Article(id=1325530026434904201, tenantId=1146029695717560320, journalId=1256213402557890569, issueId=1325529948685091532, articleNumber=null, orderNo=null, doi=10.16835/j.cnki.1000-9817.2025142, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1736179200000, receivedDateStr=2025-01-07, revisedDate=1742745600000, revisedDateStr=2025-03-24, acceptedDate=null, acceptedDateStr=null, onlineDate=1793960585384, onlineDateStr=2026-11-06, pubDate=1756051200000, pubDateStr=2025-08-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793960585384, onlineIssueDateStr=2026-11-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793960585384, creator=13701087609, updateTime=1793960585384, updator=13701087609, issue=Issue{id=1325529948685091532, tenantId=1146029695717560320, journalId=1256213402557890569, year='2025', volume='46', issue='8', pageStart='1065', pageEnd='1216', issueExtLink='null', onlineDate='null', pubDate='1756051200000', pubDateStr='2025-08-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793960566921, creator='13701087609', updateTime=1793960566921, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=1088, endPage=1092, ext={EN=ArticleExt(id=1325530026913054858, articleId=1325530026434904201, tenantId=1146029695717560320, journalId=1256213402557890569, language=EN, title=A prospective cohort study of association between maternal metal exposure during early pregnancy and physical development in offspring at ages 1 and 3, columnId=1325529950425735235, journalTitle=Chinese Journal of School Health, columnName=Impact of Maternal Adverse Factors during Pregnancy on Childhood Growth and Development, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health.

Methods

From 2024 to 2018, a total of 1 588 mother-child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height-for-age Z-score(HAZ), weight-for-age Z-score(WAZ), weight-for-length/height Z-score(WHZ), and head circumference-for-age Z-score(HCAZ) at 1 and 3 years of age.

Results

After adjusting for confounders, GEE analysis revealed that each natural log-unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62%, 5.04%, and 8.33%, respectively, at 1 and 3 years of age (FDR-P < 0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR-P < 0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%).

Conclusions

Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

, authors=Xiao ZHANG1, 2, Yangqian JIANG1, 3, Liya PANG1, 3, Jiangbo DU1, 2, Yuan LIN1, 3, Hongxia MA1, 2, authorsList=Xiao ZHANG, Yangqian JIANG, Liya PANG, Jiangbo DU, Yuan LIN, Hongxia MA, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2025 Chinese Journal of School Health. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1325530029748404365, articleId=1325530026434904201, tenantId=1146029695717560320, journalId=1256213402557890569, language=CN, title=母亲孕早期金属暴露与子代1岁及3岁体格发育关联的前瞻性队列研究, columnId=1325529950916465375, journalTitle=中国学校卫生, columnName=母亲妊娠期不良因素对儿童生长发育影响专栏, runingTitle=null, highlight=null, articleAbstract=
目的

分析母亲孕早期金属暴露对子代1岁及3岁时体格发育的影响,为减少重金属对婴幼儿健康的影响提供科学依据。

方法

选取2014—2018年江苏出生队列(JBC)的1 588对母子为研究对象,采用多元线性回归模型、广义估计方程(GEE)和加权分位数和(WQS)回归模型评估母亲孕早期尿液中经尿比重(SG)校正的24种金属质量体积浓度与子代1和3岁时年龄别身长/身高Z评分(HAZ)、年龄别体重Z评分(WAZ)、身长/身高别体重Z评分(WHZ)、年龄别头围Z评分(HCAZ)的关联。

结果

GEE分析发现,在调整混杂因素后,母亲孕早期尿液中钒、锡、铈、铅和铀浓度每增加1个自然对数单位,子代1和3岁时HCAZ平均降低14.29%,4.82%,2.62%,5.04%,8.33%(校正P值均 < 0.05)。多元线性回归分析发现,尿液中钒质量体积浓度增加与子代1岁时HAZ降低相关,尿液中钒、铬、锡、锑和铀质量体积浓度增加与子代1岁时HCAZ降低相关(校正P值均 < 0.05)。在WQS回归模型中,WQS指数每增加1个单位,子代1岁时HCAZ降低22.64%,其中锡在关联中具有最大贡献权重(22.2%),其次是铀(16.2%)、铅(11.5%)、钒(10.0%)、砷(6.5%)和铬(5.0%)。

