肖亦爽(綜述),李　燕(審校)

(1.昆明市兒童醫(yī)院眼科，昆明 650034； 2.昆明醫(yī)科大學(xué)第一附屬醫(yī)院眼科，昆明 650031)

早產(chǎn)兒視網(wǎng)膜病變患兒母親孕期風(fēng)險(xiǎn)因素研究進(jìn)展

肖亦爽1(綜述),李燕2※(審校)

(1.昆明市兒童醫(yī)院眼科，昆明 650034； 2.昆明醫(yī)科大學(xué)第一附屬醫(yī)院眼科，昆明 650031)

摘要：早產(chǎn)兒視網(wǎng)膜病變(ROP)是發(fā)展中國家主要的兒童致盲性疾病。ROP是一個(gè)發(fā)生于低體質(zhì)量、小胎齡嬰兒、多因素綜合作用所致的眼部疾病,其發(fā)病原因至今仍未明確。出生體質(zhì)量和孕周是公認(rèn)的發(fā)生ROP的主要危險(xiǎn)因素。近年來國內(nèi)外大量研究關(guān)注ROP母親孕期的風(fēng)險(xiǎn)因素，并得到相關(guān)結(jié)論，因此有必要就近年來ROP患兒母親孕期風(fēng)險(xiǎn)因素研究予以綜述，旨在提高對(duì)ROP防治工作的認(rèn)識(shí)。

關(guān)鍵詞:早產(chǎn)兒視網(wǎng)膜病變；孕期；風(fēng)險(xiǎn)因素

早產(chǎn)兒視網(wǎng)膜病變(retino-pathy of prematurity，ROP)是指發(fā)生在早產(chǎn)兒和低體質(zhì)量?jī)旱囊暰W(wǎng)膜血管增生性病變。對(duì)于ROP的發(fā)病原因，國內(nèi)外多關(guān)注早產(chǎn)兒出生后情況，而對(duì)圍生期的情況，特別是母親在懷孕期間的情況關(guān)注和了解相對(duì)較少。然而，母體內(nèi)的胎兒相比早產(chǎn)兒來說，體質(zhì)量更低，胎齡更短，全身各器官系統(tǒng)發(fā)育更加不成熟，也更容易受到體內(nèi)外各種因素的影響而導(dǎo)致視網(wǎng)膜病變發(fā)生。

ROP公認(rèn)的重要發(fā)病原因是低胎齡及低出生體質(zhì)量[1]。隨著對(duì)發(fā)病原因的進(jìn)一步研究，學(xué)者們也開始關(guān)注與圍生期的其他風(fēng)險(xiǎn)因素之間的關(guān)系。希望通過對(duì)這些因素的探究，尋找在圍生期早期預(yù)防ROP的方法，并規(guī)范對(duì)母親圍生期的相關(guān)保健和治療，從而降低ROP的發(fā)病率?，F(xiàn)就ROP患兒母親孕期風(fēng)險(xiǎn)因素研究進(jìn)展予以綜述。

1孕周與出生體質(zhì)量對(duì)ROP的影響

2多胎對(duì)ROP的影響

目前，國內(nèi)外研究就妊娠胎數(shù)對(duì)ROP的影響(即多胎是否比單胎更容易發(fā)生ROP)觀點(diǎn)不一。王志立和董應(yīng)麗[16]收集2005年5月至2006年6月的多胎36例(雙胎31例，三胎5例)早產(chǎn)兒，研究認(rèn)為ROP的發(fā)生率除了與早產(chǎn)兒體質(zhì)量、胎齡和吸氧等因素有關(guān)外，還由于多胎早產(chǎn)兒的平均吸氧時(shí)間明顯長(zhǎng)于單胎早產(chǎn)兒，平均出生體質(zhì)量明顯低于單臺(tái)早產(chǎn)兒，而孕周也明顯短于單胎早產(chǎn)兒，因此多胎早產(chǎn)兒ROP發(fā)生率明顯高于單胎早產(chǎn)兒。但對(duì)于及時(shí)篩查和得到及時(shí)治療的ROP閾值病變，預(yù)后均良好，多胎與單胎比較無明顯差異。研究者認(rèn)為ROP的高危因素包括多胎，由于多胎妊娠早產(chǎn)發(fā)生率高，故未成熟兒和極低體質(zhì)量?jī)旱陌l(fā)生率也高于正常的單胎妊娠[17]。

