Matthew J. Strickland

Prevalence of Congenital Heart Defects in Metropolitan Atlanta, 1998-2005

OBJECTIVE To determine an accurate estimate of the prevalence of congenital heart defects (CHD) using current standard diagnostic modalities. STUDY DESIGN We obtained data on infants with CHD delivered during 1998 to 2005 identified by the Metropolitan Atlanta Congenital Defects Program, an active, population-based, birth defects surveillance system. Physiologic shunts in infancy and shunts associated with prematurity were excluded. Selected infant and maternal characteristics of the cases were compared with those of the overall birth cohort. RESULTS From 1998 to 2005 there were 398 140 births, of which 3240 infants had CHD, for an overall prevalence of 81.4/10 000 births. The most common CHD were muscular ventricular septal defect, perimembranous ventricular septal defect, and secundum atrial septal defect, with prevalence of 27.5, 10.6, and 10.3/10 000 births, respectively. The prevalence of tetralogy of Fallot, the most common cyanotic CHD, was twice that of transposition of the great arteries (4.7 vs 2.3/10 000 births). Many common CHD were associated with older maternal age and multiple-gestation pregnancy; several were found to vary by sex. CONCLUSIONS This study, using a standardized cardiac nomenclature and classification, provides current prevalence estimates of the various CHD subtypes. These estimates can be used to assess variations in prevalence across populations, time, or space.

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.

Short-term associations between ambient air pollutants and pediatric asthma emergency department visits.

RATIONALE Certain outdoor air pollutants cause asthma exacerbations in children. To advance understanding of these relationships, further characterization of the dose-response and pollutant lag effects are needed, as are investigations of pollutant species beyond the commonly measured criteria pollutants. OBJECTIVES Investigate short-term associations between ambient air pollutant concentrations and emergency department visits for pediatric asthma. METHODS Daily counts of emergency department visits for asthma or wheeze among children aged 5 to 17 years were collected from 41 Metropolitan Atlanta hospitals during 1993-2004 (n = 91,386 visits). Ambient concentrations of gaseous pollutants and speciated particulate matter were available from stationary monitors during this time period. Rate ratios for the warm season (May to October) and cold season (November to April) were estimated using Poisson generalized linear models in the framework of a case-crossover analysis. MEASUREMENTS AND MAIN RESULTS Both ozone and primary pollutants from traffic sources were associated with emergency department visits for asthma or wheeze; evidence for independent effects of ozone and primary pollutants from traffic sources were observed in multipollutant models. These associations tended to be of the highest magnitude for concentrations on the day of the emergency department visit and were present at relatively low ambient concentrations. CONCLUSIONS Even at relatively low ambient concentrations, ozone and primary pollutants from traffic sources independently contributed to the burden of emergency department visits for pediatric asthma.

Meeting Report: Atmospheric Pollution and Human Reproduction

Background There is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration. Objectives The objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research. Discussion Participants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time–activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case–control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed. Conclusions To make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies.

The importance of nomenclature for congenital cardiac disease: implications for research and evaluation.

BACKGROUND Administrative databases are often used for congenital cardiac disease research and evaluation, with little validation of the accuracy of the diagnostic codes. METHODS Metropolitan Atlanta Congenital Defects Program surveillance records were reviewed and classified using a version of the International Pediatric and Congenital Cardiac Code. Using this clinical nomenclature as the referent, we report the sensitivity and false positive fraction (1 - positive predictive value) of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for tetralogy of Fallot, transposition of the great arteries, and hypoplastic left heart syndrome. RESULTS We identified 4918 infants and foetuses with congenital cardiac disease from the surveillance records. Using only the International Classification of Diseases diagnosis codes, there were 280 records with tetralogy, 317 records with transposition, and 192 records with hypoplastic left heart syndrome. Based on the International Pediatric and Congenital Cardiac Code, 330 records were classified as tetralogy, 163 records as transposition, and 179 records as hypoplastic left heart syndrome. The sensitivity of International Classification of Diseases diagnosis codes was 83% for tetralogy, 100% for transposition, and 95% for hypoplastic left heart syndrome. The false positive fraction was 2% for tetralogy, 49% for transposition, and 11% for hypoplastic left heart syndrome. CONCLUSIONS Analyses based on International Classification of Diseases diagnosis codes may have substantial misclassification of congenital heart disease. Isolating the major defect is difficult, and certain codes do not differentiate between variants that are clinically and developmentally different.

