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Article(id=1322608113916690440, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1322608013010120712, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202504459, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1745510400000, receivedDateStr=2025-04-25, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793263947228, onlineDateStr=2026-10-29, pubDate=1762704000000, pubDateStr=2025-11-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793263947228, onlineIssueDateStr=2026-10-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793263947228, creator=13701087609, updateTime=1793263947228, updator=13701087609, issue=Issue{id=1322608013010120712, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='21', pageStart='3841', pageEnd='4032', issueExtLink='null', onlineDate='null', pubDate='1762704000000', pubDateStr='2025-11-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793263923169, creator='13701087609', updateTime=1793264266929, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322609454932149086, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1322608013010120712, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322609454932149087, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1322608013010120712, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3909, endPage=3915, ext={EN=ArticleExt(id=1322608114696830985, articleId=1322608113916690440, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Association between mixed exposure to perfluoroalkyl and polyfluoroalkyl substances and metabolic abnormalities in overweight and obese children and adolescents, columnId=1228016570660745413, journalTitle=Modern Preventive Medicine, columnName=Environmental and Occupational Health, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the relationship between serum perfluorinated and polyfluoroalkyl substances (PFAS) exposure and metabolic abnormalities in overweight and obese children and adolescents.

Methods

This study was a cross-sectional design. The study subjects were overweight and obese children and adolescents aged 5-17 years who visited the Department of Child Health Care at the Children’s Hospital Affiliated to Nanjing Medical University from July to October 2022. Logistic regression analysis was used to investigate the association between PFAS exposure and high blood glucose, high triglyceride, high cholesterol, low high-density lipoprotein, hypertension, high uric acid, insulin resistance and ≥2 cardiometabolic abnormalities in overweight and obese children and adolescents. Bayesian kernel machine regression and quantile g-computation were used to analyze the relationship between mixed exposure to PFAS and the risk of metabolic abnormalities in overweight and obese children.

Results

Among the 220 overweight and obese children, 166 were male(75.5%), with an age of 10.7 (8.8, 12.3) years. A total of 131 children (59.1%) had ≥2 cardiometabolic abnormalities. The levels of PFHxA and PFNA were positively correlated with the risk of hypertriglyceridemia in overweight and obese children (ORPFHxA=1.670, 95% CI: 1.005-2.776; ORPFNA=1.415, 95% CI: 1.062-1.883). The concentration of PFHpA was positively correlated with the risk of hypertension (OR=1.980, 95% CI: 1.269-3.087). Four serum PFAS concentrations were positively correlated with the risk of insulin resistance. Serum PFHpA and PFNA concentrations were positively correlated with the risk of ≥2 cardiometabolic abnormalities (ORPFHpA=1.716, 95% CI: 1.155-2.551; ORPFNA=1.324, 95% CI: 1.003-1.749). In overweight and obese children, the mixed exposure to PFAS was positively correlated with the risk of hyperglycemia, insulin resistance, hypertension, hypertriglyceridemia, and ≥2 cardiometabolic abnormalities, with PFHpA having the largest weight.

Conclusion

Exposure to serum PFAS could increase the risk of abnormal glucose and lipid metabolism, hypertension and ≥2 obesity-related metabolic abnormalities in overweight and obese children and adolescents.

, authors=Qing-qing ZHENG1, Wu YAN2, Sheng-hu GAO1, Ya-nan SHI1, Meng-yao CAO1, Xiao-nan LI1, authorsList=Qing-qing ZHENG, Wu YAN, Sheng-hu GAO, Ya-nan SHI, Meng-yao CAO, Xiao-nan LI, authorCompany=null, correspAuthors=Xiao-nan LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, 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=1322608118501064719, articleId=1322608113916690440, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=全氟及多氟烷基化合物混合暴露与超重/肥胖儿童及青少年代谢异常的关系研究, columnId=1228016571273113811, journalTitle=现代预防医学, columnName=环境与职业卫生, runingTitle=null, highlight=null, articleAbstract=
目的

探讨超重/肥胖儿童及青少年血清全氟及多氟烷基化合物（perfluoroalkyl and polyfluoroalkyl substances，PFAS）暴露与其代谢异常的关系。

方法

横断面设计，研究对象为2022年7—10月在南京医科大学附属儿童医院儿童保健科就诊的5～17岁的超重/肥胖儿童及青少年。采用logistic回归探讨超重/肥胖儿童及青少年PFAS暴露与高血糖、高甘油三酯、高胆固醇、低高密度脂蛋白、高血压、高尿酸、胰岛素抵抗及存在≥2种心血管代谢异常的关联；利用贝叶斯核机器回归和分位数g计算回归分析超重/肥胖儿童PFAS混合暴露与代谢异常风险的关系。

结果

220名超重/肥胖儿童中，男童占75.5%，年龄10.7（8.8，12.3）岁，131名（59.1%）存在≥2种心血管代谢异常。超重/肥胖儿童血清全氟己酸（perfluorohexanoic acid，PFHxA）、全氟壬酸（perfluorononanoic acid，PFNA）的浓度与高甘油三酯发生风险呈正相关（ORPFHxA= 1.670，95% CI：1.005～2.776; ORPFNA=1.415，95% CI：1.062～1.883）；血清全氟庚烷酸（perfluoroheptanoic acid，PFHpA）的浓度与高血压发生风险呈正相关(OR=1.980，95% CI：1.269～3.087）。四种PFAS的暴露水平与胰岛素抵抗发生风险呈正相关；而血清PFHpA和PFNA浓度与超重/肥胖儿童合并≥2种心血管代谢异常的风险呈正相关(ORPFHpA=1.716，95% CI：1.155～2.551;ORPFNA=1.324，95% CI：1.003～1.749)。超重/肥胖儿童PFAS混合暴露水平与高血糖、胰岛素抵抗、高血压、高甘油三酯及合并≥2种心血管代谢异常的风险呈正相关，其中PFHpA权重最大。

