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1.  Both Variability and Level of Mouse Allergen Exposure Influence the Phenotype of the Immune Response in Workers at a Mouse Facility 
Background
The role of natural aeroallergen exposure in modulating allergen-specific immune responses is not well understood.
Objective
To examine relationships between mouse allergen exposure and mouse-specific immune responses.
Methods
New employees (n=179) at a mouse facility underwent repeated assessment of mouse allergen exposure, skin prick testing (SPT), and measurement of mouse-specific IgG. Relationships between the mean level of exposure, variability of exposure (calculated as log standard deviation), and time to development of immunologic outcomes were examined using Cox proportional hazards models.
Results
By 24 months, 32 (23%) participants had developed a +SPT and 10 (8%) had developed mouse-specific IgG4. The incidence of a +SPT increased as levels of exposure increased from low to moderate, peaking at 1.2 ng/m3 and decreased beyond this point (p=.04). The more variable the exposure was across visits, the lower the incidence of a +SPT (HR [95% CI]: 0.17 [0.07–0.41]). Variability of exposure was an independent predictor of +SPT in a model that included both exposure metrics. In contrast, the incidence of mouse-specific IgG4 increased with increasing levels of mouse allergen exposure (2.9 [1.4–6.0]), and there was evidence of a higher risk of mouse-specific IgG4 with greater variability of exposure (6.3 [0.4–95.2]).
Conclusion
Both level and variability of mouse allergen exposure influence the humoral immune response, with specific patterns of exposure associated with specific immunophenotypes. Exposure variability may be a more important predictor of +SPT, while average exposure level may be a more important predictor of mouse-specific IgG4.
doi:10.1016/j.jaci.2011.04.050
PMCID: PMC3149759  PMID: 21696812
mouse allergen; IgE; IgG4; laboratory animal allergy
2.  Occupational Mouse Allergen Exposure Among Non-Mouse Handlers 
This study assessed mouse allergen exposure across a range of jobs, including non-mouse handling jobs, at a mouse facility. Baseline data from 220 new employees enrolled in the Jackson Laboratory (JAXCohort) were analyzed. The baseline assessment included a questionnaire, allergy skin testing, and spirometry. Exposure assessments consisted of collection of two full-shift breathing zone air samples during a 1-week period. Air samples were analyzed for mouse allergen content, and the mean concentration of the two shifts represented mouse allergen exposure for that employee. The mean age of the 220 participants was 33 years. Ten percent reported current asthma and 56% were atopic. Thirty-eight percent were animal caretakers, 20% scientists, 20% administrative/support personnel, 10% materials/supplies handlers, and 9% laboratory technicians. Sixty percent of the population handled mice. Eighty-two percent of study participants had detectable breathing zone mouse allergen, and breathing zone mouse allergen concentrations were 1.02 ng/m3 (0.13–6.91) (median [interquartile range (IQR)]. Although mouse handlers had significantly higher concentrations of breathing zone mouse allergen than non-handlers (median [IQR]: 4.13 ng/m3 [0.69–12.12] and 0.21 ng/m3 [below detection (BD)–0.63], respectively; p < 0.001), 66% of non-handlers had detectable breathing zone mouse allergen. Mouse allergen concentrations among administrative/support personnel and materials/supplies handlers, jobs that generally do not entail handling mice, were median [IQR]: 0.23 ng/m3 [BD–0.59] and 0.63 ng/m3 [BD–18.91], respectively. Seventy-one percent of administrative/support personnel, and 68% of materials/supplies handlers had detectable breathing zone mouse allergen. As many as half of non-mouse handlers may have levels of exposure that are similar to levels observed among mouse handlers.
doi:10.1080/15459624.2010.530906
PMCID: PMC3143460  PMID: 21058157
allergen-specific antibody responses; laboratory animal allergy; mouse allergen
3.  Household Smoking Behavior: Effects on Indoor Air Quality and Health of Urban Children with Asthma 
Maternal and child health journal  2011;15(4):460-468.
