不同孕期服用葉酸與嬰幼兒喘息相關(guān)性的病例對(duì)照研究

·論著·

不同孕期服用葉酸與嬰幼兒喘息相關(guān)性的病例對(duì)照研究

楊靜，于艷艷，王宜芬，錢前，李偉

作者單位：222006江蘇省連云港市婦幼保健院

通信作者：于艷艷，222006江蘇省連云港市婦幼保健院；E-mail：wangjunhuayyy@sina.com

【摘要】目的探討不同孕期服用葉酸與嬰幼兒喘息發(fā)生的關(guān)系，為孕期服用葉酸選擇合適時(shí)機(jī)提供依據(jù)。方法選取2011年4月—2012年4月于連云港市婦幼保健院出生的嬰幼兒1 320例為研究對(duì)象。以電話或門診問卷調(diào)查的方式收集嬰幼兒及其母親臨床資料，包括嬰幼兒性別、出生體質(zhì)量、胎次、出生季節(jié)及出生2年內(nèi)是否發(fā)生嬰幼兒喘息；母親受教育程度、吸煙史、喂養(yǎng)方式、孕期是否服用維生素A或維生素D、是否為特應(yīng)性體質(zhì)及服用葉酸的時(shí)期。根據(jù)嬰幼兒是否發(fā)生喘息分為病例組(397例)和對(duì)照組(923例)。結(jié)果兩組嬰幼兒性別、出生體質(zhì)量、第一胎比例、出生季節(jié)及其母親受教育程度、母親吸煙率、喂養(yǎng)方式、孕期服用維生素A或維生素D率比較，差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)。特應(yīng)性體質(zhì)母親中，兩組嬰幼兒的母親開始服用葉酸時(shí)期比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其中，孕中后期開始服用葉酸的母親的嬰幼兒發(fā)生喘息的風(fēng)險(xiǎn)是未服用葉酸母親的嬰幼兒的1.95倍。非特應(yīng)性體質(zhì)母親中，兩組嬰幼兒的母親開始服用葉酸時(shí)期比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。結(jié)論特應(yīng)性體質(zhì)母親孕中后期開始服用葉酸可能使嬰幼兒喘息的發(fā)生風(fēng)險(xiǎn)增加。

【關(guān)鍵詞】葉酸；嬰幼兒喘息；妊娠；病例對(duì)照研究

基金項(xiàng)目：江蘇省連云港市科技局自然科學(xué)基金資助項(xiàng)目(SH1126)

【中圖分類號(hào)】R 562.25

收稿日期：(2015-03-06；修回日期：2015-09-03)

楊靜，于艷艷，王宜芬，等.不同孕期服用葉酸與嬰幼兒喘息相關(guān)性的病例對(duì)照研究[J].中國全科醫(yī)學(xué)，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

葉酸是由喋啶、對(duì)氨基苯甲酸和谷氨酸殘基組成的一種水溶性B族維生素，為機(jī)體細(xì)胞生長和增殖所必需的物質(zhì)。研究發(fā)現(xiàn)，孕婦服用葉酸，可防止胎兒神經(jīng)管發(fā)育缺陷、新生兒體質(zhì)量過輕、早產(chǎn)以及腭裂等[1]。服用葉酸已成為全球多個(gè)國家孕期營養(yǎng)保健的重要措施，美國等國家強(qiáng)制食品添加葉酸，我國也建議孕期服用葉酸預(yù)防神經(jīng)管發(fā)育缺陷。但是最新研究顯示，葉酸作為甲基供體在孕期服用，可能會(huì)影響后代的表觀遺傳機(jī)制，從而影響基因的表達(dá)與疾病表型，如使后代過敏性哮喘表型增加等[2-3]。本研究從表觀遺傳學(xué)角度研究妊娠期服用葉酸的時(shí)機(jī)與嬰幼兒喘息發(fā)生的關(guān)系，探討妊娠期生物學(xué)因素與嬰幼兒喘息的相關(guān)性。

1對(duì)象與方法

1.1研究對(duì)象選取2011年4月—2012年4月于連云港市婦幼保健院出生的嬰幼兒1 320例為研究對(duì)象。納入標(biāo)準(zhǔn)：(1)無先天性心臟病等心血管疾??；(2)無嚴(yán)重肝腎功能損害；(3)無其他先天性、代謝性疾病。排除母親具有哮喘、嚴(yán)重心肝腎等疾病及精神、心理疾病的嬰幼兒。

