Sensitivity analysis for live birth bias in the Ulaanbaatar Gestation and Air Pollution Research study

Abstract

Background: The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a randomized controlled trial of the effects of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth and child health outcomes. A challenge with the study is that the outcome variables cannot be measured in the absence of a live birth. Thus pregnancy loss is a competing event for the outcome variables that can obscure the intervention-outcome relationship. This phenomenon is called “live birth bias” in the epidemiological literature, and it is an example of selection bias due to adjustment for variables affected by previous exposure. Methods: In this investigation, we reanalyzed data from the UGAAR study and examined the impacts of the intervention on three health outcomes: preterm birth (PTB), birth weight, and full-scale IQ (FSIQ) measured with the Wechsler Preschool and Primary Scale of Intelligence III when children were four years old, while accounting for live birth bias. Specifically, we used a novel multiple imputation approach to simulate scenarios in which pregnancy losses had instead been born alive and experienced a range of health outcomes. Results: After accounting for live birth bias, the association between the intervention and PTB diminished. Additionally, the magnitude of intervention effect on birth weight and FSIQ increased. FSIQ was less sensitive to live birth bias than birth weight. Conclusion: We introduced a novel analysis approach to examine the role of live birth bias, and the findings will be useful in environmental epidemiology studies of birth cohorts.