The goal of the study was to examine the association between biomarkers and environmental measures of second hand smoke (SHS) with caregiver, i.e. parent or legal guardian, report of household smoking behavior and morbidity measures among children with asthma. Baseline data were drawn from a longitudinal intervention for 126 inner city children with asthma, residing with a smoker. Most children met criteria for moderate to severe persistent asthma (63%) versus mild intermittent (20%) or mild persistent (17%). Household smoking behavior and asthma morbidity were compared with child urine cotinine and indoor measures of air quality including fine particulate matter (PM2.5) and air nicotine (AN). Kruskal–Wallis, Wilcoxon rank-sum and Spearman rho correlation tests were used to determine the level of association between biomarkers of SHS exposure and household smoking behavior and asthma morbidity. Most children had uncontrolled asthma (62%). The primary household smoker was the child's caregiver (86/126, 68%) of which 66 (77%) were the child's mother. Significantly higher mean PM2.5, AN and cotinine concentrations were detected in households where the caregiver was the smoker (caregiver smoker: PM2.5 μg/m3: 44.16, AN: 1.79 μg/m3, cotinine: 27.39 ng/ml; caregiver non-smoker: PM2.5: 28.88 μg/m3, AN: 0.71 μg/m3, cotinine:10.78 ng/ml, all P ≤ 0.01). Urine cotinine concentrations trended higher in children who reported 5 or more symptom days within the past 2 weeks (>5 days/past 2 weeks, cotinine: 28.1 ng/ml vs. <5 days/past 2 weeks, cotinine: 16.2 ng/ml; P = 0.08). However, environmental measures of SHS exposures were not associated with asthma symptoms. Urban children with persistent asthma, residing with a smoker are exposed to high levels of SHS predominantly from their primary caregiver. Because cotinine was more strongly associated with asthma symptoms than environmental measures of SHS exposure and is independent of the site of exposure, it remains the gold standard for SHS exposure assessment in children with asthma.
doi:10.1007/s10995-010-0606-7
PMCID: PMC3113654  PMID: 20401688
Asthma; Children; Cotinine; Particulate matter; Air Nicotine
4.  Adding Exhaled Nitric Oxide to Guideline-based Asthma Treatment in Inner-City Adolescents and Young Adults: a randomized controlled trial 
Lancet  2008;372(9643):1065-1072.
Background
Preliminary evidence is equivocal regarding the role of exhaled nitric oxide in clinical asthma management. This study evaluates the usefulness of eNO as an adjunct to asthma guidelines-based clinical care among inner-city adolescents and young adults.
Methods
A randomized, double-blind, parallel-group trial was conducted with 546 inner-city participants, aged 12–20 years, with persistent asthma (Clinicaltrials.gov Identifier: NCT00114413). A run-in characterization period of 3 weeks on an initial controller regimen preceded a 46-week double-blind treatment strategy. Participants were randomized to either, treatment based on NAEPP guidelines alone (Reference Group) or the guidelines plus FENO measurements (FENO Group). Primary outcome was asthma symptom days and secondary outcome was acute asthma exacerbations.
Findings
During the 46-week treatment period, the number of asthma symptom days, pulmonary function, unscheduled care visits, and hospitalizations did not differ between the treatment groups (mean asthma symptom days were 1.93 [95% CI 1.74-2.11] in the FENO group vs. 1.89 [1.71-1.74] in the control group; difference 0.04 [-0.29-0.22], p=0.7796). The FENO Group received a significantly higher inhaled corticosteroid dose (118.9 mcg/day difference, 95% CI: 48.5-189.3, P=0.0010) as compared to the Reference Group. Asthma symptoms remained low in both groups following randomization with 57% (306/534) of the participants well controlled for at least 80% of visits..
Interpretation
A coordinated asthma management program facilitated achieving good control in the majority of participants. The addition of FENO as a control indicator resulted in a higher dose of inhaled corticosteroids without a clinically important improvement in symptomatic asthma control.
