中华预防医学杂志    2020年05期 母亲妊娠相关焦虑与学龄前儿童执行功能关联的队列研究    PDF     文章点击量:455    
中华预防医学杂志2020年05期
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王晓旭 吴雅 严双琴 徐叶清 朱鹏 郝加虎 陶芳标 黄锟
WangXiaoxu,WuYa,YanShuangqin,XuYeqing,ZhuPeng,HaoJiahu,TaoFangbiao,HuangKun
母亲妊娠相关焦虑与学龄前儿童执行功能关联的队列研究
The relationship between maternal pregnancy-related anxiety and executive function in preschool children: a cohort study
中华预防医学杂志, 2020,54(5)
http://dx.doi.org/10.3760/cma.j.cn112150-20190815-00662
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投稿日期: 2019-08-15
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母亲妊娠相关焦虑与学龄前儿童执行功能关联的队列研究
王晓旭 吴雅 严双琴 徐叶清 朱鹏 郝加虎 陶芳标 黄锟     
王晓旭 安徽医科大学公共卫生学院儿少卫生与妇幼保健学系出生人口健康教育部重点实验室国家卫生健康委配子及生殖道异常研究重点实验室人口健康与优生安徽省重点实验室,合肥 230032
吴雅 安徽医科大学公共卫生学院儿少卫生与妇幼保健学系出生人口健康教育部重点实验室国家卫生健康委配子及生殖道异常研究重点实验室人口健康与优生安徽省重点实验室,合肥 230032
严双琴 安徽省马鞍山市妇幼保健院 243000
徐叶清 安徽省马鞍山市妇幼保健院 243000
朱鹏 安徽医科大学公共卫生学院儿少卫生与妇幼保健学系出生人口健康教育部重点实验室国家卫生健康委配子及生殖道异常研究重点实验室人口健康与优生安徽省重点实验室,合肥 230032
郝加虎 安徽医科大学公共卫生学院儿少卫生与妇幼保健学系出生人口健康教育部重点实验室国家卫生健康委配子及生殖道异常研究重点实验室人口健康与优生安徽省重点实验室,合肥 230032
陶芳标 安徽医科大学公共卫生学院儿少卫生与妇幼保健学系出生人口健康教育部重点实验室国家卫生健康委配子及生殖道异常研究重点实验室人口健康与优生安徽省重点实验室,合肥 230032
黄锟 安徽医科大学公共卫生学院儿少卫生与妇幼保健学系出生人口健康教育部重点实验室国家卫生健康委配子及生殖道异常研究重点实验室人口健康与优生安徽省重点实验室,合肥 230032
摘要: 目的  探讨妊娠相关焦虑与学龄前儿童执行功能的关联。方法  于2008年10月至2010年10月,在马鞍山市妇幼保健院产前保健门诊招募待产孕妇及其单胎活产儿为研究对象;于2014年4月至2015年6月进行随访,最终纳入3 556对母亲-儿童。问卷收集孕妇相关信息和儿童随访资料,并采用《妊娠相关焦虑量表》和《学龄前儿童执行功能评定量表》(父母版)分别评定孕妇妊娠相关焦虑情况及学龄前儿童的执行功能。采用二分类logistic回归模型,分析妊娠相关焦虑对学龄前儿童执行功能的影响。结果  3 556名孕妇年龄为(26.78±3.42)岁,学龄前儿童年龄为(4.32±0.46)岁,初产妇、独生子女和市区儿童所占比分别为94.96%(3 375名)、91.37%(3 249名)和88.98%(3 164名)。仅孕早、晚期存在妊娠相关焦虑检出率分别为17.60%(626名)和6.30%(224名),孕早、晚期同时存在妊娠相关焦虑检出率为7.68%(273名);儿童总执行功能异常检出率为8.54%(304名)。调整混杂因素后,与孕早、晚期均无妊娠相关焦虑相比,仅孕早期存在妊娠相关焦虑会增加学龄前儿童抑制、工作记忆、计划/组织功能和总执行功能异常的风险,OR(95%CI)分别为1.52(1.08~2.13)、1.41(1.14~1.74)、1.62(1.13~2.33)和1.60(1.18~2.17);仅孕晚期存在妊娠相关焦虑会增加学龄前儿童抑制功能和总执行功能异常的风险,OR(95%CI)为1.90(1.15~3.12)和1.69(1.05~2.71);孕早、晚期同时存在妊娠相关焦虑会增加抑制、工作记忆、计划/组织功能和总执行异常的风险,OR(95%CI)分别为2.41(1.61~ 3.62)、2.19(1.66~2.88)、1.80(1.11~2.92)和2.41(1.65~3.52)。结论  母亲孕期暴露妊娠相关焦虑可能增加学龄前儿童执行功能发育异常的风险。
关键词 :妊娠;焦虑;儿童,学龄前;执行功能;队列研究
The relationship between maternal pregnancy-related anxiety and executive function in preschool children: a cohort study
WangXiaoxu,WuYa,YanShuangqin,XuYeqing,ZhuPeng,HaoJiahu,TaoFangbiao,HuangKun     
Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University/Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People′s Republic of China/Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, National Health and Health Commission of the People′s Republic of China/Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei 230032, China
Corresponding author: Huang Kun, Email: wuweihk8028@163.com
Abstract:Objective  To investigate the relationship between pregnancy-related anxiety and executive function in preschool children.Methods  From October 2008 to October 2010, pregnant women and live births were enrolled in the study. The expectant pregnant women and their live singleton fetuses were recruited from the antenatal care clinic of Ma'anshan maternal and Child Health Care Hospital. The cohort was followed up from April 2014 to June 2015. A total of 3 556 pairs of maternal and child were included in the final analysis. The questionnaire was used to collect the relevant information of pregnant women and the follow-up data of children. Pregnancy-related anxiety was assessed by using the Pregnancy-Related Anxiety Questionnaire, and the executive function of preschool children was assessed by using the Behavior Rating Inventory of Executive Function-Preschool (BRIEF) (Parent Version). Bi-nominal logistic regression was used to analyze the effect of pregnancy-related anxiety on executive function in preschool children.Results  The average age of 3 556 pregnant women was (26.78±3.42) years old, and the average age of preschool children was (4.32±0.46) years old. The proportion of primipara, only child and urban children was 94.96% (3 375/3 556), 91.37% (3 249/3 556) and 88.98% (3 164/3 556), respectively. The prevalence of pregnancy-related anxiety in the 1st and 3rd trimester was 17.60% (626/3 556) and 6.30% (224/3 556) respectively. The prevalence of abnormal global executive composite was 8.54% (304/3 556). The prevalence of anxiety in both trimesters was 7.68% (273/3 556). After controlling for confounding factors such as monthly family income, education years of parents, maternal age, pre-pregnancy weight, previous adverse pregnant outcomes, number of pregnancy, pregnant complications, the main residence of the children in the past six months, and Z score of birth weight, compared with the group without pregnancy-related anxiety in either 1st or 3rd trimester, pregnancy-related anxiety in the 1st trimester increased the risk of preschool children's abnormality in inhibition, working memory, planning/organization and global executive composite, and the OR (95%CI) value was 1.52 (1.08-2.13), 1.41 (1.14-1.74), 1.62 (1.13-2.33), and 1.60 (1.18- 2.17), respectively. Anxiety in the 3rd trimester increased the risk of children's abnormality in inhibition and global executive composite, and the OR (95%CI) value was 1.90 (1.15-3.12) and 1.69(1.05-2.71). Pregnancy-related anxiety in both trimesters increased the risk of abnormality in inhibition, working memory, planning/organization, and global executive composite in preschool children, and the OR (95% CI) value was 2.41 (1.61-3.62), 2.19 (1.66-2.88), 1.80 (1.11-2.92), and 2.41 (1.65-3.52), respectively.Conclusion  The exposure to pregnancy-related anxiety during pregnancy increases the risk of executive dysfunction in preschool children.
Key words :Pregnancy;Anxiety;Child, preschool;Executive function;Cohort study
全文

