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Article(id=1325501772621553736, tenantId=1146029695717560320, journalId=1256213402557890569, issueId=1325501647736156411, articleNumber=null, orderNo=null, doi=10.16835/j.cnki.1000-9817.2025088, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1727280000000, receivedDateStr=2024-09-26, revisedDate=1738684800000, revisedDateStr=2025-02-05, acceptedDate=null, acceptedDateStr=null, onlineDate=1793953849224, onlineDateStr=2026-11-06, pubDate=1742832000000, pubDateStr=2025-03-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793953849224, onlineIssueDateStr=2026-11-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793953849224, creator=13701087609, updateTime=1793953849224, updator=13701087609, issue=Issue{id=1325501647736156411, tenantId=1146029695717560320, journalId=1256213402557890569, year='2025', volume='46', issue='3', pageStart='305', pageEnd='456', issueExtLink='null', onlineDate='null', pubDate='1742832000000', pubDateStr='2025-03-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793953819450, creator='13701087609', updateTime=1793953819450, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=396, endPage=401, ext={EN=ArticleExt(id=1325501773171007561, articleId=1325501772621553736, tenantId=1146029695717560320, journalId=1256213402557890569, language=EN, title=Effects of postnatal cadmium exposure on physical and pubertal development in children: a systematic review and Meta-analysis, columnId=1259565862181286284, journalTitle=Chinese Journal of School Health, columnName=Growth, Development and Surveillance, runingTitle=null, highlight=null, articleAbstract=
Objective

To systematically evaluate the effects of postnatal cadmium exposure on children's pubertal and physical development, so as to provide reference for the latter research on cadmium exposure.

Methods

A computer search of PubMed, EBSCO, Web of Science, OVID, CNKI, WanFang, VIP and CBM database were conducted to collect relevant studies, and the search period was from the time of database construction to 27 February 2024. Two reviewers independently screened the literature, extracted data and evaluated the risk of bias of the included studies, and used GRADE to assess the certainty of the evidence for each outcome. Meta-analysis of the risk ratio (HR) for the occurrence of menarche was performed using Stata 17.0 software, and the results were summarized qualitatively for other indicators.

Results

A total of 6 cohort studies were included, comprising four pubertal development and two physical development studies with a total of 2 899 children. Studies of cadmium exposure and menarche in girls all found that late menarche in children with higher urinary cadmium concentrations (HR=0.86, 95%CI=0.74-0.99, P < 0.05; 3 studies; moderate-certainty evidence), and one of these studies found no statistically significant effect of cadmium exposure on breast and pubic hair development in children (aOR=0.90, 95%CI=0.72-1.14; aOR=0.85, 95%CI=0.64-1.13, P>0.05; low-quality evidence); the only study testicular volume, external genitalia and pubic hair development in boys found on effects of urinary cadmium exposure on pubertal development (aOR=0.76, 95%CI=0.50-1.15; aOR=1.07, 95%CI=0.79-1.45; aOR=0.79, 95%CI=0.51-1.23, P>0.05; low-certainty evidence). Regarding the effects of cadmium exposure on children's height and weight (2 studies, low-certainty evidence), the results of one study showed that cadmium exposure was negatively associated with children's physical growth (multivariable-adjusted attributable differences in height and weight study, being -1.60 cm, 95%CI=-2.40 to -0.77 cm; and -0.57 kg, 95%CI=-0.88 to -0.26 kg, P < 0.05), while the other showed no effect of cadmium exposure on children's height and weight (F=1.35, 1.76, P>0.05), but a negative effect on head and chest circumference (F=3.43, 4.50, P < 0.05; low-certainty evidence).

Conclusion

Cadmium exposure in childhood causes delayed menarche in girls and affects physical growth to some extent.