结论

孕早期特定金属及其混合物暴露对子代1岁及3岁时体格发育,尤其是头围可能产生重要影响。应加强孕早期金属暴露的监测,以减少环境金属污染对婴幼儿健康的潜在威胁。

, authors=张晓1, 2, 蒋杨倩1, 3, 庞丽雅1, 3, 杜江波1, 2, 林苑1, 3, 马红霞1, 2, authorsList=张晓, 蒋杨倩, 庞丽雅, 杜江波, 林苑, 马红霞, authorCompany=null, correspAuthors=null, authorNote=

张晓(2000-),女,四川德阳人,在读硕士,主要研究方向为孕期环境暴露与儿童生长发育

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张晓(2000-),女,四川德阳人,在读硕士,主要研究方向为孕期环境暴露与儿童生长发育

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张晓(2000-),女,四川德阳人,在读硕士,主要研究方向为孕期环境暴露与儿童生长发育

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The detection rates and mass concentration distributions of maternal SG-corrected urinary metal concentrations [M(P25, P75)]

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金属检测限/
(μg·L-1)
检出率/%尿比重校正
质量体积浓度/(μg·L-1)
砷0.017 3100.026.90(18.72, 41.56)
钡0.006 799.720.74(5.07, 57.91)
镉0.000 2100.00.57(0.37, 0.96)
铈0.000 399.70.19(0.02, 0.64)
钴0.001 099.80.43(0.27, 0.72)
铬0.003 099.90.69(0.39, 1.14)
铯0.772 899.912.15(9.81, 15.33)
铜0.035 099.917.6(13.51, 22.59)
镧0.000 796.40.02(0.01, 0.06)
锰0.083 495.70.62(0.33, 1.17)
钼0.010 5100.058.72(45.62, 75.37)
镍0.009 799.93.45(2.29, 5.35)
铅0.003 0100.01.83(1.03, 3.16)
铷0.274 4100.02 289.60(1 782.34, 2 862.61)
铼0.000 1100.00.05(0.03, 0.07)
锑0.001 399.80.13(0.09, 0.19)
硒0.016 2100.011.03(8.42, 14.25)
锡0.032 799.61.16(0.57, 3.13)
锶0.036 5100.0147.20(94.01, 212.82)
铊0.000 7100.00.41(0.31, 0.54)
铀0.000 697.40.01(0.01, 0.02)
钒0.000 1100.00.21(0.16, 0.30)
钛0.024 8100.0147.01(95.59, 211.71)
锌0.553 9100.0443.25(288.30, 672.27)
), ArticleFig(id=1325530035582681287, tenantId=1146029695717560320, journalId=1256213402557890569, articleId=1325530026434904201, language=CN, label=表1, caption=

母亲尿液中金属检出率及经尿比重校正后的质量体积浓度分布[M(P25, P75)]

