Prenatal Organophosphate Pesticide Exposure and Social Cognition Among Adolescents in an Agricultural Community

Background: Organophosphate (OP) pesticides are cholinesterase-inhibiting insecticides used primarily in agriculture. Low-dose exposure to OPs could adversely impact human neurodevelopment, particularly if exposure occurs during the prenatal period when the fetal brain is undergoing rapid development and the ability to detoxify OPs is not yet mature. The CHAMACOS (Center for Health Assessment of Mothers and Children of Salinas) longitudinal birth cohort study, designed to investigate pesticide exposure and the health of pregnant women and their children living in a predominantly Mexican-American agricultural community, has previously reported associations of prenatal OPs with lower IQ, poorer attention and parental report of behaviors at 24 months related to pervasive developmental disorder (PDD), which includes symptoms consistent with ASD. Social cognition, a measure of how individuals perceive and respond to social interaction, is a central trait impaired in individuals with an autism spectrum disorder (ASD).

Objectives: To investigate the association of prenatal exposure to OP pesticides with social cognition among adolescents in CHAMACOS. 

Methods: We estimated exposure to OPs using measures of dialkyl phosphate (DAP) metabolites in maternal urine collected during the first and second half of pregnancy. When the CHAMACOS children were age 14 years parents were asked to assess their children using the Social Responsiveness Scale (SRS), a rating scale quantifying the frequency of traits related to social behavior and stereotypic behavior/restricted interests. We estimated associations of maternal DAP concentrations (average of the 2 pregnancy measures) with SRS scores using linear regression models, adjusting for maternal age, education, country of birth, years in the United States, marital status, depression, child’s age at assessment, sex and quality of the home environment. 

Results: For the 247 children with prenatal DAPs and a completed SRS, the median (25%ile, 75%ile) DAP concentration was 130.5 (61.9, 279.7) nmol/L. Prenatal DAPs were associated with poorer 14-year SRS scores, represented by a higher score (β=7.3; 95% Confidence Interval (CI): 2.6, 12.1 per 10-fold increase in average maternal DAP concentration). We found a linear, monotonic dose-response relationship between DAPs and SRS score, confirmed by splines and by categorical analysis, where we detected a 10.8 point increase (95% CI: 4.6, 17.1) in SRS score for the 4^th vs. 1^st quartile of DAP concentration. Associations were consistent across males and females and across the 5 subscales of the SRS (social awareness, cognition, communication, motivation and restricted interests and repetitive behaviors). 

Conclusions: We found that prenatal exposure to OP pesticides was associated with poorer parent-reported social cognition among adolescents in the CHAMACOS cohort. Prenatal DAP concentrations in CHAMACOS mothers were high, though in range with concentrations in the general U.S. population. Associations are consistent with CHAMACOS findings at earlier ages as well as with other epidemiologic studies showing associations of OPs with poorer neurodevelopment. Examination of continuously distributed traits, such as social cognition, offers a statistically powerful approach to studying modifiable environmental risk factors for ASDs.