doi:10.1016/S0140-6736(08)61448-8
PMCID: PMC2610850  PMID: 18805335
asthma; biomarker; exhaled nitric oxide; inhaled corticosteroid; inner-city asthma; long-acting ß2-agonist; medication adherence; asthma exacerbations; asthma outcomes; asthma guidelines; impairment; risk
5.  Does neighborhood violence lead to depression among caregivers of children with asthma? 
Prior studies have related community violence to depression among children, but few studies have examined this relationship among adults. We hypothesized that victimization, awareness, and fear of neighborhood violence would increase the odds of depression among adult caregivers of children with asthma. We surveyed caregivers in the Baltimore Indoor Environment Study of Asthma in Kids (BIESAK), USA. The primary outcome was screening positive for depression on the Center for Epidemiological Studies Depression index. We assessed victimization, awareness, and fear of neighborhood violence, and conducted spatial analysis identifying subject homes within 500 ft of a homicide to validate survey measures of neighborhood violence. A multilevel logistic model with clustering by neighborhood estimated odds ratios and 95% confidence intervals. Survey responses about fear of neighborhood violence were strongly predicted by having a home within 500 ft of a homicide. Of 150 caregivers of children with asthma, 49% were aware of a neighborhood violent event, 36% were fearful of neighborhood violence, 22% reported victimization, and 27% had a homicide within 500 ft of the home. In our multilevel model, fear of violence increased the odds of depression by 6.7. Victimization was associated with a possible trend towards depression, and awareness of neighborhood violence did not increase the odds of depression. Based on our findings, personal experience with neighborhood violence may be more important than simple awareness. Health care workers should consider screening for depression among patients exposed to community violence.
doi:10.1016/j.socscimed.2008.02.028
PMCID: PMC2409198  PMID: 18406503
CES-D; Community; Inner-city; Mental health; Survey; USA
6.  Childhood Asthma and Environmental Exposures at Swimming Pools: State of the Science and Research Recommendations 
Environmental Health Perspectives  2008;117(4):500-507.
Objectives
Recent studies have explored the potential for swimming pool disinfection by-products (DBPs), which are respiratory irritants, to cause asthma in young children. Here we describe the state of the science on methods for understanding children’s exposure to DBPs and biologics at swimming pools and associations with new-onset childhood asthma and recommend a research agenda to improve our understanding of this issue.
Data sources
A workshop was held in Leuven, Belgium, 21–23 August 2007, to evaluate the literature and to develop a research agenda to better understand children’s exposures in the swimming pool environment and their potential associations with new-onset asthma. Participants, including clinicians, epidemiologists, exposure scientists, pool operations experts, and chemists, reviewed the literature, prepared background summaries, and held extensive discussions on the relevant published studies, knowledge of asthma characterization and exposures at swimming pools, and epidemiologic study designs.
Synthesis
Childhood swimming and new-onset childhood asthma have clear implications for public health. If attendance at indoor pools increases risk of childhood asthma, then concerns are warranted and action is necessary. If there is no such relationship, these concerns could unnecessarily deter children from indoor swimming and/or compromise water disinfection.
Conclusions
Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists.
doi:10.1289/ehp.11513
PMCID: PMC2679591  PMID: 19440486
aerosols; biologics; childhood asthma; DBPs; disinfection by-products; epidemiology; study design; swimming pools
7.  Common Household Activities are Associated with Elevated Particulate Matter Concentrations in Bedrooms of Inner-City Baltimore Pre-School Children 
Environmental research  2007;106(2):148-155.
Asthma disproportionately affects inner-city, minority children in the U.S. Outdoor pollutant concentrations, including particulate matter (PM), are higher in inner-cities and contribute to childhood asthma morbidity. Although children spend the majority of time indoors, indoor PM exposures have been less extensively characterized. There is a public health imperative to characterize indoor sources of PM within this vulnerable population to enable effective intervention strategies. In the present study, we sought to identify determinants of indoor PM in homes of Baltimore inner-city pre-school children.
Children ages 2-6 (n=300) who were predominantly African-American (90%) and from lower socioeconomic backgrounds were enrolled. Integrated PM2.5 and PM10 air sampling was conducted over a 3-day period in the children’s bedrooms and at a central monitoring site while caregivers completed daily activity diaries. Homes of pre-school children in inner-city Baltimore had indoor PM concentrations that were twice as high as simultaneous outdoor concentrations. The mean indoor PM2.5 and PM10 concentrations were 39.5±34.5 μg/m3 and 56.2±44.8 μg/m3, compared to the simultaneously measured ambient PM2.5 and PM10 (15.6±6.9 and 21.8±9.53 μg/m3, respectively). Common modifiable household activities, especially smoking and sweeping, contributed significantly to higher indoor PM, as did ambient PM concentrations. Open windows were associated with significantly lower indoor PM. Further investigation of the health effects of indoor PM exposure is warranted, as are studies to evaluate the efficacy of PM reduction strategies on asthma health of inner-city children.
doi:10.1016/j.envres.2007.08.012
PMCID: PMC2291550  PMID: 17927974
Particulate matter; Air pollution; Asthma; Pediatric; Urban
8.  In-Home Particle Concentrations and Childhood Asthma Morbidity 
Environmental Health Perspectives  2008;117(2):294-298.
