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Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Prenatal pyrethroid exposure, placental gene network modules, and neonatal neurobehavior
Yewei Wang1, Jacqueline Holstein1, Karen Hermetz1
1Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Insights
Prenatal pesticide exposure, specifically pyrethroids, can negatively impact infant neurodevelopment by altering placental gene expression. These effects vary by trimester, highlighting critical windows for intervention.
Area of Science:
- Environmental Health
- Developmental Neuroscience
- Molecular Biology
Background:
- Prenatal pesticide exposure is a potential risk factor for adverse child neurodevelopment.
- Placental function is crucial for fetal development and may be a target for pesticide-induced neurotoxicity.
Purpose of the Study:
- To investigate the association between prenatal pyrethroid pesticide exposure, placental gene expression, and newborn neurobehavior.
- To identify specific placental gene networks and critical exposure periods linking pyrethroids to neurodevelopmental outcomes.
Main Methods:
- A cohort of 248 pregnant farmworkers in Thailand was studied.
- Urinary pyrethroid metabolites, placental transcriptome sequencing, and NICU Network Neurobehavioral Scales (NNNS) were analyzed.
- Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules associated with exposure and neurobehavior.
Main Results:
- Pyrethroid metabolites were linked to nine placental gene network modules, and thirteen modules correlated with NNNS scores, with eight overlapping modules.
- Specific modules, including interferon alpha response and Myc targets, were associated with neonatal stress, attention, arousal, and movement quality.
- Early pregnancy exposure was linked to the protein secretion module, while late pregnancy exposure affected oxidative phosphorylation (OXPHOS) and DNA repair modules.
Conclusions:
- Prenatal pyrethroid exposure may affect neonatal neurobehavior via placental gene expression changes in metabolic and response pathways.
- The timing of pyrethroid exposure during pregnancy is critical, influencing distinct placental functions.
- Findings support targeted risk assessment and interventions to mitigate neurodevelopmental risks from pesticide exposure.
Abstract:
Prenatal pesticide exposure may adversely affect child neurodevelopment which may partly arise from impairing the placenta's 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, 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 exposures influence 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 pyrethroids may influence neonatal neurobehavior through specific placental mechanisms that impact gene expression of metabolic pathways, and these effects may be pregnancy period specific. These results offer valuable insights for future risk assessment and intervention strategies.
