Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA 94704, USA.
Neurotoxicology. 2011 Oct;32(5):646-55. doi: 10.1016/j.neuro.2011.05.017. Epub 2011 Jun 29.
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.
有机磷农药(OP)因其对胆碱能纤维的影响,可能会干扰自主神经系统(ANS)的功能。我们进行了一项研究,以评估宫内和儿童期接触有机磷农药与儿童在休息和应激状态下自主神经系统(ANS)失调之间的关系。我们假设,OP 水平较高的儿童在休息时会表现出副交感神经激活,而没有交感神经激活,在应激状态下则会同时出现副交感神经和交感神经激活。
通过测量母体和儿童点尿样中的二烷基磷酸代谢物(DAPs,总二乙基-DEs 和总二甲基-DMs)来评估 OP 暴露情况。在 149 名 6 个月和 1 岁、97 名 3 岁半和 274 名 5 岁的儿童中,我们根据母体和儿童 DAP 评估了 ANS 调节情况。我们使用心率(HR)、呼吸窦性心律失常(RSA)和射前间期(PEP)评估了在标准化方案给药期间的休息和反应性(即应激减去休息)指标。我们进行了横断面(在每个年龄)和纵向回归模型来评估 OP 和 ANS 之间的关系。为了估计 5 岁时的累积暴露量,我们使用了浓度时间曲线下面积(AUC)方法。我们还评估了在 5 岁时,DAP 浓度持续较高的儿童与 DAP 浓度持续较低的儿童的平均 ANS 评分是否存在显著差异。
儿童 DMs 和 DAPs 与 6 个月时的静息 RSA 显著负相关,而母体 DMs 和儿童 DEs 与 1 岁时的静息 PEP 显著正相关。在 3 岁半或 5 岁的儿童中,以及在任何年龄的反应性中,均未观察到与静息相关的关联。在反应性特征与母体或儿童 DAP 之间没有明显的关系。母体总 DEs 的累积量与 HR 降低相关(-3.19 bpm 下降;95%CI:-6.29 至-0.09,p=0.04),仅在 5 岁时存在。此外,在 5 岁时,DAP 浓度持续较高的儿童与 DAP 浓度持续较低的儿童在 ANS 测量方面没有显著差异。
尽管我们在婴儿期观察到一些自主神经功能失调的证据,但我们没有发现母体和儿童接触有机磷农药(通过尿液中的 DAPs 测量)与儿童在休息和应激状态下的自主神经系统(HR、RSA 和 PEP)调节之间存在一致的关联,直至 5 岁。