楊紅玲,梁怡華,鮑俊杰,孫 玲,郭彩嬌,邱先桃

(廣州市婦女兒童醫(yī)療中心1.檢驗(yàn)部;2.生殖中心,廣東 廣州 510180)

白細(xì)胞參數(shù)對(duì)妊娠期高血壓紊亂早期預(yù)測(cè)能力的研究

楊紅玲1,梁怡華1,鮑俊杰1,孫 玲2,郭彩嬌1,邱先桃1

(廣州市婦女兒童醫(yī)療中心1.檢驗(yàn)部;2.生殖中心,廣東 廣州 510180)

目的研究白細(xì)胞參數(shù)與妊娠期高血壓紊亂(HDP)發(fā)生的關(guān)系及其對(duì)HDP的早期預(yù)測(cè)價(jià)值。方法對(duì)99例HDP、129例正常妊娠婦女和200例妊娠期糖尿病婦女妊娠20周前的全血白細(xì)胞參數(shù)進(jìn)行研究分析。結(jié)果妊娠20周前三組間白細(xì)胞計(jì)數(shù)(WBC)、中性粒細(xì)胞絕對(duì)數(shù)(NC)、淋巴細(xì)胞絕對(duì)數(shù)(LC)和單核細(xì)胞絕對(duì)數(shù)(MC)差異具有顯著性統(tǒng)計(jì)學(xué)意義;HDP組WBC、NC和LC在妊娠20周前明顯增高,與正常妊娠組間差異具有顯著性統(tǒng)計(jì)學(xué)意義,當(dāng)與GMD組比較時(shí),差異均無(wú)統(tǒng)計(jì)學(xué)意義。ROC曲線下的面積:WBC為0.616(95%CI,0.541-0.691;P=0.003)、NC為0.612(95%CI,0.536-0.687;P=0.004)和LC為0.615(95%CI,0.540-0.690;P=0.003)。當(dāng)WBC、NC和LC分別高于9.375×109/L,6.625×109/L和1.975×109/L時(shí),對(duì)HDP的陽(yáng)性預(yù)測(cè)值在53.48%-59.09%之間,陰性預(yù)測(cè)值在65.66%-69.69%之間。LC和WBC或NC串聯(lián)用于預(yù)測(cè)HDP的陽(yáng)性預(yù)測(cè)值達(dá)(70.77%)和特異性達(dá)(85.27%)。結(jié)論該研究表明白細(xì)胞的升高和異常激活可能在HDP的發(fā)病中起一定的作用,白細(xì)胞參數(shù)特別是其聯(lián)合應(yīng)用對(duì)HDP的早期預(yù)測(cè)有一定的臨床應(yīng)用價(jià)值。

高血壓紊亂;炎癥;白細(xì)胞;預(yù)測(cè);妊娠

(Chin J Lab Diagn,2010,14:0051)

妊娠期高血壓紊亂(HDP)是妊娠期常見的一組并發(fā)癥,主要包括妊娠高血壓、慢性高血壓、輕度子癇前期、重度子癇前期和子癇等。HDP發(fā)病率高(6%-20%),與母嬰圍產(chǎn)期發(fā)病率和死亡率密切相關(guān)[1-3]。HDP確切的發(fā)病原因至今尚不清楚[2],本文對(duì)妊娠期20周前的白細(xì)胞參數(shù)進(jìn)行分析,探討白細(xì)胞與HDP的關(guān)系及其對(duì)HDP的早期預(yù)測(cè)價(jià)值。

1 材料與方法

樣本來(lái)自于2002-2006年間廣州市婦女兒童醫(yī)療中心門診和住院的妊娠婦女。孕婦的臨床資料和全血細(xì)胞計(jì)數(shù)數(shù)據(jù)從臨床住院病歷和實(shí)驗(yàn)室信息系統(tǒng)獲得。正常對(duì)照的納入標(biāo)準(zhǔn):單胎妊娠、無(wú)蛋白尿、血壓正常、無(wú)胎兒畸形及其他妊娠并發(fā)癥的妊娠婦女。妊娠期糖尿病(GDM)的篩查標(biāo)準(zhǔn):空腹葡萄糖檢測(cè)至少兩次,血清葡萄糖≧5.8 mmol/L;或者75 g糖耐量試驗(yàn)兩次以上血清葡萄糖≧臨界值(FGT 5.6 mmol/L,1 h 10.3 mmol/L,2 h 8.6 mmol/L,3 h 6.7 mmol/L)。

