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Association between maternal organophosphate flame retardants (OPFRs) metabolite levels during pregnancy and internalizing and externalizing behaviors in children at 2-5 years

Cheng, Y.; Abrishamcar, S.; Ma, T.; Eick, S. M.; Barr, D. B.; Hoffman, N.; Andra, S. S.; Wright, R. O.; Zar, H. J.; Stein, D. J.; Huels, A.

2025-11-09 epidemiology
10.1101/2025.10.28.25338905 medRxiv
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BackgroundOrganophosphorus flame retardants (OPFRs) metabolites are frequently detected in human samples. Their structural similarity to polybrominated diphenyl ethers raises concerns about potential neurotoxicity. Animal and limited human studies suggest prenatal exposure to OPFRs may affect offsprings neurobehavioral problems. ObjectivesWe investigated the association between maternal OPFRs exposure and neurobehavioral problems in children aged two to five years from the South African Drakenstein Child Health Study (N=705). MethodsWe measured urinary metabolites of OPFRs, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPHP) during the 2nd trimester of pregnancy or at birth, using a targeted multiclass assay. Childhood behaviors were repeatedly assessed at 24, 42 and 60 months using the Child Behavior Checklist (CBCL). After natural log transformation of metabolite concentrations, we used linear regression to analyze the association between BDCPP and DPHP levels and internalizing/externalizing behaviors t-scores, adjusting for maternal age, body mass index, ancestry, and socioeconomic status. ResultsAt 24 months, each standard deviation (SD) increase in log-BDCPP levels was associated with higher externalizing (1.26, 95% CI: 0.30, 2.21) and internalizing (1.14, 95% CI: 0.02, 2.25) subscores. Similarly, one SD increase in log-DPHP was associated with higher externalizing (+1.19, 95% CI: 0.23, 2.16) and internalizing (1.00, 95% CI: -0.12, 2.13) subscores. Only DPHP levels were associated with internalizing subscores at 60 months. ConclusionWe observed a positive association between prenatal metabolite levels of OPFRs and neurobehavioral problems among children at age two, raising concerns about prenatal chemical exposures and awareness of developing interventions to promote healthier developmental outcomes for children.

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