尿液中错误折叠蛋白对子痫前期的预测价值

Predictive value of misfolded proteins in urine for pre-eclampsia

目的评估尿液中错误折叠蛋白在孕妇高危人群中预测子痫前期的价值。方法采用前瞻性研究,选择2021年10月—2022年7月在本院定期产检和分娩的孕12~27+6周的高危孕妇702例作为研究对象,收集临床信息,检测尿液中的错误折叠蛋白,随访妊娠过程和母儿结局。根据是否发生子痫前期(pre-eclampsia,PE)分为未发生PE(unaffected PE)组、早发型PE(early onset PE,ePE,在孕34周前因子痫前期进展而终止妊娠者)组和晚发型PE(late onset PE,lPE,在孕34周时或以后发生子痫前期者)组,采用方差分析、卡方检验及ROC曲线等分析其对子痫前期的预测价值。结果共有620例孕妇被纳入研究,发生PE者45例(7.3%),其中ePE为16例(2.6%),lPE为29例(4.7%)。研究发现未发生子痫前期者在服用叶酸、钙片、平均收缩压、平均舒张压(新增)、平均动脉压、子痫前期史或慢性高血压史及尿蛋白定性阳性方面和子痫前期孕妇比较,差异均有统计学意义(P<0.05),且子痫前期孕妇的妊娠并发症和新生儿并发症均高于未发生子痫前期的孕妇(P<0.05);使用母体因素、平均动脉压、错误折叠蛋白在孕12~15+6周、孕16~27+6周、ePE、lPE及整体PE中单独预测子痫前期的ROC曲线下面积中,错误折叠蛋白阳性的曲线下面积均最大,分别为0.837(95%CI:0.720~0.954)、0.859(95%CI:0.762~0.956)、0.879(95%CI:0.776~0.991),0.834(0.737~0.932)和0.849(0.774~0.924);三者联合在孕12~15+6周、lPE及整体PE中预测ROC曲线下面积高于单项指标的预测,分别为0.886(95%CI:0.792~0.980)、0.876(0.793~0.958)和0.872(0.803~0.942)。此外,虽错误折叠蛋白阳性在孕早、中期中预测PE的阳性预测值和敏感度较低,均约50%左右,但在预测PE的阴性预测值和特异度方面均达90%以上。结论孕妇高危人群中可在孕早中期行尿液中错误折叠蛋白的检测,若为阳性,孕早期可以尽早口服阿司匹林进行PE的预防,孕中期可加强监测;若为阴性,则提示发生PE的概率较低,不需要临床医生过度检查和干预。

Objective To evaluate the value of misfolded proteins(MP)in urinary in predicting pre-eclampsia(PE)in pregnant women at high risk.Methods A prospective study was conducted on 702 high-risk pregnant women(gestational weeks between 12 and 27 plus 6 days)who underwent regular antenatal examination and delivery in Maternal and Child Health Hospital of Jiading District,Shanghai from October 2021 to July 2022.The clinical information was collected,the MP in urine were detected,and the pregnancy process and maternal and fetal outcome were followed up.According to the presence and absence of PE,the patients were divided into three groups:Unaffected-PE group,early-onset PE(ePE)group(termination of pregnancy due to progression of pre-eclampsia before 34 pregnancy weeks)and late-onset PE(lPE)group(Pre-eclampsia occurs at or after 34 pregnancy weeks).The predictive value of PE was analyzed by variance analysis,chi-square test and ROC curve.Results A total of 620 pregnant women were enrolled in the study,45 cases(7.3%)had PE,including 16 cases(2.6%)of ePE and 29 cases(4.7%)of lPE.It was found that there were significant differences in taking folic acid,taking calcium tablets,mean systolic pressure,mean diastolic pressure,mean arterial pressure(MAP),history of PE and chronic hypertension,urine protein was positive between patients with PE and unaffected-PE(P<0.05).Moreover,the maternal and neonatal complications of patients with PE were higher than unaffected-PE(P<0.05).When maternal factor(MF),MAP and MP were used alone to predict PE in 12~15+6 gestational weeks,16~27+6 gestational weeks,ePE,lPE and all PE,the area under the curve of MP was the largest,which was 0.837(95%CI:0.720~0.954),0.859(95%CI:0.762~0.956),0.879(95%CI:0.776~0.991),0.834(0.737~0.932)and 0.849(0.774~0.924),respectively.The area under the ROC curve predicted by the combination of the three factors in 12~15+6 gestational weeks,lPE and overall PE was higher than that predicted by a single index,which was 0.886(95%CI:0.792~0.980),0.876(0.793~0.958)and 0.872(0.803~0.942),respectively.The study also found that although the MP had a low positive predictive value and sensitivity(about 50%)in predicting PE in the first and second trimester of pregnancy,it had a negative predictive value and specificity of more than 90%in predicting PE.Conclusions The MP in urine can be detected in the high risk group of pregnant women in the first and second trimester of pregnancy,if it is positive,aspirin can be taken as early as possible to prevent PE in early pregnancy;monitoring can be strengthened in the second trimester.If it is negative,it indicates that the probability of PE is lower and does not require excessive examination and intervention by clinicians.