Associations between Prenatal Exposure to Environmental Phenols and Child Neurodevelopment at Two Years of Age in a South African Birth Cohort

Abstract

ObjectiveEvidence suggests that prenatal environmental phenol exposures negatively impact child neurodevelopment, however there is little research on the effects of mixtures of multiple phenol exposures. We analyzed associations between prenatal exposure to phenol mixtures and cognitive neurodevelopment at two years of age among 545 mother-child pairs from the South African Drakenstein Child Health Study.Material and MethodsWe measured maternal urine environmental phenol concentrations once during the second trimester of pregnancy. We used the Bayley Scales of Infant and Toddler Development III to assess cognitive development at two years of age. We used linear regression models adjusted for maternal HIV status, maternal age, ethnicity, prenatal tobacco exposure, child sex, and socioeconomic status (SES) to examine individual associations. We compared four mixture methods: self-organizing maps (SOM), Bayesian kernel machine regression (BKMR), quantile-based G-computation (qgcomp) and weighted quantile sum (WQS) regression to explore joint effects of the exposure mixture. We assessed effect modification by SES, sex, prenatal tobacco, and ethnicity.ResultsAcross all methods, we found no association between individual phenol exposures or the joint exposure mixture with the cognitive score. Prenatal tobacco exposure modified the association between pentachlorophenol (PCP) and cognitive neurodevelopment (interaction p-value=0.012), with higher PCP concentrations associated with lower cognitive scores among non-smokers (beta=- 2.17; 95% CI: -3.85, -0.49). Sex modified the association between bisphenol A (BPA) and cognitive neurodevelopment (interaction p-value=0.021), with males having a significant adverse association (beta=-1.39; 95% CI: -2.54, -0.23).ConclusionWhile we found no main effects of prenatal phenol exposure on cognitive neurodevelopment, the associations with PCP and BPA were more pronounced among certain subgroups.

Note:
Funding Declaration: The Drakenstein Child Health Study was funded by the Bill & Melinda Gates Foundation (OPP1017641), Discovery Foundation, South African Medical Research Council, National Research Foundation South Africa, CIDRI Clinical Fellowship and Wellcome Trust (204755/2/16/z). AH and SME were supported by the HERCULES Center (NIEHS P30ES019776). AH was also supported by the National Institute on Aging (NIA R01AG079170). The National Institutes of Health/National Institute of Environmental Health Sciences funded lab analysis of environmental phenol exposure biomarkers and creatinine in urine under award numbers U2CES026561 to Robert O. Wright (Mount Sinai HHEAR Targeted Analysis Laboratory) and P30ES023515 to Robert O. Wright (Mount Sinai Center for Health and Environment Across the LifeSpan).

Conflict of Interests: Dr. Stein has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. The other authors have nothing to disclose.

Ethical Approval: The DCHS was approved by the Human Research Ethics Committee (HREC) of the University of Cape Town (HREC 401/2009), Stellenbosch University (N12/02/0002) and Western Cape Provincial Health Research Committee (2011RP45). Written informed consent was provided by each mother for herself and her child and is renewed annually.

Keywords: Environmental mixture methods, environmental phenols, chemical exposures during pregnancy, Bayley Scales of Infant and Toddler Development III, pentachlorophenol (PCP), bisphenol A (BPA)