, authors=Tianwenjing HUANG, Zeqin PENG, Qin LIU*, authorsList=Tianwenjing HUANG, Zeqin PENG, Qin LIU, authorCompany=null, correspAuthors=Qin LIU, 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=1325501776438370383, articleId=1325501772621553736, tenantId=1146029695717560320, journalId=1256213402557890569, language=CN, title=出生后镉暴露对儿童体格和青春发育影响的系统评价及Meta分析, columnId=1259565866786632093, journalTitle=中国学校卫生, columnName=生长发育与健康监测, runingTitle=null, highlight=null, articleAbstract=
目的

系统评价出生后镉暴露对儿童青春发育和体格发育的影响，为后期开展镉暴露相关研究提供参考依据。

方法

检索PubMed、EBSCO、Web of Science、OVID、中国知网、万方、维普、中国生物医学文献数据库搜集相关研究，检索时间为建库至2024年2月27日。由2名研究者独立筛选文献、提取资料，评价纳入研究的偏倚风险，并使用定量系统评价证据分级工具(GRADE)分级标准评估每个结局指标的证据质量。使用Stata 17.0软件对发生月经初潮的风险比(HR)进行Meta分析，对其他指标采用定性方法归纳总结。

结果

共纳入6项队列研究，包含4项青春发育和2项体格发育研究，共计2 899名儿童。镉暴露与女童月经初潮的研究均发现尿镉质量体积浓度高的儿童月经初潮到来的更迟(HR=0.86，95%CI=0.74~0.99，P < 0.05；3项研究；中等质量证据)，其中1项研究发现镉暴露对儿童乳房和阴毛发育的影响无统计学意义(aOR=0.90，95%CI=0.72~1.14；aOR=0.85，95%CI=0.64~1.13，P值均＞0.05，低质量证据)；仅1项关于男童睾丸体积、外生殖器和阴毛发育的研究发现尿镉与青春发育的关联无统计学意义(aOR=0.76，95%CI=0.50~1.15；aOR=1.07，95%CI=0.79~1.45；aOR=0.79，95%CI=0.51~1.23，P值均＞0.05，低质量证据)。关于镉暴露对儿童身高、体重的影响(2项研究；低质量证据)，其中1项研究结果显示，镉暴露与儿童体格生长发育呈负相关(身高和体重的多变量调整归因差异分别为-1.60 cm，95%CI=-2.40~-0.77 cm；-0.57 kg，95%CI=-0.88~-0.26 kg，P值均 < 0.05)，另1项研究表明镉暴露对儿童的身高和体重无影响(F值分别为1.35，1.76，P值均＞0.05)，但对头围和胸围产生负向影响(F值分别为3.43，4.50，P值均 < 0.05；低质量证据)。

结论

儿童时期镉暴露会导致女童月经初潮延迟，在一定程度上影响儿童的体格发育。

, authors=黄添文婧, 彭泽钦, 刘琴*, authorsList=黄添文婧, 彭泽钦, 刘琴, authorCompany=null, correspAuthors=刘琴, authorNote=

黄添文婧(1997-)，女，四川省人，在读硕士，主要研究方向为儿童青少年发育与健康

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刘琴，E-mail：
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Basic characteristics of the included literature on the effects of postnatal cadmium exposure on children's pubertal and physical development

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第一作者与年份国家地区样本来源基线样本量分组情况生物样本镉暴露检测年龄/岁结局指标结局指标随访时间
Reynolds(2020)[10]美国社区、学校女：211按照尿镉质量体积浓度(μg/L)分为4组：1组(< 0.2)；2组(0.2~0.3)；3组(0.3~0.4)；4组(≥0.4)尿10~13月经初潮时间每月1次，共随访2年
Ashrap(2019)[11]墨西哥医院女：132未分组尿8~13月经初潮时间，阴毛发育期、乳房发育Tanner分期14~18岁
Ashrap(2020)[12]墨西哥医院男：118未分组尿8~14外生殖器发育期、阴毛发育Tanner分期，睾丸体积10~18岁
Malin Igra (2023)[13]孟加拉国社区女：750按照尿镉质量体积浓度(μg/L)四分位数分为4组：Q1(0.12~0.16)、Q2(0.16~0.23)、Q3(0.23~0.36)、Q4(0.36~3.80)尿5月经初潮时间每6个月随访1次，12~15岁
按照尿镉质量体积浓度(μg/L)四分位数分为4组：Q1(0.02~0.17)、Q2(0.17~0.25)、Q3(0.26~0.39)、Q4(0.39~2.90)尿10
Gardner(2013)[14]孟加拉国社区总：1 505(男：794，女：711)5岁时：(1)尿镉质量体积浓度高(≥P95)、尿镉质量体积浓度低(≤P5)；(2)<0.16，0.16~<0.27，≥0.27 μg/L尿1.5；5身高、体重(1)出生后第1年每月1次；(2)出生后第2年每3个月1次；(3)第5年
姜帅(2014)[15]中国医院横：461(男：236、女：225) 纵：184(1)根据尿镉质量体积浓度的P25、P75分为低、中、高3组；尿镉极高值≥P95，尿镉极低值≤P25。(2)未分组：尿镉质量体积浓度对数值尿1；2；3身高、体重、头围、胸围(1)2岁；(2)3岁
), ArticleFig(id=1325501798190030969, tenantId=1146029695717560320, journalId=1256213402557890569, articleId=1325501772621553736, language=CN, label=表1, caption=

