During pregnancy, maternal lead from earlier exposures mobilizes and crosses placental barriers, placing the developing fetus at risk for lead exposure and neurodevelopmental deficits. Some neuronal circuits known to be affected in neurodevelopment disorders can be probed with simple physiological behavioral paradigms. One such neural biomarker is Pre-Pulse Inhibition (PPI), an indicator of adequate sensorimotor gating processing. In clinical studies, deficits in PPI have been associated with neurodevelopmental disorders in human subjects. To our knowledge, no studies have examined the use of PPI as a biomarker of toxicant effects on the brain in epidemiological studies. We aimed to estimate the causal effect of prenatal lead exposure, assessed by maternal cortical bone lead concentrations, on PPI in 279 children from Mexico City. in vivo maternal cortical bone lead measurements were taken at four weeks postpartum at the mid-tibia shaft using a K-Shell X-ray fluorescence instrument. PPI recording occurred in an isolated clinical setting and eye blink responses were measured using electromyography. We assessed if the conditions for causal inference held in our study and used the results of our assessment to estimate the causal effect of prenatal lead exposure on PPI using an ordinary least squares regression model, a marginal structural model, and the parametric g-formula. Results were consistent across the three modeling approaches. For the parametric g-formula, a one standard deviation (10.0 μg/g) increase in prenatal lead significantly reduced PPI by approximately 19.0 % (95 % CI: 5.4 %, 34.3 %). This decrease is similar in magnitude to clinical studies on schizophrenia, which have observed PPI impairments in patients with schizophrenia as compared to controls. Our results are consistent with findings from other studies establishing an association between lead exposure and neurodevelopmental disorders in children and suggest that PPI may be useful as an objective biomarker of toxicant effects on the brain.

中文翻译：

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估计产前铅暴露对儿童和青少年前脉冲抑制缺陷的因果影响。


在怀孕期间，母亲早期接触的铅会移动并穿过胎盘屏障，使发育中的胎儿面临铅暴露和神经发育缺陷的风险。一些已知在神经发育障碍中受到影响的神经元回路可以通过简单的生理行为范例进行探测。此类神经生物标志物之一是脉冲前抑制 (PPI)，它是感觉运动门控处理是否充分的指标。在临床研究中，PPI 缺陷与人类受试者的神经发育障碍有关。据我们所知，尚无研究在流行病学研究中检验 PPI 作为大脑毒性作用生物标志物的用途。我们旨在评估产前铅暴露（通过母亲皮质骨铅浓度评估）对墨西哥城 279 名儿童 PPI 的因果影响。产后 4 周，使用 K-Shell X 射线荧光仪器在胫骨中部进行体内母体皮质骨铅测量。 PPI 记录在孤立的临床环境中进行，并使用肌电图测量眨眼反应。我们评估了研究中因果推断的条件是否成立，并使用我们的评估结果，使用普通最小二乘回归模型、边际结构模型和参数 g 公式来估计产前铅暴露对 PPI 的因果影响。三种建模方法的结果是一致的。对于参数 g 公式，产前铅增加 1 个标准差 (10.0 μg/g) 会显着降低 PPI 约 19.0%（95% CI：5.4%、34.3%）。这种下降的幅度与精神分裂症的临床研究相似，临床研究观察到与对照组相比，精神分裂症患者的 PPI 受损。 我们的结果与其他研究的结果一致，这些研究确定了铅暴露与儿童神经发育障碍之间的关联，并表明 PPI 可能可作为大脑毒性作用的客观生物标志物。