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金属检测限/
(μg·L-1)
检出率/%尿比重校正
质量体积浓度/(μg·L-1)
砷0.017 3100.026.90(18.72, 41.56)
钡0.006 799.720.74(5.07, 57.91)
镉0.000 2100.00.57(0.37, 0.96)
铈0.000 399.70.19(0.02, 0.64)
钴0.001 099.80.43(0.27, 0.72)
铬0.003 099.90.69(0.39, 1.14)
铯0.772 899.912.15(9.81, 15.33)
铜0.035 099.917.6(13.51, 22.59)
镧0.000 796.40.02(0.01, 0.06)
锰0.083 495.70.62(0.33, 1.17)
钼0.010 5100.058.72(45.62, 75.37)
镍0.009 799.93.45(2.29, 5.35)
铅0.003 0100.01.83(1.03, 3.16)
铷0.274 4100.02 289.60(1 782.34, 2 862.61)
铼0.000 1100.00.05(0.03, 0.07)
锑0.001 399.80.13(0.09, 0.19)
硒0.016 2100.011.03(8.42, 14.25)
锡0.032 799.61.16(0.57, 3.13)
锶0.036 5100.0147.20(94.01, 212.82)
铊0.000 7100.00.41(0.31, 0.54)
铀0.000 697.40.01(0.01, 0.02)
钒0.000 1100.00.21(0.16, 0.30)
钛0.024 8100.0147.01(95.59, 211.71)
锌0.553 9100.0443.25(288.30, 672.27)
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母亲孕早期金属暴露与子代1岁及3岁体格发育关联的前瞻性队列研究
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张晓 1, 2 , 蒋杨倩 1, 3 , 庞丽雅 1, 3 , 杜江波 1, 2 , 林苑 1, 3 , 马红霞 1, 2
中国学校卫生 | 母亲妊娠期不良因素对儿童生长发育影响专栏 2025,46(8): 1088-1092
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中国学校卫生 |母亲妊娠期不良因素对儿童生长发育影响专栏 2025 , 46 (8) : 1088 -1092
母亲孕早期金属暴露与子代1岁及3岁体格发育关联的前瞻性队列研究
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张晓(2000-),女,四川德阳人,在读硕士,主要研究方向为孕期环境暴露与儿童生长发育

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张晓1, 2, 蒋杨倩1, 3, 庞丽雅1, 3, 杜江波1, 2, 林苑1, 3, 马红霞1, 2
作者信息
  • 1南京医科大学生殖医学与子代健康全国重点实验室,江苏 211166
  • 2南京医科大学公共卫生学院流行病学系
  • 3南京医科大学公共卫生学院儿少卫生与妇幼保健学系
作者简介:

张晓(2000-),女,四川德阳人,在读硕士,主要研究方向为孕期环境暴露与儿童生长发育

A prospective cohort study of association between maternal metal exposure during early pregnancy and physical development in offspring at ages 1 and 3
Xiao ZHANG1, 2, Yangqian JIANG1, 3, Liya PANG1, 3, Jiangbo DU1, 2, Yuan LIN1, 3, Hongxia MA1, 2
Affiliations
  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
出版时间: 2025-08-25 doi: 10.16835/j.cnki.1000-9817.2025142
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目的

分析母亲孕早期金属暴露对子代1岁及3岁时体格发育的影响,为减少重金属对婴幼儿健康的影响提供科学依据。

方法

选取2014—2018年江苏出生队列(JBC)的1 588对母子为研究对象,采用多元线性回归模型、广义估计方程(GEE)和加权分位数和(WQS)回归模型评估母亲孕早期尿液中经尿比重(SG)校正的24种金属质量体积浓度与子代1和3岁时年龄别身长/身高Z评分(HAZ)、年龄别体重Z评分(WAZ)、身长/身高别体重Z评分(WHZ)、年龄别头围Z评分(HCAZ)的关联。

结果

GEE分析发现,在调整混杂因素后,母亲孕早期尿液中钒、锡、铈、铅和铀浓度每增加1个自然对数单位,子代1和3岁时HCAZ平均降低14.29%,4.82%,2.62%,5.04%,8.33%(校正P值均 < 0.05)。多元线性回归分析发现,尿液中钒质量体积浓度增加与子代1岁时HAZ降低相关,尿液中钒、铬、锡、锑和铀质量体积浓度增加与子代1岁时HCAZ降低相关(校正P值均 < 0.05)。在WQS回归模型中,WQS指数每增加1个单位,子代1岁时HCAZ降低22.64%,其中锡在关联中具有最大贡献权重(22.2%),其次是铀(16.2%)、铅(11.5%)、钒(10.0%)、砷(6.5%)和铬(5.0%)。

结论

孕早期特定金属及其混合物暴露对子代1岁及3岁时体格发育,尤其是头围可能产生重要影响。应加强孕早期金属暴露的监测,以减少环境金属污染对婴幼儿健康的潜在威胁。

母亲  /  受孕期  /  金属  /  体格检查  /  队列研究
Objective

To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health.