出生后镉暴露对儿童青春发育和体格发育影响纳入文献的基本特征

, figureFileSmall=null, figureFileBig=null, tableContent=
第一作者与年份国家地区样本来源基线样本量分组情况生物样本镉暴露检测年龄/岁结局指标结局指标随访时间
Reynolds(2020)[10]美国社区、学校女：211按照尿镉质量体积浓度(μg/L)分为4组：1组(< 0.2)；2组(0.2~0.3)；3组(0.3~0.4)；4组(≥0.4)尿10~13月经初潮时间每月1次，共随访2年
Ashrap(2019)[11]墨西哥医院女：132未分组尿8~13月经初潮时间，阴毛发育期、乳房发育Tanner分期14~18岁
Ashrap(2020)[12]墨西哥医院男：118未分组尿8~14外生殖器发育期、阴毛发育Tanner分期，睾丸体积10~18岁
Malin Igra (2023)[13]孟加拉国社区女：750按照尿镉质量体积浓度(μg/L)四分位数分为4组：Q1(0.12~0.16)、Q2(0.16~0.23)、Q3(0.23~0.36)、Q4(0.36~3.80)尿5月经初潮时间每6个月随访1次，12~15岁
按照尿镉质量体积浓度(μg/L)四分位数分为4组：Q1(0.02~0.17)、Q2(0.17~0.25)、Q3(0.26~0.39)、Q4(0.39~2.90)尿10
Gardner(2013)[14]孟加拉国社区总：1 505(男：794，女：711)5岁时：(1)尿镉质量体积浓度高(≥P95)、尿镉质量体积浓度低(≤P5)；(2)<0.16，0.16~<0.27，≥0.27 μg/L尿1.5；5身高、体重(1)出生后第1年每月1次；(2)出生后第2年每3个月1次；(3)第5年
姜帅(2014)[15]中国医院横：461(男：236、女：225) 纵：184(1)根据尿镉质量体积浓度的P25、P75分为低、中、高3组；尿镉极高值≥P95，尿镉极低值≤P25。(2)未分组：尿镉质量体积浓度对数值尿1；2；3身高、体重、头围、胸围(1)2岁；(2)3岁
), ArticleFig(id=1325501798655598714, tenantId=1146029695717560320, journalId=1256213402557890569, articleId=1325501772621553736, language=EN, label=Tab.2, caption=

Evaluation of bias risk of included studies on the effect of postnatal cadmium exposure on children's pubertal and physical development

, figureFileSmall=null, figureFileBig=null, tableContent=
第一作者与年份研究对象的代表性研究对象的选择暴露因素的测量方法感兴趣的结局在干预前是否发生是否考虑混杂因素研究组和对照组是否相似对研究对象的结局进行准确无偏倚的评估结果的随访时间是否足够长随访质量是否高总分
Reynolds(2020)[10]1111111018
Ashrap(2019)[11]1011101106
Ashrap(2020)[12]1011101117
Malin Igra(2023)[13]1111110107
Gardner(2013)[14]1111111119
姜帅(2014)[15]1111111108
), ArticleFig(id=1325501799066640507, tenantId=1146029695717560320, journalId=1256213402557890569, articleId=1325501772621553736, language=CN, label=表2, caption=

