狼疮肾炎患者妊娠结局分析

Maternal and fetal outcomes in women complicated with lupus nephritis

目的探讨系统性红斑狼疮（systemiclupuserythematosus，SI。E）合并狼疮肾炎（1upusnephritis，LN）患者妊娠的母婴不良结局及危险因素。方法对北京协和医院1990年1月1日至2012年12月31日期间收治的93例LN患者共97例次妊娠进行回顾性分析。根据LN发病时间和病情程度分为3组：妊娠前疾病稳定组（52例次）、妊娠前疾病活动组（26例次）和妊娠期新确诊I。N组（19例次）。孕产妇不良结局包括妊娠期疾病加重、子痫前期、妊娠期或产后尿蛋白加重、妊娠期或产后。肾功能损伤加重、孕产妇死亡、低血小板血症和低补体血症。胎儿或新生儿不良结局包括治疗性终止妊娠（因孕妇疾病加重需要终止妊娠）、胎儿丢失、新生儿死亡、早产、小于胎龄儿和新生儿窒息。组间率的比较采用y。检验和Fisher精确概率法，母婴不良结局的危险因素采用二项分类Logistic回归分析。结果（1）孕产妇不良妊娠结局：妊娠前稳定组与活动组比较，在妊娠期疾病加重的比例差异无统计学意义[53．8％（28／52）与61．5％（16／26），x2=0．417，P〉0．053。除外妊娠20周前流产的病例（稳定组和活动组分别为5例次和4例次），2组子痫前期发生率差异也无统计学意义[-36．2％（17／47）与59．1％（13／22），y。一3．204，P〉0．05]。19例次妊娠期新确诊LN患者中，18例次妊娠≥20周，其中子痫前期发生率为6／18。（2）胎儿或新生儿不良结局：妊娠前疾病活动组治疗性终止妊娠的比例高于稳定组[42．3％（10／26）与7．7％（4／52），Fisher精确概率法，P〈0．01]，差异有统计学意义。除外主动要求终止妊娠（稳定组3例次）和治疗性终止妊娠（稳定组4例次，活动组10例次）的病例，稳定组与活动组分别为45例次与16例次，活动组胎儿丢失和新生儿死亡的比例高于稳定组[5／16与6．7％（3／45），Fisher精确概率法，P％0．os]，差异有统计学意义。妊娠前活动组胎儿或新生儿不良结局发生率高于稳定组[92．3％（24／26）与50．0％（26／52），y。一13．483，P〈0．001]，差异有统计学意义。19例次妊娠期新确诊LN组的患者中，治疗性终止妊娠5例次，胎儿丢失3例次，活产11例次，新生儿重度窒息并死亡2例次，早产9例次。（3）母婴不良结局危险因素Logistic回归分析：妊娠期疾病加重的独立危险因素为低补体血症（OR=0．300，95％CI：0．104～0．863）和低血小板血症（OR=0．054，95％C1：0．007～0．439）；I。N孕妇发生子痫前期的独立危险因素为低血小板血症（OR=0．151，95％C1：0．046～0．499）和妊娠期I。N复发或新发（OR=0．135，95％CI：0．027～0．679）；胎儿或新生儿不良结局的独立危险因素为孕妇发生子痫前期（OR=0．134，95％CI：0．028～0．637）和妊娠期疾病活动（OR=0．026，95％CI：0．005～0．138）。结论LN患者妊娠前疾病活动增加胎儿或新生儿不良结局的风险。建议LN患者疾病稳定至少6个月以上再计划妊娠，妊娠期间应密切监测血压、肾功能、尿蛋白、血小板和补体水平等指标，及早发现疾病活动并及时治疗。

Objective To evaluate the maternal and fetal outcomes of pregnant women with lupus nephritis （LN） and the risk factors. Methods Ninety-three patients with 97 pregnancies from January lst,1990 to December 31st,2012 in Peking Union Medical College Hospital were evaluated retrospectively. Objects of study were divided into three groups： stable lupus before pregnancy （stable group, 52 cases）, active lupus before pregnancy （active group, 26 cases）, and newly diagnosed LN during pregnancy （19 cases）. Adverse maternal outcomes included exacerbated disease during pregnancy, preeclampsia, increased proteinuria and impaired renal function during pregnancy or postpartum, maternal death, thrombocytopenia and hypocomplementemia. Adverse fetal or neonatal outcomes included therapeutically termination of pregnancy, fetal loss, neonatal death, preterm labor, small gestational age and asphyxia. Statistical analysis was performed by Chi square test or Fisherrs exact test. A binary logistic regression model was used to evaluate the risk factors for adverse maternal and fetal outcomes. Results （1） Adverse maternal outcomes： There was no significant difference between exacerbated cases during pregnancies in stable group and that in active group [53.8%（28/52） vs61.5%（16/26）, Z2=0.417, P〈0.05]. After deleting abortions before 20 weeks of gestation （5 cases in stable group and 4 cases in active group）, there was no significant difference between preeclampsia incidence in stable group and that in active group [36.2% （17/47） vs 59.1% （13/22）, %% =3. 204, P〈0.05]. In nineteen newly diagnosed LN women, eighteen cases were over 20 weeks of gestation, during which preeclampsia incidence was 6/18. （2） Adverse fetal or neonatal outcomes ： Therapeutically termination of pregnancy rate was higher in active group than that in stable group E42.3%%（10/26） vs 7.7%（4/52）, Fisher＇s exact test, P〈0.01]. After deleting patients who required termination of pregnancy （three cases in stable group） and therapeutically termination of pregnancy （four cases in stable group and ten cases in active group）, the rate of fetal loss and neonatal death was higher in active group than that in stable group[5/16 vs 6.7%（3/45）, Fisher%s exact test, P〈0.05]. The rate of adverse fetal or neonatal outcomes was higher in active group than that in stable group [-92.3%0（24/26） vs 50%（26/52）, %2=13.483, P〈0.001]. Among the nineteen newly diagnosed LN cases during pregnancy, the numbers of therapeutically termination of pregnancy and fetal loss were five and three cases respectively% among eleven live birth cases, two newborns died from severe asphyxia, and nine cases were preterm birth. （3） Binary logistic regression analysis showed that the independent risk factors for exacerbated lupus during pregnancy were hypocomplementemia （OR = 0. 300, 95 % CI： 0. 104-0. 863 ） and thrombocytopenia （OR = 0. 054, 95%CI：0. 007-0. 439）. The independent risk factors for preeclampsia in LN pregnant women were thrombocytopenia （OR=0. 151, 95%CI： 0. 046-0. 499） and LN recurrence or first diagnosed during pregnancy （OR = 0. 135, 95%CI： 0. 027-0. 679）. The independent risk factors for adverse fetal or neonatal outcomes were preeclampsia （OR = 0. 134, 95 % CI： O. 028-0. 637） and lupus active during pregnancy （OR = 0. 026, 95% CI： O. 005 0. 138）. Conclusions Active lupus before pregnancy is associated with poor maternal and fetal outcomes in lupus nephritis pregnancy. All pregnancies with LN should be planned, preferably after more than six months of quiescent disease. Blood pressure, renal function, proteinuria and level of platelet and serum complements should be closely monitored.