本研究只納入妊娠20周后發(fā)病的HDP,包括:①妊娠誘發(fā)的高血壓:無(wú)蛋白尿,收縮壓≧140 mmHg或舒張壓≥90 mmHg。②輕度子癇前期:血壓≥140/90 mmHg,蛋白尿(24 h尿總蛋白≥300 mg或者干化學(xué)法≥1+)。③重度子癇前期:收縮壓≥160 mmHg或舒張壓≥110 mmHg,蛋白尿(24 h尿總蛋白≥2.0 g或者干化學(xué)≥3+)。

2 結(jié)果

排除胎兒畸形、有妊娠并發(fā)癥、有感染征兆或多胎妊娠者后,共有428例妊娠婦女被納入本研究,其中HDP 99例,GDM 200例,正常妊娠129例。99例PHD中31例(31.31%)為妊娠高血壓,5例(5%)為輕度子癇前期,63例(63.63%)為重度子癇前期。三組之間比較,白細(xì)胞參數(shù)差異無(wú)顯著性統(tǒng)計(jì)學(xué)意義(P＞0.05)。

如表1所示,在20周之前HDP組和正常妊娠組WBC、NC和LC間存在顯著性差異,故用ROC曲線繼續(xù)分析這三個(gè)變量對(duì)HDP的預(yù)測(cè)價(jià)值。ROC曲線下的面積:WBC為0.616(95%CI,0.541-0.691;P=0.003)、NC 為 0.612(95%CI,0.536-0.687;P=0.004)和LC為0.615(95%CI,0.540-0.690;P=0.003)。當(dāng)WBC、NC和 LC分別高于9.375×109/L,6.625×109/L和 1.975×109/L時(shí),對(duì)HDP的陽(yáng)性預(yù)測(cè)值在53.48%-59.09%之間,陰性預(yù)測(cè)值在65.66%-69.69%之間。當(dāng)把這些參數(shù)進(jìn)行串聯(lián)分析時(shí),可見ROC曲線下的面積、特異性和陽(yáng)性預(yù)測(cè)值都顯著提高了。例如,LC和NC串聯(lián)后的ROC曲線下的面積為0.784(95%CI,0.723-0.846;P＜0.001)。

三個(gè)參數(shù)及串聯(lián)后預(yù)測(cè)HDP的敏感性、特異性、陽(yáng)性預(yù)測(cè)值和陰性預(yù)測(cè)值情況見表2。LC預(yù)測(cè)的敏感性(69%)和陰性預(yù)測(cè)值(69.69%)最好,而LC與WBC或NC串聯(lián)用于20周以前預(yù)測(cè)HDP的陽(yáng)性預(yù)測(cè)值(70.77%)和特異性(85.27%)最好。

表1 妊娠20周前HDP妊娠婦女與與正常妊娠婦女白細(xì)胞參數(shù)的關(guān)系比較

表2 妊娠20周前白細(xì)胞參數(shù)對(duì)HDP的臨床診斷效率

3 討論

子癇前期婦女循環(huán)血中的炎癥細(xì)胞被明顯激活,預(yù)示著炎癥反應(yīng)的發(fā)生,這說(shuō)明免疫系統(tǒng)的異常激活可能在其發(fā)病中扮演著重要的角色[4,5]。最近有資料表明子癇前期是一種以Th1占主導(dǎo)的Th1/Th2的免疫失衡,在正常晚期妊娠中,外周血白細(xì)胞被激活,白細(xì)胞數(shù)量在子癇前期進(jìn)一步升高。子癇前期的妊娠婦女在妊娠晚期時(shí)其血漿炎癥參數(shù)CRP和IL-6的濃度升高[6]。在子癇前期的大鼠模型中,升高的白細(xì)胞和粒細(xì)胞數(shù)也表明炎癥反應(yīng)在HDP發(fā)生中被激活[7]。我們的研究也支持上述觀點(diǎn),HDP相關(guān)綜合癥的妊娠婦女WBC、NC和LC顯著高于正常妊娠婦女。然而,也有一些相反的觀點(diǎn),Ceyhan T[8]對(duì)56例子癇前期和43例正常孕婦的研究發(fā)現(xiàn)白細(xì)胞參數(shù)在兩組間的差異并無(wú)顯著統(tǒng)計(jì)學(xué)意義。這些不同結(jié)果的產(chǎn)生可能是因?yàn)闄z測(cè)儀器和檢測(cè)方法的不同。另外,由于血細(xì)胞參數(shù)是隨著妊娠的進(jìn)展而變化的,如果沒(méi)有把孕周考慮進(jìn)去,也會(huì)使結(jié)果受到影響而得出不同結(jié)論。