3性別對(duì)ROP的影響

大多數(shù)研究認(rèn)為性別對(duì)ROP的發(fā)生沒有直接影響。但Darlow等[18]研究表明，性別是重度ROP的危險(xiǎn)因素。他們收集了澳大利亞及新西蘭三級(jí)醫(yī)院新生兒部的高?；純汗?105例，其中患有3期或以上的ROP 203例。其結(jié)論表明除了未成熟度、宮內(nèi)生長(zhǎng)受限等因素外，男性也是發(fā)生重度ROP的危險(xiǎn)因素。丁國芳[19]也認(rèn)為ROP中男性比女性多。

4類固醇對(duì)ROP的影響

類固醇在ROP發(fā)生過程中的作用仍存在爭(zhēng)議[20]。產(chǎn)后使用類固醇治療支氣管發(fā)育不良會(huì)增加嚴(yán)重ROP的發(fā)生率[21-22]。與此相反，使用類固醇可以保護(hù)那些需要進(jìn)行視網(wǎng)膜冷凝治療的ROP患兒[23-24]。意大利一項(xiàng)多中心研究顯示產(chǎn)前使用類固醇對(duì)ROP有明顯的保護(hù)作用[25]，并認(rèn)為這是因?yàn)轭惞檀几纳屏撕粑δ躘26]，減少患兒對(duì)氧氣和呼吸道支持的依賴，也可能是加快了胎兒抗氧化能力的成熟[23]。Higgins等[27]認(rèn)為在城市人口中，早產(chǎn)兒母親產(chǎn)前注射地塞米松后，可以顯著降低ROP進(jìn)展至2期或更嚴(yán)重的階段。Seiberth和Linderkamp[28]篩查447例早產(chǎn)兒后認(rèn)為產(chǎn)前使用地塞米松促進(jìn)患兒肺部發(fā)育后，ROP發(fā)病率降低。Simth等[29]同樣報(bào)道產(chǎn)前使用地塞米松可以降低ROP發(fā)生率。與此相反，Cuculich等[30]篩查72例早產(chǎn)兒后報(bào)道，產(chǎn)前沒有使用地塞米松的ROP發(fā)病率為26%，而產(chǎn)前使用低劑量(<1.8 mg/kg)地塞米松的發(fā)病率為61%。使用大劑量(1.8 mg/kg)地塞米松的發(fā)病率為85%。Shah等[31]報(bào)道757例早產(chǎn)兒篩查情況，認(rèn)為產(chǎn)前使用地塞米松并沒有明顯降低ROP的發(fā)生率。

5孕期疾病對(duì)ROP的影響

5.1子癇通常子癇被認(rèn)為是導(dǎo)致ROP進(jìn)展的重要原因。Shah等[31]報(bào)道子癇是發(fā)生閾值期ROP的主要原因之一。Seiberth和Linderkamp[28]認(rèn)為產(chǎn)婦先兆子癇是ROP發(fā)病的獨(dú)立影響因素。Yang等[32]認(rèn)為先兆子癇是閾值ROP的風(fēng)險(xiǎn)因素之一。Ozkan等[33]對(duì)產(chǎn)婦先兆子癇對(duì)ROP進(jìn)展和嚴(yán)重程度的影響進(jìn)行了研究，結(jié)果顯示，先兆子癇增加了ROP的發(fā)病風(fēng)險(xiǎn)。Hansen等[34]也認(rèn)為由于先兆子癇可能導(dǎo)致早產(chǎn)兒支氣管發(fā)育不良而導(dǎo)致ROP的發(fā)生。然而Yu等[35]篩查了25 473例早產(chǎn)兒后利用大隊(duì)列數(shù)據(jù)研究妊娠期高血壓綜合征和先兆子癇對(duì)ROP發(fā)病率的影響，認(rèn)為先兆子癇與減少ROP的發(fā)病有關(guān)。Fortes Filho等[36]也同樣認(rèn)為先兆子癇對(duì)ROP有保護(hù)作用。

5.2妊娠期高血壓綜合征Holmstrom等[37]篩查260例早產(chǎn)兒后報(bào)道，妊娠期高血壓綜合征是僅有的引起ROP發(fā)生的圍生期因素。Zayed等[38]對(duì)孕婦新發(fā)妊娠期高血壓綜合征與嚴(yán)重ROP的相關(guān)性進(jìn)行研究，結(jié)果顯示妊娠期高血壓綜合征與ROP的嚴(yán)重程度無明顯相關(guān)性。

