Association between maternal organophosphate esters metabolite levels during pregnancy and internalizing and externalizing behaviors in children at 2–5 years

Background: Organophosphate esters (OPEs) metabolites are frequently detected in human samples. Their structural similarity to organophosphate pesticides raises concerns about potential neurotoxicity. Animal and limited human studies suggest prenatal exposure to OPEs may affect offspring’s neurobehaviors. Objectives: We investigated the association between maternal OPE exposure and internalizing/externalizing behaviors in children age 2–5 years from the South African Drakenstein Child Health Study (N = 702). Methods: We measured urinary metabolites of OPEs, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate, during the second trimester of pregnancy or at birth, using a targeted multiclass assay. Childhood behaviors were assessed at 24, 42, and 60 months using the Child Behavior Checklist (CBCL). We used linear mixed-effects models with random intercepts and slopes to estimate associations. Results: BDCPP detection was associated with higher externalizing behavior scores at earlier ages, with attenuation over time (β = −1.57, 95% confidence interval: −2.74, −0.40 per 18-month increment). Age-specific estimates were 2.91 (1.08, 4.75) at 24 months, 1.34 (0.09, 2.59) at 42 months, and −0.23 (−1.81, 1.35) at 60 months. No consistent time-varying association was observed for internalizing behaviors, although a significant association was noted at 24 months (β = 2.28; 95% confidence interval: 0.20, 4.37). Diphenyl phosphate showed no associations with CBCL outcomes. Both metabolites were associated with higher CBCL scores among males, particularly for externalizing behaviors. Conclusions: Prenatal OPE exposures, particularly BDCPP, were associated with worse behavior outcomes in early childhood with attenuation over time. Further research is needed to clarify exposure timing and sex-specific susceptibility in low- and middle-income countries settings.