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脐带血元素水平对早产和足月婴幼儿神经行为发育影响的队列研究

Effects of cord blood element levels on neurodevelopment of preterm and full-term children:A cohort study
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摘要 [背景]在胎儿发育进程中,必需和非必需元素对中枢神经系统发育有重要影响。早产儿由于大脑发育的不完善,对元素暴露更加敏感,是神经行为发育异常的高危人群。然而,宫内元素暴露水平对胎儿出生后神经行为发育的影响在足月儿和早产儿中是否有差异尚不明确。[目的]评估脐带血元素水平与6~24(校正)月龄婴幼儿神经行为发育的纵向关联,并比较其在早产儿和足月儿中的差异。[方法]依托2015年10月至2018年12月在广东省茂名市开展的茂名市出生队列研究(MBCS),采用前瞻性研究设计,测定197例早产儿和297例足月儿脐带血中20种元素,包括11种必需微量元素:钒(V)、铬(Cr)、锰(Mn)、钴(Co)、镍(Ni)、铜(Cu)、锌(Zn)、硒(Se)、锶(Sr)、锡(Sn)、铁(Fe),以及9种非必需微量元素:铝(Al)、砷(As)、铊(Tl)、铅(Pb)、铀(U)、铈(Ce)、锑(Sb)、镉(Cd)、钇(Y)。分别在胎儿出生后6、12、24月龄时采用年龄与发育进程问卷第三版(ASQ-3)评估婴幼儿神经行为发育状况。采用广义估计方程(GEE)模型评估足月儿和早产儿脐带血元素与ASQ-3问卷各能区发育异常的纵向关联。[结果]脐带血中10种元素(Mn、Cu、Zn、Se、Sr、Fe、Sb、Tl、Pb和As)的检出率大于80%。GEE结果显示,校正协变量后,在早产儿中,脐带血元素自然对数浓度每增加1个四分位距(IQR),As与沟通和解决问题能区发育异常风险的调整后比值比(OR)及其95%置信区间(CI)分别为1.36(1.03~1.80)和1.55(1.10~2.20);Sb与精细动作和解决问题能区发育异常风险的调整后OR及其95%CI分别为1.44(1.00~2.07)和1.76(1.09~2.84);Se与沟通能区发育异常风险的调整后OR及其95%CI为1.37(1.09~1.74)。未观察到脐带血元素水平与足月儿神经行为发育异常的关联有统计学意义。按照性别进行分层分析,结果显示脐带血元素(As、Se、Sb)水平与婴幼儿神经行为发育异常风险的关联仅在女性早产儿中有统计学意义。[结论]孕期As、Se和Sb暴露可能增加6~24月龄早产儿神经行为发育异常风险,且女性早产儿更易受到影响。 [Background] Essential and non-essential elements have an important impact on the development of the central nervous system during fetal development.Due to their less developed brain,preterm infants are more sensitive to element exposure,and are high-risk groups of neurodevelopmental abnormalities.However,it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants.[Objective] To evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months(of corrected age),and compare the effects between preterm and full-term children.[Methods] A prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study(MBCS) in Maoming City,Guangdong Province.Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured,including 11 essential trace elements [vanadium(V),chromium(Cr),manganese(Mn),cobalt(Co),nickel(Ni),copper(Cu),zinc(Zn),selenium(Se),strontium(Sr),tin(Sn),and iron(Fe)],and 9 non-essential trace elements [aluminum(Al),arsenic(As),thallium(Tl),lead(Pb),uranium(U),cerium(Ce),antimony(Sb),cadmium(Cd),and yttrium(Y)].The neurodevelopment of the children at 6,12,and24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition(ASQ-3).A generalized estimating equation(GEE)model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately.[Results] The positive rates of 10 elements(Mn,Cu,Zn,Se,Sr,Fe,Sb,Tl,Pb,and As) in cord blood were greater than 80%.Among the preterm birth children,the results of GEE analysis showed that after adjusting for the covariates,for each increase of interquartile range(IQR) in ln-transformed concentration,As was associated with problems/delay in the communication and problem-solving sub-scales,with the adjusted odds ratios(OR) and 95% confidence intervals(CI) of 1.36(1.03-1.80) and 1.55(1.10-2.20),respectively;the adjusted OR(95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44(1.00-2.07) and 1.76(1.09-2.84) for Sb,respectively;the adjusted OR(95%CI) of problems/delay in the communication sub-scale was 1.37(1.09-1.74) for Se.No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children.The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children.[Conclusion] Exposures to As,Se,and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months,and female seem to be more vulnerable.
作者 王兆坤 张文楼 曾晓雯 楚楚 李青青 崔鑫鑫 吴奇桢 董光辉 黄金波 孔敏莉 邓芙蓉 WANG Zhaokun;ZHANG Wenlou;ZENG Xiaowen;CHU Chu;LI Qingqing;CUI Xinxin;WU Qizhen;DONG Guanghui;HUANG Jinbo;KONG Minli;DENG Furong(Department of Occupational and Environmental Health Sciences,School of Public Health,Peking University,Beijing 100191,China;Department of Occupational and Environmental Health,School of Public Health,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;Department of Gynaecology and Obstetrics,Maternal and Child Health Hospital of Maoming City,Maoming,Guangdong 525000,China)
出处 《环境与职业医学》 CAS CSCD 北大核心 2022年第7期723-729,共7页 Journal of Environmental and Occupational Medicine
基金 国家重点研发计划项目(2018 YFC1004302,2018 YFE0106900) 国家自然科学基金项目(82173471,82073503,82003409,81950410633)。
关键词 脐带血 微量元素 早产 婴幼儿 神经行为发育 cord blood trace element preterm birth infant neurodevelopment
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