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Prenatal Exposure to Organophosphate Esters and Cognitive Development in Young Children in the Pregnancy, Infection, and Nutrition Study


Doherty, Brett T.; Hoffman, Kate; Keil, Alexander P.; Engel, Stephanie M.; Stapleton, Heather M.; Goldman, Barbara Davis; Olshan, Andrew F.; & Daniels, Julie L. (2019). Prenatal Exposure to Organophosphate Esters and Cognitive Development in Young Children in the Pregnancy, Infection, and Nutrition Study. Environmental Research, 169, 33-40. PMCID: PMC6347494


Organophosphate esters (OPEs) are a class of chemicals commonly used as flame retardants and plasticizers. OPEs are applied to a wide variety of consumer products and have a propensity to leach from these products. Consequently, OPEs are ubiquitous contaminants in many human environments and human exposure is pervasive. Accumulating evidence suggests that OPEs are capable of interfering with childhood cognitive development through both neurologic- and endocrine-mediated mechanisms. However, observational evidence of cognitive effects is limited. We used data collected in the third phase of the Pregnancy, Infection, and Nutrition Study to investigate cognitive effects of prenatal exposure to OPEs. In a spot prenatal maternal urine sample, we measured the following OPE metabolites: diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP). We assessed children's language and multi-faceted and overall cognitive development between two and three years of age using the MacArthur-Bates Communicative Development Inventories (MB-CDI) and the Mullen Scales of Early Learning (MSEL). We used linear regression to estimate the change in children's scores on these developmental assessments per interquartile range (IQR) increase in log-transformed, specific-gravity-corrected prenatal OPE metabolite concentrations, adjusted for maternal age, education, income, race/ethnicity, BMI, and child's sex. A total of 149 children had both OPE metabolite measurements and MB-CDI scores, and 227 children had both OPE metabolite measurements and MSEL scores. We observed that higher concentrations of ip-PPP (ng/ml) were associated with lower scores on the MSEL Cognitive Composite Score (beta=-2.61; 95% CI: -5.69, 0.46), and separately on two of the four MSEL Scales that comprise the Cognitive Composite, specifically the Fine Motor Scale (beta=-3.08; 95% CI: -5.26, -0.91) and the Expressive Language Scale (beta=-1.21; 95% CI: -2.91, 0.49). We similarly observed that prenatal ip-PPP concentrations were inversely associated with age-standardized scores on the MB-CDI Vocabulary assessment (beta=-1.19; 95% CI: -2.53, 0.16). Other OPE metabolites were not strongly associated with performance on either assessment. Our results suggest that isopropylated triarylphosphate isomers, the presumed parent compounds of ip-PPP, may adversely impact cognitive development, including fine motor skills and early language abilities. Our study contributes to the growing body of observational evidence that suggests prenatal exposure to OPEs may adversely affect cognitive development.


Reference Type

Journal Article

Year Published


Journal Title

Environmental Research


Doherty, Brett T.
Hoffman, Kate
Keil, Alexander P.
Engel, Stephanie M.
Stapleton, Heather M.
Goldman, Barbara Davis
Olshan, Andrew F.
Daniels, Julie L.