结论

儿童青少年血清中的PFAS暴露可能增加超重/肥胖儿童发生糖脂代谢异常、高血压和合并两种及以上肥胖相关代谢异常的风险。

, authors=郑青青1, 燕武2, 高胜虎1, 师亚楠1, 曹梦瑶1, 李晓南1, authorsList=郑青青, 燕武, 高胜虎, 师亚楠, 曹梦瑶, 李晓南, authorCompany=null, correspAuthors=李晓南, authorNote=

郑青青与燕武为共同第一作者

郑青青（1998—），女，硕士，医师，研究方向：环境暴露与儿童健康；

燕武（1993—），女，博士，助理研究员，研究方向：环境暴露与妇幼健康；

, correspAuthorsNote=
李晓南，E-mail：
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Toxics, 2023, 11 (11): 905., articleTitle=Association between Urinary BPA Substitutes and Precocious Puberty among Girls: A Single-Exposure and Mixed Exposure Approach from a Chinese Case-Control Study, refAbstract=null)], funds=[Fund(id=1322608126898061385, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, awardId=F202213, language=CN, fundingSource=江苏省妇幼保健科研项目(F202213), fundOrder=null, country=null), Fund(id=1322608126973558858, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, awardId=YKK22156, language=CN, fundingSource=南京市卫生科技项目(YKK22156), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1322608119360897040, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, xref=1., ext=[AuthorCompanyExt(id=1322608119369285649, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, companyId=1322608119360897040, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Child Health, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China), AuthorCompanyExt(id=1322608119377674258, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, companyId=1322608119360897040, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.南京医科大学附属儿童医院儿童保健科，江苏　南京　210008)]), AuthorCompany(id=1322608119453171731, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, xref=2., ext=[AuthorCompanyExt(id=1322608119461560340, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, companyId=1322608119453171731, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.南京医科大学附属儿童医院临床医学研究中心，江苏　南京　210008)])], figs=[ArticleFig(id=1322608124381478975, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=EN, label=Figure 1, caption=BKMR model analysis of the association between PFAS mixture exposure and metabolic abnormalities in overweight and obese children, figureFileSmall=lhE/t0tcW71Id+rlL6WXTg==, figureFileBig=ZwUgz/QFceNN30X6UK9jNQ==, tableContent=null), ArticleFig(id=1322608124461170752, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=CN, label=图1, caption=BKMR模型探讨超重/肥胖儿童中PFAS混合暴露与代谢异常的关系

注：A高血糖; B高甘油三酯; C高胆固醇; D低HDL-C; E高血压; F高尿酸; G胰岛素抵抗; H≥2种心血管代谢异常。

, figureFileSmall=lhE/t0tcW71Id+rlL6WXTg==, figureFileBig=ZwUgz/QFceNN30X6UK9jNQ==, tableContent=null), ArticleFig(id=1322608126260527171, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=EN, label=Table 1, caption=

Baseline characteristics of overweight and obese children and adolescents in the included study［n=220，M（P25，P75），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
特征分类统计描述
年龄（岁）10.7(8.8, 12.3)
性别男166(75.5)
女54(24.5)
BMI（kg/m2）25.4(21.7, 28.2)
BMI-Z2.6(2.0, 3.1)
体脂百分比（%）34.6(29.0, 39.8)
父亲BMI（kg/m2）26.3(24.5, 27.8)
母亲BMI（kg/m2）23.5(21.5, 28.2)
父亲学历高中及以下62(28.2)
大专54(24.5)
本科及以上104(47.3)
母亲学历高中及以下64(29.1)
大专59(26.8)
本科及以上97(44.1)
家族史（种）031(14.1)
144(20.0)
252(23.6)
≥393(42.3)
喂养方式母乳喂养105(47.8)
人工喂养37(16.8)
混合喂养78(35.5)
代谢异常高血糖14(6.4)
高甘油三酯52(23.6)
高胆固醇18(8.2)
低HDL-C21(9.5)
高血压61(27.7)
高尿酸120(54.5)
胰岛素抵抗148(67.3)
≥2种心血管代谢异常131(59.1)
), ArticleFig(id=1322608126352801860, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=CN, label=表1, caption=

纳入研究的超重/肥胖儿童青少年的基本特征［n=220，M（P25，P75），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
特征分类统计描述
年龄（岁）10.7(8.8, 12.3)
性别男166(75.5)
女54(24.5)
BMI（kg/m2）25.4(21.7, 28.2)
BMI-Z2.6(2.0, 3.1)
体脂百分比（%）34.6(29.0, 39.8)
父亲BMI（kg/m2）26.3(24.5, 27.8)
母亲BMI（kg/m2）23.5(21.5, 28.2)
父亲学历高中及以下62(28.2)
大专54(24.5)
本科及以上104(47.3)
母亲学历高中及以下64(29.1)
大专59(26.8)
本科及以上97(44.1)
家族史（种）031(14.1)
144(20.0)
252(23.6)
≥393(42.3)
喂养方式母乳喂养105(47.8)
人工喂养37(16.8)
混合喂养78(35.5)
代谢异常高血糖14(6.4)
高甘油三酯52(23.6)
高胆固醇18(8.2)
低HDL-C21(9.5)
高血压61(27.7)
高尿酸120(54.5)
胰岛素抵抗148(67.3)
≥2种心血管代谢异常131(59.1)
), ArticleFig(id=1322608126445076549, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=EN, label=Table 2, caption=

