Unconventional natural gas development and adverse birth outcomes in Pennsylvania: The potential mediating role of antenatal anxiety and depression.

BACKGROUND: Studies have reported associations between unconventional natural gas development (UNGD) and adverse birth outcomes. None have evaluated potential mediating mechanisms. OBJECTIVES: To evaluate associations between (1) UNGD and antenatal anxiety and depression and (2) antenatal anxiety and depression and preterm birth (<37 weeks gestation) and reduced term birth weight, (3) stochastic direct and indirect effects of UNGD on preterm birth and term birth weight operating through antenatal anxiety and depression, and (4) effect modification by family-level socioeconomic status. METHODS: This retrospective cohort study included mothers without prevalent anxiety or depression at time of conception, who delivered at Geisinger in Pennsylvania between January 2009-January 2013. We assembled phase-specific UNGD activity data from public sources. Mothers were categorized as exposed (quartile 4) or unexposed (quartiles 1-3) based on average daily inverse distance-squared UNGD activity metric between conception and the week prior to anxiety or depression (cases) or the pregnancy-average daily metric (non-cases). We estimated associations with a doubly robust estimator (targeted minimum loss-based estimation) and adjusted for potential individual- and community-level confounding variables. RESULTS: Analyses included 8,371 births to 7,715 mothers, 12.2% of whom had antenatal anxiety or depression. We found 4.3 additional cases of antenatal anxiety or depression per 100 women (95% CI: 1.5, 7.0) under the scenario where all mothers lived in the highest quartile of UNGD activity versus quartiles 1-3. The risk difference appeared larger among mothers receiving Medical Assistance (indicator of low family income) compared to those who did not, 5.6 (95% CI: 0.5, 10.6) versus 2.9 (95% CI: -0.7, 6.5) additional cases of antenatal anxiety or depression per 100 women. We found no relationship between antenatal anxiety or depression and adverse birth outcomes and no mediation effect either overall or when stratifying by Medical Assistance. CONCLUSION: We observed a relationship between UNGD activity and antenatal anxiety and depression, which did not mediate the overall association between UNGD activity and adverse birth outcomes.

Unconventional Natural Gas Development and Birth Outcomes in Pennsylvania, USA.

BACKGROUND: Unconventional natural gas development has expanded rapidly. In Pennsylvania, the number of producing wells increased from 0 in 2005 to 3,689 in 2013. Few publications have focused on unconventional natural gas development and birth outcomes. METHODS: We performed a retrospective cohort study using electronic health record data on 9,384 mothers linked to 10,946 neonates in the Geisinger Health System from January 2009 to January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother's home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5-minute Apgar score and small size for gestational age birth, while controlling for potential confounding variables. RESULTS: In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% confidence interval = 1.0, 1.9). There were no associations of activity with Apgar score, small for gestational age birth, or term birth weight (after adjustment for year). In a posthoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 [95% confidence interval = 1.1, 1.7]). CONCLUSION: Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health.See Video Abstract at http://links.lww.com/EDE/B14.

Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 (COX-1) enzyme. The prevalence of AERD remains unclear, and few studies have compared the clinical characteristics of patients with AERD to those with CRSwNP alone, asthma alone, or both CRSwNP and asthma. OBJECTIVE: To determine the prevalence of AERD within a tertiary care setting, and to identify unique clinical features that could distinguish these patients from those with both CRSwNP and asthma or with CRSwNP alone. METHODS: Electronic medical records of patients at Northwestern in Chicago, Illinois, were searched by computer algorithm and then manual chart review to identify 459 patients with CRSwNP alone, 412 with both CRSwNP and asthma, 171 with AERD, and 300 with asthma only. Demographic and clinical features including sex, atopy, and sinus disease severity were characterized. RESULTS: The prevalence of AERD among patients with CRSwNP was 16%. Patients with AERD had undergone 2-fold more sinus surgeries (P < .001) and were significantly younger at the time of their first surgery (40 ± 13 years) than were patients with CRSwNP (43 ± 14 years; P < .05). Atopy was significantly more prevalent in patients with AERD (84%) or asthma (85%) than in patients with CRSwNP (66%, P < .05). More patients with AERD (13%) had corticosteroid-dependent disease than patients with both CRSwNP and asthma (4%, P < .01) or asthma (1%, P < .001). CONCLUSIONS: AERD is common among patients with CRSwNP; even though patients with AERD have CRSwNP and asthma, the clinical course of their disease is not the same as of patients who have CRSwNP and asthma but are tolerant to COX-1 inhibitors.

Association Between Unconventional Natural Gas Development in the Marcellus Shale and Asthma Exacerbations.

