Measuring lung diffusing capacity: an opportunity for improved medical surveillance and disability evaluation of coal miners.

OBJECTIVES: Spirometry is the primary lung function test utilised for medical surveillance and disability examination for coal mine dust lung disease. However, spirometry likely underestimates physiologic impairment. We sought to characterise abnormalities of single-breath diffusing capacity for carbon monoxide (DLCO) among a population of former coal miners. METHODS: Data from 3115 former coal miners evaluated at a West Virginia black lung clinic between 2006 and 2015 were retrospectively analysed to study the association between diffusion impairment (abnormally low DLCO), resting spirometry and the presence and severity of coal workers' pneumoconiosis on chest radiography. We developed ordinary least squares linear regression models to evaluate factors associated with per cent predicted DLCO (DLCOpp). RESULTS: Diffusion impairment was identified in 20.2% of subjects. Ten per cent of all miners with normal spirometry had diffusion impairment including 7.4% of never smokers. The prevalence of diffusion impairment increased with worsening radiographic category of pneumoconiosis. Mean DLCOpp decreased with increasing small opacity profusion subcategory in miners without progressive massive fibrosis. Linear regression analysis also showed significant decreases in DLCOpp with increasing small opacity profusion and presence of large opacities. CONCLUSIONS: Diffusion impairment is common among former coal miners, including among never smokers, miners without radiographic pneumoconiosis and miners with normal spirometry. These findings demonstrate the value of including DLCO testing in disability examinations of former coal miners and an important role for its use in medical surveillance of working miners to detect early chronic lung disease.

Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

BACKGROUND: The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. METHODS: We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. RESULTS: Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. CONCLUSIONS: DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

Thin seams and small mines are associated with higher exposures to respirable crystalline silica in US underground coal mines.

OBJECTIVES: Previous radiologic and histopathologic studies suggest respirable crystalline silica (RCS) overexposure has been driving the resurgence of pneumoconiosis among contemporary US coal miners, with a higher prevalence of severe disease in Central Appalachia. We sought to better understand RCS exposure among US underground coal miners. METHODS: We analysed RCS levels, as measured by respirable quartz, from coal mine dust compliance data from 1982 to 2021. RESULTS: We analysed 322 919 respirable quartz samples from 5064 US underground coal mines. Mean mine-level respirable quartz percentage and mass concentrations were consistently higher for Central Appalachian mines than the rest of the USA. Mean mine-level respirable quartz mass concentrations decreased significantly over time, from 0.116 mg/m3 in 1982 to as low as 0.017 mg/m3 for Central Appalachian mines, and from 0.089 mg/m3 in 1983 to 0.015 mg/m3 in 2020 for the rest of the USA. Smaller mine size, location in Central Appalachia, lack of mine safety committee and thinner coal seams were predictive of higher respirable quartz mass concentrations. CONCLUSIONS: These data substantially support the association between RCS overexposure and the resurgence of coal workers' pneumoconiosis in the USA, particularly in smaller mines in Central Appalachia.

Progressive Massive Fibrosis Identified at Federally Funded Black Lung Clinics in the US.

This study of US Black Lung Clinics (established to treat coal miners) reports the prevalence of progressive massive fibrosis identified through June 2023.

Characterizing Lung Particulates Using Quantitative Microscopy in Coal Miners With Severe Pneumoconiosis.

CONTEXT.­: Current approaches for characterizing retained lung dust using pathologists' qualitative assessment or scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) have limitations. OBJECTIVE.­: To explore polarized light microscopy coupled with image-processing software, termed quantitative microscopy-particulate matter (QM-PM), as a tool to characterize in situ dust in lung tissue of US coal miners with progressive massive fibrosis. DESIGN.­: We developed a standardized protocol using microscopy images to characterize the in situ burden of birefringent crystalline silica/silicate particles (mineral density) and carbonaceous particles (pigment fraction). Mineral density and pigment fraction were compared with pathologists' qualitative assessments and SEM/EDS analyses. Particle features were compared between historical (born before 1930) and contemporary coal miners, who likely had different exposures following changes in mining technology. RESULTS.­: Lung tissue samples from 85 coal miners (62 historical and 23 contemporary) and 10 healthy controls were analyzed using QM-PM. Mineral density and pigment fraction measurements with QM-PM were comparable to consensus pathologists' scoring and SEM/EDS analyses. Contemporary miners had greater mineral density than historical miners (186 456 versus 63 727/mm3; P = .02) and controls (4542/mm3), consistent with higher amounts of silica/silicate dust. Contemporary and historical miners had similar particle sizes (median area, 1.00 versus 1.14 µm2; P = .46) and birefringence under polarized light (median grayscale brightness: 80.9 versus 87.6; P = .29). CONCLUSIONS.­: QM-PM reliably characterizes in situ silica/silicate and carbonaceous particles in a reproducible, automated, accessible, and time/cost/labor-efficient manner, and shows promise as a tool for understanding occupational lung pathology and targeting exposure controls.