Regression analysis of individual PFAS exposure and metabolic abnormalities in overweight and obese children

, figureFileSmall=null, figureFileBig=null, tableContent=
PFAS高血糖高甘油三酯高胆固醇低HDL-C高血压高尿酸胰岛素抵抗≥2种心血管代谢异常
OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值
PFBA1.049(0.416～2.646)0.9190.838(0.485～1.447)0.5260.449(0.195～1.036)0.0601.212(0.562～2.616)0.6240.816(0.491～1.356)0.4310.695(0.424～1.140)0.1492.317(1.298～4.137)0.0041.097(0.641～1.877)0.736
PFPeA0.677(0.322～1.427)0.3060.767(0.498～1.182)0.2290.614(0.324～1.163)0.1340.621(0.344～1.121)0.1140.982(0.652～1.478)0.9310.830(0.565～1.219)0.3421.441(0.941～2.204)0.0931.106(0.716～1.708)0.649
PFHxA1.441(0.617～3.367)0.3991.670(1.005～2.776)0.0480.817(0.442～1.507)0.5170.812(0.463～1.422)0.4650.827(0.560～1.221)0.3401.100(0.747～1.622)0.6291.887(1.230～2.893)0.0041.476(0.945～2.305)0.087
PFHpA1.582(0.718～3.487)0.2551.117(0.759～1.643)0.5740.745(0.423～1.311)0.3071.009(0.592～1.718)0.9741.980(1.269～3.087)0.0031.029(0.749～1.412)0.8621.724(1.188～2.501)0.0041.716(1.155～2.551)0.008
PFOA1.615(0.975～2.677)0.0631.138(0.951～1.363)0.1591.723(1.129～2.629)0.0120.982(0.768～1.254)0.8820.980(0.842～1.140)0.7901.007(0.874～1.160)0.9261.149(0.980～1.348)0.0871.075(0.913～1.266)0.384
PFNA1.599(0.986～2.594)0.0571.415(1.062～1.883)0.0181.504(0.973～2.324)0.0661.171(0.798～1.719)0.4191.302(0.997～1.700)0.0531.072(0.846～1.358)0.5651.263(0.963～1.657)0.0911.324(1.003～1.749)0.047
PFOS0.895(0.653～1.226)0.4901.113(0.880～1.408)0.3730.888(0.657～1.202)0.4431.212(0.562～2.616)0.6240.975(0.791～1.202)0.8101.015(0.840～1.226)0.8801.243(1.012～1.527)0.0381.116(0.900～1.384)0.317
), ArticleFig(id=1322608126512185414, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=CN, label=表2, caption=

超重/肥胖儿童的PFAS单一暴露与代谢异常的回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
PFAS高血糖高甘油三酯高胆固醇低HDL-C高血压高尿酸胰岛素抵抗≥2种心血管代谢异常
OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值OR（95% CI）P值
PFBA1.049(0.416～2.646)0.9190.838(0.485～1.447)0.5260.449(0.195～1.036)0.0601.212(0.562～2.616)0.6240.816(0.491～1.356)0.4310.695(0.424～1.140)0.1492.317(1.298～4.137)0.0041.097(0.641～1.877)0.736
PFPeA0.677(0.322～1.427)0.3060.767(0.498～1.182)0.2290.614(0.324～1.163)0.1340.621(0.344～1.121)0.1140.982(0.652～1.478)0.9310.830(0.565～1.219)0.3421.441(0.941～2.204)0.0931.106(0.716～1.708)0.649
PFHxA1.441(0.617～3.367)0.3991.670(1.005～2.776)0.0480.817(0.442～1.507)0.5170.812(0.463～1.422)0.4650.827(0.560～1.221)0.3401.100(0.747～1.622)0.6291.887(1.230～2.893)0.0041.476(0.945～2.305)0.087
PFHpA1.582(0.718～3.487)0.2551.117(0.759～1.643)0.5740.745(0.423～1.311)0.3071.009(0.592～1.718)0.9741.980(1.269～3.087)0.0031.029(0.749～1.412)0.8621.724(1.188～2.501)0.0041.716(1.155～2.551)0.008
PFOA1.615(0.975～2.677)0.0631.138(0.951～1.363)0.1591.723(1.129～2.629)0.0120.982(0.768～1.254)0.8820.980(0.842～1.140)0.7901.007(0.874～1.160)0.9261.149(0.980～1.348)0.0871.075(0.913～1.266)0.384
PFNA1.599(0.986～2.594)0.0571.415(1.062～1.883)0.0181.504(0.973～2.324)0.0661.171(0.798～1.719)0.4191.302(0.997～1.700)0.0531.072(0.846～1.358)0.5651.263(0.963～1.657)0.0911.324(1.003～1.749)0.047
PFOS0.895(0.653～1.226)0.4901.113(0.880～1.408)0.3730.888(0.657～1.202)0.4431.212(0.562～2.616)0.6240.975(0.791～1.202)0.8101.015(0.840～1.226)0.8801.243(1.012～1.527)0.0381.116(0.900～1.384)0.317
), ArticleFig(id=1322608126596071495, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=EN, label=Table 3, caption=

