Prenatal Pyrethroid Exposure, Placental Gene Network Modules, and Neonatal Neurobehavior

Prenatal pesticide exposure may adversely affect child neurodevelopment which may partly arise from impairing the placentas vital role in fetal development. In a cohort of pregnant farmworkers from Thailand (N=248), we examined the links between urinary metabolites of pyrethroid pesticides during pregnancy, placental gene expression networks derived from transcriptome sequencing, and newborn neurobehavior assessed using the NICU Network Neurobehavioral Scales (NNNS) at 5 weeks of age. Focusing on the 21 gene network modules in the placenta identified by Weighted Gene Co-expression Network Analysis (WGCNA), our analysis revealed significant associations between metabolites and nine distinct modules, and between thirteen modules and NNNS, with eight modules showing overlap. Notably, stress was negatively associated with the interferon alpha response and Myc target modules, and the interferon alpha response module was correlated positively with attention, and negatively with arousal, and quality of movement. The analysis also highlighted the early and late trimesters as critical periods for the influence of exposures on placental function, with pyrethroid metabolites measured early in pregnancy significantly negatively associated with the protein secretion module, and those measured later in pregnancy negatively associated with modules related to oxidative phosphorylation (OXPHOS) and DNA repair. Additionally, the cumulative sum of 3-phenoxybenzoic acid across pregnancy was significantly negatively associated with the OXPHOS module. These findings suggest that prenatal exposure to pyrethroid pesticides may influence neonatal neurobehavior through specific placental mechanisms that impact gene expression of metabolic pathway, and these effects may be pregnancy period specific. These results offer valuable insights for future risk assessment and intervention strategies.