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2岁儿童神经发育异常与其母亲孕期毒死蜱暴露关系

Association of maternal exposure to chlorpyrifos during pregnancy with neurodevelopmental abnormality in two-year-old children: a survey in Wuhan city

  • 摘要:
    目的 了解2岁儿童神经发育异常与其母亲孕期毒死蜱暴露的关系,为开展毒死蜱暴露健康风险评估与控制提供参考依据。
    方法 基于湖北省武汉市健康宝贝出生队列,将其中2014年1月 — 2017 年6月分娩并提供了完整孕早期、孕中期和孕晚期尿液样本的893对母婴纳入分析,采用贝利婴幼儿发展量表中国修订版(BSID-CR)评估2岁儿童的智力发展指数(MDI)和运动发展指数(PDI),采用高效液相色谱 – 串联质谱法测定母亲孕早期、孕中期和孕晚期共2679份尿液样本中毒死蜱特异性代谢物3,5,6 – 三氯 – 2 – 吡啶醇(TCPy)的浓度并评价其内暴露水平,分析儿童神经认知发育异常与其母亲孕期尿液中TCPy浓度水平的关系。
    结果 2岁儿童MDI和PDI的平均得分分别为(110.0 ± 21.7)和(111.0 ± 17.1)分,其中MDI和PDI发育异常分别为99人(11.1%)和23人(2.58%);儿童母亲孕早期、孕中期和孕晚期尿液样本中经尿比重校正后的TCPy中位数(P25P75)浓度分别为2.02(1.30,3.38)、1.58(0.98,2.45)和1.29(0.79,2.05)ng/mL,TCPy的检出率分别为99.4%、98.8%和95.9%;在调整了母亲生育年龄、孕前体质指数、文化程度、家庭年均收入、孕期是否被动吸烟、孕期是否补充叶酸、产次、新生儿性别、母乳喂养时间和尿样采集季节等混杂因素后,多因素广义估计方程分析结果显示,母亲孕早期尿液中TCPy浓度每增加2倍,2岁儿童MDI发育异常和PDI发育异常的风险分别增加15%(OR = 1.15,95%CI = 1.01~1.32)和34%(OR = 1.34,95%CI = 1.04~1.73);分层分析结果显示,在调整了母亲生育年龄、孕前体质指数、文化程度、家庭年均收入、孕期是否被动吸烟、孕期是否补充叶酸、产次、母乳喂养时间和尿样采集季节等混杂因素后,母亲孕早期尿液中TCPy浓度每增加2倍,男孩PDI发育异常的风险可增加47%(OR = 1.47,95%CI = 1.09~1.99)。
    结论 母亲孕期毒死蜱暴露尤其是孕早期暴露可导致2岁儿童神经发育异常,对男童神经发育的影响更为显著。

     

    Abstract:
    Objective To explore the influence of maternal exposure to chlorpyrifos during pregnancy on neuro-developmental abnormalities of children at age of 2 years for health risk assessment and control of maternal chlorpyrifos exposure.
    Methods The participants of the study were 893 healthy mother-infant pairs enrolled in the Health Baby Birth Cohort in Wuhan municipality, Hubei province from January 2014 through June 2017. Urine samples (n = 2679) were collected from all the surveyed mothers at first, second, and third trimester of pregnancy for detection of 3, 5, 6-trichloro-2-pyridinol (TCPy, a specific metabolite of chlorpyrifos) by high-performance liquid chromatography coupled with tandem mass spectrometry to evaluate internal exposure of chlorpyrifos. The mental development index (MDI) and psychomotor development index (PDI) of surveyed children at age of 2 years were measured using domestically modified Bayley Scales of Infant Development (BSID-CR). The correlation between the children′s neurodevelopmental abnor-malities and maternal chlorpyrifos exposure during pregnancy was analyzed.
    Results The mean scores of MDI and PDI were 110.0 ± 21.7 and 111.0 ± 17.1 for all the 2-year-old children and 99 (11.1%) and 23 (2.58%) of the children were assessed as having abnormal mental and psychomotor development (with the MDI or PDI score of less than 80), respectively. The median (25th percentile, 75th percentile) of urine specific gravity adjusted concentration (ng/mL) of TCPy for urine samples the mothers in the first, second, and third trimesters were 2.02 (1.30, 3.38), 1.58 (0.98, 2.45), and 1.29 (0.79, 2.05), with the detection rate of 99.4%, 98.8%, and 95.9%, respectively. After adjusting for age at delivery, pre-pregnancy body mass index, maternal education, passive smoking during pregnancy, folic acid supplementation during pregnancy, child sex, parity, breastfeeding duration, and season of urine sample collection, the results of the multifactorial generalized estimating equation analysis indicated that each two-fold increase in maternal urinary TCPy concentration at first trimester was associated with the increased risks of mental and psychomotor developmental abnormalities for all the mothers′ children of 2-year-old, with the odds ratio (OR) and 95% confidence interval (95%CI) of 1.15 (95%CI: 1.01 – 1.32) and 1.34 (95%CI: 1.04 – 1.73); while, for the mother′s boys of 2-year-old, each two-fold increase in maternal urinary TCPy concentration at first trimester was correlated with increased risk of psychomotor developmental abnormality (OR = 1.47, 95%CI: 1.09 – 1.99).
    Conclusion Maternal exposure to chlorpyrifos during pregnancy, especially in the first trimester, could lead to neurodevelopmental abnormalities in children at age of 2 years, with a more pronounced effect on the neurodevelopment of boys.

     

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