QGC model analysis of the association between PFAS mixture exposure and metabolic abnormalities in overweight and obese children

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代谢异常OR（95% CI）P值权重方向总效应PFBAPFPeAPFHxAPFHpAPFOAPFNAPFOS
高血糖5.686(1.162～27.818)0.032正2.1100.3510.1710.2870.191
负-0.3670.8180.1030.079
高甘油三酯1.593(0.774～3.279)0.206正1.2100.3450.0090.0590.2400.347
负-0.7420.4760.524
高胆固醇1.051(0.326～3.392)0.934正1.0900.0490.5780.2940.079
负-1.040.3350.2690.396
低HDL-C0.858(0.325～2.267)0.758正0.5520.6110.2900.100
负-0.7050.6640.1920.0890.056
高血压2.692(1.276～5.678)0.009正1.2700.0370.4390.0970.2410.188
负-0.2810.1220.878
高尿酸1.021(0.546～1.910)0.949正0.2820.1520.2120.637
负-0.2610.3840.2090.3090.099
胰岛素抵抗5.276(2.380～11.695)<0.001正1.6600.2300.0620.0110.3500.0680.1980.081
负0
≥2种心血管代谢异常3.091(1.464～6.525)0.003正1.2400.1150.0040.0070.4310.3320.112
负-0.1101
), ArticleFig(id=1322608126684151880, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608113916690440, language=CN, label=表3, caption=

QGC模型探讨超重/肥胖儿童PFAS混合暴露与代谢异常的关系

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代谢异常OR（95% CI）P值权重方向总效应PFBAPFPeAPFHxAPFHpAPFOAPFNAPFOS
高血糖5.686(1.162～27.818)0.032正2.1100.3510.1710.2870.191
负-0.3670.8180.1030.079
高甘油三酯1.593(0.774～3.279)0.206正1.2100.3450.0090.0590.2400.347
负-0.7420.4760.524
高胆固醇1.051(0.326～3.392)0.934正1.0900.0490.5780.2940.079
负-1.040.3350.2690.396
低HDL-C0.858(0.325～2.267)0.758正0.5520.6110.2900.100
负-0.7050.6640.1920.0890.056
高血压2.692(1.276～5.678)0.009正1.2700.0370.4390.0970.2410.188
负-0.2810.1220.878
高尿酸1.021(0.546～1.910)0.949正0.2820.1520.2120.637
负-0.2610.3840.2090.3090.099
胰岛素抵抗5.276(2.380～11.695)<0.001正1.6600.2300.0620.0110.3500.0680.1980.081
负0
≥2种心血管代谢异常3.091(1.464～6.525)0.003正1.2400.1150.0040.0070.4310.3320.112
负-0.1101
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全氟及多氟烷基化合物混合暴露与超重/肥胖儿童及青少年代谢异常的关系研究
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郑青青 1 , 燕武 2 , 高胜虎 1 , 师亚楠 1 , 曹梦瑶 1 , 李晓南 1
现代预防医学 | 环境与职业卫生 2025,52(21): 3909-3915
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现代预防医学 |环境与职业卫生 2025 , 52 (21) : 3909 -3915
全氟及多氟烷基化合物混合暴露与超重/肥胖儿童及青少年代谢异常的关系研究
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郑青青1, 燕武2, 高胜虎1, 师亚楠1, 曹梦瑶1, 李晓南1
作者信息
  • 1.南京医科大学附属儿童医院儿童保健科，江苏　南京　210008
  • 2.南京医科大学附属儿童医院临床医学研究中心，江苏　南京　210008
通讯作者:
李晓南，E-mail：
作者简介:

郑青青与燕武为共同第一作者

郑青青（1998—），女，硕士，医师，研究方向：环境暴露与儿童健康；

燕武（1993—），女，博士，助理研究员，研究方向：环境暴露与妇幼健康；

Association between mixed exposure to perfluoroalkyl and polyfluoroalkyl substances and metabolic abnormalities in overweight and obese children and adolescents
Qing-qing ZHENG1, Wu YAN2, Sheng-hu GAO1, Ya-nan SHI1, Meng-yao CAO1, Xiao-nan LI1
Affiliations
  • Department of Child Health, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China
出版时间: 2025-11-10 doi: 10.20043/j.cnki.MPM.202504459
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摘要
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目的

探讨超重/肥胖儿童及青少年血清全氟及多氟烷基化合物（perfluoroalkyl and polyfluoroalkyl substances，PFAS）暴露与其代谢异常的关系。

方法

横断面设计，研究对象为2022年7—10月在南京医科大学附属儿童医院儿童保健科就诊的5～17岁的超重/肥胖儿童及青少年。采用logistic回归探讨超重/肥胖儿童及青少年PFAS暴露与高血糖、高甘油三酯、高胆固醇、低高密度脂蛋白、高血压、高尿酸、胰岛素抵抗及存在≥2种心血管代谢异常的关联；利用贝叶斯核机器回归和分位数g计算回归分析超重/肥胖儿童PFAS混合暴露与代谢异常风险的关系。

