孕期铊暴露对胎儿生长发育影响的出生队列研究

Prenatal thallium exposure and fetal growth: A prospective birth cohort study

  • 摘要:
    背景 流行病学研究发现孕期铊暴露会导致不良出生结局。
    目的 探讨孕期铊暴露对胎儿生长发育和出生结局的影响及铊暴露健康效应的关键窗口期。
    方法 基于上海市亲子队列,共146对母子纳入本研究中。采用自制的问卷调查研究对象的人口学信息以及母婴健康数据。在孕早、中、晚期抽取孕妇血液,分娩后立刻采集新生儿脐血,通过电感耦合等离子质谱法检测不同孕期孕妇血液及脐血中铊浓度。采用混合效应模型探究孕期铊暴露对胎儿生长发育(双顶径、头围、腹围、股骨长、肱骨长)的影响,进一步运用线性回归模型探索铊暴露健康效应的关键窗口期。
    结果 血液样本中铊的检出率均大于99.0%。孕早、中、晚期母血铊质量浓度的M(P25P75)分别为38.7(32.3,50.1)、44.3(34.3,56.7)、45.0(34.9,54.6)ng·L-1,全孕期母血中铊质量浓度为42.7(34.2,53.3)ng·L-1,脐血铊质量浓度为23.8(17.2,35.0)ng·L-1。调整混杂因素后,混合效应模型分析结果发现,孕期铊暴露与胎儿双顶径呈负相关(b=-0.91,95%CI:-1.78~-0.02),与其余指标关联均无统计学意义(P>0.05);校正铅、镉、钙、锰的影响后,关联一致。对铊暴露水平进行四分位数法分组,发现孕早期血液中铊质量浓度每增加一个四分位数,孕早期胎儿双顶径、头围、股骨长和肱骨长分别减少3.0、10.9、2.6、3.1 mm;孕晚期胎儿头围、腹围分别增加8.3、16.3 mm;孕晚期血液中铊质量浓度每增加一个四分位数,孕晚期胎儿腹围、股骨长分别增加7.3、2.1 mm;脐血铊质量浓度每增加一个四分位数,胎儿出生体长增加0.07mm,其余指标关联均无统计学意义(P>0.05)。
    结论 孕期铊暴露对胎儿宫内生长发育及出生结局存在不良影响,孕早期为铊暴露健康效应的关键窗口期。

     

    Abstract:
    Background Epidemiological studies have revealed that prenatal thallium exposure can lead to adverse birth outcomes.
    Objective This study is designed to explore the effects of prenatal thallium exposure on fetal growth and birth outcomes, and assess the critical window period for the health effects of thallium exposure.
    Methods A total of 146 pregnant women and their children participated in this study, who were recruited to the Shanghai Maternal-Child Pairs Cohort (MCPC). Information of demographic characteristics and mother and child health was collected by self-designed questionnaires. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentration of thallium in maternal blood in different gestational periods and cord blood of newborns. A mixed-effect model was used to explore the effect of thallium exposure during pregnancy on fetal growth and development (such as double top diameter, head circumference, abdominal circumference, femur length, and humerus length), and a linear regression model was further used to explore the critical window period for the health effects of thallium exposure.
    Results The positive rate of thallium in blood samples was more than 99.0%. The median (P25, P75) values of thallium in maternal blood were 38.7 (32.3, 50.1), 44.3 (34.3, 56.7), and 45.0 (34.9, 54.6) ng·L-1 in the first, second, and third trimesters of pregnancy, respectively. The thallium concentrations in maternal blood during whole pregnancy were 42.7 (34.2, 53.3) ng·L-1, and 23.8 (17.2, 35.0) ng·L-1 in umbilical cord blood. After adjusting for confounding factors, the results of mixed-effect model showed that the exposure level of thallium during pregnancy was negatively correlated with fetal double top diameter (b=-0.91, 95% CI: -1.78--0.02), and not correlated with the other fetal growth indicators (P>0.05); the results were consistent after excluding the influence of lead, cadmium, manganese, and calcium. After thallium concentration was grouped by quartiles, it was found that when thallium concentration was increased by one quartile in the first trimester, the fetal double top diameter, head circumference, femur length, and humerus length were reduced by 3.0, 10.9, 2.6, and 3.1 mm, and the head circumference and abdominal circumference of the fetuses were increased by 8.3 and 16.3 mm, respectively; the fetal abdominal circumference and femur length were increased by 7.3 and 2.1 mm for each quartile increase of thallium concentration in blood in the third trimester, respectively; each quartile increase in thallium concentration in umbilical cord blood resulted in an increase in birth body length of 0.07 mm, but was not associated with other indicators (P>0.05).
    Conclusion Thallium exposure during pregnancy has a negative effect on intrauterine growth and development and birth outcomes of the fetuses. The first trimester might be the critical exposure window for thallium to affect fetal growth and development.

     

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