出生后镉暴露对儿童青春发育和体格发育影响纳入研究的偏倚风险评分

, figureFileSmall=null, figureFileBig=null, tableContent=
第一作者与年份研究对象的代表性研究对象的选择暴露因素的测量方法感兴趣的结局在干预前是否发生是否考虑混杂因素研究组和对照组是否相似对研究对象的结局进行准确无偏倚的评估结果的随访时间是否足够长随访质量是否高总分
Reynolds(2020)[10]1111111018
Ashrap(2019)[11]1011101106
Ashrap(2020)[12]1011101117
Malin Igra(2023)[13]1111110107
Gardner(2013)[14]1111111119
姜帅(2014)[15]1111111108
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出生后镉暴露对儿童体格和青春发育影响的系统评价及Meta分析
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黄添文婧 , 彭泽钦 , 刘琴 *
中国学校卫生 | 生长发育与健康监测 2025,46(3): 396-401
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中国学校卫生 |生长发育与健康监测 2025 , 46 (3) : 396 -401
出生后镉暴露对儿童体格和青春发育影响的系统评价及Meta分析
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黄添文婧, 彭泽钦, 刘琴*
作者信息
  • 重庆医科大学公共卫生学院/环境与人群健康研究中心/医学与社会发展研究中心，重庆 401331
通讯作者:
刘琴，E-mail：
作者简介:

黄添文婧(1997-)，女，四川省人，在读硕士，主要研究方向为儿童青少年发育与健康

Effects of postnatal cadmium exposure on physical and pubertal development in children: a systematic review and Meta-analysis
Tianwenjing HUANG, Zeqin PENG, Qin LIU*
Affiliations
  • School of Public Health, Chongqing Medical University/Research Center for Environment and Human Health/Research Center for Medicine and Social Development, Chongqing (401331), China
出版时间: 2025-03-25 doi: 10.16835/j.cnki.1000-9817.2025088
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摘要
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目的

系统评价出生后镉暴露对儿童青春发育和体格发育的影响，为后期开展镉暴露相关研究提供参考依据。

方法

检索PubMed、EBSCO、Web of Science、OVID、中国知网、万方、维普、中国生物医学文献数据库搜集相关研究，检索时间为建库至2024年2月27日。由2名研究者独立筛选文献、提取资料，评价纳入研究的偏倚风险，并使用定量系统评价证据分级工具(GRADE)分级标准评估每个结局指标的证据质量。使用Stata 17.0软件对发生月经初潮的风险比(HR)进行Meta分析，对其他指标采用定性方法归纳总结。

结果

共纳入6项队列研究，包含4项青春发育和2项体格发育研究，共计2 899名儿童。镉暴露与女童月经初潮的研究均发现尿镉质量体积浓度高的儿童月经初潮到来的更迟(HR=0.86，95%CI=0.74~0.99，P < 0.05；3项研究；中等质量证据)，其中1项研究发现镉暴露对儿童乳房和阴毛发育的影响无统计学意义(aOR=0.90，95%CI=0.72~1.14；aOR=0.85，95%CI=0.64~1.13，P值均＞0.05，低质量证据)；仅1项关于男童睾丸体积、外生殖器和阴毛发育的研究发现尿镉与青春发育的关联无统计学意义(aOR=0.76，95%CI=0.50~1.15；aOR=1.07，95%CI=0.79~1.45；aOR=0.79，95%CI=0.51~1.23，P值均＞0.05，低质量证据)。关于镉暴露对儿童身高、体重的影响(2项研究；低质量证据)，其中1项研究结果显示，镉暴露与儿童体格生长发育呈负相关(身高和体重的多变量调整归因差异分别为-1.60 cm，95%CI=-2.40~-0.77 cm；-0.57 kg，95%CI=-0.88~-0.26 kg，P值均 < 0.05)，另1项研究表明镉暴露对儿童的身高和体重无影响(F值分别为1.35，1.76，P值均＞0.05)，但对头围和胸围产生负向影响(F值分别为3.43，4.50，P值均 < 0.05；低质量证据)。

结论

儿童时期镉暴露会导致女童月经初潮延迟，在一定程度上影响儿童的体格发育。

镉  /  体格生长  /  青春期发育  /  Meta分析  /  儿童
Objective

To systematically evaluate the effects of postnatal cadmium exposure on children's pubertal and physical development, so as to provide reference for the latter research on cadmium exposure.

Methods

A computer search of PubMed, EBSCO, Web of Science, OVID, CNKI, WanFang, VIP and CBM database were conducted to collect relevant studies, and the search period was from the time of database construction to 27 February 2024. Two reviewers independently screened the literature, extracted data and evaluated the risk of bias of the included studies, and used GRADE to assess the certainty of the evidence for each outcome. Meta-analysis of the risk ratio (HR) for the occurrence of menarche was performed using Stata 17.0 software, and the results were summarized qualitatively for other indicators.