Background
Although outdoor particulate matter (PM) has been linked to mortality and asthma morbidity, the impact of indoor PM on asthma has not been well established.
Objective
This study was designed to investigate the effect of in-home PM on asthma morbidity.
Methods
For a cohort of 150 asthmatic children (2–6 years of age) from Baltimore, Maryland, a technician deployed environmental monitoring equipment in the children’s bedrooms for 3-day intervals at baseline and at 3 and 6 months. Caregivers completed questionnaires and daily diaries during air sampling. Longitudinal data analyses included regression models with generalized estimating equations.
Results
Children were primarily African Americans (91%) from lower socioeconomic backgrounds and spent most of their time in the home. Mean (± SD) indoor PM2.5–10 (PM with aerodynamic diameter 2.5–10 μm) and PM2.5 (aerodynamic diameter < 2.5 μm) concentrations were 17.4 ± 21.0 and 40.3 ± 35.4 μg/m3. In adjusted models, 10-μg/m3 increases in indoor PM2.5–10 and PM2.5 were associated with increased incidences of asthma symptoms: 6% [95% confidence interval (CI), 1 to 12%] and 3% (95% CI, –1 to 7%), respectively; symptoms causing children to slow down: 8% (95% CI, 2 to 14%) and 4% (95% CI, 0 to 9%), respectively; nocturnal symptoms: 8% (95% CI, 1 to 14%) and 6% (95% CI, 1 to 10%), respectively; wheezing that limited speech: 11% (95% CI, 3 to 19%) and 7% (95% CI, 0 to 14%), respectively; and use of rescue medication: 6% (95% CI, 1 to 10%) and 4% (95% CI, 1 to 8%), respectively. Increases of 10 μg/m3 in indoor and ambient PM2.5 were associated with 7% (95% CI, 2 to 11%) and 26% (95% CI, 1 to 52%) increases in exercise-related symptoms, respectively.
Conclusions
Among preschool asthmatic children in Baltimore, increases in in-home PM2.5–10 and PM2.5 were associated with respiratory symptoms and rescue medication use. Increases in in-home and ambient PM2.5 were associated with exercise-related symptoms. Although reducing PM outdoors may decrease asthma morbidity, reducing PM indoors, especially in homes of inner-city children, may lead to improved asthma health.
doi:10.1289/ehp.11770
PMCID: PMC2649234  PMID: 19270802
air pollution; asthma; indoor; particulate matter; pediatric; urban
9.  Rodent Allergen in Los Angeles Inner City Homes of Children with Asthma 
Journal of Urban Health   2007;85(1):52-61.
Recent studies have examined the presence of mouse allergen in inner city children with asthma. Researchers have found high levels of rodent allergen in homes sampled in the northeast and midwest United States, but there has been considerable variation between cities, and there have been few studies conducted in western states. We evaluated the frequency of rodent sightings and detectable mouse allergen and the housing conditions associated with these outcomes in inner city homes in Los Angeles. Two hundred and two families of school children, ages 6–16 living in inner city neighborhoods, participated in the study. Families were predominantly Latino (94%), and Spanish speaking (92%). At study entry, parents completed a home assessment questionnaire, and staff conducted a home evaluation and collected kitchen dust, which was analyzed for the presence of mouse allergen. Fifty-one percent of homes had detectable allergen in kitchen dust. All 33 families who reported the presence of rodents had detectable allergen in the home and were also more likely to have increased levels of allergen compared to those who did not report rodents. Unwashed dishes or food crumbs, lack of a working vacuum, and a caretaker report of a smoker in the home were all significantly associated with a greater risk of rodent sightings or detectable allergen (P < 0.05). Detached homes were significantly more likely to have detectable allergen. The prevalence of allergen is common enough that it may have public health implications for asthmatic children, and detectable allergen was not routinely identified based on rodent sightings. Many of the predictors of rodent allergen are amenable to low-cost interventions that can be integrated with other measures to reduce exposure to indoor allergens.