Maternal Smoking and Congenital Heart Defects in the Baltimore-Washington Infant Study

OBJECTIVE: We investigated associations between maternal cigarette smoking during the first trimester and the risk of congenital heart defects (CHDs) among the infants. METHODS: The Baltimore-Washington Infant Study was the first population-based case-control study of CHDs conducted in the United States. Case and control infants were enrolled during the period 1981–1989. We excluded mothers with overt pregestational diabetes and case mothers whose infants had noncardiac anomalies (with the exception of atrioventricular septal defects with Down syndrome) from the analysis, which resulted in 2525 case and 3435 control infants. Self-reported first-trimester maternal cigarette consumption was ascertained via an in-person interview after delivery. Associations for 26 different groups of CHDs with maternal cigarette consumption were estimated by using logistic regression models. Odds ratios (ORs) corresponded to a 20-cigarette-per-day increase in consumption. RESULTS: We observed statistically significant positive associations between self-reported first-trimester maternal cigarette consumption and the risk of secundum-type atrial septal defects (OR: 1.36 [95% confidence interval (CI): 1.04–1.78]), right ventricular outflow tract defects (OR: 1.32 [95% CI: 1.06–1.65]), pulmonary valve stenosis (OR: 1.35 [95% CI: 1.05–1.74]), truncus arteriosus (OR: 1.90 [95% CI: 1.04–3.45]), and levo-transposition of the great arteries (OR: 1.79 [95% CI: 1.04–3.10]). A suggestive association was observed for atrioventricular septal defects among infants without Down syndrome (OR: 1.50 [95% CI: 0.99–2.29]). CONCLUSIONS: These findings add to the existing body of evidence that implicates first-trimester maternal cigarette smoking as a modest risk factor for select CHD phenotypes.

Reactive Oxygen Species Generation Linked to Sources of Atmospheric Particulate Matter and Cardiorespiratory Effects.

Exposure to atmospheric fine particulate matter (PM2.5) is associated with cardiorespiratory morbidity and mortality, but the mechanisms are not well understood. We assess the hypothesis that PM2.5 induces oxidative stress in the body via catalytic generation of reactive oxygen species (ROS). A dithiothreitol (DTT) assay was used to measure the ROS-generation potential of water-soluble PM2.5. Source apportionment on ambient (Atlanta, GA) PM2.5 was performed using the chemical mass balance method with ensemble-averaged source impact profiles. Linear regression analysis was used to relate PM2.5 emission sources to ROS-generation potential and to estimate historical levels of DTT activity for use in an epidemiologic analysis for the period of 1998-2009. Light-duty gasoline vehicles (LDGV) exhibited the highest intrinsic DTT activity, followed by biomass burning (BURN) and heavy-duty diesel vehicles (HDDV) (0.11 ± 0.02, 0.069 ± 0.02, and 0.052 ± 0.01 nmol min(-1) μg(-1)source, respectively). BURN contributed the largest fraction to total DTT activity over the study period, followed by LDGV and HDDV (45, 20, and 14%, respectively). DTT activity was more strongly associated with emergency department visits for asthma/wheezing and congestive heart failure than PM2.5. This work provides further epidemiologic evidence of a biologically plausible mechanism, that of oxidative stress, for associations of adverse health outcomes with PM2.5 mass and supports continued assessment of the utility of the DTT activity assay as a measure of ROS-generating potential of particles.

Seasonality of birth and implications for temporal studies of preterm birth.