Methods

From 2024 to 2018, a total of 1 588 mother-child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height-for-age Z-score(HAZ), weight-for-age Z-score(WAZ), weight-for-length/height Z-score(WHZ), and head circumference-for-age Z-score(HCAZ) at 1 and 3 years of age.

Results

After adjusting for confounders, GEE analysis revealed that each natural log-unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62%, 5.04%, and 8.33%, respectively, at 1 and 3 years of age (FDR-P < 0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR-P < 0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%).

Conclusions

Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

Mothers  /  Fertile period  /  Mental health  /  Physical examination  /  Cohort studies
张晓, 蒋杨倩, 庞丽雅, 杜江波, 林苑, 马红霞. 母亲孕早期金属暴露与子代1岁及3岁体格发育关联的前瞻性队列研究. 中国学校卫生, 2025 , 46 (8) : 1088 -1092 . DOI: 10.16835/j.cnki.1000-9817.2025142
Xiao ZHANG, Yangqian JIANG, Liya PANG, Jiangbo DU, Yuan LIN, Hongxia MA. A prospective cohort study of association between maternal metal exposure during early pregnancy and physical development in offspring at ages 1 and 3[J]. Chinese Journal of School Health, 2025 , 46 (8) : 1088 -1092 . DOI: 10.16835/j.cnki.1000-9817.2025142
胎儿期是生命早期发育的关键时期,这个阶段由于细胞快速的分裂和分化,致使胎儿对外界环境暴露的影响尤为敏感[1]。胎儿期金属暴露不仅影响胎儿宫内生长发育,导致低出生体重、早产和小于胎龄儿等不良出生结局,还可能对婴幼儿期的生长发育产生持续影响[2-3]。既往研究表明,孕期暴露于铅、钒、镉等单一金属可影响婴幼儿体重、身长、头围等体格发育指标[4-6]。然而,孕妇在实际环境中通常暴露于多种金属混合物[7],因此,其联合效应及健康风险已成为近年来的研究热点[8-10]。
研究表明,婴幼儿期的体格发育与个体远期健康密切相关[11]。因此,探究孕期金属暴露与婴幼儿体格发育的关联对于预防和减少重金属对婴幼儿健康的不良影响具有重要意义。本研究基于前瞻性出生队列研究,检测母亲孕早期尿液中24种金属暴露水平,测量子代1和3岁时的身长/身高、体重和头围,旨在揭示孕早期金属暴露与婴幼儿体格发育的关联,为进一步理解孕早期环境水平金属暴露对婴幼儿生长发育的影响提供更多科学证据。
依托于江苏出生队列(Jiangsu Birth Cohort, JBC)[12],本研究将2014—2018年间在南京医科大学附属妇产医院和南京医科大学附属苏州医院接受产前检查并完成单胎活产分娩的自然妊娠妇女及其子代作为研究对象。具体纳入标准:分娩单胎活产婴儿;完成孕早期[孕(12.3±1.4)周]尿样采集;子代在1,3岁时至少接受一次体格测量。研究最终纳入1 588对符合纳入标准的母子。本研究方案已获得南京医科大学伦理委员会批准(伦理学批号:南医大伦审[2024]880号),所有参与者均签署知情同意书。
