Daniel Wartenberg

Spatial Epidemiology: Current Approaches and Future Challenges

Spatial epidemiology is the description and analysis of geographic variations in disease with respect to demographic, environmental, behavioral, socioeconomic, genetic, and infectious risk factors. We focus on small-area analyses, encompassing disease mapping, geographic correlation studies, disease clusters, and clustering. Advances in geographic information systems, statistical methodology, and availability of high-resolution, geographically referenced health and environmental quality data have created unprecedented new opportunities to investigate environmental and other factors in explaining local geographic variations in disease. They also present new challenges. Problems include the large random component that may predominate disease rates across small areas. Though this can be dealt with appropriately using Bayesian statistics to provide smooth estimates of disease risks, sensitivity to detect areas at high risk is limited when expected numbers of cases are small. Potential biases and confounding, particularly due to socioeconomic factors, and a detailed understanding of data quality are important. Data errors can result in large apparent disease excess in a locality. Disease cluster reports often arise nonsystematically because of media, physician, or public concern. One ready means of investigating such concerns is the replication of analyses in different areas based on routine data, as is done in the United Kingdom through the Small Area Health Statistics Unit (and increasingly in other European countries, e.g., through the European Health and Environment Information System collaboration). In the future, developments in exposure modeling and mapping, enhanced study designs, and new methods of surveillance of large health databases promise to improve our ability to understand the complex relationships of environment to health.

Maternal exposure to particulate air pollution and term birth weight : a multi-country evaluation of effect and heterogeneity

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent. Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association. Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates. Results: In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (–8.9 g; 95% CI: –13.2, –4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations. Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.

Current practices in spatial analysis of cancer data: mapping health statistics to inform policymakers and the public

BackgroundTo communicate population-based cancer statistics, cancer researchers have a long tradition of presenting data in a spatial representation, or map. Historically, health data were presented in printed atlases in which the map producer selected the content and format. The availability of geographic information systems (GIS) with comprehensive mapping and spatial analysis capability for desktop and Internet mapping has greatly expanded the number of producers and consumers of health maps, including policymakers and the public.Because health maps, particularly ones that show elevated cancer rates, historically have raised public concerns, it is essential that these maps be designed to be accurate, clear, and interpretable for the broad range of users who may view them. This article focuses on designing maps to communicate effectively. It is based on years of research into the use of health maps for communicating among public health researchers.ResultsThe basics for designing maps that communicate effectively are similar to the basics for any mode of communication. Tasks include deciding on the purpose, knowing the audience and its characteristics, choosing a media suitable for both the purpose and the audience, and finally testing the map design to ensure that it suits the purpose with the intended audience, and communicates accurately and effectively. Special considerations for health maps include ensuring confidentiality and reflecting the uncertainty of small area statistics. Statistical maps need to be based on sound practices and principles developed by the statistical and cartographic communities.ConclusionThe biggest challenge is to ensure that maps of health statistics inform without misinforming. Advances in the sciences of cartography, statistics, and visualization of spatial data are constantly expanding the toolkit available to mapmakers to meet this challenge. Asking potential users to answer questions or to talk about what they see is still the best way to evaluate the effectiveness of a specific map design.

Ambient air pollutant concentrations during pregnancy and the risk of fetal growth restriction

Background: Previous studies of air pollution and birth outcomes have not evaluated whether complicated pregnancies might be susceptible to the adverse effects of air pollution. It was hypothesised that trimester mean pollutant concentrations could be associated with fetal growth restriction, with larger risks among complicated pregnancies. Methods: A multiyear linked birth certificate and maternal/newborn hospital discharge dataset of singleton, term births to mothers residing in New Jersey at the time of birth, who were white (non-Hispanic), African–American (non-Hispanic) or Hispanic was used. Very small for gestational age (VSGA) was defined as a fetal growth ratio <0.75, small for gestational age (SGA) as ⩾0.75 and <0.85, and ‘reference’ births as ⩾0.85. Using polytomous logistic regression, associations between mean pollutant concentrations during the first, second and third trimesters and the risks of SGA/VSGA were examined, as well as effect modification of these associations by several pregnancy complications. Results: Significantly increased risk of SGA was associated with first and third trimester PM2.5 (particulate matter <2.5 μm in aerodynamic diameter), and increased risk of VSGA associated with first, second and third trimester nitrogen dioxide (NO2) concentrations. Pregnancies complicated by placental abruption and premature rupture of the membrane had ∼two- to fivefold greater excess risks of SGA/VSGA than pregnancies not complicated by these conditions, although these estimates were not statistically significant. Conclusions: These findings suggest that ambient air pollution, perhaps specifically traffic emissions during early and late pregnancy and/or factors associated with residence near a roadway during pregnancy, may affect fetal growth. Further, pregnancy complications may increase susceptibility to these effects in late pregnancy.

Symptom patterns among Gulf War Registry veterans

OBJECTIVES We identify symptom patterns among veterans who believe they suffer from Gulf War-related illnesses and characterize groups of individuals with similar patterns. METHODS A mail survey was completed by 1161 veterans drawn from the Gulf War Health Registry. RESULTS An exploratory factor analysis revealed 4 symptom factors. A K-means cluster analysis revealed 2 groups: (1) veterans reporting good health and few moderate/severe symptoms, and (2) veterans reporting fair/poor health and endorsing an average of 37 symptoms, 75% as moderate/severe. Those in Cluster 2 were more likely to report having 1 or more of 24 medical conditions. CONCLUSIONS These findings are consistent with previous investigations of symptom patterns in Gulf War veterans. This multisymptom illness may be more fully characterized by the extent, breadth, and severity of symptoms reported.

Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application

The Children’s Post-Pesticide Application Exposure Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for 2 weeks after a routine professional crack-and-crevice application and to determine the amount of the chlorpyrifos that is absorbed by a child living within the home. Ten residential homes with a 2- to 5-year-old child in each were selected for study, and the homes were treated with chlorpyrifos. Pesticide measurements were made from the indoor air, indoor surfaces, and plush toys. In addition, periodic morning urine samples were collected from each of the children throughout the 2-week period. We analyzed the urine samples for 3,5,6-trichloropyridinol, the primary urinary metabolite of chlorpyrifos, and used the results to estimate the children’s absorbed dose. Average chlorpyrifos levels in the indoor air and surfaces were 26 (pretreatment)/120 (posttreatment) ng/m3 and 0.48 (pretreatment)/2.8 (posttreatment) ng/cm2, respectively, reaching peak levels between days 0 and 2; subsequently, concentrations decreased throughout the 2-week period. Chlorpyrifos in/on the plush toys ranged from 7.3 to 1,949 ng/toy postapplication, with concentrations increasing throughout the 2-week period, demonstrating a cumulative adsorption/absorption process indoors. The daily amount of chlorpyrifos estimated to be absorbed by the CPPAES children postapplication ranged from 0.04 to 4.8 μg/kg/day. During the 2 weeks after the crack-and-crevice application, there was no significant increase in the amount of chlorpyrifos absorbed by the CPPAES children.

Three dimensional staging of breast cancer.

SummaryPurposeBreast cancers are three dimensional solids but very few are spherical. We hypothesized that calculations based on the greatest diameter would not accurately reflect tumor volume and that three dimensional measurements would affect tumor staging.Materials and methods: 165 invasive carcinomas measuring 2.5 cm or less and having three measured diameters (a ≥ b ≥ c) noted were evaluated. Tumor volume was calculated using four geometric models: the spherical 4/3π (a/2)3, prolate spheroid 4/3π (a/2) (c/2)2, oblate spheroid 4/3π (a/2)2 (b/2), and ellipsoid 4/3π (a/2 × b/2 × c/2). The ellipsoid correctly determined the volume for any tumor shape. All cases were stratified according to the TNM staging system. Differences in mean volume calculated as a sphere and ellipsoid for each tumor subclass were analyzed using Students T test. The reclassification of tumors by the ellipsoid formula was determined.Results: Seventy-six (46.1%) had tumors with three different diameters while only six (3.6%) were true spheres having three identical diameters. Mean tumor volume analysis of T1a, T1b, T1c, and T2 tumors demonstrated a statistically significant overestimation of volume when utilizing the sphere formula instead of the ellipsoid formula (p < 0.05). The differences in volume were more dramatic as the diameters increased. A total of 41 tumors were moved into smaller T subclasses including 10 node positive patients.Conclusions: Tumor volume analysis demonstrates that use of only the greatest diameter poorly reflects the true volume of a lesion and consistently overestimates volume. The ellipsoid formula accurately calculates volume for these three dimensional tumors and when utilized has significant relevance to staging small invasive breast cancers.

Oral cleft defects and maternal exposure to ambient air pollutants in New Jersey

BACKGROUND Evidence links exposure to ambient air pollution during pregnancy, particularly gaseous pollutants and particulate matter, to an increased risk of adverse reproductive outcomes though the results for birth defects have been inconsistent. METHODS We compared estimated exposure to ambient air pollutants during early pregnancy among mothers of children with oral cleft defects (cases) to that among mothers of controls, adjusting for available risk factors from birth certificates. We obtained ambient air pollutant data from air monitoring sites in New Jersey for carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO(2)), particulate matter <10 microm in aerodynamic diameter (PM10) and particulate matter <2.5 microm in aerodynamic diameter (PM2.5). We used values from the nearest monitor (within 40 km of the residence at birth) for controls, cleft lip with or without cleft palate (CLP) and cleft palate only (CPO). RESULTS Based on logistic regression analyses for each contaminant and all contaminants together, there were no consistent elevated associations between selected air pollutants and cleft malformations. Quartile of CO concentration showed a consistent protective association with CPO (p < 0.01). For other contaminants, confidence intervals (95%) of the odds ratios for some quartiles excluded one. CLP showed limited evidence of an association with increasing SO(2) exposure while CPO showed weak associations with increasing O3 exposure. CONCLUSION There was little consistent evidence associating cleft malformations with maternal exposure to ambient air pollutants. Evaluating particular pollutants or disease subgroups would require more detailed measurement of exposure and classification of cleft defects.

The International Collaboration on Air Pollution and Pregnancy Outcomes: initial results.

Background: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design. Objectives: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach. Methods: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter ≤ 10 μm in aerodynamic diameter (PM10) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables. Results: Among locations with data for the PM10 analysis, ORs estimating the relative risk of term LBW associated with a 10-μg/m3 increase in average PM10 concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30–1.35] for the Netherlands to 1.15 (95% CI, 0.61–2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations. Conclusions: Variability in PM10–LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.

The importance of histologic type on breast cancer survival

Breast cancer is a morphologically and genetically heterogeneous disease. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute provides the large number of cases necessary to study individual histologic types of female invasive breast cancer that for practical reasons are otherwise unattainable. Attention was specifically focused on 4082 cases of mucinous adenocarcinoma and 139,154 cases of infiltrating duct carcinoma identified for the years 1973-1990. Life table analyses were conducted to compare survival by histologic type using death due to breast cancer as the outcome; Cox proportional hazards analysis was used to adjust for important covariates. Findings were that women diagnosed with mucinous adenocarcinoma have a rate of mortality due to breast cancer that is 0.38 that of the rate of women diagnosed with infiltrating duct carcinoma (95% confidence interval 0.34-0.42). We conclude that histologic type is important to consider in the prognosis and treatment of women diagnosed with breast cancer.