Time-Varying Exposures and Miscarriage: A Comparison of Statistical Models Through Simulation

Alexandra C. Sundermann, James C. Slaughter, Digna R. Velez Edwards, Katherine E. Hartmann

Research output: Contribution to journalArticlepeer-review


Epidemiologists face a unique challenge in measuring risk relationships involving time-varying exposures in early pregnancy. Each week in early pregnancy is distinct in its contribution to fetal development, and this period is commonly characterized by shifts in maternal behavior and, consequently, exposures. In this simulation study, we used alcohol as an example of an exposure that often changes during early pregnancy and miscarriage as an outcome affected by early exposures. Data on alcohol consumption patterns from more than 5,000 women in the Right From the Start cohort study (United States, 2000-2012) informed measures of the prevalence of alcohol exposure, the distribution of gestational age at cessation of alcohol use, and the likelihood of miscarriage by week of gestation. We then compared the bias and precision of effect estimates and statistical power from 5 different modeling approaches in distinct simulated relationships. We demonstrate how the accuracy and precision of effect estimates depended on alignment between model assumptions and the underlying simulated relationship. Approaches that incorporated data about patterns of exposure were more powerful and less biased than simpler models when risk depended on timing or duration of exposure. To uncover risk relationships in early pregnancy, it is critical to carefully define the role of exposure timing in the underlying causal hypothesis.

Original languageEnglish
Pages (from-to)790-799
Number of pages10
JournalAmerican Journal of Epidemiology
Issue number5
StatePublished - May 1 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.


  • alcohol consumption
  • bias
  • data analysis
  • maternal exposure
  • pregnancy
  • spontaneous abortion
  • statistical models

ASJC Scopus subject areas

  • General Medicine


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