结果

220名超重/肥胖儿童中，男童占75.5%，年龄10.7（8.8，12.3）岁，131名（59.1%）存在≥2种心血管代谢异常。超重/肥胖儿童血清全氟己酸（perfluorohexanoic acid，PFHxA）、全氟壬酸（perfluorononanoic acid，PFNA）的浓度与高甘油三酯发生风险呈正相关（ORPFHxA= 1.670，95% CI：1.005～2.776; ORPFNA=1.415，95% CI：1.062～1.883）；血清全氟庚烷酸（perfluoroheptanoic acid，PFHpA）的浓度与高血压发生风险呈正相关(OR=1.980，95% CI：1.269～3.087）。四种PFAS的暴露水平与胰岛素抵抗发生风险呈正相关；而血清PFHpA和PFNA浓度与超重/肥胖儿童合并≥2种心血管代谢异常的风险呈正相关(ORPFHpA=1.716，95% CI：1.155～2.551;ORPFNA=1.324，95% CI：1.003～1.749)。超重/肥胖儿童PFAS混合暴露水平与高血糖、胰岛素抵抗、高血压、高甘油三酯及合并≥2种心血管代谢异常的风险呈正相关，其中PFHpA权重最大。

结论

儿童青少年血清中的PFAS暴露可能增加超重/肥胖儿童发生糖脂代谢异常、高血压和合并两种及以上肥胖相关代谢异常的风险。

PFAS  /  肥胖  /  儿童  /  混合暴露  /  代谢异常
Objective

To investigate the relationship between serum perfluorinated and polyfluoroalkyl substances (PFAS) exposure and metabolic abnormalities in overweight and obese children and adolescents.

Methods

This study was a cross-sectional design. The study subjects were overweight and obese children and adolescents aged 5-17 years who visited the Department of Child Health Care at the Children’s Hospital Affiliated to Nanjing Medical University from July to October 2022. Logistic regression analysis was used to investigate the association between PFAS exposure and high blood glucose, high triglyceride, high cholesterol, low high-density lipoprotein, hypertension, high uric acid, insulin resistance and ≥2 cardiometabolic abnormalities in overweight and obese children and adolescents. Bayesian kernel machine regression and quantile g-computation were used to analyze the relationship between mixed exposure to PFAS and the risk of metabolic abnormalities in overweight and obese children.

Results

Among the 220 overweight and obese children, 166 were male(75.5%), with an age of 10.7 (8.8, 12.3) years. A total of 131 children (59.1%) had ≥2 cardiometabolic abnormalities. The levels of PFHxA and PFNA were positively correlated with the risk of hypertriglyceridemia in overweight and obese children (ORPFHxA=1.670, 95% CI: 1.005-2.776; ORPFNA=1.415, 95% CI: 1.062-1.883). The concentration of PFHpA was positively correlated with the risk of hypertension (OR=1.980, 95% CI: 1.269-3.087). Four serum PFAS concentrations were positively correlated with the risk of insulin resistance. Serum PFHpA and PFNA concentrations were positively correlated with the risk of ≥2 cardiometabolic abnormalities (ORPFHpA=1.716, 95% CI: 1.155-2.551; ORPFNA=1.324, 95% CI: 1.003-1.749). In overweight and obese children, the mixed exposure to PFAS was positively correlated with the risk of hyperglycemia, insulin resistance, hypertension, hypertriglyceridemia, and ≥2 cardiometabolic abnormalities, with PFHpA having the largest weight.

Conclusion

Exposure to serum PFAS could increase the risk of abnormal glucose and lipid metabolism, hypertension and ≥2 obesity-related metabolic abnormalities in overweight and obese children and adolescents.

