不同胎龄神经管缺陷患儿脐带组织内甲基汞和总汞含量的比较
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摘要
[背景]神经管缺陷是由遗传因素和环境因素共同导致的一组严重出生缺陷,除叶酸缺乏外,其他致病因素仍有待探索。前期研究发现胎盘组织中高水平的甲基汞与总汞会增加神经管缺陷发病风险。在通过脐带组织甲基汞和总汞含量观察孕期汞暴露与神经管缺陷发病风险关联的病例对照研究中,因病例组与对照组存在明显胎龄差异,故需先探明脐带组织甲基汞、总汞含量是否受胎龄影响,但先前仅见一项小样本相关研究。[目的 ]比较不同胎龄期神经管缺陷患儿脐带组织中甲基汞和总汞含量,分析胎龄与甲基汞和总汞含量的关系,为描述甲基汞和总汞在胎儿体内的代谢和分布规律提供信息。[方法 ]以全自动甲基汞分析系统和手动总汞分析系统检测177例产前诊断引产或分娩时诊断的神经管缺陷患儿的冻干脐带组织中甲基汞与总汞含量。采用中位数M和百分位数间距(P_(25)～P_(75))表示甲基汞和总汞含量(单位ng/g,以干重计)的平均水平和离散程度。按胎龄分为4组(13～23周、24～29周、30～35周和36～43周),比较不同胎龄组间甲基汞和总汞含量差异。用Spearman相关分析胎龄与脐带组织甲基汞和总汞含量的相关性。通过自然对数转换将脐带组织甲基汞含量转为正态分布后,采用多元线性回归模型分析甲基汞含量随胎龄的变化情况,调整的混杂因素包括母亲年龄、文化程度、职业、引产或分娩年份、孕期饮酒以及孕期食用海产品情况。[结果]脐带组织甲基汞浓度的M(P_(25)～P_(75))为1.99 (1.30～3.20)ng/g;总汞浓度的M(P_(25)～P_(75))为5.85(4.11～8.48)ng/g。甲基汞含量在不同胎龄组间存在差异(P=0.015),随着胎龄增大,甲基汞含量从1.73 ng/g增加至3.04 ng/g。胎龄与甲基汞含量呈正相关(rs=0.188,P=0.012),调整母亲年龄、文化程度、职业、引产或分娩年份、孕期饮酒和孕期食用海产品后,脐带组织中甲基汞含量仍随胎龄改变而增大(b=0.024,P <0.001)。脐带组织甲基汞的蓄积效应在男性和女性患儿以及脊柱裂亚型中均存在。未发现脐带组织总汞含量在不同胎龄组间存在差异。[结论 ]甲基汞在神经管缺陷患儿脐带组织中随着胎龄增大存在一定的蓄积效应,未发现总汞含量随胎龄而变化。
[Background] Neural tube defects(NTDs) are a group of severe birth defects caused by bothgenetic and environmental factors, and in addition to maternal folate deficiency, other risk factors remain to be explored. Previous studies have found that high levels of methylmercury(MeHg) and total mercury(T-Hg) in placental tissues increase the risk of NTDs. In a case-control study evaluating the association between prenatal mercury exposure and the risk of NTDs by detecting the concentrations of MeHg and T-Hg in umbilical cord tissues, it is necessary to determine whether the MeHg or T-Hg in umbilical cord tissues is affected by gestational age because of the significant difference in gestational age between two groups. But to our knowledge, only one related study with a small sample size is available. [Objective] This study is to compare the concentrations of MeHg and T-Hg in umbilical cord tissues of fetuses with NTDs at different gestational ages, evaluate relationships of gestational age with MeHg or T-Hg, and describe the metabolism and distribution characteristics of MeHg and T-Hg in fetuses.[Methods] Automated methylmercury system and manual total mercury system were used to measured MeHg and T-Hg in frozendried umbilical cord tissue samples of 177 fetuses with NTDs who were diagnosed prenatally or at birth. Median(M) and interquartile range(P_(25)-P_(75)) were used to describe the average level and dispersion of MeHg and T-Hg(ng/g, in terms of dry weight). According to gestational age, the samples were divided into four groups(13-23, 24-29, 30-35, and 36-43 weeks old) to compare MeHg and T-Hg concentrations. Spearman rank correlation was used to evaluate the correlations of gestational age with MeHg and T-Hg concentrations. Multivariate linear regression was used to evaluate the relationship between gestational age and MeHg concentrations after natural log transformation, adjusting for confounders including maternal age, education level, occupation, year of induction labor or delivery, and drinking alcohol and consumption of seafood during pregnancy.[Results] The MeHg and T-Hg concentrations in M(P_(25)-P_(75)) were 1.99(1.30-3.20) ng/g and 5.85(4.11-8.48) ng/g, respectively. The MeHg concentrations among the four groups of different gestational ages were significantly different(P=0.015), and raised from 1.73 ng/g to 3.04 ng/g with the increasing of gestational age. Gestational age was positively correlated with MeHg concentration in umbilical cord(rs=0.188, P=0.012), and after adjusting for maternal age, education level, occupation, year of induction labor or delivery, and drinking alcohol and consumption of seafood during pregnancy, MeHg concentration in umbilical cord still increased with older gestational age(b=0.024, P < 0.001). The accumulation trend of MeHg consistently existed in male or female NTDs fetuses and spina bifida subtype. No significant difference in T-Hg concentration was found among the four groups of different gestational ages.[Conclusion] MeHg might accumulate in the umbilical cord tissues of NTDs fetuses in a gestational age-dependent manner, but T-Hg concentration does not follow such pattern.