在孕早期招募时,由经过专业培训的调查人员采用自行设计问卷开展面对面的问卷调查,收集母亲的基线信息,包括社会人口学特征(如居住地、家庭年收入、教育程度等)、生活方式(如吸烟和饮酒状况)、孕前体重、身高、生育史等。母亲孕前体质量指数(body mass index,BMI)由自报的孕前体重和身高数据计算获得,BMI=体重(kg)/[身高(m)]2。通过分娩住院病历获取新生儿出生信息,包括孕周、出生体重和性别。
收集母亲孕早期尿液样本并分装于无菌聚丙烯离心管中,于-20 ℃冰箱保存供后续分析。使用电感耦合等离子体质谱检测尿液中的钛、钒、铬、锰、钴、镍、铜、锌、砷、硒、铷、锶、钼、镉、锡、锑、铯、钡、镧、铈、铼、铊、铅和铀共24种金属元素的质量体积浓度。为校正尿液稀释度,按照公式:Pc=P[(SGm-1)/(SG-1)]计算尿比重校正浓度(Pc),其中P为未校正浓度,SG为尿比重,SGm为研究人群尿比重中位数(1.018 5)。
子代在1和3岁时,由队列工作人员通过电话邀约至现场随访,并由经过专业培训的护士按照标准流程测量身长/身高(cm)、体重(kg)和头围(cm)。依据2006年世界卫生组织发布的儿童生长发育标准计算Z评分[13],包括年龄别身长/身高Z评分(length/height-for-age Z-score,HAZ)、年龄别体重Z评分(weight-for-age Z-score,WAZ)、身长/身高别体重Z评分(weight-for-length/height Z-score,WHZ)和年龄别头围Z评分(head circumference-for-age Z-score,HCAZ)。
研究基于有向无环图系统筛选统计分析中的潜在混杂因素,最终纳入的协变量包括家庭年总收入、居住地,以及母亲妊娠年龄、孕前BMI、教育程度、被动吸烟情况和产次学。
使用R 4.3.2软件进行统计分析,对连续性资料进行正态性检验,尿比重校正后的金属质量体积浓度均不满足正态分布,采用M(P25, P75)进行统计描述;子代体格测量值及其Z评分满足正态分布,采用(x±s)进行统计描述。对尿比重校正后的金属质量体积浓度进行自然对数(ln)转换,以进行后续分析。首先采用广义估计方程(generalized estimating equation,GEE)评估母亲孕早期金属暴露对子代1和3岁时整体体格发育的影响。随后,采用多元线性回归模型分别分析单金属暴露与子代1,3岁时体格发育的关联。单金属分析中采用错误发现率(false discovery rate,FDR)对P值进行校正,以降低假阳性率。本研究采用加权分位数和(weighted quantile sum,WQS)回归模型,假定24种金属效应方向一致(负向),通过计算WQS指数反映金属混合暴露负荷,并分析其与子代体格发育Z评分的关系。WQS指数每增加1个单位表示尿液中金属混合物浓度增加1个三分位数水平。模型为每种金属分配权重,权重高于阈值(1/金属总数,约4.2%)的金属表明其对WQS指数的贡献高于平均水平。GEE、多元线性回归模型以及WQS回归模型计算得出的回归系数及其95%CI均乘以100,表示母亲尿液中金属浓度每增加1个自然对数单位或WQS指数每增加1个单位,子代体格发育Z评分的百分比变化。双侧检验水准α=0.05。
由表1可知,母亲孕早期尿样中24种金属检出率均高于95%。
分别有1 523和1 023名子代完成了1和3岁现场体格测量。子代1和3岁时的平均身长/身高分别为(76.67±2.82)和(97.62±3.67)cm,平均体重分别为(10.18±1.15)和(14.98±1.78)kg,平均头围分别为(45.93±1.42)和(49.46±1.42)cm。子代1和3岁时的年龄别身长/身高Z评分分别为(0.58±1.06)和(0.54±0.96),年龄别体重Z评分分别为(0.67±0.92)和(0.42±0.91),身长别体重Z评分分别为(0.56±0.96)和(0.17±0.96),年龄别头围Z评分分别为(0.28±0.96)和(0.33±0.94)。
