不同孕期服用叶酸与婴幼儿喘息相关性的病例对照研究

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不同孕期服用叶酸与婴幼儿喘息相关性的病例对照研究

杨静，于艳艳，王宜芬，钱前，李伟

作者单位：222006江苏省连云港市妇幼保健院

通信作者：于艳艳，222006江苏省连云港市妇幼保健院；E-mail：wangjunhuayyy@sina.com

【摘要】目的探讨不同孕期服用叶酸与婴幼儿喘息发生的关系，为孕期服用叶酸选择合适时机提供依据。方法选取2011年4月—2012年4月于连云港市妇幼保健院出生的婴幼儿1 320例为研究对象。以电话或门诊问卷调查的方式收集婴幼儿及其母亲临床资料，包括婴幼儿性别、出生体质量、胎次、出生季节及出生2年内是否发生婴幼儿喘息；母亲受教育程度、吸烟史、喂养方式、孕期是否服用维生素A或维生素D、是否为特应性体质及服用叶酸的时期。根据婴幼儿是否发生喘息分为病例组(397例)和对照组(923例)。结果两组婴幼儿性别、出生体质量、第一胎比例、出生季节及其母亲受教育程度、母亲吸烟率、喂养方式、孕期服用维生素A或维生素D率比较，差异均无统计学意义(P>0.05)。特应性体质母亲中，两组婴幼儿的母亲开始服用叶酸时期比较，差异有统计学意义(P<0.05)；其中，孕中后期开始服用叶酸的母亲的婴幼儿发生喘息的风险是未服用叶酸母亲的婴幼儿的1.95倍。非特应性体质母亲中，两组婴幼儿的母亲开始服用叶酸时期比较，差异无统计学意义(P>0.05)。结论特应性体质母亲孕中后期开始服用叶酸可能使婴幼儿喘息的发生风险增加。

【关键词】叶酸；婴幼儿喘息；妊娠；病例对照研究

基金项目：江苏省连云港市科技局自然科学基金资助项目(SH1126)

【中图分类号】R 562.25

收稿日期：(2015-03-06；修回日期：2015-09-03)

杨静，于艳艳，王宜芬，等.不同孕期服用叶酸与婴幼儿喘息相关性的病例对照研究[J].中国全科医学，2015，18(35)：4310-4312.[www.chinagp.net]

Yang J，Yu YY，Wang YF，et al.Correlation between folic acid supplement in different stages of pregnancy and wheezing of infants:a case-control study[J].Chinese General Practice，2015，18(35)：4310-4312.

Correlation Between Folic Acid Supplement in Different Stages of Pregnancy and Wheezing of Infants:A Case-control StudyYANGJing，YUYan-yan，WANGYi-fen，etal.LianyungangMaternalandChildHealth-careCenterofJiangsuProvince,Lianyungang222006,China

Abstract【】ObjectiveTo investigate the relation between folic acid supplement at different stages of pregnancy and wheezing of infants,in order to provide references for the choice of good timing of folic acid supplement during pregnancy.MethodsWe enrolled 1 320 infants who were born in Lianyungang Maternal and Child Health-care Center from April 2011 to April 2012.By phone calls and questionnaire survey in clinics,the data about the infants and their mothers were collected,including infants′ gender,birth weight,first child or not,birth season and whether wheezing occurred within 2 years after birth,mother′s education degree,smoking history,feeding method,whether vitamin A or vitamin D was complemented during pregnancy,family-specific constitution or not,and stages of pregnancy supplying folic acid.According to whether wheezing occurred,the infants were divided into case group(n=397) and control group(n=923).ResultsThe two groups were not significantly different (P>0.05) in gender,birth weight,proportion of infants being first child,birth season,education level of the mothers,proportion of smoking,feeding method,proportion of mothers who had supplement of vitamin A and vitamin D during pregnancy.For their mothers with family-specific constitution，two groups were significantly different in the pregnancy stage when began to take folic acid(P<0.05);the infants whose mothers began to take folic acid in middle and late stages of pregnancy had a risk of wheezing 1.95 times greater than the that of infants whose mothers didn′t take folic acid.For their mothers without family-specific constitution,two groups were not significantly different in the pregnancy stage when the mothers began to take folic acid (P>0.05).ConclusionMothers with family-specific constitution begin to take folic acid in middle and late stages of pregnancy may increase the risk of wheezing in infants.