[Background] Neural tube defects(NTDs) are a group of severe birth defects caused by bothgenetic and environmental factors, and in addition to maternal folate deficiency, other risk factors remain to be explored. Previous studies have found that high levels of methylmercury(MeHg) and total mercury(T-Hg) in placental tissues increase the risk of NTDs. In a case-control study evaluating the association between prenatal mercury exposure and the risk of NTDs by detecting the concentrations of MeHg and T-Hg in umbilical cord tissues, it is necessary to determine whether the MeHg or T-Hg in umbilical cord tissues is affected by gestational age because of the significant difference in gestational age between two groups. But to our knowledge, only one related study with a small sample size is available. [Objective] This study is to compare the concentrations of MeHg and T-Hg in umbilical cord tissues of fetuses with NTDs at different gestational ages, evaluate relationships of gestational age with MeHg or T-Hg, and describe the metabolism and distribution characteristics of MeHg and T-Hg in fetuses.[Methods] Automated methylmercury system and manual total mercury system were used to measured MeHg and T-Hg in frozendried umbilical cord tissue samples of 177 fetuses with NTDs who were diagnosed prenatally or at birth. Median(M) and interquartile range(P_(25)-P_(75)) were used to describe the average level and dispersion of MeHg and T-Hg(ng/g, in terms of dry weight). According to gestational age, the samples were divided into four groups(13-23, 24-29, 30-35, and 36-43 weeks old) to compare MeHg and T-Hg concentrations. Spearman rank correlation was used to evaluate the correlations of gestational age with MeHg and T-Hg concentrations. Multivariate linear regression was used to evaluate the relationship between gestational age and MeHg concentrations after natural log transformation, adjusting for confounders including maternal age, education level, occupation, year of induction labor or delivery, and drinking alcohol and consumption of seafood during pregnancy.[Results] The MeHg and T-Hg concentrations in M(P_(25)-P_(75)) were 1.99(1.30-3.20) ng/g and 5.85(4.11-8.48) ng/g, respectively. The MeHg concentrations among the four groups of different gestational ages were significantly different(P=0.015), and raised from 1.73 ng/g to 3.04 ng/g with the increasing of gestational age. Gestational age was positively correlated with MeHg concentration in umbilical cord(rs=0.188, P=0.012), and after adjusting for maternal age, education level, occupation, year of induction labor or delivery, and drinking alcohol and consumption of seafood during pregnancy, MeHg concentration in umbilical cord still increased with older gestational age(b=0.024, P < 0.001). The accumulation trend of MeHg consistently existed in male or female NTDs fetuses and spina bifida subtype. No significant difference in T-Hg concentration was found among the four groups of different gestational ages.[Conclusion] MeHg might accumulate in the umbilical cord tissues of NTDs fetuses in a gestational age-dependent manner, but T-Hg concentration does not follow such pattern.
引文
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[4]钱浩骏,叶细标,傅华.汞及其化合物的慢性神经毒性[J].环境与职业医学,2005,22(2):160-162,166.
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[7]JIN L,ZHANG L,LI Z,et al.Placental concentrations of mercury,lead,cadmium,and arsenic and the risk of neural tube defects in a Chinese population[J].Reprod Toxicol,2013,35:25-31.
[8]JIN L,LIU M,ZHANG L,et al.Exposure of methyl mercury in utero and the risk of neural tube defects in a Chinese population[J].Reprod Toxicol,2016,61:131-135.
[9]关铭,张立,张贵荣,等.不同孕周胎儿5种脏器中甲基汞含量的测定与研究[J].中国公共卫生学报,1997,16(2):87-89.