Results

A total of 6 cohort studies were included, comprising four pubertal development and two physical development studies with a total of 2 899 children. Studies of cadmium exposure and menarche in girls all found that late menarche in children with higher urinary cadmium concentrations (HR=0.86, 95%CI=0.74-0.99, P < 0.05; 3 studies; moderate-certainty evidence), and one of these studies found no statistically significant effect of cadmium exposure on breast and pubic hair development in children (aOR=0.90, 95%CI=0.72-1.14; aOR=0.85, 95%CI=0.64-1.13, P>0.05; low-quality evidence); the only study testicular volume, external genitalia and pubic hair development in boys found on effects of urinary cadmium exposure on pubertal development (aOR=0.76, 95%CI=0.50-1.15; aOR=1.07, 95%CI=0.79-1.45; aOR=0.79, 95%CI=0.51-1.23, P>0.05; low-certainty evidence). Regarding the effects of cadmium exposure on children's height and weight (2 studies, low-certainty evidence), the results of one study showed that cadmium exposure was negatively associated with children's physical growth (multivariable-adjusted attributable differences in height and weight study, being -1.60 cm, 95%CI=-2.40 to -0.77 cm; and -0.57 kg, 95%CI=-0.88 to -0.26 kg, P < 0.05), while the other showed no effect of cadmium exposure on children's height and weight (F=1.35, 1.76, P>0.05), but a negative effect on head and chest circumference (F=3.43, 4.50, P < 0.05; low-certainty evidence).

Conclusion

Cadmium exposure in childhood causes delayed menarche in girls and affects physical growth to some extent.