對(duì)PDH不同階段白細(xì)胞參數(shù)進(jìn)行分析,見妊娠高血壓、輕度子癇前期和重度子癇前期三組之間白細(xì)胞參數(shù)的統(tǒng)計(jì)無(wú)顯著性意義(P＜0.05),因此,白細(xì)胞參數(shù)不能用于預(yù)測(cè)HDP的嚴(yán)重程度。但這也可能是不同妊娠周混雜的影響而造成的,這點(diǎn)需要加大樣本量進(jìn)行進(jìn)一步分層研究。另外,HDP與GDM組的白細(xì)胞參數(shù)的統(tǒng)計(jì)無(wú)顯著性意義,說(shuō)明GDM可能同HDP一樣也伴隨有免疫系統(tǒng)的激活。

對(duì)于臨床婦產(chǎn)專家而言,在癥狀出現(xiàn)前篩選出高風(fēng)險(xiǎn)的HDP的婦女是非常重要的。HDP發(fā)病率高,引發(fā)的母嬰不良預(yù)后多,臨床醫(yī)師需要對(duì)其進(jìn)行早期的密切監(jiān)護(hù),以降低母嬰的發(fā)病率和死亡率。最近的研究認(rèn)為阿斯匹林、維生素C選擇性地用于這些HDP高風(fēng)險(xiǎn)的婦女可及時(shí)、經(jīng)濟(jì)地進(jìn)行干預(yù),最終有效地降低圍產(chǎn)期母嬰的發(fā)病率和死亡率[9,10]。我們對(duì)妊娠20周前的白細(xì)胞參數(shù)進(jìn)行分析以了解其對(duì)HDP癥狀出現(xiàn)前的預(yù)測(cè)能力。使臨床醫(yī)師爭(zhēng)取時(shí)間,防治HDP的發(fā)生及其臨床妊娠不良結(jié)局。本研究表明,白細(xì)胞計(jì)數(shù)是一個(gè)對(duì)HDP有預(yù)測(cè)作用的指標(biāo)。特別是當(dāng)NC和LC串聯(lián)后診斷特異性和陽(yáng)性預(yù)測(cè)值明顯升高(表2)。這些參數(shù)的聯(lián)合使用可增強(qiáng)其對(duì)HDP的預(yù)測(cè)價(jià)值。

本研究發(fā)現(xiàn)妊娠20周前,HDP的白細(xì)胞參數(shù)明顯升高,說(shuō)明免疫系統(tǒng)的異常激活可能在HDP的發(fā)病中起一定的作用,白細(xì)胞參數(shù)特別是其聯(lián)合應(yīng)用對(duì)預(yù)測(cè)HDP有一定的臨床應(yīng)用價(jià)值,但其潛在意義還需要進(jìn)一步的前瞻性研究加以證實(shí),生物化學(xué)、物理及臨床多指標(biāo)的聯(lián)合應(yīng)用更有利于HDP這一復(fù)雜綜合征的早期預(yù)測(cè)[10,11]。

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Leukocyte Parameters in Hypertensive Disorders of Pregnancy in the South of China

YANG Hong-ling,LIANGYi-hua,BAO Jun-jie,et al.(Department of Clinical Laboratory,Guangzhou Women and Children's Medical Center,Guangzhou510180,China)

ObjectiveThe current study was to compare the leukocytes in HDP with that in the control groups and to evaluate whether these parametershave a predictive value of the HDP in the pre-clinical stage.MethodsThe study was carried out retrospectively and included 99 HPD patients,129 normal gravidas and 200 gestational diabets mellitus(GDM).The leukocyte parameters in pregnancy were comparedbetween in the three groups and receiver operator characteristic(ROC)curvewas plotted for different values of the parameters.ResultsIn the pre-clinical stage,womanwho developed HDP had significant higher leukocyte(WBC),neutrophil(NC),lymphocyte(LC)and monocyte counts(MC),compared to the normal gravidas,but there was no significant difference between HDP and GD M.And the area under the ROC curve was 0.616 for WBC,0.612 for NC and 0.615 for LC.With a cut off WBC,NC and LC greater than 9.375×109/L,6.625×109/L,and 1.795×109/L respectively,the positive predictive value was between 53.48%-59.09%and negative predictive value was between 65.66%-69.69%.When combined two leukocyte parameters by a serial test,the positive predictive value could be significant increased.For example,using the LC in combined with WBC or NC,the positive predictive value for the HDP was increased to 70.77%,the specificity increased to 85.27%.ConclusionWe hypothesized that HDP may be the result of an inflammatory response,and leukocytes especially the combination to two parameters,is helpful the prediction of HDP-related complications at the placentation period.

hypertensive disorders;inflammation;leukocyte;prediction;pregnancy

R544.1

A

1007-4287(2010)01-0051-03

2008-11-29)