妊娠相关焦虑是指孕妇对胎儿健康、自身健康与外表,以及对妊娠、分娩、子女养育相关的医疗、经济和社会支持等问题而产生的特殊心理压力和失眠等症状[1]。我国孕妇早、中、晚期妊娠相关焦虑检出率分别为21.0%、17.7%和13. 6%,远远高于一般人群的7.3%[2,3,4],且仍在不断升高。越来越多的研究证实妊娠焦虑可能影响子代认知发育[5],高水平妊娠相关焦虑对儿童认知的损伤将会持续到青春期甚至成年期[6,7]。妊娠相关焦虑比孕期一般焦虑和抑郁更能对儿童发育产生不良影响[8],更能准确预测儿童的认知能力发育[9]。执行功能指个体在设定目标、制定计划并有效实施计划中所需的互相协同的一系列高级认知功能[10],近年来成为认知发展领域研究的热点和前沿。现有研究多关注妊娠相关焦虑对学龄儿童一般认知发育的影响,对学龄前儿童执行功能影响的研究较少,且通常基于普适性焦虑评价量表,如状态-特质焦虑问卷(State-Trait Anxiety Inventory,STAI)[6],妊娠相关焦虑导致儿童执行功能异常的关键期及剂量反应关系尚不明确。本研究基于中国安徽出生队列的前瞻性队列研究,探讨妊娠相关焦虑对学龄前儿童执行功能发育的影响,以期针对性开展孕期心理健康促进,优化子代生命早期发育环境。

