with breast cancer in mothers and daughters, with breast density in daughters, and with breast cancer risk factors in granddaughters. We show the results of next steps to uncover mechanisms, including DNA methylation patterns in breast cancer-related genes in the daughters’ generation associated with in utero DDT exposure, and the correlation of the maternal metabolome with DDT in mothers. We also compare the human, observational metabolomics data in maternal perinatal serum with parallel data from controlled experimental studies in mice designed to replicate the DDT dose and perinatal exposure in our human cohort. Along with DDT, we show findings on the relation of in utero exposure to PFASs, a class of chemicals of current concern that were also present in the 1960s. Along with grandmaternal associations, we also show early findings on some grandpaternal variables that are independently correlated with granddaughter breast cancer risk factors. We highlight findings based on high-resolution metabolomics data and exposome analyses in conjunction with epidemiologic data. These metabolomics data serve as important molecular footprints that result from gene and environmental interactions. We employ novel computational and statistical approaches to facilitate the interpretation of these high-dimensional data and integrative analysis, draw insights on the biologic effects of DDT and PFASs compounds, and explore the implication of findings on risk for breast cancer. Citation Format: Barbara A. Cohn. Timing of environmental contributions to cancer in a multigenerational cohort [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA11.

The impact of population mobility on estimates of environmental exposure effects in a case‐control study

In many studies of environmental risk factors for disease, researchers use the location at diagnosis as a geographic reference for environmental exposures. However, many environmental pollutants change continuously over space and time. The dynamic characteristics of these pollutants coupled with population mobility in the United States suggest that for diseases with long latencies like cancer, historic exposures may be more relevant than exposure at the time of diagnosis. In this article, we evaluated to what extent the commonly used assumption of no population mobility results in increased bias in the estimates of the relationship between environmental exposures and long-latency health outcomes disease in a case-control study. We conducted a simulation study using the residential histories of a random sample from the National Institutes of Health-AARP (formerly American Association of Retired Persons) Diet and Health Study. We simulated case-control status based on subject exposure and true exposure effects that varied temporally. We compared estimates from models using only subject location at diagnosis to estimates where subjects were assumed to be mobile. Ignoring population mobility resulted in underestimates of subject exposure, with largest deviations observed at time points further away from study enrollment. In general, the effect of population mobility on the bias of the estimates of the relationship between the exposure and the outcome was more prominent with exposures that showed substantial spatial and temporal variability. Based on our results, we recommend using residential histories when environmental exposures and disease latencies span a long enough time period that mobility is important.

Using Mendelian randomization to understand and develop treatments for neurodegenerative disease

Common neurodegenerative diseases are thought to arise from a combination of environmental and genetic exposures. Mendelian randomization is a powerful way to leverage existing genetic data to investigate causal relationships between risk factors and disease. In recent years, Mendelian randomization has gathered considerable traction in neurodegenerative disease research, providing valuable insights into the aetiology of these conditions. This review aims to evaluate the impact of Mendelian randomization studies on translational medicine for neurodegenerative diseases, highlighting the advances made and challenges faced. We will first describe the fundamental principles and limitations of Mendelian randomization and then discuss the lessons from Mendelian randomization studies of environmental risk factors for neurodegeneration. We will illustrate how Mendelian randomization projects have used novel resources to study molecular pathways of neurodegenerative disease and discuss the emerging role of Mendelian randomization in drug development. Finally, we will conclude with our view of the future of Mendelian randomization in these conditions, underscoring unanswered questions in this field.

Morbidity of Abdominal Wall Hernia Repair With Mesh: Study of Environmental Risk Factors in Operating Room in the CHRU of Nancy- a Prospective Study

Morbidity of Abdominal Wall Hernia Repair With Mesh: Study of Environmental Risk Factors in Operating Room in the CHRU of Nancy- a Prospective Study

American cutaneous leishmaniasis in French Guiana: an epidemiological update and study of environmental risk factors.