doi:10.1007/s11524-007-9232-0
PMCID: PMC2430140  PMID: 18004665
Asthma; Mouse allergen; House dust; Rodent; Environment
10.  Indoor Environmental Differences between Inner City and Suburban Homes of Children with Asthma 
We conducted this study to compare environmental exposures in suburban homes of children with asthma to exposures in inner city homes of children with asthma, to better understand important differences of indoor pollutant exposure that might contribute to increased asthma morbidity in the inner city. Indoor PM10, PM2.5, NO2, O3, and airborne and dust allergen levels were measured in the homes of 120 children with asthma, 100 living in inner city Baltimore and 20 living in the surrounding counties. Home conditions and health outcome measures were also compared. The inner city and suburban homes differed in ways that might affect airborne environmental exposures. The inner city homes had more cigarette smoking (67% vs. 5%, p < .001), signs of disrepair (77% vs. 5%, p < .001), and cockroach (64% vs. 0%, p < .001) and mouse (80% vs. 5%, p < .001) infestation. The inner city homes had higher geometric mean (GM) levels (p < .001) of PM10 (47 vs. 18 μg/m3), PM2.5 (34 vs. 8.7 μg/m3), NO2 [19 ppb vs. below detection (BD)], and O3 (1.9 vs. .015 ppb) than suburban homes. The inner city homes had lower GM bedroom dust allergen levels of dust mite (.29 vs. 1.2 μg/g, p = .022), dog (.38 vs. 5.5 μg/g, p < .001) and cat (.75 vs. 2.4 μg/g, p = .039), but higher levels of mouse (3.2 vs. .013 μg/g, p < .001) and cockroach (4.5 vs. .42 U/g, p < .001). The inner city homes also had higher GM airborne mouse allergen levels (.055 vs. .016 ng/m3, p = .002). Compared with the homes of suburban children with asthma, the homes of inner city Baltimore children with asthma had higher levels of airborne pollutants and home characteristics that predispose to greater asthma morbidity.
doi:10.1007/s11524-007-9205-3
PMCID: PMC2219555  PMID: 17551839
Indoor air; Inner city asthma; Particulate matter; Air pollution; Allergens
11.  Effect of environmental intervention on mouse allergen levels in homes of inner-city Boston children with asthma 
Background: Recent studies have suggested that mouse allergen exposure and sensitization are common in urban children with asthma. The effectiveness of environmental intervention in reducing mouse allergen exposure has not been established.
Objective: To evaluate whether environmental intervention of mouse extermination and cleaning results in a reduction in mouse allergen levels.
Methods: Eighteen homes of children with positive mouse allergen skin test results and at least mild persistent asthma in urban Boston, MA, with evidence of mouse infestation or exposure were randomized in a 2:1 ratio (12 intervention and 6 control homes). The intervention homes received an integrated pest management intervention, which consisted of filling holes with copper mesh, vacuuming and cleaning, and using low-toxicity pesticides and traps. Dust samples were collected and analyzed for major mouse allergen (Mus m 1) and cockroach allergen (Bla g 1) at baseline and 1, 3, and 5 months after the intervention was started and compared with control homes.
Results: Mouse allergen levels were significantly decreased compared with control homes by the end of the intervention period at month 5 in the kitchen and bedroom (kitchen intervention, 78.8% reduction; control, 319% increase; P = .02; bedroom intervention, 77.3% reduction; control, 358% increase; P < .01; and living room intervention, 67.6% reduction; control, 32% reduction; P = .07).
Conclusions: Mouse allergen levels were significantly reduced during a 5-month period using an integrated pest management intervention.
PMCID: PMC1360245  PMID: 15104193
12.  Home Indoor Pollutant Exposures among Inner-City Children With and Without Asthma 
Environmental Health Perspectives  2007;115(11):1665-1669.
Background
Evidence for environmental causes of asthma is limited, especially among African Americans. To look for systematic differences in early life domestic exposures between inner-city preschool children with and without asthma, we performed a study of home indoor air pollutants and allergens.