PFAS  /  Obesity  /  Children  /  Mixed exposure  /  Metabolic abnormalities
郑青青, 燕武, 高胜虎, 师亚楠, 曹梦瑶, 李晓南. 全氟及多氟烷基化合物混合暴露与超重/肥胖儿童及青少年代谢异常的关系研究. 现代预防医学, 2025 , 52 (21) : 3909 -3915 . DOI: 10.20043/j.cnki.MPM.202504459
Qing-qing ZHENG, Wu YAN, Sheng-hu GAO, Ya-nan SHI, Meng-yao CAO, Xiao-nan LI. Association between mixed exposure to perfluoroalkyl and polyfluoroalkyl substances and metabolic abnormalities in overweight and obese children and adolescents[J]. Modern Preventive Medicine, 2025 , 52 (21) : 3909 -3915 . DOI: 10.20043/j.cnki.MPM.202504459
正文
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随着全球儿童超重/肥胖率的逐年上升，其相关代谢紊乱如高血糖、高脂血症、高血压、高尿酸、胰岛素抵抗等检出率也显著增加。这些代谢紊乱的聚集增加了超重/肥胖儿童成年期患心血管疾病的风险[1-2]。随着工业化和城市化的快速发展，环境暴露问题日益显著，环境化学物暴露对儿童肥胖的发生发展也引起高度重视。全氟及多氟烷基化合物（perfluoroalkyl and polyfluoroalkyl substances，PFAS）是一类含有C-F高能化合键的化学污染物，被认为是一类环境内分泌干扰物[3]。PFAS在食品包装、灭火剂、不沾锅涂层、杀虫剂、洗涤剂、服装、地毯和皮革等的人类生产生活中广泛应用[4-7]。儿童内分泌等代谢系统尚未发育成熟，是PFAS暴露的易感人群，大量研究表明PFAS暴露升高了儿童的糖脂代谢水平，然而现有研究大多未考虑肥胖本身对糖脂代谢的影响[8]。因此，本研究采用logistic回归、贝叶斯核机器回归（Bayesian kerel machine regression, BKMR）和基于分位数的g计算（quantile based g-computation,QGC）的暴露模型评估和分析超重/肥胖儿童PFAS单一及混合暴露水平与血脂、血糖、血压等代谢紊乱的关系。为认识PFAS暴露对超重/肥胖儿童相关代谢疾病的危害性提供了理论依据。
1　对象与方法
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1.1　对象
本研究采用横断面设计，纳入2022年7—10月在南京医科大学附属儿童医院儿童保健科门诊就诊的超重/肥胖儿童和青少年，排除因遗传代谢性疾病等引起的继发性病理性肥胖，以及正在或近期接受口服降糖降脂药治疗的儿童。已获得南京医科大学附属儿童医院医学伦理委员会批准（202011084-1），并取得了家属的知情同意。
1.2　方法
1.2.1　体格指标测量
经培训的研究人员对研究对象进行体格测量。采用人体成分测定仪（InBody J20,Biospace公司，韩国）测定人体成分。要求儿童测试前空腹，身穿轻薄衣物并直立。精确测量身高（0.1 cm）和体重（0.1 kg）。计算身体质量指数（body mass index, BMI）：体重（kg）/身高的二次方（m2），并根据世界卫生组织（World Health Organization, WHO）儿童体格生长标准，将BMI进行年龄和性别标准化（BMI-Z评分）。使用电子血压仪（HBP-1300，欧姆龙，中国）坐姿测量血压，测试者要求在安静环境休息10 min后测量右上臂收缩压、舒张压（mm Hg），连续测量三次取平均值并记录。
1.2.2　实验室检查
（1）代谢指标检测: 空腹12 h后，采集受试者3 ml静脉血，使用日立7 600-1全自动生化仪测定空腹血糖、甘油三酯、总胆固醇、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol,HDL-C）和尿酸水平；使用放射免疫分析法检测空腹胰岛素，并计算胰岛素抵抗指数（homeostasis model assessment insulin resistance，HOMA-IR）：空腹血糖×空腹胰岛素/22.5。（2）血清PFAS检测: 采用高效液相色谱-三重四极杆质谱法（ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry，HPLC MS/MS）测定血清中全氟辛烷磺酸（perfluorooctane sulphonate, PFOS）、全氟辛酸（perfluorooctanoic acid, PFOA）、全氟壬酸（perfluorononanoic acid, PFNA）、全氟庚烷酸（perfluoroheptanoic acid, PFHpA）、全氟丁烷磺酸（perfluorobutanoic acid, PFBS）、全氟己酸（perfluorohexanoic acid, PFHxA）、全氟丁酸（perfluorobutanoic acid, PFBA）、全氟戊酸（perfluoropentanoic acid, PFPeA）8种PFAS暴露水平。严格按照说明书及实验室标准进行样品制备、分离、定量和质量控制等程序。定量限（limit of quantitation, LOQ）分别为：PFBA 0.16 ng/ml, PFPeA 0.16 ng/ml，PFHxA 0.80 ng/ml, PFHpA 0.40 ng/ml,PFOA 0.8 ng/ml, PFNA 0.80 ng/ml, PFBS 0.16 ng/ml,PFOS 0.16 ng/ml 。
