Maternal prenatal and child organophosphate pesticide exposures and children's autonomic function

Organophosphate pesticides (OP), because of their effects on cholinergic fibers, may interfere with the functions of the autonomic nervous system (ANS). We conducted a study to assess the relation of in utero and child OP pesticide exposures and children's autonomic nervous system (ANS) dysregulation under resting and challenge conditions. We hypothesized that children with high OP levels would show parasympathetic activation and no sympathetic activation during rest and concomitant parasympathetic and sympathetic activation during challenging conditions.

OP exposures were assessed by measuring urinary dialkylphosphate metabolites (DAPs, total diethyls-DEs, and total dimethyls-DMs) in maternal and children's spot urine samples. ANS regulation was examined in relation to maternal and child DAPs in 149 children at 6 months and 1 year, 97 at 3 1/2 years and 274 at 5 years. We assessed resting and reactivity (i.e., challenge minus rest) measures using heart rate (HR), respiratory sinus arrhythmia (RSA), and preejection period (PEP) during the administration of a standardized protocol. Cross-sectional (at each age) and longitudinal regression models were conducted to assess OP and ANS associations. To estimate cumulative exposure at 5 years, we used an area-under-the-concentration-time-curve (AUC) methodology. We also evaluated whether children with consistently high versus low DAP concentrations had significantly different mean ANS scores at 5 years.

Child DMs and DAPs were significantly negatively associated with resting RSA at 6 months and maternal DMs and child DEs were significantly positively associated with resting PEP at 1 year. No associations with resting were observed in 3 1/2- or 5-year-old children nor with reactivity at any age. There was no significant relationship between the reactivity profiles and maternal or child DAPs. Cumulative maternal total DEs were associated with low HR (-3.19 bpm decrease; 95% CI: -6.29 to -0.09, p=0.04) only at 5 years. In addition, there were no significant differences in ANS measures for 5-year-olds with consistently high versus low DAPs.

Although we observe some evidence of ANS dysregulation in infancy, we report no consistent associations of maternal and child OP pesticide exposure, as measured by urinary DAPs, on children's ANS (HR, RSA, and PEP) regulation during resting and challenging conditions up to age 5 years.