Using a Mixture of Bivariate Regression Model to Explore Heterogeneity of Effects of Use of Inhaled Corticosteroids on Gestational Age and Birthweight among Pregnant Women with Asthma

Abstract

Asthma is a heterogeneous disease, and responses to asthma medications vary noticeably among patients. A substantively oriented objective of this study was to explore the potential heterogeneous effects of maternal inhaled corticosteroids (ICS) exposure on gestational age (GA) at delivery and birthweight (BW) using a cohort of 6,197 pregnancies from women with asthma (Quebec, Canada, 1998-2008). A methodologically oriented objective was to comprehensively describe the application of a Bayesian two-component mixture of bivariate regressions to address this issue and estimate the effects of ICS on GA and BW jointly. Based on proposed model, no association between ICS and GA/BW was found for a large proportion of asthmatic pregnancies. However, a positive association between ICS exposure and GA/BW was revealed in a small subset of pregnancies mainly formed of preterm and low-birthweight infants. A novel application of this model was also subsequently performed using BW z-score instead of BW as outcome variable. In conclusion, the studied mixture of bivariate regressions was useful to detect heterogeneity of ICS effect on GA and BW in our population of women with asthma; these analyses pave the way for analogous uses of this model for general assessment of exposure effect heterogeneity for these perinatal outcomes.