Maternal and Child HealthThe Effect of Prenatal Treatments on Offspring Events in the Presence of Competing Events An Application to a Randomized Trial of Fertility TherapiesChiu, Yu-Hana,b; Stensrud, Mats J.a; Dahabreh, Issa J.a,c,d; Rinaudo, Paoloe; Diamond, Michael P.f; Hsu, Johnb,g; Hernández-Díaz, Soniaa; Hernán, Miguel A.a,h,iAuthor Information From the aDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA bMongan Institute, Massachusetts General Hospital, Boston, MA cDepartment of Health Services Policy and Practice, Center for Evidence Synthesis in Health, School of Public Health, Brown University, Providence, RI dDepartment of Epidemiology, School of Public Health, Brown University, Providence, RI; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA eCenter for Reproductive Health, University of California, San Francisco, CA fDepartment of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA gDepartment of Health Care Policy, Harvard Medical School, Boston, MA hDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA iHarvard-MIT Division of Health Sciences and Technology, Boston, MA. Submitted June 7, 2019; accepted May 29, 2020. This work was supported by National Institute of Child Health and Human Development Grant R01HD088393. Dr. Diamond reports serving on Board of the Directors and being a stockholder of Advanced Reproductive Care, outside the submitted work. The other authors have no conflicts to report. Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). Data availability: The data were obtained from NICHD Data and Specimen Hub (DASH). Data access can be requested from the website https://dash.nichd.nih.gov/. SAS codes are available at https://github.com/hanchiu/competingRisk Editors’ note: A related article appears on p. 644. Correspondence: Yu-Han Chiu, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115. E-mail: firstname.lastname@example.org. Epidemiology: September 2020 - Volume 31 - Issue 5 - p 636-643 doi: 10.1097/EDE.0000000000001222 Buy SDC Metrics Abstract When studying the effect of a prenatal treatment on events in the offspring, failure to produce a live birth is a competing event for events in the offspring. A common approach to handle this competing event is reporting both the treatment-specific probabilities of live births and of the event of interest among live births. However, when the treatment affects the competing event, the latter probability cannot be interpreted as the causal effect among live births. Here we provide guidance for researchers interested in the effects of prenatal treatments on events in the offspring in the presence of the competing event “no live birth.” We review the total effect of treatment on a composite event and the total effect of treatment on the event of interest. These causal effects are helpful for decision making but are agnostic about the pathways through which treatment affects the event of interest. Therefore, based on recent work, we also review three causal effects that explicitly consider the pathways through which treatment may affect the event of interest in the presence of competing events: the direct effect of treatment on the event of interest under an intervention to eliminate the competing event, the separable direct and indirect effects of treatment on the event of interest, and the effect of treatment in the principal stratum of those who would have had a live birth irrespective of treatment choice. As an illustrative example, we use a randomized trial of fertility treatments and risk of neonatal complications. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.