1.2.3　诊断标准及分组
（1）根据WHO儿童体格生长标准，1≤BMI-Z<2为超重，BMI-Z≥2为肥胖。（2）空腹血糖≥5.6 mmol/L为空腹血糖受损；HOMA-IR≥3.0为胰岛素抵抗。（3）①HDL-C<1.03 mmol/L为低HDL-C；②胆固醇≥5.18 mmol/L为高胆固醇；③甘油三酯≥1.47 mmol/L为高甘油三酯[2]。（4）高血压：若收缩压和（或）舒张压≥同年龄同性别人群的P95，则被定义为高血压[9]。（5）高尿酸：1～10岁儿童>320 μmol/L，11～15岁女童>350 μmol/L，11～15岁男童>470 μmol/L，>15岁男童>420 μmol/L，>15岁女童>360 μmol/ L。根据以上诊断标准分为<2种心血管代谢异常组和≥2种心血管代谢异常组。
1.2.4　协变量
通过环境暴露问卷获得研究对象的环境暴露信息，并获得本研究的协变量。问卷一共包括五个维度：（1）一般情况：性别、年龄、民族、BMI、喂养情况、父母亲教育程度，肥胖、高血压、糖尿病、高血脂等家族史；（2）饮食、饮水因素：如平均每周快餐、烧烤等的摄入频率,及食品包装（一次性餐盒）的使用频率；饮水因素主要指家庭饮用水的来源（自来水、桶装水、纯净水）及处理方式（煮沸和过滤）；（3）家庭环境因素：家庭中家具（地板、地毯）、厨具种类和近2年家中有无装修情况；（4）周围环境因素：家或学校附近有无化学性物质排放的工厂、有无通风不良情况、有无施工等引起的尘土飞扬等；（5）皮肤等其他接触因素：包括牙齿涂氟经历、日常户外用品的使用频次。本研究将不同代谢类型超重/肥胖儿童存在差异性的环境暴露因素作为协变量（P<0.05）。此外，本研究选择儿童年龄、性别、BMI、父母亲BMI、父母亲学历、家族史等因素纳入协变量。
1.2.5　统计分析
运用R Studio（4.1.1）进行统计学分析。PFAS暴露水平多呈偏态分布，故进行ln转换。低于LOQ的水平以填补，总体样本中检出率≥60%被纳入后续分析。
非正态分布的定量资料以［M（P25，P75）］表示，分类变量以频数（%）描述。采用logistic回归分析超重/肥胖儿童中PFAS暴露与代谢异常风险的关联，检验水准α=0.05。并进一步应用BKMR和QGC混合暴露模型评估肥胖儿童人群中各PFAS混合暴露与其代谢异常风险的关系。
BKMR模型为贝叶斯非参数回归方法[10]，本研究采用马尔科夫链蒙特卡罗算法迭代10 000次来拟合模型。QGC模型基于加权分位数回归，通过g 计算估计混合暴露每增加一个分位数对结局的边际效应。QGC模型和BKMR模型分别采用R软件包"qgcomp"（4.0.5版）和"BKMR"（0.2.0版）计算。
2　结果
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2.1　研究对象基本情况
共纳入220名超重/肥胖儿童青少年，其年龄为10.7（8.8, 12.3)岁，BMI 为25.4(21.7, 28.2) kg/m2，BMI-Z为2.6(2.0, 3.1)，其中男童166名（75.5%）、女童54名（24.5%），基本特征见表1。在饮食来源因素中，≥2种心血管代谢异常组的超重/肥胖儿童的每周快餐摄入频次低于<2种异常组（P=0.035）；每周烧烤频率、一次性餐盒使用频率、饮水来源因素、家庭环境暴露及周围环境暴露因素均无统计学差异。
2.2　超重/肥胖儿童血清PFAS暴露水平
本研究共7种血清PFAS检出率大于80%。其中，PFPeA的中位浓度最高为1 632 ng/ml。依次为PFBA、PFOA、PFOS、PFNA、PFHxA、PFHpA、PFBS。由于PFBS的检出率为55%，因此没有纳入后续分析。
2.3　超重/肥胖儿童单一PFAS暴露与代谢异常的关系
Logistic回归分析表明，随着超重/肥胖儿童血清中PFHxA和PFNA的水平升高，其高甘油三酯的发生风险增加（P<0.05）；另外，当PFOA、PFHpA浓度增加时，分别与高胆固醇、高血压的发生风险增加（P<0.05）；超重/肥胖儿童血清PFBA、PFHxA、PFHpA和PFOS与胰岛素抵抗的发生风险呈正相关（P<0.05）；而血清PFHpA和PFNA浓度升高可使得超重/肥胖儿童合并≥2种心血管代谢异常的风险增加（P<0.05）。本研究尚未发现超重/肥胖儿童单一PFAS暴露与高血糖、高尿酸、低HDL-C的风险具有统计学意义。见表2。
2.4　超重/肥胖儿童混合PFAS暴露与代谢异常的关系
2.4.1　BKMR混合暴露模型
进一步采用BKMR模型分析超重/肥胖儿童PFAS混合暴露水平与代谢异常之间的总效应关系。如图1A、B、E、G、H所示，在超重/肥胖儿童中，PFAS混合暴露与高血糖、高甘油三酯、高血压、胰岛素抵抗及合并≥2种心血管代谢异常风险呈正相关（P<0.05）；未发现PFAS混合暴露与超重/肥胖儿童发生高胆固醇、低HDL-C、高尿酸的风险有统计学意义。
2.4.2　QGC混合暴露模型
QGC和BKMR模型结果较为一致，结果显示混合暴露PFAS与超重/肥胖儿童的高血糖、高血压、胰岛素抵抗及合并≥2种心血管代谢异常风险呈正相关（P<0.05）。不同的PFAS在超重/肥胖儿童的代谢紊乱风险中呈现了不同的效应。见表3。
3　讨论
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儿童是PFAS暴露的高危人群[7,11-13]。超重/肥胖儿童体表面积更大，摄入更多食物和水，相同暴露水平下健康风险更高。本研究发现，单一及混合PFAS暴露均增加超重/肥胖儿童高脂血症、高血压、胰岛素抵抗等代谢紊乱，以及增加罹患≥2种心血管代谢异常的风险。
前期meta分析尚未发现PFAS暴露与儿童血糖水平存在统计学关联[8]。但本研究发现超重/肥胖儿童中，混合PFAS暴露与高血糖风险呈正相关，提示PFAS混合浓度的升高可能会加剧肥胖儿童血糖升高。单一PFAS未显示统计学关联，表明其影响可能与其混合叠加效应有关，即单独作用未达到生物效应阈值的PFAS，可以通过混合叠加的方式诱发糖代谢异常[14]。未来研究应同时评估单一与混合PFAS暴露效应，以深入解析其复杂毒理作用。