【Key words】Folic acid；Wheezing of infants；Pregnancy；Case-control studies

叶酸是由喋啶、对氨基苯甲酸和谷氨酸残基组成的一种水溶性B族维生素，为机体细胞生长和增殖所必需的物质。研究发现，孕妇服用叶酸，可防止胎儿神经管发育缺陷、新生儿体质量过轻、早产以及腭裂等[1]。服用叶酸已成为全球多个国家孕期营养保健的重要措施，美国等国家强制食品添加叶酸，我国也建议孕期服用叶酸预防神经管发育缺陷。但是最新研究显示，叶酸作为甲基供体在孕期服用，可能会影响后代的表观遗传机制，从而影响基因的表达与疾病表型，如使后代过敏性哮喘表型增加等[2-3]。本研究从表观遗传学角度研究妊娠期服用叶酸的时机与婴幼儿喘息发生的关系，探讨妊娠期生物学因素与婴幼儿喘息的相关性。

1对象与方法

1.1研究对象选取2011年4月—2012年4月于连云港市妇幼保健院出生的婴幼儿1 320例为研究对象。纳入标准：(1)无先天性心脏病等心血管疾病；(2)无严重肝肾功能损害；(3)无其他先天性、代谢性疾病。排除母亲具有哮喘、严重心肝肾等疾病及精神、心理疾病的婴幼儿。

1.2方法以电话或门诊问卷调查的方式收集婴幼儿及其母亲以下临床资料：(1)婴幼儿性别、出生体质量、胎次、出生季节及出生2年内是否发生婴幼儿喘息；(2)母亲受教育程度、吸烟史、喂养方式、孕期是否服用维生素A或维生素D、是否为特应性体质及服用叶酸的时期。婴幼儿喘息由二级及以上医院专科医生诊断，符合《诸福棠实用儿科学》[4]中毛细支气管炎、喘息样支气管炎、喘息型支气管肺炎的诊断标准。特应性体质的判定依据二级及以上医院诊断的特应性皮炎、荨麻疹、过敏性鼻炎等特应性疾病史。根据婴幼儿是否发生喘息分为病例组(397例)和对照组(923例)。

2结果

2.1两组一般资料比较两组婴幼儿性别、出生体质量、第一胎比例、出生季节及其母亲受教育程度、母亲吸烟率、喂养方式、孕期服用维生素A或维生素D率比较，差异均无统计学意义(P>0.05,见表1)。

2.2分层分析特应性体质母亲中，两组婴幼儿的母亲开始服用叶酸时期比较，差异有统计学意义(P<0.05)；其中，孕中后期开始服用叶酸的母亲的婴幼儿发生喘息的风险是未服用叶酸母亲的婴幼儿的1.95倍(见表2)。非特应性体质母亲中，两组婴幼儿的母亲开始服用叶酸时期比较，差异无统计学意义(P>0.05，见表3)。

表2 特应性体质母亲开始服用叶酸时期与婴幼儿喘息的关联性

〔n(%)〕

Table 2Correlation between pregnancy stage of mothers began to take folic acid with family-specific constitution and wheezing of infants

组别例数未服用孕前1个月孕初期孕中后期对照组27361(22.3)71(26.0)85(31.1)56(20.6)病例组12524(19.2)26(20.8)32(25.6)43(34.4)OR(95%CI)10.93(0.49,1.79)0.96(0.51,1.78)1.95(1.05,3.62)χ2值8.89P值0.03

表1　两组一般资料比较

注：a为t值；b受教育程度分类：初中及以下学历为低教育程度，高中或专科学历为中教育程度，本科及以上学历为高教育程度

表3 非特应性体质母亲开始服用叶酸时期与婴幼儿喘息的关联性

〔n(%)〕

Table 3Correlation between pregnancy stage of mothers began to take folic acid without family-specific constitution and wheezing of infants

组别例数未服用孕前1个月孕初期孕中后期对照组650184(28.3)132(20.3)191(29.4)143(22.0)病例组27279(29.0)53(19.5)77(28.3)63(23.2)OR(95%CI)10.94(0.62,1.41)0.94(0.65,1.36)1.03(0.69,1.53)χ2值0.29P值0.96

3讨论

婴幼儿喘息是小儿时期最常见的呼吸道疾病，是导致小儿住院的首要原因，若喘息反复发作，最终可发展为哮喘。目前，基因组学方法尚不能解释婴幼儿喘息性疾病及哮喘的发病机制和发病率逐年升高的原因。人及动物实验表明，孕期关键阶段的暴露(包括微生物风险、饮食改变和环境污染等)可改变基因的表达，并可能导致永久性的变化[5-6]，而基因表达的改变是通过表观遗传机制介导[7]。

综上所述，特应性体质母亲孕中后期开始服用叶酸可能与婴幼儿喘息的发生有关。在下一步研究中，需探索服用叶酸的关键期以及服用的合适剂量，既优化叶酸的神经保护作用，又不增加发生婴幼儿喘息及哮喘的风险。

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(本文编辑：吴立波)