BackgroundAmerican cutaneous leishmaniasis (ACL) is endemic in French Guiana. Its epidemiology is evolving, notably because of immigration, anthropization of natural areas, and new microbiological methods. Our first objective was to update epidemiological data. Our second objective was to look for risk factors of ACL.MethodsThis multicentric study was conducted from October 2017 to June 2018 in French Guiana. Patients with suspicion of mucocutaneous leishmaniasis were included in case of positive smear, culture, or PCR‐RFLP on skin biopsy. ResultsOne hundred and twenty‐three patients met the inclusion criteria. Among those patients, 59.3% were Brazilian, mostly gold miners. Most of them (58%) were between 16 and 40 years old, and 69% were male. A large proportion of patients lived in traditional wooden houses (51%). Patients living in coastal towns were usually infected during trips to the primary forest (60%) and had a shorter time to diagnosis than workers of the hinterland. Among environmental risk factors, the presence of a water spring (40%) and dogs around houses (40%) were frequently reported. Leishmania guyanensis represented 80% of cases, followed by Leishmania braziliensis (6%), Leishmania naiffi (2%), and Leishmania amazonensis (1%).ConclusionsGold mining and trips to the primary forest represent high‐risk situations for ACL in French Guiana, where the population of infected patients is dominated by Brazilian immigrants. Possible environmental risk factors such as the presence of dogs, water sources, and traditional wooden houses require further investigation.

Capital social, santé mentale et immigration

The concept of social capital is useful to study the impact of the interpersonal relationships/networks on the development, outcome, prevention and recovery of mental disorders. Among migrant populations, it seems to play a protective role in mental health, associated to better social support, resilience and less exposure to discrimination. In this paper, we will present the current data on this subject. Then we will discuss the use of this concept in the study of environmental risk factors of mental disorders and the need to construct contextual indicators, especially in minority groups.

Understanding the role of environmental factors in the development of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disease with a complex etiology. Its risk is higher among women, racial and ethnic minorities, and individuals with a family history of SLE or related autoimmune diseases. It is believed that genetic factors interact with environmental exposures throughout the lifespan to influence susceptibility to developing SLE. The strongest epidemiologic evidence exists for increased risk of SLE associated with exposure to crystalline silica, current cigarette smoking, use of oral contraceptives, and postmenopausal hormone replacement therapy, while there is an inverse association with alcohol use. Emerging research results suggest possible associations of SLE risk with exposure to solvents, residential and agricultural pesticides, heavy metals, and air pollution. Ultraviolet light, certain infections, and vaccinations have also been hypothesized to be related to SLE risk. Mechanisms linking environmental exposures and SLE include epigenetic modifications resulting from exposures, increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal effects. Research needs to include new studies of environmental risk factors for SLE in general, with a focus on lifetime exposure assessment. In addition, studies in susceptible subgroups, such as family members, studies based on genetic risk profiles, and studies in individuals with evidence of pre-clinical autoimmunity based on the detection of specific auto-antibodies are also required. Understanding the role of environmental exposures in the development of SLE may help identify modifiable risk factors and potential etiological mechanisms.

Independent Maternal and Fetal Genetic Effects on Midgestational Circulating Levels of Environmental Pollutants.

Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal midpregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large-scale maternal and fetal genetic study of the midpregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project. Levels of PCB (polychlorinated biphenyl) and PBDE (polybrominated diphenyl ether) congeners showed high maternal and fetal estimated SNP-based heritability (h2g) accounting for 39–99% of the total variance. Genome-wide association analyses identified significant maternal loci for p,p′-DDE (P = 7.8 × 10−11) in the CYP2B6 gene and for BDE-28 (P = 3.2 × 10−8) near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism. Fetal genetic loci contributed to the levels of BDE-100 (P = 4.6 × 10−8) and PCB187 (P = 2.8 × 10−8), near the potential metabolic genes LOXHD1 and PTPRD, previously implicated in neurodevelopment. Negative associations were observed for BDE-100, BDE153, and the sum of PBDEs with ASD, partly explained by genome-wide additive genetic effects that predicted PBDE levels. Our results support genetic control of midgestational biomarkers for environmental exposures by nonoverlapping maternal and fetal genetic determinants, suggesting that future studies of environmental risk factors should take genetic variation into consideration. The independent influence of fetal genetics supports previous hypotheses that fetal genotypes expressed in placenta can influence maternal physiology and the transplacental transfer of organohalogens.

Dependence of cancer risk from environmental exposures on underlying genetic susceptibility: an illustration with polycyclic aromatic hydrocarbons and breast cancer

Background:Most studies of environmental risk factors and breast cancer are conducted using average risk cohorts.Methods:We examined the association between polycyclic aromatic hydrocarbon (PAH)-albumin adducts in bloods from baseline and breast cancer risk in a prospective nested case–control study (New York site of the BCFR, 80 cases and 156 controls). We estimated the 10-year absolute breast cancer risk by a risk model that uses pedigree information (BOADICEA) and evaluated whether the increased risk from PAH differed by absolute risk.Results:Women with detectable levels of PAH had a twofold association with breast cancer risk (odds ratio (OR)=2.04; 95% CI=1.06–3.93) relative to women with non-detectable levels. The association increased with higher levels of PAH (⩾median) and by a higher level of absolute breast cancer risk (10-year risk ⩾3.4%: OR=4.09, 95% CI=1.38–12.13).Conclusions:These results support that family-based cohorts can be an efficient way to examine gene–environment interactions.

