Methodological issues in studies of air pollution and reproductive health.

In the past decade there have been an increasing number of scientific studies describing possible effects of air pollution on perinatal health. These papers have mostly focused on commonly monitored air pollutants, primarily ozone (O(3)), particulate matter (PM), sulfur dioxide (SO(2)), carbon monoxide (CO), and nitrogen dioxide (NO(2)), and various indices of perinatal health, including fetal growth, pregnancy duration, and infant mortality. While most published studies have found some marker of air pollution related to some types of perinatal outcomes, variability exists in the nature of the pollutants and outcomes associated. Synthesis of the findings has been difficult for various reasons, including differences in study design and analysis. A workshop was held in September 2007 to discuss methodological differences in the published studies as a basis for understanding differences in study findings and to identify priorities for future research, including novel approaches for existing data. Four broad topic areas were considered: confounding and effect modification, spatial and temporal exposure variations, vulnerable windows of exposure, and multiple pollutants. Here we present a synopsis of the methodological issues and challenges in each area and make recommendations for future study. Two key recommendations include: (1) parallel analyses of existing data sets using a standardized methodological approach to disentangle true differences in associations from methodological differences among studies; and (2) identification of animal studies to inform important mechanistic research gaps. This work is of critical public health importance because of widespread exposure and because perinatal outcomes are important markers of future child and adult health.