[10]SAKAMOTO M,KANEOKA T,MURATA K,et al.Correlations between mercury concentrations in umbilical cord tissue and other biomarkers of fetal exposure to methylmercury in the Japanese population[J].Environ Res,2007,103(1):106-111.
[11]SAKAMOTO M,MURATA K,DOMINGO J L,et al.Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury[J].Environ Res,2016,149:282-287.
[12]胡卫萱,王文华,贾金平.甲基汞在脑组织中的积累和脂质过氧化作用[J].环境与职业医学,2003,20(5):331-333.
[13]HIRAYAMA K,YASUTAKE A.Sex and age differences in mercury distribution and excretion in methylmercuryadministered mice[J].J Toxicol Environ Health,1986,18(1):49-60.
[14]National Research Council(US)Committee on the Toxicological Effects of Methylmercury.Toxicological effects of methylmercury[M].Washington,DC:National Academies Press,2000.
[15]田琳,郭慧芬,罗宏,等.山西某地区汞环境污染及对居民肾功能的影响[J].环境与职业医学,2008,25(5):417-419.
[16]PI X,QIAO Y,WEI Y,et al.Concentrations of selected heavy metals in placental tissues and risk for neonatal orofacial clefts[J].Environ Pollut,2018,242:1652-1658.
[17]GRANDJEAN P,BUDTZ-J?RGENSEN E,J?RGENSEN P J,et al.Umbilical cord mercury concentration as biomarker of prenatal exposure to methylmercury[J].Environ Health Perspect,2005,113(7):905-908.
[2]BLOM H J,SHAW G M,DEN HEIJER M,et al.Neural tube defects and folate:case far from closed[J].Nat Rev Neurosci,2006,7(9):724-731.
[3]CLARKSON T W,VYAS J B,BALLATORI N.Mechanisms of mercury disposition in the body[J].Am J Ind Med,2007,50(10):757-764.
[4]钱浩骏,叶细标,傅华.汞及其化合物的慢性神经毒性[J].环境与职业医学,2005,22(2):160-162,166.
[5]KAJIWARA Y,YASUTAKE A,ADACHI T,et al.Methylmercury transport across the placenta via neutral amino acid carrier[J].Arch Toxicol,1996,70(5):310-314.
[6]CLARKSON T W.The three modern faces of mercury[J].Environ Health Perspect,2002,110(Suppl 1):11-23.
[7]JIN L,ZHANG L,LI Z,et al.Placental concentrations of mercury,lead,cadmium,and arsenic and the risk of neural tube defects in a Chinese population[J].Reprod Toxicol,2013,35:25-31.
[8]JIN L,LIU M,ZHANG L,et al.Exposure of methyl mercury in utero and the risk of neural tube defects in a Chinese population[J].Reprod Toxicol,2016,61:131-135.
[9]关铭,张立,张贵荣,等.不同孕周胎儿5种脏器中甲基汞含量的测定与研究[J].中国公共卫生学报,1997,16(2):87-89.
[10]SAKAMOTO M,KANEOKA T,MURATA K,et al.Correlations between mercury concentrations in umbilical cord tissue and other biomarkers of fetal exposure to methylmercury in the Japanese population[J].Environ Res,2007,103(1):106-111.
[11]SAKAMOTO M,MURATA K,DOMINGO J L,et al.Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury[J].Environ Res,2016,149:282-287.
[12]胡卫萱,王文华,贾金平.甲基汞在脑组织中的积累和脂质过氧化作用[J].环境与职业医学,2003,20(5):331-333.
[13]HIRAYAMA K,YASUTAKE A.Sex and age differences in mercury distribution and excretion in methylmercuryadministered mice[J].J Toxicol Environ Health,1986,18(1):49-60.
[14]National Research Council(US)Committee on the Toxicological Effects of Methylmercury.Toxicological effects of methylmercury[M].Washington,DC:National Academies Press,2000.
[15]田琳,郭慧芬,罗宏,等.山西某地区汞环境污染及对居民肾功能的影响[J].环境与职业医学,2008,25(5):417-419.
[16]PI X,QIAO Y,WEI Y,et al.Concentrations of selected heavy metals in placental tissues and risk for neonatal orofacial clefts[J].Environ Pollut,2018,242:1652-1658.
[17]GRANDJEAN P,BUDTZ-J?RGENSEN E,J?RGENSEN P J,et al.Umbilical cord mercury concentration as biomarker of prenatal exposure to methylmercury[J].Environ Health Perspect,2005,113(7):905-908.