Pathologic Findings in Severe Coal Workers' Pneumoconiosis in Contemporary US Coal Miners.

CONTEXT.­: The pathology of coal workers' pneumoconiosis (CWP) and its most severe form-progressive massive fibrosis (PMF)-in US coal miners has changed in recent years. Severe disease is occurring in younger miners and has been linked to an increase in silica dust exposure. OBJECTIVE.­: To update the description of the pathologic features of CWP in contemporary miners compared to historical miners. DESIGN.­: This study is a retrospective expert classification of lung tissue from 85 historical and contemporary coal miners with PMF. Significant pathologic features were scored by using a standardized instrument with consensus achieved for major findings, including newly defined categories of PMF as coal-type, mixed-type, and silica-type. RESULTS.­: Pathologic features associated with silica dust exposure, including silica-type PMF, mineral dust alveolar proteinosis (MDAP), and immature (early stage) silicotic nodules were increased in contemporary miners. Detailed descriptions of the pathology of contemporary CWP with illustrative figures are provided. CONCLUSIONS.­: Silica-related pathologies are more common in contemporary miners. Severe forms of CWP can be detected by subtyping PMF lesions (if present) or by identification of mature and immature silicotic nodules, coal mine dust-related alveolar proteinosis, and severe inflammation in coal miners' lungs. Silica-type PMF cases showed significantly higher levels of MDAP than either mixed- or coal-type PMF (P < .001). High profusion of birefringent silica/silicate particles was observed more frequently in cases with immature (early stage) silicotic nodules (P = .04). Severe inflammation was also significantly increased in contemporary miners (P = .03). Our findings underscore the urgent need to revise current exposure limits and monitoring of respirable crystalline silica in US coal mines.

Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA.

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.

Poor adherence to dust, noise and safety regulations predict injury rates in underground coal mines.

BACKGROUND: While safety in US coal mining has improved over the past two decades, general occupational health research shows that risk of injury varies across individual worksites and is influenced by worksite safety cultures and practices. METHODS: In this longitudinal study, we evaluated whether mine-level characteristics reflecting poor adherence to health and safety regulations in underground coal mines are associated with higher acute injury rates. We aggregated Mine Safety and Health Administration (MSHA) data by year for each underground coal mine for the period 2000-2019. Data included part-50 injuries, mine characteristics, employment and production, dust sampling, noise sampling, and violations. Multivariable hierarchical generalised estimating equations (GEE) models were developed. RESULTS: Based on the final GEE model, despite an average annual decline in injury rates by 5.5%, the following indicators of inadequate adherence to health and safety regulations were associated with increased average annual injury rates: +2.9% for each 10% increase in dust samples exceeding the permissible exposure limit; +0.6% for each 10% increase of permitted 90 dBA 8-hour noise exposure dose; +2.0% for every 10 substantial-significant MSHA violations in a year; +1.8% for each rescue/recovery procedure violation; +2.6% for each safeguard violation. If a fatality occurred in a mine, injury rates increased by 11.9% in the same year, but declined by 10.4% in the following year. The presence of safety committees was associated with a 14.5% decline in injury rates. DISCUSSION: In US underground coal mines, injury rates are associated with poor adherence to dust, noise and safety regulations.

Mining Tenure and Job Duties Differ Among Contemporary and Historic Underground Coal Miners With Progressive Massive Fibrosis.