Comparing epidemiology and baseline characteristic of multiple sclerosis and neuromyelitis optica: A case-control study

BackgroundAutoimmune syndromes such as Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) are chronic, demyelinating diseases of the central nervous system which usually affect young adults. Both environmental risk factors and genetic susceptibility have been proposed to explain the etiology of these diseases. The aim of this study was to compare epidemiology and possible risk factors in MS and NMO in Tehran, Iran. MethodA population-based incident case-control study was performed in Tehran based on a study conducted on1513 MS patients from Iranian MS Society registry center of Tehran, from 2014 to 2015, and 83 NMO patients diagnosed with NMO in 2015 at Sina hospital, a tertiary care referral center in Tehran. The random digit dialing (RDD) methods were established to select 400 population-based controls. A checklist was designed to cover the epidemiological variables to estimate the possible risk factors for MS and NMO based on a questionnaire designed for multinational case-control studies of environmental risk factors in multiple sclerosis. Structured face to face interviews with cases, and telephone interviews with controls were conducted by trained interviewers to collect data. The multiple logistic regression analysis was done via SPSS package. ResultsThe adjusted odds ratio (OR) estimate of MS for females compared to males was (OR =1.47; 95% CI: 1.12, 1.95), and it was (OR=1.54; 95% CI: 1.17, 2.02) for people aged 18–27 years compared to younger ones aged 28–37 years. The adjusted OR estimate of NMO for people aged over 48 years compared to those aged 28–37 years was (OR=3.49; 95% CI: 1.59, 7.64).The point estimates were greater than eight-fold increased risk associated with MS among patients with a positive familial history 8.80 (95% CI: 4.10, 18.90). ConclusionThe results of this study reveal that the risk of MS is significantly higher in female and younger people in comparison to NMO. Having positive family history of MS can increase the risk of MS substantially. The findings of the study indicated that factors that predict susceptibility to MS, including a positive history of MS in relatives, do not appear to have any association with NMO.

Influence of food and lifestyle on the risk of developing inflammatory bowel disease.

The Barwon area in Australia has one of the highest incidence rates of inflammatory bowel disease (IBD) and therefore is an ideal location to study the impact of environmental exposures on the disease's development. To study these exposures prior to the development of IBD in a population-based cohort. One hundred and thirty-two incident cases (81 Crohn disease (CD) and 51 ulcerative colitis (UC)) from an IBD registry and 104 controls replied to the International Organization of Inflammatory Bowel Diseases environmental questionnaire. This included 87 questions about pre-illness exposures that included childhood illnesses, vaccinations, breastfeeding, house amenities, pets and swimming, diet and smoking. The factors associated with CD included smoking (odds ratio (OR): 1.42, confidence interval (CI): 1-2.02, P = 0.029); childhood events, including tonsillectomy (OR: 1.74, CI: 1.15-2.6, P = 0.003) and chicken pox infection (OR: 3.89, CI: 1.61-9.4, P = 0.005) and pre-diagnosis intake of frequent fast food (OR: 2.26, CI: 1.76-4.33, P = 0.003). In UC, the risk factors included smoking (OR: 1.39, CI: 1.1-1.92, P = 0.026) and pre-diagnosis intake of frequent fast food (OR: 2.91, CI: 1.54-5.58, P < 0.001), and high caffeine intake was protective (OR: 0.51, 95% CI: 0.3-0.87, P = 0.002). Other protective exposures for UC included high fruit intake (OR: 0.59, CI: 0.4-0.88, P = 0.003) and having pets as a child (OR: 0.36, CI: 0.2-0.79, P = 0.001). This first Australian population-based study of environmental risk factors confirms that smoking, childhood immunological events and dietary factors play a role in IBD development; while high caffeine intake and pet ownership offer a protective effect.

Birth Outcomes in a Prospective Pregnancy-Birth Cohort Study of Environmental Risk Factors in Kuwait: The TRACER Study.