Methods
Children 2–6 years of age were enrolled in a cohort study in East Baltimore, Maryland. From the child’s bedroom, air was monitored for 3 days for particulate matter ≤ 2.5 and ≤ 10 μm in aerodynamic diameter (PM2.5, PM10), nitrogen dioxide, and ozone. Median baseline values were compared for children with (n = 150) and without (n = 150) asthma. Housing characteristics related to indoor air pollution were assessed by caregiver report and home inspection. In addition, indoor allergen levels were measured in settled dust.
Results
Children were 58% male, 91% African American, and 88% with public health insurance. Housing characteristics related to pollutant exposure and bedroom air pollutant concentrations did not differ significantly between asthmatic and control subjects [median: PM2.5, 28.7 vs. 28.5 μg/m3; PM10, 43.6 vs. 41.4 μg/m3; NO2, 21.6 vs. 20.9 ppb; O3, 1.4 vs. 1.8 ppb; all p > 0.05]. Settled dust allergen levels (cat, dust mite, cockroach, dog, and mouse) were also similar in bedrooms of asthmatic and control children.
Conclusions
Exposures to common home indoor pollutants and allergens are similar for inner-city preschool children with and without asthma. Although these exposures may exacerbate existing asthma, this study does not support a causative role of these factors for risk of developing childhood asthma.
doi:10.1289/ehp.10088
PMCID: PMC2072822  PMID: 18008001
African American; air pollution; allergens; asthma; particulate matter; pediatric; urban
14.  How Exposures to Biologics Influence the Induction and Incidence of Asthma 
Environmental Health Perspectives  2006;114(4):620-626.
A number of environmental factors can affect the development and severity of allergy and asthma; however, it can be argued that the most significant inhaled agents that modulate the development of these conditions are biologics. Sensitization to environmental allergens is an important risk factor for the development of asthma. Innate immune responses are often mediated by receptors on mononuclear cells whose primary ligands arise from microorganisms. Many pathogens, especially viruses, target epithelial cells and affect the host immune response to those pathogens. The acquired immune response to an allergen is influenced by the nature of the innate immune system. Products of innate immune responses to microbes promote TH1-acquired responses. In the absence of TH1 responses, TH2 responses can dominate. Central to TH1/TH2 balance is the composition of contaminants that derive from microbes. In this review we examine the biology of the response to allergens, viruses, and bacterial products in the context of the development of allergy and asthma.
doi:10.1289/ehp.8379
PMCID: PMC1440791  PMID: 16581556
asthma; allergy; allergens; endotoxin; respiratory virus; immunoglobulins; tolerance; leukotrienes; neurotrophins
15.  Lessons Learned for the Study of Childhood Asthma from the Centers for Children’s Environmental Health and Disease Prevention Research 
Environmental Health Perspectives  2005;113(10):1430-1436.
The National Children’s Study will address, among other illnesses, the environmental causes of both incident asthma and exacerbations of asthma in children. Seven of the Centers for Children’s Environmental Health and Disease Prevention Research (Children’s Centers), funded by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, conducted studies relating to asthma. The design of these studies was diverse and included cohorts, longitudinal studies of older children, and intervention trials involving asthmatic children. In addition to the general lessons provided regarding the conduct of clinical studies in both urban and rural populations, these studies provide important lessons regarding the successful conduct of community research addressing asthma. They demonstrate that it is necessary and feasible to conduct repeated evaluation of environmental exposures in the home to address environmental exposures relevant to asthma. The time and staff required were usually underestimated by the investigators, but through resourceful efforts, the studies were completed with a remarkably high completion rate. The definition of asthma and assessment of disease severity proved to be complex and required a combination of questionnaires, pulmonary function tests, and biologic samples for markers of immune response and disease activity. The definition of asthma was particularly problematic in younger children, who may exhibit typical asthma symptoms sporadically with respiratory infections without developing chronic asthma. Medications confounded the definition of asthma disease activity, and must be repeatedly and systematically estimated. Despite these many challenges, the Children’s Centers successfully conducted long-term studies of asthma.
doi:10.1289/ehp.7671
PMCID: PMC1281292  PMID: 16203259
asthma; children; Children’s Centers; environmental health; National Children’s Study; pregnancy

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