OBJECTIVE: To characterize differences in mining jobs and tenure between contemporary (born 1930+, working primarily with modern mining technologies) and historic coal miners with progressive massive fibrosis (PMF). METHODS: We classified jobs as designated occupations (DOs) and non-DOs based on regulatory sampling requirements. Demographic, occupational characteristics, and histopathological PMF type were compared between groups. RESULTS: Contemporary miners ( n = 33) had significantly shorter mean total (30.4 years vs 37.1 years, P = 0.0006) and underground (28.8 years vs 35.8 years, P = 0.001) mining tenure compared with historic miners ( n = 289). Silica-type PMF was significantly more common among miners in non-DOs (30.1% vs 15.8%, P = 0.03) and contemporary miners (58.1% vs 15.2%, P < 0.0001). CONCLUSIONS: Primary jobs changed over time with the introduction of modern mining technologies and likely changed exposures for workers. Elevated crystalline silica exposures are likely in non-DOs and require attention.

Increased odds of mortality from non-malignant respiratory disease and lung cancer are highest among US coal miners born after 1939.

OBJECTIVES: Coal miners suffer increased mortality from non-malignant respiratory diseases (NMRD), including pneumoconioses and chronic obstructive pulmonary disease, compared with the US population. We characterised mortality trends from NMRD, lung cancer and ischaemic heart disease (IHD) using data from the Federal Black Lung Program, National Coal Workers' Health Surveillance Program and the National Death Index. METHODS: We compared mortality ORs (MORs) for NMRD, lung cancer and IHD in former US coal miners to US white males. MORs were computed for the study period 1979-2017 by birth cohort (<1920, 1920-1929, 1930-1939, ≥1940), with a subanalysis restricted to Central Appalachia. RESULTS: The study population totalled 235 550 deceased miners, aged >45 years. Odds of death from NMRD and lung cancer across all miner birth cohorts averaged twice those of US males. In Central Appalachia, MORs significantly increased across birth cohorts. There was an eightfold increase in odds of death from NMRD among miners born after 1940 (MORBC≥1940 8.25; 95% CI 7.67 to 8.87). Miners with progressive massive fibrosis (PMF) were younger at death than those without PMF (74 vs 78 years; p<0.0001). We observed a pattern of reduced MORs from IHD in coal miners compared with national and regional counterparts. CONCLUSION: US coal miners have excess mortality from NMRD and lung cancer compared with total US and Appalachian populations. Mortality is highest in the most recent birth cohorts, perhaps reflecting increased rates of severe pneumoconiosis.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

Pathology and Mineralogy Demonstrate Respirable Crystalline Silica Is a Major Cause of Severe Pneumoconiosis in U.S. Coal Miners.

Rationale: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States are not yet fully understood. Objectives: To compare the pathologic and mineralogic features of contemporary coal miners with severe pneumoconiosis with those of their historical counterparts. Methods: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) with those in miners born in or after 1930 (contemporary). Results: We found a significantly higher proportion of silica-type PMF (57% vs. 18%; P < 0.001) among contemporary miners compared with their historical counterparts. Mineral dust alveolar proteinosis was also more common in contemporary miners compared with their historical counterparts (70% vs. 37%; P < 0.01). In situ mineralogic analysis showed that the percentage (26.1% vs. 17.8%; P < 0.01) and concentration (47.3 × 108 vs. 25.8 × 108 particles/cm3; P = 0.036) of silica particles were significantly greater in specimens from contemporary miners compared with their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, mineral dust alveolar proteinosis, silicotic nodules, or immature silicotic nodules were present (P < 0.05). Conclusions: Exposure to respirable crystalline silica appears causal in the unexpected surge of severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure to prevent the disabling and untreatable adverse health effects afflicting U.S. coal miners.

Prevalence and severity of abnormal lung function among US former coal miners with and without radiographic coal workers' pneumoconiosis.

OBJECTIVES: Examination of lung function abnormalities among coal miners has historically focused on actively working miners. This likely underestimates the true burden of chronic respiratory disease. The objective of this study was to characterise patterns and severity of lung function impairment among a population of former coal miners. METHODS: Cross-sectional data from 2568 former coal miners evaluated at eight US Black Lung clinics in a 12-month period were retrospectively analysed for patterns of prebronchodilator spirometric abnormality and severity of lung function impairment. Spirometry data from a subset of former miners with chest radiographs were analysed based on the presence and severity of coal workers' pneumoconiosis (CWP). RESULTS: Abnormal spirometry was identified in 56.6% of subjects. The age-standardised prevalence of airflow obstruction among miners aged ≥45 years was 18.9% overall and 12.2% among never smokers. Among 1624 subjects who underwent chest radiography, the prevalence and severity of abnormal spirometry increased with worsening radiographic category for pneumoconiosis. Of never-smoking former miners without radiographic CWP, 39.0% had abnormal spirometry; 25.1% had abnormally low forced expiratory volume in 1 s (FEV1), and 17.1% had moderate to severe FEV1 impairment. CONCLUSIONS: Abnormal spirometry is common among former coal miners. While ever-smoking former miners had higher rates of airflow obstruction, never-smoking former miners also demonstrated clinically significant airflow obstruction, including those without radiographic pneumoconiosis. These findings demonstrate the importance of recognising physiological as well as imaging manifestations of coal mine dust lung diseases in former miners.