Rapid development and westernisation in Kuwait and other Gulf states have been accompanied by rising rates of obesity, diabetes, asthma, and other chronic conditions. Prenatal experiences and exposures may be important targets for intervention. We undertook a prospective pregnancy-birth cohort study in Kuwait, the TRansgenerational Assessment of Children's Environmental Risk (TRACER) Study, to examine prenatal risk factors for early childhood obesity. This article describes the methodology and results of follow-up through birth. Women were recruited at antenatal clinical visits. Interviewers administered questionnaires during the pregnancy and collected and banked biological samples. Children are being followed up with quarterly maternal interviews, annual anthropometric measurements, and periodic collection of biosamples. Frequencies of birth outcomes (i.e. stillbirth, preterm birth, small and large for gestational age, and macrosomia) were calculated as a function of maternal characteristics and behaviours. Two thousand four hundred seventy-eight women were enrolled, and 2254 women were followed to delivery. Overall, frequencies of stillbirth (0.6%), preterm birth (9.3%), and small for gestational age (7.4%) were comparable to other developed countries, but not strongly associated with maternal characteristics or behaviours. Macrosomia (6.1%) and large for gestational age (23.0%) were higher than expected and positively associated with pre-pregnancy maternal overweight/obesity. A large birth cohort has been established in Kuwait. The collected risk factors and banked biosamples will allow examination of the effects of prenatal exposures on the development of chronic disease in children. Initial results suggest that maternal overweight/obesity before pregnancy should be targeted to prevent macrosomia and its associated sequelae of childhood overweight/obesity.

Biased Exposure-Health Effect Estimates from Selection in Cohort Studies: Are Environmental Studies at Particular Risk?

BackgroundThe process of creating a cohort or cohort substudy may induce misleading exposure–health effect associations through collider stratification bias (i.e., selection bias) or bias due to conditioning on an intermediate. Studies of environmental risk factors may be at particular risk.ObjectivesWe aimed to demonstrate how such biases of the exposure–health effect association arise and how one may mitigate them.MethodsWe used directed acyclic graphs and the example of bone lead and mortality (all-cause, cardiovascular, and ischemic heart disease) among 835 white men in the Normative Aging Study (NAS) to illustrate potential bias related to recruitment into the NAS and the bone lead substudy. We then applied methods (adjustment, restriction, and inverse probability of attrition weighting) to mitigate these biases in analyses using Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsAnalyses adjusted for age at bone lead measurement, smoking, and education among all men found HRs (95% CI) for the highest versus lowest tertile of patella lead of 1.34 (0.90, 2.00), 1.46 (0.86, 2.48), and 2.01 (0.86, 4.68) for all-cause, cardiovascular, and ischemic heart disease mortality, respectively. After applying methods to mitigate the biases, the HR (95% CI) among the 637 men analyzed were 1.86 (1.12, 3.09), 2.47 (1.23, 4.96), and 5.20 (1.61, 16.8), respectively.ConclusionsCareful attention to the underlying structure of the observed data is critical to identifying potential biases and methods to mitigate them. Understanding factors that influence initial study participation and study loss to follow-up is critical. Recruitment of population-based samples and enrolling participants at a younger age, before the potential onset of exposure-related health effects, can help reduce these potential pitfalls.CitationWeisskopf MG, Sparrow D, Hu H, Power MC. 2015. Biased exposure–health effect estimates from selection in cohort studies: are environmental studies at particular risk? Environ Health Perspect 123:1113–1122; http://dx.doi.org/10.1289/ehp.1408888

The EnvIMS Study: Design and Methodology of an International Case-Control Study of Environmental Risk Factors in Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, often resulting in significant neurological disability. The causes of MS are not known; however, the incidence of MS is increasing, thereby suggesting that changes in lifestyle and/or environmental factors may be responsible. On this background, the Environmental Risk Factors in MS Study or EnvIMS study was designed to further explore the etiology of MS. The design and methodology are described, providing details to enable investigators to (i) use our experiences to design their own studies; (ii) take advantage of, and build on the methodological work completed for, the EnvIMS study; (iii) become aware of this data source that is available for use by the research community. Methods: EnvIMS is a multinational case-control study, enrolling 2,800 cases with MS and 5,012 population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study was designed to investigate the most commonly implicated risk factors for MS etiology using a self-report questionnaire. Results/Conclusions: The use of a common methodology to study MS etiology across several countries enhances the comparability of results in different geographic regions and research settings, reduces the resources required for study design and enhances the opportunity for data harmonization.

A questionnaire for multinational case-control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q)

The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case-control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented. EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including 'core' and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability. EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case-control studies of MS risk factors.