Cadmium  /  Physical growth  /  Adolescent development  /  Meta-analysis  /  Child
黄添文婧, 彭泽钦, 刘琴. 出生后镉暴露对儿童体格和青春发育影响的系统评价及Meta分析. 中国学校卫生, 2025 , 46 (3) : 396 -401 . DOI: 10.16835/j.cnki.1000-9817.2025088
Tianwenjing HUANG, Zeqin PENG, Qin LIU. Effects of postnatal cadmium exposure on physical and pubertal development in children: a systematic review and Meta-analysis[J]. Chinese Journal of School Health, 2025 , 46 (3) : 396 -401 . DOI: 10.16835/j.cnki.1000-9817.2025088
正文
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镉(Cd)是一种重金属，国际癌症研究机构已将镉列为Ⅰ类致癌物，世界卫生组织确定镉为优先研究的食品污染物，联合国环境规划署提出12种具有全球性意义的危险化学物质，镉被列为首位[1]。环境污染、吸烟和饮食是人群镉暴露的主要来源[2]，有研究表明，约90%的镉暴露是通过饮食暴露[3]。镉在体内蓄积随年龄增长而升高，儿童处于生长发育关键时期，身体与外界环境进行物质交换的能力较强，较成年人更为敏感，儿童长期暴露于低水平镉可能对生长发育产生影响。内分泌干扰物可干扰正常的激素功能和新陈代谢，从而推迟或加速青春期的到来[4]。镉具有雌激素活性，能模仿雌激素的作用或生物功能[2]。有证据表明，镉可能从幼年就开始影响骨组织，这种毒性效应可导致儿童骨骼生长受阻[5]。目前，关于镉暴露与儿童体格发育和青春发育的关系已开展较多研究[6-7]，但结果尚无统一定论。本研究通过全面检索和严格评价相关研究文献，归纳探究出生后镉暴露对儿童生长发育的影响，为后期开展镉暴露相关研究提供参考依据。
1　资料来源与方法
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1.1　资料来源
检索PubMed、EBSCO、Web of Science、OVID、中国知网、万方、维普、中国生物医学文献数据库获取所有相关研究，检索时间为建库至2024年2月27日。检索词共包含三类：(1)儿童相关检索词。中文检索词为婴幼儿，儿童，男童，女童，青少年，未成年，学生；英文检索词为Infant*，Child*，Adolescent*，Teen*，Teenager*，Youth*，Student*，Pupil，Juvenile，Underage，Boy，Girl。(2)第二类中文检索词为镉，英文检索词为Cadmium。(3)体格和青春发育相关检索词。中文检索词为青春期，青春发育，青春发动时相，月经初潮，首次遗精，Tanner，乳房，腋毛，阴毛，睾丸体积，身材，身高，体重，腰围，臀围，胸围，头围，矮小，肥胖，BMI，腰臀比，腰高比；英文检索词为Pubert*，Onset puberty，Menarche，First spermatorrhea，Tanner，Thelarche，Pubarche，Pubic hair，Testicular volume，Genitalia，Body Sizes，Stature，Height，Short，Wei-ght，Waist-height Ratio，Height-weight Ratio，WHtR，Waist，Waist-hip Ratio，Waist-to-hip Ratio，WHR，Hip，Overweight，Obesity，Body mass index，BMI，Quetelet*Index。同一类检索词间用“OR”连接，不同类检索词间用“AND”连接。
1.2　纳入排除标准
纳入标准：(1)研究对象为 < 18岁的儿童；(2)暴露因素为出生后重金属镉的内暴露情况；(3)结局指标中，体格发育指标包括身高、体重、腰围、臀围、腰臀比、腰高比、胸围、头围、体质量指数(body mass index, BMI)；青春发育指标包括月经初潮时间、首次遗精时间、乳房发育Tanner分期、阴毛发育Tanner分期、腋毛发育Tanner分期、外生殖器发育Tanner分期、睾丸体积；(4)研究设计为队列研究。排除标准：(1)研究对象为新生儿，患有任何会影响青春发育和体格发育的疾病；(2)镉的外暴露，重金属的混合暴露，产前镉暴露；(3)结局是青春发育和体格发育以外的其他生长发育指标；(4)研究和文献类型不符，如动物实验、观点性文章、评论、项目介绍、会议摘要等；(5)语言非中英文文献；(6)重复研究。
1.3　文献筛选和资料提取
2人独立筛选标题和摘要，再对满足纳入标准的文献进行全文评估。从每个符合条件的研究中，使用Excel表格分别独立提取作者、发表年份、国家、研究类型、研究对象基本特征、暴露的测量情况、体格发育指标、青春发育指标信息。在正式提取数据前进行预提取。
1.4　纳入研究的质量评价