GEE分析结果显示,在调整家庭年总收入、居住地,以及母亲的妊娠年龄、孕前BMI、教育程度、被动吸烟情况和产次后,母亲孕早期尿液中钒质量体积浓度每增加1个自然对数单位,子代1岁和3岁时HAZ平均降低11.50%(95%CI=-19.56%~-2.64%);尿钒、锡、铈、铅和铀质量体积浓度每增加1个自然对数单位,子代1和3岁时HCAZ平均分别降低14.29%(95%CI=-21.53%~-6.38%)、4.82%(95%CI=-8.48%~-1.01%)、2.62%(95%CI=-4.51%~-0.68%)、5.04%(95%CI=-8.73%~-1.19%)和8.33%(95%CI=-12.52%~-3.94%)(P值均 < 0.05)。经过FDR校正后,母亲尿液中钒、锡、铈、铅和铀质量体积浓度与子代1和3岁时整体HCAZ间关联有统计学意义(P值均 < 0.05)。而孕早期金属暴露与子代1和3岁时整体WAZ和WHZ间关联无统计学意义(P值均>0.05)。
分时点进行多元线性回归分析发现,在调整协变量后,母亲孕早期尿液中钒质量体积浓度每增加1个自然对数单位,子代1岁时HAZ降低15.85%(95%CI=-24.23%~-6.54%);尿钒、镉和铈质量体积浓度每增加1个自然对数单位,子代1岁时WAZ分别降低8.69%(95%CI=-16.60%~-0.03%)、6.42%(95%CI=-12.26%~-0.19%)和2.36%(95%CI=-4.38%~-0.29%);尿铈质量体积浓度每增加1个自然对数单位,子代1岁时WHZ降低2.72%(95%CI=-4.83%~-0.58%);尿钒、铬、锰、铜、砷、锡、锑、铅和铀质量体积浓度每增加1个自然对数单位,子代1岁时HCAZ分别降低18.73%(95%CI=-26.07%~-10.66%)、6.28%(95%CI=-10.98%~-1.34%)、5.29%(95%CI=-9.58%~-0.81%)、10.26%(95%CI=-18.62%~-1.05%)、7.41%(95%CI=-13.97%~-0.35%)、8.11%(95%CI=-11.89%~-4.16%)、9.74%(95%CI=-15.18%~-3.95%)、5.01%(95%CI=-9.13%~-0.71%)和8.74%(95%CI=-13.36%~-3.86%);尿铈和铀质量体积浓度每增加1个自然对数单位,子代3岁时HCAZ分别降低3.19%(95%CI=-5.70%~-0.62%)和6.52%(95%CI=-12.22%~-0.45%)(P值均 < 0.05)。经过FDR校正后,母亲尿液中钒质量体积浓度与子代1岁时HAZ间关联以及尿钒、铬、锡、锑和铀质量体积浓度与子代1岁时HCAZ间关联仍有统计学意义(P值均 < 0.05)。研究未观察到母亲孕早期尿液金属暴露与子代3岁时HAZ、WAZ和WHZ间的统计学关联(P值均>0.05)。
由GEE和多元线性回归模型结果显示,母亲孕早期多种金属暴露均与子代1岁时的HCAZ呈负相关。本研究进一步构建WQS回归模型探究多金属暴露的联合效应,在调整家庭年总收入、居住地,以及母亲的妊娠年龄、孕前BMI、教育程度、被动吸烟情况和产次等协变量后,由24种金属混合暴露情况构建的WQS指数每增加1个单位,子代1岁时HCAZ降低22.64%(95%CI=-30.22%~-15.07%,P < 0.01),其中锡(22.2%)、铀(16.2%)、铅(11.5%)、钒(10.0%)、砷(6.5%)和铬(5.0%)对WQS指数的贡献权重大于平均水平。见图1。
本研究基于前瞻性队列研究的1 588对母子探讨了母亲孕早期尿液样本中金属暴露与子代1和3岁体格发育的关联,结果显示,钒、锡、铈、铅和铀暴露与子代1和3岁时整体HCAZ下降相关。钒暴露与1岁时HAZ呈负相关,而钒、铬、锡、锑和铀暴露分别与1岁时HCAZ呈负相关。此外,母亲孕早期24种金属的混合暴露与子代1岁时HCAZ呈负相关,且该效应主要由锡、铀、铅、钒、砷和铬驱动。本研究揭示了母亲孕早期金属混合暴露对子代早期生长发育的影响,特别是头围指标,提示孕早期金属暴露可能对婴幼儿体格发育产生潜在危害。
本研究通过WQS模型分析发现,母亲孕早期金属混合暴露与子代1岁时头围呈负相关,其中锡、铀、铅、钒、砷和铬在该关联中发挥了重要作用。尽管铅和砷在本研究的单金属模型中未显示出关联,但已有研究证明,以上2种金属与婴幼儿头围减小相关[4, 14]。与此同时,锡、铀、钒和铬在单金属模型中均与1岁时HCAZ呈负相关。Kim等[15]发现,在母亲孕26周左右的尿液中,砷、汞、锡3种金属的混合暴露与出生头围减小相关,与本研究中砷和锡在多金属混合暴露中的重要作用一致。一项基于江苏省919对母子的纵向研究[8]发现,母亲孕早期尿液中钒浓度与子代6月龄HCAZ呈负相关,但未观察到与1岁时HCAZ关联有统计学意义。