Maternal gestational exposure to di-butyl phthalate (DBP) from medications and birthweight of progeny

Abstract

TPS 742: Adverse birth outcomes 1, Exhibition Hall, Ground floor, August 27, 2019, 3:00 PM - 4:30 PM Background: Birthweight, an important predictor of long-term morbidity, is affected by several environmental factors. Thus, birthweight can be used as an early indicator for adverse health conditions that are linked with suboptimal in-utero development, including those possibly caused by gestational exposures to environmental toxicants. Di-butyl phthalate (DBP) is used as an excipient in some mesalamine medications prescribed for treatment of inflammatory bowel disease (IBD), leading to extremely high exposures among patients. DBP is an endocrine disruptor, yet its effects on birthweight have not been conclusively elucidated. We evaluated whether maternal gestational use of DBP-containing medications is linked with alterations in birthweight of progeny. Methods: We conducted a population-based analysis of 546,432 singletons born in 1999-2015 in a large Israeli health fund. Medication dispensing, birthweight, and demographic data were abstracted from electronic medical records. Analyses were performed using generalized estimating equation (GEE) and generalized additive linear regression models. Results: 2,276 singletons were exposed to mesalamine medications during gestation, of which 162 were exposed to a mesalamine formulation with DBP. In models adjusted for sociodemographic factors and other known predictors of birthweight, maternal gestational use of DBP-containing mesalamine formulation was associated with a reduction of 132.0g [95% C.I.:-240.8,-23.1] in birthweight, whereas use of non-DBP mesalamine formulations was associated with a decrease of 77.8g [95% C.I.:-104.7,-51.0] as compared to singletons from mothers not treated with mesalamine. Additional adjustment for gestational age did not alter results. Conclusions: Maternal gestational use of DBP-containing mesalamine medications was associated with a reduction in birthweight, although some of the effect is likely attributed to the underlying IBD. Subsequent analyses will examine longer-term adverse developmental outcomes possibly associated with gestational pharmaceutical exposure to DBP and other phthalate congeners. Future studies should evaluate whether similar findings are observed with less extreme exposures that more closely reflect background environmental levels.