对象与方法  

一、对象  研究对象来源于中国安徽出生队列(China-Anhui Birth Cohort Study,C-ABCS)的马鞍山市出生队列人群[11]。于2008年10月至2010年10月,在马鞍山市妇幼保健院产前保健门诊招募待产孕妇为研究对象,纳入标准为:首次来院建立孕产妇保健手册、在马鞍山居住时间≥6个月、孕周在12周以内、无神经精神疾病,且能够独立完成孕期相关问卷者;排除标准为:自然流产、死胎/死产及引产、双胎。最终共计纳入4 669名孕妇及其单胎活产儿。于2014年4月—2015年6月进行随访,排除866名失访者后,随访到学龄前儿童(3~5岁) 3 803名(81.5%);进一步排除144名辅助生殖儿童、31名无执行功能评定结局的儿童及孕晚期焦虑问卷不完整者72名,最终将3 556对母亲-儿童纳入分析。本研究方案通过安徽医科大学生物医学伦理委员会审查(批号:2008020)。所有研究对象均签署知情同意书。

二、调查内容与方法  

1.问卷调查:  采用自制的《孕产期母婴健康记录表》和《学龄前儿童健康与行为记录表》分别收集孕妇相关信息和儿童随访资料。孕妇人口学信息包括家庭人均月收入、父母文化程度等。孕产期情况包括母亲怀孕时年龄、孕前体重指数(body mass index,BMI)(<18.5 kg/m2为偏瘦、18.5~24.0 kg/m2为正常体重、≥24 kg/m2为超重/肥胖)、不良孕产史、孕次、产次等。对学龄前儿童随访调查时,由家长或主要监护人填写调查问卷,收集儿童月龄、是否独生子女、6个月内母乳喂养情况、3岁前和3岁后带养方式、近半年儿童主要居住地等信息并评价儿童执行功能。病历摘录:从产科病历中摘录产时情况,包括分娩时孕周、分娩方式、胎数、新生儿性别和出生体重,并结合孕周和出生体重,计算在不同孕周水平上的出生体重Z分。

2.妊娠相关焦虑评估:  采用自制的妊娠相关焦虑量表分别于孕早期(10~14周)和孕晚期(30~ 34周)评估孕妇妊娠相关焦虑情况。该量表包含13个条目,分为关注自我、担心胎儿健康、担心分娩3个维度,采用4级评分法,1~4分别代表"没有担心""偶尔担心""经常担心""一直担心",总分为52分,得分越高表示妊娠相关焦虑水平越高。总分≥24分评价为存在妊娠相关焦虑。该量表重测相关系数和Cronbach α系数分别为0.79和0.81[12]。结合孕早期和孕晚期的评定结果,将孕妇分为4个组:仅孕早期存在焦虑组、仅孕晚期存在焦虑组、孕早期和孕晚期同时存在焦虑组和孕早期和孕晚期都无焦虑组(对照组)。