Background: A strength of time-series analyses is the inherent control of individual-level risk factors that do not vary temporally. However, in studies of adverse pregnancy outcomes, risk factors considered time-invariant at the individual level may vary seasonally when aggregated into a pregnancy risk set. To illustrate, we describe the seasonal patterns of birth in Atlanta and demonstrate how these patterns could lead to confounding in time-series studies of seasonally-varying exposures and preterm birth. Methods: The study cohort included all births in 20-county metropolitan Atlanta delivered during the period 1994–2004 (n = 715,875). We assessed the seasonal patterns of estimated conception and birth for the full cohort and for subgroups stratified by sociodemographic factors. Based on the observed patterns, we quantified the degree of potential confounding created by (1) differences in the gestational age distribution in the risk set across calendar months and (2) differences in the sociodemographic composition of the risk set across calendar months. Results: The overall seasonal pattern of birth was characterized by a peak in August–September and troughs in April–May and November–January. Seasonal patterns differed among racial and ethnic groups, maternal education levels, and marital status. As a consequence of these seasonal patterns, systematic seasonal differences in the gestational age distribution and the sociodemographic composition of the risk set led to differences in expected rates of preterm birth across calendar months. Conclusions: Time-series investigations of seasonally-varying exposures and adverse pregnancy outcomes should consider the potential for bias due to seasonal heterogeneity in the risk set.

Impact of exposure measurement error in air pollution epidemiology: effect of error type in time-series studies

BackgroundTwo distinctly different types of measurement error are Berkson and classical. Impacts of measurement error in epidemiologic studies of ambient air pollution are expected to depend on error type. We characterize measurement error due to instrument imprecision and spatial variability as multiplicative (i.e. additive on the log scale) and model it over a range of error types to assess impacts on risk ratio estimates both on a per measurement unit basis and on a per interquartile range (IQR) basis in a time-series study in Atlanta.MethodsDaily measures of twelve ambient air pollutants were analyzed: NO2, NOx, O3, SO2, CO, PM10 mass, PM2.5 mass, and PM2.5 components sulfate, nitrate, ammonium, elemental carbon and organic carbon. Semivariogram analysis was applied to assess spatial variability. Error due to this spatial variability was added to a reference pollutant time-series on the log scale using Monte Carlo simulations. Each of these time-series was exponentiated and introduced to a Poisson generalized linear model of cardiovascular disease emergency department visits.ResultsMeasurement error resulted in reduced statistical significance for the risk ratio estimates for all amounts (corresponding to different pollutants) and types of error. When modelled as classical-type error, risk ratios were attenuated, particularly for primary air pollutants, with average attenuation in risk ratios on a per unit of measurement basis ranging from 18% to 92% and on an IQR basis ranging from 18% to 86%. When modelled as Berkson-type error, risk ratios per unit of measurement were biased away from the null hypothesis by 2% to 31%, whereas risk ratios per IQR were attenuated (i.e. biased toward the null) by 5% to 34%. For CO modelled error amount, a range of error types were simulated and effects on risk ratio bias and significance were observed.ConclusionsFor multiplicative error, both the amount and type of measurement error impact health effect estimates in air pollution epidemiology. By modelling instrument imprecision and spatial variability as different error types, we estimate direction and magnitude of the effects of error over a range of error types.

Air Pollution and Acute Respiratory Infections Among Children 0–4 Years of Age: An 18-Year Time-Series Study

Upper and lower respiratory infections are common in early childhood and may be exacerbated by air pollution. We investigated short-term changes in ambient air pollutant concentrations, including speciated particulate matter less than 2.5 μm in diameter (PM2.5), in relation to emergency department (ED) visits for respiratory infections in young children. Daily counts of ED visits for bronchitis and bronchiolitis (n = 80,399), pneumonia (n = 63,359), and upper respiratory infection (URI) (n = 359,246) among children 0-4 years of age were collected from hospitals in the Atlanta, Georgia, area for the period 1993-2010. Daily pollutant measurements were combined across monitoring stations using population weighting. In Poisson generalized linear models, 3-day moving average concentrations of ozone, nitrogen dioxide, and the organic carbon fraction of particulate matter less than 2.5 μm in diameter (PM2.5) were associated with ED visits for pneumonia and URI. Ozone associations were strongest and were observed at low (cold-season) concentrations; a 1-interquartile range increase predicted a 4% increase (95% confidence interval: 2%, 6%) in visits for URI and an 8% increase (95% confidence interval: 4%, 13%) in visits for pneumonia. Rate ratios tended to be higher in the 1- to 4-year age group compared with infants. Results suggest that primary traffic pollutants, ozone, and the organic carbon fraction of PM2.5 exacerbate upper and lower respiratory infections in early life, and that the carbon fraction of PM2.5 is a particularly harmful component of the ambient particulate matter mixture.