Bias due to Selection on Live Births in Studies of Environmental Exposures during Pregnancy: A Simulation Study

Background: Studies of the effects of prenatal environmental exposures on postnatal outcomes are particularly vulnerable to live birth bias; i.e., the bias that arises from the necessary restriction of the analysis to live births when that is influenced by both the exposure under study A and unmeasured factors U that also affect the outcome.Objectives: In the context of a recent publication of nitrogen dioxide (NO2) and autism spectrum disorder (ASD) that found an odds ratio (OR) of 0.77 per 5.85 ppb NO2 during pregnancy, we aimed to examine what parameters would be needed to account for this protective association through live birth bias.Methods: We simulated the magnitude of bias under two selection mechanisms and when both mechanisms co-occur, assuming a true null effect. Simulation input parameters were based on characteristics of the original study and a range of plausible values for the prevalence of unmeasured factor U and the ORs for the selection effects (i.e., the effects of NO2 and U on loss and of U on ASD). Each scenario was simulated 1,000 times.Results: We found that the magnitude of bias was small when NO2 and U independently influenced pregnancy loss (collider-stratification without interaction), was stronger when NO2-induced loss preferentially occurred in U=1 (depletion of susceptibles), and was strongest when both mechanisms worked together. For example, ORs of 3.0 for NO2-loss, U-loss, U-ASD, and U prevalence=0.75 yielded NO2-ASD ORs per 5.85 ppb NO2 of 0.95, 0.89, and 0.75 for the three scenarios, respectively. The bias is amplified with multiple Us, yielding ORs as low as 0.51.Discussion: Our simulations illustrate that live birth bias may lead to exposure–outcome associations that are biased downward, where the extent of the bias depends on the fetal selection mechanism, the strength of that selection, and the prevalence of U. https://doi.org/10.1289/EHP7961     

Long-term PM2.5 Exposure and Neurological Hospital Admissions in the Northeastern United States

Background

Long-term exposure to fine particles (particulate matter ≤ 2.5 μm; PM_2.5) has been consistently linked to heart and lung disease. Recently, there has been increased interest in examining the effects of air pollution on the nervous system, with evidence showing potentially harmful effects on neurodegeneration.

Objective

Our objective was to assess the potential impact of long-term PM_2.5 exposure on event time, defined as time to first admission for dementia, Alzheimer’s (AD), or Parkinson’s (PD) diseases in an elderly population across the northeastern United States.

Methods

We estimated the effects of PM_2.5 on first hospital admission for dementia, AD, and PD among all Medicare enrollees ≥ 65 years in 50 northeastern U.S. cities (1999–2010). For each outcome, we first ran a Cox proportional hazards model for each city, adjusting for prior cardiopulmonary-related hospitalizations and year, and stratified by follow-up time, age, sex, and race. We then pooled the city-specific estimates by employing a random effects meta-regression.

Results

We followed approximately 9.8 million subjects and observed significant associations of long-term PM_2.5 city-wide exposure with all three outcomes. Specifically, we estimated a hazard ratio (HR) of 1.08 (95% CI: 1.05, 1.11) for dementia, an HR of 1.15 (95% CI: 1.11, 1.19) for AD, and an HR of 1.08 (95% CI: 1.04, 1.12) for PD admissions per 1-μg/m³ increase in annual PM_2.5 concentrations.

Conclusions

To our knowledge, this is the first study to examine the relationship between long-term exposure to PM_2.5 and time to first hospitalization for common neurodegenerative diseases. We found strong evidence of association for all three outcomes. Our findings provide the basis for further studies, as the implications of such exposures could be crucial to public health.

Citation

Kioumourtzoglou MA, Schwartz JD, Weisskopf MG, Melly SJ, Wang Y, Dominici F, Zanobetti A. 2016. Long-term PM_2.5 exposure and neurological hospital admissions in the northeastern United States. Environ Health Perspect 124:23–29; http://dx.doi.org/10.1289/ehp.1408973     

Differences in self-reported perceived and objective measures of duration and intensity of physical activity for adults in skiing

The effect of physical activity (PA) on health is well documented. The assessment of PA is a valuable and important issue, however, there are several methodological issues among the available methods of measurement that may have implications for the prevention of specific diseases. The purpose of this study was to examine the differences between an objective method of measurement and the subjective estimation of the PA for novice skiers. Seventy-five students aged 19–21 years old with no previous experience in ski participated in this study. Participants wore a heart rate monitor during practice in order to record the exercise intensity. Simultaneously, a trained observer recorded their time on task. A day after the objective measurement, the participants filled a questionnaire in order to estimate their perceived exertion during practice as well as their perceived time on task. The results showed (1) differences between the observed time on task and the perceived recalled time, (2) no differences overall between the recorded and perceived recalled intensity of exercise but when groups were split according to their objective intensity a difference was found for each group respectively. Participants overall had overestimated the time on task, but they had underestimated the intensity of their effort recalled 1 day after their practice. These results raise the question whether a questionnaire as method of measuring PA is reliable, especially when it is used to estimate energy expenditure. However, further studies must be made in order to examine the implications of such a question.     

Occupational formaldehyde and amyotrophic lateral sclerosis

Prior studies have yielded inconsistent evidence regarding the association between formaldehyde exposure and amyotrophic lateral sclerosis (ALS). We conducted a population case–control study in the Danish National Registries on the relationship between occupationally-derived formaldehyde exposure and ALS. Occupational history was obtained from a comprehensive and prospectively recorded pension database of all paid work in Denmark since 1964, and was linked to a job-exposure matrix to derive individual exposure estimates. Each case was matched to 4 age- and sex-matched population controls alive on the date of the case diagnosis via risk set sampling, and odds ratios and confidence intervals (CI) were calculated via conditional logistic regression, adjusting for potential confounders. There were 3650 incident cases of ALS in the Danish National Patient Register from 1982 to 2009. Among controls, 25% were ever employed in jobs with a positive prevalence of formaldehyde exposure. Exposure to formaldehyde was associated with a 1.3-fold increased rate of ALS (95% CI 1.2–1.4). This study suggests that formaldehyde exposure, or employment in formaldehyde-exposed occupations, is related to the risk of ALS.