3.学龄前儿童执行功能评价:  采用《学龄前儿童执行功能评定量表》(父母版)(Behavior Rating Inventory of Executive Function-Preschool,BRIEF-P)(Parent Version),由儿童的主要监护人依据儿童在过去6个月内日常生活中某些行为问题的发生频率对其执行功能进行评估。该量表总计63个条目,各条目按"从不=1、有时=2、经常=3"3个评定等级进行评价。通过不同条目得分相加评价学龄前儿童执行功能的不同维度,包括五个非重叠量表:抑制、转换、情绪控制、工作记忆和计划/组织。每个量表的分数合并为总执行功能(global executive composite,GEC)。根据Gioia等[13]标准,将每个量表的原始分数转换为标准T得分,各量表T得分≥65为GEC发育异常。

三、质量控制  在资料收集前,对调查员进行严格培训和考核,严格控制数据质量。自制问卷经多位专家指导反复修改最终确认,并在实施前进行预调查。对收集的问卷及时录入和逻辑检错。数据库建立以后进行系统的逻辑检查与核对,并对缺失值进行必要的分析和填补。如有失访,尽量了解失访者的结局,与完成随访者的结局进行比较,以推测失访的影响。

四、统计学分析  采用EpiData 3.1软件建立数据库,采用SPSS 23.0软件进行统计分析。孕妇、学龄前儿童年龄符合正态分布,以±s表示;分类资料采用构成比/率表示。采用χ2检验比较不同人口学、产科特征及不同妊娠相关焦虑组学龄前儿童执行功能异常检出率的差异。采用二分类logistic回归模型,以妊娠相关焦虑为自变量,采用逐步回归法纳入相关混杂因素,分析妊娠相关焦虑与学龄前儿童执行功能的关联。模型1:未调整混杂因素;模型2:根据文献检索以及实际公共卫生意义[14,15,16],调整家庭人均月收入、父母亲文化程度、母亲怀孕时年龄、母亲孕前BMI、不良孕产史、孕次、妊娠合并症、分娩方式、产次、儿童月龄、性别、独生子女、6个月内母乳喂养情况、3岁前和3岁后父母带养比例、近半年儿童主要居住地、问卷填写人等混杂变量,混杂变量的纳入采用逐步向前的方法进行;模型3:在模型2的基础上进一步进行调整出生体重Z分。双侧检验,检验水准α=0.05。

结果  

一、基本情况  3 556名孕妇年龄(26.78±3.42)岁,学龄前儿童年龄(4.32±0.46)岁,初产妇、独生子女和市区儿童所占比分别为94.96%(3 375/3 556)、91.37%(3 249/3 556)和88.98%(3 164/3 556)。学龄前儿童GEC异常检出率为8.54%(304/3 556)。不同家庭月收入、父母的文化程度、妊娠时母亲年龄、妊娠合并症、分娩方式、儿童出生月龄及性别的学龄前儿童GEC异常检出率差异有统计学意义(P值均<0.05)(表1)。

表1不同人口学特征学龄前儿童执行功能异常检出情况比较[例(%)]

二、不同妊娠相关焦虑状态学龄前儿童GEC异常的检出情况  仅孕早、晚期妊娠相关焦虑检出率分别为17.60%(626/3 556)和6.30%(224/3 556),孕早、晚期同时存在妊娠相关焦虑的检出率为7.68%(273/3 556)。不同妊娠相关焦虑状态儿童的GEC异常检出率有差异,孕早、晚期同时存在妊娠相关焦虑组的GEC异常检出率最高(P<0.001)。见表2

表2不同母亲妊娠相关焦虑状态的学龄前儿童执行功能异常检出率比较[例(%)]

