低劑量阿司匹林對(duì)亞洲和非亞洲子癇前期高危孕婦妊娠結(jié)局影響的meta分析

張曉雯，崔世紅

（鄭州大學(xué)第三附屬醫(yī)院婦產(chǎn)科，河南 鄭州 450000）

子癇前期是一個(gè)以蛋白尿及高血壓為特征的綜合征，是孕產(chǎn)婦和圍產(chǎn)兒高死亡率的重要原因之一，在所有妊娠孕婦中其發(fā)病率大約為2%～8%[1]。低劑量阿司匹林可以選擇性的降低血栓素A2的水平而不會(huì)干擾內(nèi)皮細(xì)胞前列腺環(huán)素的生成，同時(shí)其可以有效的降低血小板的激活與聚集，最終維持血管收縮與舒張平衡，使得血管血流量增加，有效改善胎盤功能[2]。目前低劑量阿司匹林（75mg/d）已經(jīng)被世界衛(wèi)生組織推薦為高危孕婦預(yù)防子癇前期的常規(guī)劑量。Xu[3]等的Meta分析提示，低劑量阿司匹林可以有效降低子癇前期及早產(chǎn)等的發(fā)生率。但是到目前為止，沒有相關(guān)Meta分析來探討低劑量阿司匹林對(duì)不同種族高危孕婦的療效，而這對(duì)于臨床來說很重要。已有文獻(xiàn)報(bào)道，阿司匹林對(duì)亞洲人群的作用存在差異性是由于環(huán)氧化酶1、糖蛋白IIIa、嘌呤能受體P2Y等基因多態(tài)性所致[4]。因此，該研究旨在利用meta分析系統(tǒng)性評(píng)價(jià)低劑量阿司匹林對(duì)亞洲及非亞洲子癇前期高危孕婦妊娠結(jié)局的影響。

1 資料與方法

1.1 檢索策略

以“子癇前期”、“低劑量阿司匹林”、“aspirin”等為關(guān)鍵詞在中英文數(shù)據(jù)庫檢索。

1.2 文獻(xiàn)納入及排除標(biāo)準(zhǔn)

納入標(biāo)準(zhǔn)：(1)研究類型：均為隨機(jī)對(duì)照試驗(yàn)。(2)研究對(duì)象：子癇前期高危孕婦，高危孕婦指符合①側(cè)翻試驗(yàn)陽性②子宮動(dòng)脈多普勒超聲異常③血管緊張?jiān)囼?yàn)陽性④有子癇前期病史、初孕等PE高危因素4項(xiàng)中任一項(xiàng)的孕婦。(3)干預(yù)措施：阿司匹林組口服阿司匹林50～100mg/d。對(duì)照組行安慰劑、空白對(duì)照等處理。(4)結(jié)局指標(biāo)包括子癇前期、早產(chǎn)及圍產(chǎn)兒死亡等。排除標(biāo)準(zhǔn)：(1)統(tǒng)計(jì)學(xué)方法錯(cuò)誤文獻(xiàn)。(2)重復(fù)發(fā)表文獻(xiàn)或文獻(xiàn)中數(shù)據(jù)存在重復(fù)。(3)可能有嚴(yán)重偏倚或阿司匹林組與對(duì)照組納入例數(shù)差別較大的文獻(xiàn)。

1.3 文獻(xiàn)質(zhì)量評(píng)價(jià)及數(shù)據(jù)提取

由兩位研究者對(duì)文獻(xiàn)進(jìn)行質(zhì)量評(píng)價(jià)，并提取文獻(xiàn)一般資料。對(duì)納入研究按照J(rèn)adad Scale量表進(jìn)行評(píng)估。

1.4 統(tǒng)計(jì)學(xué)方法

采用SPSS20.00統(tǒng)計(jì)學(xué)軟件進(jìn)行分析，計(jì)數(shù)資料以“±s”表示，采用x2檢驗(yàn)，以P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié) 果

2.1 文獻(xiàn)檢索結(jié)果

對(duì)上述1980年1月～2017年1月時(shí)間內(nèi)文獻(xiàn)進(jìn)行檢索，共檢索到文獻(xiàn)1752篇，經(jīng)過其他手段檢索到文獻(xiàn)2篇，合計(jì)1754篇，最終納入文獻(xiàn)36篇。文獻(xiàn)質(zhì)量評(píng)分均高于5分。