5.3圍生期感染彭娟等[3]認(rèn)為圍生期感染及妊娠并發(fā)癥也是ROP發(fā)病機(jī)制中重要的因素。國外報(bào)道中已明確圍生期感染能增加ROP發(fā)病的敏感性，有圍生期感染的患兒更易患ROP，也更傾向于更嚴(yán)重的ROP病變[39]。Woo等[40]篩查246例韓國早產(chǎn)兒后認(rèn)為，臨床絨毛膜羊膜炎和產(chǎn)婦外周血白細(xì)胞計(jì)數(shù)是明顯而獨(dú)立的ROP相關(guān)因素。

6孕婦年齡對(duì)ROP的影響

Wu等[41]篩查新加坡144例早產(chǎn)兒后對(duì)66項(xiàng)可能的風(fēng)險(xiǎn)因素進(jìn)行分析后認(rèn)為，只有出生體質(zhì)量和母親生育年齡是引起ROP的明顯因素。Wu等[41]將發(fā)病組與對(duì)照組對(duì)比發(fā)現(xiàn)，發(fā)病組的母親生育年齡明顯大于對(duì)照組[(31.2±5.1)歲比(28.2±5.3)歲]。Giapros等[9]對(duì)ROP患兒母親年齡、病理性妊娠、體外受精、多胎妊娠和分娩方式等因素進(jìn)行研究，未發(fā)現(xiàn)母親年齡與ROP的發(fā)生有關(guān)。

7其他

7.1吸煙McGinnity和Halliday[42]對(duì)200例約9歲的極低出生體質(zhì)量?jī)和M(jìn)行研究發(fā)現(xiàn)，ROP除了與出生體質(zhì)量、進(jìn)入新生兒重癥監(jiān)護(hù)病房的時(shí)間、壞死性小腸結(jié)腸炎有關(guān)外，還與孕婦圍生期吸煙有關(guān)。而Hirabayashi等[43]認(rèn)為，孕婦吸煙對(duì)嚴(yán)重的ROP的進(jìn)展有抑制作用。

7.2人種丁國芳[19]研究認(rèn)為，ROP的發(fā)生白種人比黑種人多，而且程度重。阿拉斯加人比非本土人發(fā)生ROP早。流行病學(xué)調(diào)查也顯示，ROP在美國和英國白種人中的發(fā)病率明顯高于黑種人，男性多于女性[18]。

8小結(jié)

目前，ROP作為發(fā)展中國家重要的嬰幼兒致盲性眼病，在其病變加重甚至發(fā)生之前可以通過篩查發(fā)現(xiàn)并給予必要的治療從而防止視覺的損害。因此，早期發(fā)現(xiàn)、早期預(yù)防尤為重要。圍生期孕婦的全身情況、藥物使用、甚至年齡等因素均可能對(duì)胎兒產(chǎn)生影響。因此關(guān)注圍生期孕婦導(dǎo)致ROP的風(fēng)險(xiǎn)因素對(duì)于防治ROP和規(guī)范其篩查標(biāo)準(zhǔn)均有著積極的推動(dòng)作用。

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Progress on Study of Maternal Risk Factors of Retinopathy of Prematurity

XIAOYi-shuang1,LIYan2.

(1.DepartmentofOphthalmology,KunmingChildren′sHospital,Kunming650034,China; 2.DepartmentofOphthalmology,theFirstAffiliatedHospitalofKunmingMedicalUniversity,Kunming650031,China)

Abstract：Retinopathy of prematurity(ROP) is an important cause of children blindness in developing countries.It is defined as an eye disease in infants with low birth weight and small gestational age caused by multiple factors which are not clear.Low birth weight and small gestational age are generally accepted as main risk factors for ROP.In recent years,many studies focused on the reasons of ROP and drew some conclusions.Here is to make a review of the literatures about the maternal risk factors of ROP for further prevention and control of ROP.

Key words：Retinopathy of prematurity; Pregnancy; Risk factors

收稿日期：2014-09-15修回日期：2015-07-21編輯：伊姍

基金項(xiàng)目：云南省應(yīng)用基礎(chǔ)研究計(jì)劃項(xiàng)目(2013FZ248)

doi：10.3969/j.issn.1006-2084.2015.23.029

中圖分類號(hào)：R774

文獻(xiàn)標(biāo)識(shí)碼：A

文章編號(hào)：1006-2084(2015)23-4304-04