Association between Financial Conflicts of Interest and International Labor Office Classifications for Black Lung Disease.

Rationale: The U.S. Department of Labor administers the Federal Black Lung Program (FBLP), an administrative system charged with managing claims by coal miners for workers' compensation for totally disabling coal mine dust lung disease. Specific case reports have raised concern that financial conflicts of interest (COIs) may systematically bias physicians when they are classifying chest X-rays (CXRs) for the absence, presence, and severity of pneumoconiosis. Objectives: To evaluate the direction and magnitude of association between financial COIs of physicians participating in the FBLP and international standards for the classification of radiographs of pneumoconiosis. Methods: An epidemiologic assessment of black lung claims filed to the FBLP from 2000 to 2013 was conducted to determine physician classifications of radiographs. FBLP court decisions from 2002 to 2019 (n = 7,656) were used to evaluate financial COIs of each physician. The main outcome measures used were classifications of radiographs for the absence of pneumoconiosis (small opacity classifications of 0/0 or 0/1), simple pneumoconiosis (small opacity classifications of 1/0 through 3/+), and progressive massive fibrosis (PMF) (large opacities with classifications of A, B, or C). Results: Of 63,780 radiograph classifications made by 264 physicians, 31.4% were read positive for simple pneumoconiosis and 3.6% were read as having PMF. There were 52 physicians who classified CXRs as having no evidence of pneumoconiosis in 99%+ of their readings and 18 physicians who classified CXRs as positive for simple pneumoconiosis in 99%+ of their readings. The adjusted odds of a negative classification of pneumoconiosis was 1.46 (95% confidence interval [CI], 1.44-1.47) per 10% increase in the proportion of court records demonstrating that a physician was hired by the employer. Per 10% increase in court records indicating a physician was hired by the miner/claimant, the adjusted odds ratio for classifying simple pneumoconiosis was 1.51 (95% CI, 1.49-1.52), and the adjusted odds ratio for finding PMF was 1.28 (95% CI, 1.26-1.30). Conclusions: There was a strong association between source of payment and radiograph classification, suggesting the importance of eliminating financial COIs in what should be an objective determination of eligibility for Black Lung Workers' compensation benefits.

Injuries during the first hour at work in the U.S. mining industry.

BACKGROUND: The first hour of a shift in a mine is characterized by a large movement of miners from incoming and outgoing shifts, in addition to safety and maintenance checks of mining equipment. These activities rely on communication to ensure a safe transition between shifts. This study aims to identify risk factors for injury among miners during the first hour of a work shift and to characterize injury outcomes. METHODS: Data from U.S. Mine Safety and Health Administration Part 50 reports, 1983-2015, were used to identify injuries occurring within the first hour of a shift. Multivariable logistic regression was used to evaluate predictors of injuries occurring during the first shift-hour and to assess the outcome of these injuries. RESULTS: Out of the 545,537 cases included in the analysis, 16,446 injuries occurred during the first hour of a shift. Risk factors associated with these injuries included being female, being older, working on Sunday and Monday, having an irregular shift start, working night shifts, employed in surface mining operations, and mine operations with <200 employees, and mechanisms of injury related to falls, movement of equipment and personnel, and being struck by or caught between boxes and containers. Injurious incidents occurring during the first hour of work were associated with mass injury events involving five or more workers (aOR = 3.58; 95% CI: 2.77, 4.64). CONCLUSIONS: Although injury rates were substantially lower during the first hour of work compared to all other work hours, this study identified risk factors and mechanisms of injury that are highly preventable during the first hour of work.

Progression of coal workers' pneumoconiosis absent further exposure.