IMPORTANCE: Asthma is common and can be exacerbated by air pollution and stress. Unconventional natural gas development (UNGD) has community and environmental impacts. In Pennsylvania, UNGD began in 2005, and by 2012, 6253 wells had been drilled. There are no prior studies of UNGD and objective respiratory outcomes. OBJECTIVE: To evaluate associations between UNGD and asthma exacerbations. DESIGN: A nested case-control study comparing patients with asthma with and without exacerbations from 2005 through 2012 treated at the Geisinger Clinic, which provides primary care services to over 400 000 patients in Pennsylvania. Patients with asthma aged 5 to 90 years (n = 35 508) were identified in electronic health records; those with exacerbations were frequency matched on age, sex, and year of event to those without. EXPOSURES: On the day before each patient's index date (cases, date of event or medication order; controls, contact date), we estimated activity metrics for 4 UNGD phases (pad preparation, drilling, stimulation [hydraulic fracturing, or "fracking"], and production) using distance from the patient's home to the well, well characteristics, and the dates and durations of phases. MAIN OUTCOMES AND MEASURES: We identified and defined asthma exacerbations as mild (new oral corticosteroid medication order), moderate (emergency department encounter), or severe (hospitalization). RESULTS: We identified 20 749 mild, 1870 moderate, and 4782 severe asthma exacerbations, and frequency matched these to 18 693, 9350, and 14 104 control index dates, respectively. In 3-level adjusted models, there was an association between the highest group of the activity metric for each UNGD phase compared with the lowest group for 11 of 12 UNGD-outcome pairs: odds ratios (ORs) ranged from 1.5 (95% CI, 1.2-1.7) for the association of the pad metric with severe exacerbations to 4.4 (95% CI, 3.8-5.2) for the association of the production metric with mild exacerbations. Six of the 12 UNGD-outcome associations had increasing ORs across quartiles. Our findings were robust to increasing levels of covariate control and in sensitivity analyses that included evaluation of some possible sources of unmeasured confounding. CONCLUSIONS AND RELEVANCE: Residential UNGD activity metrics were statistically associated with increased risk of mild, moderate, and severe asthma exacerbations. Whether these associations are causal awaits further investigation, including more detailed exposure assessment.

Electronic health record-based assessment of oral corticosteroid use in a population of primary care patients with asthma: an observational study.

BACKGROUND: Oral corticosteroid prescriptions are often used in clinical studies as an indicator of asthma exacerbations. However, there is rarely the ability to link a prescription to its associated diagnosis. The objective of this study was to characterize patterns of oral corticosteroid prescription orders for asthma patients using an electronic health record database, which links each prescription order to the diagnosis assigned at the time the order was placed. METHODS: This was a retrospective cohort study of the electronic health records of asthma patients enrolled in the Geisinger Health System from January 1, 2001 to August 23, 2010. Eligible patients were 12-85 years old, had a primary care physician in the Geisinger Health System, and had asthma. Each oral corticosteroid order was classified as being prescribed for an asthma-related or non-asthma-related condition based on the associated diagnosis. Asthma-related oral corticosteroid use was classified as either chronic or acute. In patient-level analyses, we determined the number of asthma patients with asthma-related and non-asthma-related prescription orders and the number of patients with acute versus chronic use. Prescription-level analyses ascertained the percentages of oral corticosteroid prescription orders that were for asthma-related and non-asthma-related conditions. RESULTS: Among the 21,199 asthma patients identified in the electronic health record database, 15,017 (70.8%) had an oral corticosteroid prescription order. Many patients (N = 6,827; 45.5%) had prescription orders for both asthma-related and non-asthma-related conditions, but some had prescription orders exclusively for asthma-related (N = 3,450; 23.0%) or non-asthma-related conditions (N = 4,740; 31.6%). Among the patients receiving a prescription order, most (87.5%) could be classified as acute users. A total of 60,355 oral corticosteroid prescription orders were placed for the asthma patients in this study-31,397 (52.0%) for non-asthma-related conditions, 24,487 (40.6%) for asthma-related conditions, and 4,471 (7.4%) for both asthma-related and non-asthma-related conditions. CONCLUSIONS: Oral corticosteroid prescriptions for asthma patients are frequently ordered for conditions unrelated to asthma. A prescription for oral corticosteroids may be an unreliable marker of asthma exacerbations in retrospective studies utilizing administrative claims data. Investigators should consider co-morbid conditions for which oral corticosteroid use may also be indicated and/or different criteria for assessing oral corticosteroid use for asthma.

Body mass index and the built and social environments in children and adolescents using electronic health records.

BACKGROUND: No prior studies in children have evaluated how age may modify relationships of the built and social environments with BMI, nor evaluated the range of scales and contexts over which places may influence health. PURPOSE: To systematically evaluate associations of 33 environmental measures in three domains (land use, physical activity, and social environments) with BMI in children and adolescents in five geographies. METHODS: A cross-sectional, multilevel analysis was completed in 2009-2010 of electronic health record data (2001-2008) from 47,769 children aged 5-18 years residing in a 31-county region of Pennsylvania. Associations of environmental measures with BMI were evaluated using 0.5-mile network buffers; census tracts; minor civil divisions (i.e., townships, boroughs, cities); a mixed definition of place (townships, boroughs, and census tracts in cities); and counties, overall and by age strata. RESULTS: Among all children, lower levels of community socioeconomic deprivation and greater diversity of physical activity establishments were associated with lower BMI. Associations of environmental measures differed by age, depending on scale and context. For example, higher population density was associated with lower BMI in older children; this effect was strongest in the larger geographies. Similarly, a lower level of county sprawl was associated with lower BMI in older children. CONCLUSIONS: Associations differed by age and definition of place, suggesting that the benefits of environmental intervention may not be uniform across the childhood age range. The study demonstrated the utility of using electronic patient information for large-scale, population-based epidemiologic research, a research area of growing interest and investment in the U.S.