血脂异常是PFAS健康效应的热点研究领域，现有研究结果一致性较高[15-17]。但肥胖在PFAS暴露与血脂关系中的影响尚不明确。本研究发现，超重/肥胖儿童单一和混合PFAS暴露均增加高甘油三酯的风险，提示肥胖可能增强PFAS对血脂（尤其是甘油三酯）的敏感性。PFAS暴露可能通过调控PPARα通路[18]或激活下丘脑-垂体-甲状腺轴[19-20]，促进脂肪酸代谢和甘油三酯的合成。肥胖状态可能放大这种暴露-效应关系，增加血脂异常风险。
肥胖是高血压的危险因素，超重/肥胖儿童患高血压的风险高于比正常体重儿童[21]。本研究发现，在单一暴露和混合暴露模式下，血清PFAS浓度升高（尤其是PFHpA）均会增加超重/肥胖儿童的高血压风险，这与既往研究较为一致。Pan等人[22]的一项meta分析发现血清PFNA、PFOA等与高血压风险呈正相关；Averina 等[23]也证实PFAS浓度与青少年高血压风险的关联。近期研究表明，PFAS可与过氧化物酶体增殖激活受体相互作用或者通过影响下丘脑-垂体-甲状腺素轴功能，升高血脂水平，增加血液粘稠度与外周血管阻力，最终诱发高血压[24-25]。
本研究表明，单一及混合PFAS暴露均可能增加超重/肥胖儿童的胰岛素抵抗风险，其中PFHpA在混合暴露中起主导作用。虽然前期meta分析显示PFAS暴露与儿童HOMA-IR水平呈负相关[8]，但Fassler等人[26]的一项研究提示青春期女孩的PFOA暴露可能与BMI及胰岛素抵抗呈正相关。本研究的研究对象正值青春期生理性胰岛素抵抗阶段[27]，可能影响结果准确性，需扩大样本量并对青春期进行分期行进一步研究。在儿童肥胖状态下，PFAS暴露增加胰岛素抵抗的风险的潜在机制可能是外源性污染物PFAS可诱发体内的氧化应激，导致自由基累积，继而诱导胰岛素抵抗的发生[28-29]。
儿童心血管代谢耐受能力优于成人，且缺乏典型症状和临床表现，其心血管疾病的早期状态常隐匿于肥胖之下而容易被忽视。因此，本研究将“超重/肥胖合并≥2种心血管代谢异常”视为早期心血管风险标志，结果表明超重/肥胖儿童单一及混合PFAS暴露与≥2种心血管代谢异常呈正相关。值得注意的是，不同PFAS类别在单一和混合暴露模型中的相对贡献权重存在差异。这可能由于PFAS作为一类环境化合物，在混合暴露时化合物之间可能存在协同或拮抗效应[30-31]，其复杂的毒理作用需要通过动物实验进一步论证。
QGC模型不仅能量化混合物暴露的总体效应强度，还计算了各组分的贡献权重及其作用方向。本研究QGC模型的结果中，除胰岛素抵抗结局中所有PFAS均为正向贡献外，其余代谢异常结局中PFBA、PFPeA、PFHxA、PFOA等组分呈现负向贡献，但混合暴露总体效应仍为正相关。这提示在混合暴露条件下，不同PFAS组分间可能通过拮抗作用产生复杂的毒理学效应，最终导致总体效应并非与各组分效应完全一致。类似结果在Francis等七种双酚系化学物与儿童性早熟的研究中亦有报道[32]。这些结果为深入解析PFAS混合暴露的组分特异性毒理机制提供了依据。
本研究的优势在于: 首先，本研究聚焦肥胖儿童这一环境暴露的高危人群，聚焦PFAS暴露与其代谢异常风险的关系，从“环境-代谢交互作用”的新视角探索PFAS健康效应的研究领域；其次，本研究结合单一暴露和两种混合暴露模型分析，更全面、客观地评估了超重/肥胖儿童PFAS暴露对代谢健康的综合影响；最后，本研究从环境暴露角度揭示了儿童肥胖相关代谢异常的风险来源，为儿童肥胖的综合干预提供了新的思路。本研究也存在一些局限性：一是，作为一项横断面研究，尚不能明确PFAS暴露与超重/肥胖儿童代谢异常间的因果关系。二是，研究对象主要来自本地区或周边，不同地区PFAS暴露水平可能存在差异，未来需纳入更多地区人群以验证结果的普适性。此外，本研究中未对儿童进行青春分期（如Tanner分期），在解释青春期PFAS暴露与糖代谢关系时需要谨慎。未来研究可根据年龄、性别和青春分期进行分层分析，深入探讨PFAS暴露与特定代谢结局的关系。
总之，单一和混合暴露模型的分析均表明，超重/肥胖儿童的PFAS暴露与其代谢疾病存在关联，可增加其罹患高血糖、胰岛素抵抗、高甘油三酯、高血压和两种及以上心血管代谢异常的风险。因此，临床医生需提高PFAS暴露健康危害的认知（尤其关注肥胖高危人群），并减少相关暴露的接触，以预防肥胖代谢并发症的发生，以期降低远期心血管疾病风险。同时，督促相关部门加强对PFAS环境风险的管控，为完善环境内分泌干扰化学物质衡量标准的相关政策提供理论依据。
基金
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  • 江苏省妇幼保健科研项目(F202213)
  • 南京市卫生科技项目(YKK22156)
文献
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doi: 10.20043/j.cnki.MPM.202504459
  • 接收时间：2025-04-25
  • 首发时间：2026-10-29
  • 出版时间：2025-11-10
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  • 收稿日期：2025-04-25
基金
江苏省妇幼保健科研项目(F202213)
南京市卫生科技项目(YKK22156)
作者信息
    1.南京医科大学附属儿童医院儿童保健科，江苏　南京　210008
    2.南京医科大学附属儿童医院临床医学研究中心，江苏　南京　210008

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李晓南，E-mail：
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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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