1274The application of simulation to quantifying the influence of bias in reproductive and perinatal epidemiology

Background Establishing causal effects in reproductive and perinatal epidemiology is challenging due to the many selection and attrition processes from preconception to the postnatal period. Further challenging, is the potential for the misclassification of exposures, outcomes and confounders, contributing to measurement error. The application of simulation enables the illustration and quantification of the magnitude of various types of bias commonly found in observational studies. Methods A systematic search was conducted in PubMed, Medline, Embase, CINAHL and Scopus in August 2020. A gray literature search of Google and Google Scholar, followed by a search of the reference lists of included studies, was undertaken. Results Thirty-nine studies, covering information (n = 14), selection (n = 14), confounding (n = 9), protection (n = 1), and attenuation bias (n = 1) were identified. The methods of simulating data and reporting of results varied, with more recent studies including causal diagrams. Few studies included code for replication. Although there has been an increasing application of simulation in reproductive and perinatal epidemiology since 2015, overall this remains an underexplored area. Conclusions The studies demonstrated effectiveness in the quantification of multiple types of bias using simulation. The limited use implies that further effort is required to increase knowledge of the application of simulation, which will thereby improve causal interpretation in reproductive and perinatal studies. Key messages Practical guidance for researchers is required in the development, analysis and reporting of simulation methods for the quantification of bias.

Addressing special cases of bias that frequently occur in perinatal epidemiology

The epidemiologic study of pregnancy and birth outcomes may be hindered by several unique and challenging issues. Pregnancy is a time-limited period in which severe cohort attrition takes place between conception and birth and adverse outcomes are complex and multi-factorial. Biases span those familiar to epidemiologists: selection, confounding and information biases. Specific challenges include conditioning on potential intermediates, how to treat race/ethnicity, and influential windows of prolonged, seasonal and potentially time-varying exposures. Researchers studying perinatal outcomes should be cognizant of the potential pitfalls due to these factors and address their implications with respect to formulating questions of interest, choice of an appropriate analysis approach and interpretations of findings given assumptions. In this article, we catalogue some of the more important potential sources of bias in perinatal epidemiology that have more recently gained attention in the literature, provide the epidemiologic context behind each issue and propose practices for dealing with each issue to the extent possible.

Perinatal epidemiology: Issues, challenges, and potential solutions

Perinatal epidemiology research is concerned with identifying the effects of events during pregnancy on pregnancy outcomes that include maternal, fetal, and neonatal health outcomes. Randomized trials in perinatal research face many challenges, including randomization difficulties, ethical considerations, and inadequate statistical power due to the small number of subjects eligible for participation. For these reasons, most epidemiological studies conducted in this research field are observational and include different types of bias. This review describes the key methodological difficulties in the design and analysis of randomized and observational studies in perinatal epidemiology, and provides potential corrective approaches.