三、不同妊娠相关焦虑状态与学龄前儿童GEC关联的logistic回归模型分析  调整家庭人均月收入、父母亲文化程度、妊娠时母亲年龄、母亲孕前BMI、不良孕产史、孕次、妊娠合并症、近半年儿童主要居住地和出生体重的Z分等混杂因素后,与孕早、晚期均无妊娠相关焦虑组相比,仅孕早期存在妊娠相关焦虑增加学龄前儿童抑制、工作记忆、计划/组织功能和GEC异常的风险;仅孕晚期存在妊娠相关焦虑增加学龄前儿童抑制功能和GEC异常的风险;孕早、晚期同时存在妊娠相关焦虑增加抑制、工作记忆、计划/组织功能和GEC异常的风险(P值均<0.05)。见表3

表3不同母亲妊娠相关焦虑状态与学龄前儿童的执行功能异常关联的logistic回归模型分析[OR(95%CI)]

讨论  本研究结果表明,孕早、晚期同时合并妊娠相关焦虑者较单一孕期合并焦虑者子代学龄前儿童GEC异常检出率高,孕早期可能是妊娠相关焦虑影响学龄前儿童GEC异常的关键期。Buss等[17]研究发现,妊娠相关焦虑与6~9岁女童抑制功能的相关性在孕早期到中期(15~25周)较为明显。另外,高水平妊娠相关焦虑与子代前额叶皮质(prefrontal cortex,PFC)体积减少有关[18]。在妊娠第8至16周,迁移神经元形成亚板区并发生分支,与来自丘脑、基底前脑和脑干的传入神经元建立适当的连接[19]。孕早期暴露于妊娠相关焦虑可能会改变这些早期发育过程,从而影响儿童的执行功能。
        目前妊娠相关焦虑和子代执行功能关系的研究非常有限[5,17,20]。最近研究显示,母亲产前焦虑水平较高的儿童,出现额叶、颞叶和边缘区域体积和/或厚度减小,这些脑发育异常可能是联结产前焦虑和儿童认知功能的基础[21]。执行功能相关的脑区主要是PFC和海马,主要由PFC内的活动来协调[22]。人群和动物实验均表明,高水平妊娠相关焦虑与PFC体积减少有关[18,23,24],具体机制尚不明确。有研究发现孕期应激(如妊娠相关焦虑)能引起母体下丘脑-垂体-肾上腺(HPA)轴功能亢进,促进皮质醇的分泌,高浓度的皮质醇能够穿过胎盘屏障,影响胎儿外周血游离皮质醇的水平[24,25]。高浓度皮质醇通过影响海马和PFC神经元的可塑性来影响记忆功能[26]。海马主要涉及视觉空间工作记忆功能[27,28],且特别容易受到产前不良暴露的影响[29,30]。随着妊娠相关焦虑从妊娠早期到晚期,应激水平升高导致执行功能受损,这可能是孕早、晚期均存在妊娠相关焦虑儿童执行功能异常检出率高的原因。
        本研究样本来源于大规模的研究队列,研究对象依从性高,样本信息数据来源及时,减少了回忆偏倚。研究结果有助于针对性地开展孕期和儿童期心理健康促进[31]。本研究也存在不足之处。纳入人群的父母高文化程度的比例更高,较多比例居住在城市地区,初产妇的比例较高。父母文化程度高、居住地在城市地区,均与儿童的认知发育呈正向关联[32,33,34],可能在一定程度上低估了学龄前儿童执行功能异常的检出率;初产妇的妊娠相关焦虑水平较高[35,36,37],本研究中初产妇比例较高,可能高估了样本的妊娠相关焦虑水平。另外,本研究尚不能排除其他残余混杂的影响,如缺乏母亲智力水平和产后的情绪状况、儿童带养环境、儿童智力、情绪和行为以及评估者自身心理/情绪状况的评价等,这些因素对儿童执行功能均有潜在影响[38,39,40]
        儿童脑结构和功能的发育从孕期开始一直持续至青春期[41,42],尤其是发育最为持久的额叶和边缘区域[43,44]。因此,跟踪儿童的认知功能发育(如青春期至成年期),将有助于明确妊娠相关焦虑对子代执行功能的影响是否持续存在以及不同年龄段是否存在差异。

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