本研究发现,铬、铅等金属混合暴露对子代头围具有负向效应,与一项基于广东省634对母子的研究结果相呼应,该研究揭示了母亲全血中铬、铅、锰和镉的混合暴露与新生儿头围减小相关[16]。铬作为混合暴露中的重要金属之一,其单独作用对婴幼儿头围的负向影响也得到了证据支持。Zhou等[9]对杭州出生队列中743对母子研究发现,母亲孕中期全血铬浓度与女童1.5岁内头围生长速率呈负相关。流行病学研究显示,母亲铀暴露与子代胎龄较低和早产风险增加相关[17-18]。然而,本研究未发现与3岁时头围有显著关联的金属。值得注意的是,出生后第一年是婴幼儿头围快速增长和大脑发育的关键期[19-20],此阶段可能更易受到孕早期金属暴露的影响。头围作为生长发育的重要指标,反映了婴幼儿的发育状况[21],与儿童神经认知障碍、注意力缺陷多动障碍和青春期认知发育密切相关[22-24]。因此,孕早期金属暴露对生命早期头围的影响值得关注,可能对儿童的长期健康和发展产生深远影响。
本研究还发现,母亲孕早期钒暴露与子代1岁时HAZ呈负相关。上海的一项纵向出生队列研究结果显示,母亲孕期总体血清钒浓度与新生儿出生体长减少相关[25]。此外,Yao等[26]基于广州市358对母子的研究也观察到母亲孕早期尿液中钒浓度增加,子代6个月内的身长有降低趋势。然而,另一项基于江苏省919对母子的研究则显示,母亲孕早期尿钒浓度与子代1岁内HAZ呈正相关[8]。该差异可能归因于研究人群在金属暴露水平、地理位置或其他环境因素上的异质性。
孕早期金属暴露可能通过多种生物学机制影响婴幼儿体格发育。研究表明,金属暴露可诱发氧化应激、炎症和内分泌干扰等效应,进而影响胎盘功能、损害母体向胎儿的营养传输并干扰激素调控[27-28]。钒作为一种氧化还原活性金属,通过产生活性氧诱导氧化应激,进而导致细胞损伤[29]。氧化应激已被证明抑制成骨细胞和破骨细胞功能,从而影响骨骼发育[30]。此外,铀不仅能诱发氧化应激,还可能引发炎症和甲状腺功能异常,进一步干扰胎儿内分泌调控和代谢过程[31-32]。尽管现有研究揭示了孕期金属暴露影响婴幼儿发育的多种潜在机制,但其具体机制仍需进一步探索和验证。
本研究存在一定局限性:首先,研究仅评估了母亲孕早期尿液样本中的金属浓度,未能涵盖其他妊娠阶段的金属暴露情况。尽管如此,已有研究指出孕早期可能是金属暴露对婴幼儿体格发育影响的窗口时期[8]。其次,由于纳入的协变量有限,可能未能充分考虑所有潜在的混杂因素。
  • 国家重点研发计划项目(2024YFC2706904)
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2025年第46卷第8期
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doi: 10.16835/j.cnki.1000-9817.2025142
  • 接收时间:2025-01-07
  • 首发时间:2026-11-06
  • 出版时间:2025-08-25
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  • 收稿日期:2025-01-07
  • 修回日期:2025-03-24
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国家重点研发计划项目(2024YFC2706904)
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    1南京医科大学生殖医学与子代健康全国重点实验室,江苏 211166
    2南京医科大学公共卫生学院流行病学系
    3南京医科大学公共卫生学院儿少卫生与妇幼保健学系
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2种不同金属材料的力学参数
科
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genus
种数
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species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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