OBJECTIVES: The natural history of coal workers' pneumoconiosis (CWP) after cessation of exposure remains poorly understood. METHODS: We characterised the development of and progression to radiographic progressive massive fibrosis (PMF) among former US coal miners who applied for US federal benefits at least two times between 1 January 2000 and 31 December 2013. International Labour Office classifications of chest radiographs (CXRs) were used to determine initial and subsequent disease severity. Multivariable logistic regression models were used to identify major predictors of disease progression. RESULTS: A total of 3351 former miners applying for benefits without evidence of PMF at the time of their initial evaluation had subsequent CXRs. On average, these miners were 59.7 years of age and had 22 years of coal mine employment. At the time of their first CXR, 46.7% of miners had evidence of simple CWP. At the time of their last CXR, 111 miners (3.3%) had radiographic evidence of PMF. Nearly half of all miners who progressed to PMF did so in 5 years or less. Main predictors of progression included younger age and severity of simple CWP at the time of initial CXR. CONCLUSIONS: This study provides further evidence that radiographic CWP may develop and/or progress absent further exposure, even among miners with no evidence of radiographic pneumoconiosis after leaving the industry. Former miners should undergo regular medical surveillance because of the risk for disease progression.

Effects of commodity on the risk of emphysema in South African miners.

PURPOSE: To examine associations between mine commodity such as coal, platinum, or diamonds and emphysema among South African miners at autopsy. METHODS: We examined the association between mine commodity and emphysema using the Pathology Automation (PATHAUT) database, 1975-2014. Exposure was characterized as longest tenure in each commodity. We constructed separate multivariable logistic regression models for black and white miners. Smoking was assessed in a sub-analysis of white miners. RESULTS: Among black miners, coal mining was significantly associated with increased odds of emphysema [OR = 2.39 (95% CI 1.86, 3.07)] when compared to gold mining. Asbestos was also associated with significantly increased odds of emphysema among black miners [OR = 1.47 (95% CI 1.01, 2.12)]. No associations between commodity and emphysema were observed among white miners. Cumulative years of exposure and age at death were significant predictors for emphysema for both black and white miners. Smoking was a significant predictor of emphysema in the sub-analysis of white miners with smoking information, but no effect of commodity was observed. CONCLUSIONS: We observed a significant association between coal mining and emphysema among black miners. Adverse health effects of coal mining are evidenced by more than twofold increase in emphysema among black coal miners compared to gold miners. This suggests that South African Coal miners are exposed to high dust concentrations or more damaging components compared to other commodities, resulting in elevated risk of emphysema.

Prenatal exposure to nitrate in drinking water and the risk of congenital anomalies.

BACKGROUND: Nitrate is a common water contaminant that has been associated with birth defects, although the evidence is limited. The purpose of this study was to examine whether maternal consumption of nitrate through drinking water is associated with an increased risk of congenital anomalies. METHODS: The study included a total of 348,250 singletons births from the state of Missouri between January 1, 2004 and December 31, 2008. Individual-level birth defect data and maternal and child characteristics were obtained from the Missouri birth defects registry and state vital statistics records. Outcomes were linked with county-specific monthly estimates of the nitrate concentration in finished water, based on data collected for compliance with the Safe Drinking Water Standard. Poisson models were fit to examine the association between nitrate exposure and birth defects. Average nitrate exposure during the first trimester and over 12 months prior to birth were modeled as continuous variables. Sensitivity analyses included restriction of the sample to counties with <20% and <10% private well usage to reduce exposure misclassification as well as limiting the analyses to residents of rural counties only to account for potential confounding by urbanicity. RESULTS: Estimated water concentrations of nitrate were generally low and below the Environmental Protection Agency's maximum contaminant level of 10 mg/L. Nitrate exposure was associated with a significantly increased risk of limb deficiencies (RR for 1 mg/L (RR1) = 1.26, 95% CI = 1.05, 1.51) in models without well restriction. Nitrate was also weakly associated with an increased risk of congenital heart defects (RR1 = 1.13, 95%CI = 0.93, 1.51) and neural tube defects (RR1 = 1.18, 95%CI = 0.93, 1.51) in models with well restriction (<10%). CONCLUSION: The positive associations found between nitrate exposure via drinking water and congenital abnormalities are largely consistent with some previous epidemiologic studies. The results of this study should be interpreted with caution given limitations in our ability to estimate exposures and the lack information on some risk factors for congenital abnormalities. Our findings may have serious policy implications given that exposure levels in our study were well below current EPA standards for nitrate in drinking water.