2.2 Meta 及亞組分析結(jié)果

2.2.1 子癇前期及早產(chǎn)發(fā)生率比較32篇[5-36]文獻(xiàn)報(bào)道子癇前期及22篇[5-10,12-14,19,21,23-25,29-31,33-37]文獻(xiàn)報(bào)道早產(chǎn)例數(shù)。異質(zhì)性檢驗(yàn)示用隨機(jī)效應(yīng)模型。與對(duì)照組比，阿司匹林組子癇前期及早產(chǎn)發(fā)生率降低，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。亞組分析示：與非LDA相比，LDA能夠降低亞洲和非亞洲孕婦子癇前期及早產(chǎn)發(fā)生率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。

2.2.2 圍產(chǎn)兒死亡率及胎盤早剝發(fā)生率比較 17篇[7-10,12,14, 17, 18, 20, 23, 24, 32-36, 40]文獻(xiàn)報(bào)道圍產(chǎn)兒死亡及 14篇[8-10, 12, 16, 21, 23,24,31,33-36,40]文獻(xiàn)報(bào)道胎盤早剝例數(shù)。異質(zhì)性檢驗(yàn)分析示用固定效應(yīng)模型。LDA能降低圍產(chǎn)兒死亡率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05），LDA不能降低胎盤早剝發(fā)生率，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）。亞組分析示：LDA不能降低亞洲圍產(chǎn)兒死亡率及胎盤早剝發(fā)生率，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），LDA不能降低非亞洲胎盤早剝發(fā)生率，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），LDA可以降低非亞洲圍產(chǎn)兒死亡率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。

2.2.3 妊娠期高血壓發(fā)生率比較 14篇[5,8,17-20,29-31,33,34,37-39]文獻(xiàn)報(bào)道妊娠期高血壓例數(shù)。異質(zhì)性檢驗(yàn)示用隨機(jī)效應(yīng)模型。與對(duì)照組相比，阿司匹林組妊娠期高血壓發(fā)生率減低，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。亞組分析示：LDA不能降低非亞洲孕婦妊娠期高血壓發(fā)生率，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），可以降低亞洲孕婦妊娠期高血壓發(fā)生率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。

3 討 論

本研究評(píng)估了低劑量阿司匹林對(duì)亞洲與非亞洲子癇前期高危孕婦的療效，我們發(fā)現(xiàn)LDA能夠顯著降低亞洲與非亞洲高危孕婦患子癇前期的風(fēng)險(xiǎn)、同時(shí)也能降低早產(chǎn)及胎兒宮內(nèi)生長(zhǎng)受限發(fā)生率，更重的是，我們發(fā)現(xiàn)LDA不能降低亞洲高危孕婦圍產(chǎn)兒死亡率，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），但可以降低非亞洲高危孕婦的圍產(chǎn)兒死亡率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；早期口服阿司匹林不能降低非亞洲高危孕婦妊娠期高血壓發(fā)生率，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），但可以降低亞洲高危孕婦的妊娠期高血壓發(fā)生率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。說明LDA可以有效的降低亞洲與非亞洲高危孕婦子癇前期及早產(chǎn)等的發(fā)生率，并且在圍產(chǎn)兒死亡及妊娠期高血壓方面，LDA對(duì)不同種族有不同的效果。

盡管目前阿司匹林的作用機(jī)制尚不完全清楚，但其可抑制血栓烷A2介導(dǎo)的血管收縮，從而有效的防止胎盤血管的收縮，避免胎盤血流不足。盡管之前有文獻(xiàn)報(bào)道在中國(guó)人群中阿司匹林的作用較弱，但與以前的一些meta分析結(jié)果報(bào)道一致[41,42]，我們的研究證實(shí)低劑量阿司匹林可以顯著降低亞洲和非亞洲孕婦早產(chǎn)發(fā)生率，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。然而值得注意的是，本研究中阿司匹林在圍產(chǎn)兒死亡率及妊娠期高血壓發(fā)生率方面有不同的療效。

本研究存在一定局限性：①亞洲相關(guān)研究報(bào)道有限，在我們的薈萃分析中僅納入5篇中文隨機(jī)對(duì)照研究；②由于納入病例數(shù)有限，難以對(duì)妊娠期進(jìn)行更多亞組分析；③隨訪的差異可能影響我們對(duì)meta分析的評(píng)價(jià)；④亞洲和非亞洲人群在飲食習(xí)慣、生活環(huán)境、運(yùn)動(dòng)保健等方面的不同可能對(duì)結(jié)果產(chǎn)生一定影響。

總之，低劑量阿司匹林可以降低亞洲與非亞洲高危孕婦子癇前期、早產(chǎn)的風(fēng)險(xiǎn)，不能降低胎盤早剝發(fā)生率，而且在圍產(chǎn)兒死亡及妊娠期高血壓指標(biāo)上，低劑量阿司匹林對(duì)亞洲與非亞洲孕婦有著不同的療效。

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