1.2方法以電話或門診問卷調(diào)查的方式收集嬰幼兒及其母親以下臨床資料：(1)嬰幼兒性別、出生體質(zhì)量、胎次、出生季節(jié)及出生2年內(nèi)是否發(fā)生嬰幼兒喘息；(2)母親受教育程度、吸煙史、喂養(yǎng)方式、孕期是否服用維生素A或維生素D、是否為特應(yīng)性體質(zhì)及服用葉酸的時(shí)期。嬰幼兒喘息由二級(jí)及以上醫(yī)院?？漆t(yī)生診斷，符合《諸福棠實(shí)用兒科學(xué)》[4]中毛細(xì)支氣管炎、喘息樣支氣管炎、喘息型支氣管肺炎的診斷標(biāo)準(zhǔn)。特應(yīng)性體質(zhì)的判定依據(jù)二級(jí)及以上醫(yī)院診斷的特應(yīng)性皮炎、蕁麻疹、過敏性鼻炎等特應(yīng)性疾病史。根據(jù)嬰幼兒是否發(fā)生喘息分為病例組(397例)和對(duì)照組(923例)。

2結(jié)果

2.1兩組一般資料比較兩組嬰幼兒性別、出生體質(zhì)量、第一胎比例、出生季節(jié)及其母親受教育程度、母親吸煙率、喂養(yǎng)方式、孕期服用維生素A或維生素D率比較，差異均無統(tǒng)計(jì)學(xué)意義(P>0.05,見表1)。

2.2分層分析特應(yīng)性體質(zhì)母親中，兩組嬰幼兒的母親開始服用葉酸時(shí)期比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其中，孕中后期開始服用葉酸的母親的嬰幼兒發(fā)生喘息的風(fēng)險(xiǎn)是未服用葉酸母親的嬰幼兒的1.95倍(見表2)。非特應(yīng)性體質(zhì)母親中，兩組嬰幼兒的母親開始服用葉酸時(shí)期比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05，見表3)。

表2 特應(yīng)性體質(zhì)母親開始服用葉酸時(shí)期與嬰幼兒喘息的關(guān)聯(lián)性

〔n(%)〕

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

組別例數(shù)未服用孕前1個(gè)月孕初期孕中后期對(duì)照組27361(22.3)71(26.0)85(31.1)56(20.6)病例組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　兩組一般資料比較

注：a為t值；b受教育程度分類：初中及以下學(xué)歷為低教育程度，高中或?qū)？茖W(xué)歷為中教育程度，本科及以上學(xué)歷為高教育程度

表3 非特應(yīng)性體質(zhì)母親開始服用葉酸時(shí)期與嬰幼兒喘息的關(guān)聯(lián)性

〔n(%)〕

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

組別例數(shù)未服用孕前1個(gè)月孕初期孕中后期對(duì)照組650184(28.3)132(20.3)191(29.4)143(22.0)病例組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討論

嬰幼兒喘息是小兒時(shí)期最常見的呼吸道疾病，是導(dǎo)致小兒住院的首要原因，若喘息反復(fù)發(fā)作，最終可發(fā)展為哮喘。目前，基因組學(xué)方法尚不能解釋嬰幼兒喘息性疾病及哮喘的發(fā)病機(jī)制和發(fā)病率逐年升高的原因。人及動(dòng)物實(shí)驗(yàn)表明，孕期關(guān)鍵階段的暴露(包括微生物風(fēng)險(xiǎn)、飲食改變和環(huán)境污染等)可改變基因的表達(dá)，并可能導(dǎo)致永久性的變化[5-6]，而基因表達(dá)的改變是通過表觀遺傳機(jī)制介導(dǎo)[7]。

綜上所述，特應(yīng)性體質(zhì)母親孕中后期開始服用葉酸可能與嬰幼兒喘息的發(fā)生有關(guān)。在下一步研究中，需探索服用葉酸的關(guān)鍵期以及服用的合適劑量，既優(yōu)化葉酸的神經(jīng)保護(hù)作用，又不增加發(fā)生嬰幼兒喘息及哮喘的風(fēng)險(xiǎn)。

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(本文編輯：吳立波)