对于每项研究，使用纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale，NOS)由2人独立进行偏倚风险的评估，包括研究人群选择、可比性、暴露/结果评价3个维度，其中研究人群选择包括研究对象的代表性(1分)、研究对象的选择(1分)、暴露因素的测量方法(1分)、感兴趣的结局在干预前是否发生(1分)；可比性包括是否考虑混杂因素(1分)、研究组和对照组是否相似(1分)；暴露/结果评价包括对研究对象的结局进行了准确无偏倚的评估(1分)、结果的随访时间是否足够长(1分)、随访质量是否高(1分)。共8个条目，其中可比性条目拆分为2个1分的条目进行评价。除可比性一项最高可得2分外，其他条目最高可得1分，得分范围0~9分；其中＜5分为低质量，5~7分为中等质量，8~9分为高质量[8]。使用定量系统评价证据分级工具(Grade of Recommendations Assessment，Development and Evaluation，GRADE)评估每个结局指标的证据质量[9]，根据研究类型确定最开始证据质量的高低，随机对照试验(randomized controlled trial，RCT)开始被定为支持干预效果估计的高质量证据，而观察性研究定为低质量证据，5种因素(研究局限、不精确、结果不一致、间接证据、可能的发表偏倚)可导致证据质量下降，3种因素(效应量大、剂量反应、混杂因素使效应降到最低)则可提升证据质量。最终，每一结局相应的证据质量归属于高、中、低或极低分级四类之一。
1.5　统计学分析
采用定性方法总结纳入研究的基本信息，包括研究开展时间、研究国家、研究对象基本特征、生物样本检测时间等；然后分别归纳镉暴露对乳房、阴毛、睾丸体积和外生殖器发育的影响，以及对身高、体重、头围、胸围的影响。使用Stata 17.0软件对结局指标月经初潮的发生进行Meta分析，风险比(hazard ratio, HR)为效应分析统计量，计算其95%置信区间和P值，若P < 0.05为有统计学意义。根据异质性检验结果，I2 < 20%时采用固定效应模型进行Meta分析，I2≥20%时采用随机效应模型进行Meta分析，并进行亚组分析。
2　结果
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2.1　文献筛选流程及结果
通过数据库和其他途径共获得相关文献2 576篇，按照纳入排除标准进行初筛和全文筛选后，最终纳入6篇文献[10-15]。文献筛选流程及结果见图1。
2.2　纳入研究的基本特征
共纳入4项[10-13]青春发育和2项[14-15]体格发育的队列研究，涉及4个不同国家的2 899名儿童。青春发育指标包括女童月经初潮时间、乳房和阴毛发育Tanner分期，男童睾丸体积、外生殖器发育和阴毛发育Tanner分期；体格发育指标有身高、体重、胸围、头围。文献基本特征见表1。
2.3　纳入研究的偏倚风险评估结果
纳入研究的偏倚风险评价结果见表2。在纳入的6项队列研究中，3项研究被评价为高质量，3项研究被评价为中等质量。
2.4　镉暴露对儿童青春发育的影响
纳入的4项[10-13]青春发育研究中，3项[10-11, 13]关注女童月经初潮时间，其中1项[11]还关注女童乳房和阴毛发育；1项[12]关注男童睾丸发育、外生殖器发育、阴毛发育。
2.4.1　镉暴露对月经初潮的影响
3项队列研究[9, 11, 13]结果一致表明，儿童时期高尿镉水平的女童月经初潮时间更迟。对其中2项研究进行Meta分析结果显示，相较于低镉暴露，高镉暴露女童的月经初潮发生率降低了14%(HR=0.86，95%CI=0.74~0.99，I2=53.95%，P < 0.05，中等质量证据)。再根据尿镉质量体积浓度四分位数分为Q2、Q3、Q4三组进行亚组分析，HR值(95%CI)分别为0.93(0.74~1.16)(P>0.05)、0.93(0.71~1.23)(P>0.05)、0.75(0.63~0.88)(P < 0.05)；I2值分别为43.33%，58.99%，0.00%。见图2。
2.4.2　镉暴露对其他青春发育指标的影响
Ashrap等[11]研究表明，青春期尿镉质量体积浓度与女童乳房发育和阴毛发育均无关联[aOR值(95%CI)分别为0.85(0.64~1.13)，0.90(0.72~1.14)]；仅有1项针对男童的研究[12]未发现尿镉质量体积浓度与男童睾丸体积、外生殖器发育、阴毛发育之间存在关联[aOR值(95%CI)分别为1.07(0.79~1.45)，0.79(0.51~1.23)，0.76(0.50~1.15)](P值均>0.05)。
2.5　镉暴露对儿童体格发育的影响
在纳入的2项[14-15]体格发育研究中，Gardner等[14]结果表明，与低尿镉儿童相比，高尿镉儿童5岁时身高的多变量调整归因差异为-1.60(95%CI=-2.40~-0.77) cm，体重的多变量调整归因差异为-0.57(95%CI=-0.88~-0.26)kg(P值均 < 0.05)；在对性别进行分层分析后，尿镉质量体积浓度与儿童生长之间的负相关关系在女童中更为明显，即使控制其他环境暴露和儿童生长的相关因素后，这种负相关仍然存在。姜帅等[15]分析结果显示，1~3岁连续3年尿镉水平均在低暴露组与均在高暴露组的儿童3岁时的身高和体重差异无统计学意义(F值分别为1.35，1.76，P值均>0.05)；但高暴露组比低暴露组的头围和胸围更小(F值分别为3.43，4.50，P值均 < 0.05)。受研究类型的限制，身高、体重、头围、胸围均为低质量证据。
3　讨论
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本系统评价共纳入6个有关镉暴露对儿童青春发育和体格发育影响的队列研究，主要针对18岁以下的儿童青少年。结果表明，高尿镉质量体积浓度的女童月经初潮的发生会延迟，异质性可能来源于儿童来自不同国家以及暴露年龄不同。对于女生来说，月经初潮是一个重要的里程碑，是性成熟的重要标志；同时也是公认青春发育启动的可靠指标，与乳房发育的年龄高度相关[16]。与之前的横断面分析[10, 13, 17]结果不太一致，本系统评价表明镉暴露不会对乳房和阴毛发育产生影响，但仍需要开展更多的队列研究加以证实，因为仅有1项研究报道此结果。有研究发现，子宫内镉暴露可能通过诱发氧化应激，损害卵巢功能和发育，导致雌性大鼠青春期延迟以及类固醇激素水平受损[18]；在另一项青春期前暴露于有毒剂量镉的动物实验中证明，镉会通过扰乱类固醇激素浓度而延迟青春发育启动，并减少卵巢卵泡储存量[19]。
本次仅发现1项镉暴露对男童睾丸、外生殖器、阴毛发育影响的研究，但结果均无统计学意义。而有横断面研究[20]显示镉暴露会延迟男生的性成熟，睾丸体积与镉浓度呈反比。动物实验发现，镉暴露可能破坏下丘脑-垂体-睾丸轴的功能，从而改变激素环境[21-23]，通过抑制与青春期启动有关的性类固醇激素的分泌，导致性成熟推迟[24-25]。研究发现，镉对大鼠生殖器官的氧化还原系统会产生不同程度的影响，并降低睾酮水平，这些影响在延迟雄性大鼠青春期标志物的出现方面起关键作用[26]。镉暴露的动物研究通常是在高于普通人群暴露水平的条件下进行，而低剂量的镉可能具有拟性激素作用[27]，若采用与环境类似的镉暴露水平进行研究，可能会得到不同结果。
由于激素在儿童体内的预期浓度较低且激素分泌的昼夜模式及大多数激素作为标记物的不敏感性[28]，此次系统评价只针对第一和第二性征相关的指标。同时，在检索的文献中也筛选出关于激素的研究，发现仅有针对激素的横断面分析，并未有相关纵向研究结果，因此未纳入激素相关研究。
儿童时期镉暴露对体格发育影响的队列研究很少，在仅发现的2项研究中，孟加拉国的大型出生队列[14]结果显示，高尿镉水平的儿童身高更矮、体重更轻。中国的队列研究[15]结果显示，1~3岁连续测量的尿镉水平对儿童3岁时的身高和体重无影响，对头围和胸围产生负向影响，仅在现况研究的多因素回归分析中发现儿童身高与镉暴露呈负相关。2项研究的结果不一致，可能与不同地区镉暴露水平的差异及不同年龄段儿童对重金属的敏感性不同有关。流行病学研究表明，暴露于镉的10岁儿童骨吸收和脱矿增加，镉从早期就开始影响骨组织[5]，这种毒性作用可能导致儿童骨骼生长受损，从而导致身高降低。实验研究也支持流行病学证据，镉具有直接的骨毒性效应[29]；镉暴露还可能影响儿童体内钙、锌的分布和功能[14]。此外，高剂量的镉会降低血浆中胰岛素样生长因子-1的浓度，这是一种对儿童生长至关重要的激素[30]。儿童时期镉暴露对其体重影响的潜在生物学机制尚不明确，可能是由于镉对雌激素和其他类固醇激素的影响，会诱导脂质动员和脂肪分解[31]；镉作为一种内分泌干扰物，能够模拟或抑制内源性雌二醇的功能[32]。国内外虽已开展较多儿童时期镉暴露对体格发育影响的横断面研究[33-36]，但结果仍然很不一致，且镉对儿童体格发育产生影响可能需要较长时间的暴露，作用效果可能存在滞后，横断面研究也较难发现其中的关联。
目前，国内尚未开展镉暴露对儿童青春发育影响的相关研究，体格发育相关的队列研究也很少，受研究数量的限制，尚不能确定镉暴露与部分生长发育指标间的关系；未来需要开展更多高质量的前瞻性队列研究，进一步阐明儿童时期镉暴露会对体格发育产生何种影响，验证是否会导致青春发育延迟。同时报告身高、体重、腰围、臀围、月经初潮时间、首次遗精时间、乳房达到TannerⅡ时间、阴毛达到TannerⅡ时间，以便为后续相关研究提供参考依据。镉会在体内蓄积至成年，儿童时期高水平的镉暴露会导致女童青春发育延迟，在一定程度上影响儿童的生长发育，该时期的镉负荷将可能对其一生的健康产生影响，因此应尽可能从幼年开始就减少镉的接触。受纳入研究数量的限制，上述结论尚待更多高质量研究予以验证。
基金
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  • 重庆医科大学未来医学青年创新团队发展支持计划项目(W0054)
文献
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2025年第46卷第3期
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doi: 10.16835/j.cnki.1000-9817.2025088
  • 接收时间：2024-09-26
  • 首发时间：2026-11-06
  • 出版时间：2025-03-25
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  • 收稿日期：2024-09-26
  • 修回日期：2025-02-05
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重庆医科大学未来医学青年创新团队发展支持计划项目(W0054)
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    重庆医科大学公共卫生学院/环境与人群健康研究中心/医学与社会发展研究中心，重庆 401331

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刘琴，E-mail：
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https://castjournals.cast.org.cn/joweb/zgxxws/CN/10.16835/j.cnki.1000-9817.2025088
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
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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