血清D-二聚体对新生儿早发脓毒症预后的预测价值

Predictive value of serum D-dimer on prognosis of neonate with early-onset sepsis

目的分析血清D-二聚体对新生儿早发脓毒症患儿预后的预测价值。方法收集2015年4月至2020年4月入住西安交通大学附属儿童医院新生儿重症医学科的189例临床诊断为新生儿早发脓毒症患儿的人口学资料及入院8 h内的临床实验室指标;以入院7 d死亡为终点事件。将D-二聚体≥0.50 mg/L的61例患儿作为观察组,D-二聚体<0.50 mg/L的128例患儿作为对照组。比较对照组与观察组患儿以及各组内不同预后患儿的白细胞计数(WBC)、C-反应蛋白(CRP)、血清降钙素原(PCT)、血乳酸(Lac)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)、血小板计数(PLT)、血红蛋白(Hb)、儿科危重症死亡危险评分(PRISMⅢ)、国际血栓形成与止血学会(ISTH)显性弥散性血管内凝血(DIC)评分的差异。采用受试者工作特征曲线(ROC)和ROC曲线下面积(AUC)并联合Logistic回归分析D-二聚体对新生儿早发脓毒症预后的预测价值;根据最佳截断值绘制7 d Kaplan-Meier生存曲线。结果189例患儿中7 d死亡42例,病死率为22.22%。观察组患儿的母源性感染、窒息史、羊水污染、脐带/胎盘病变、胎膜早破发生率以及革兰阴性(G^(-))菌阳性率均明显高于对照组〔母源性感染:34.43%(21/61)比9.38%(12/128),窒息史:34.43%(21/61)比11.72%(15/128),羊水污染:26.23%(16/61)比8.59%(11/128),脐带/胎盘病变:24.59%(15/61)比10.94%(14/128),胎膜早破:29.51%(18/61)比9.38%(12/128),G-菌阳性率:27.87%(17/61)比9.38%(12/128),均P<0.05〕。观察组患儿WBC、PCT、Lac、PT、APTT、PRISMⅢ评分、CRP等均明显高于对照组〔WBC(×10^(9)/L):24.2(4.4,29.4)比21.2(19.1,28.4),PCT(ng/L):67.3±40.4比37.8±25.1,Lac(mmol/L):8.7±7.2比2.3±1.1,PT(s):47.5±12.2比36.6±32.0,APTT(s):85.1±49.6比64.3±29.8,CRP(mg/L):67.8±23.1比41.4±19.6,PRISMⅢ(分):19.5±6.3比10.6±2.1,均P<0.05〕;Fib、PLT、Hb、ISTH显性DIC评分均明显低于对照组〔Fib(g/L):1.5±1.2比2.4±0.8,PLT(×10^(9)/L):154.4±57.9比189.1±29.4,Hb(g/L):168.9±49.9比181.5±52.3,ISTH显性DIC评分(分):5.1±1.6比6.1±2.7,均P<0.05〕。两组内不同预后患儿比较,死亡组的APTT、PT、PCT、Lac、D-二聚体、CRP、PRISMⅢ评分均明显高于存活组,而WBC、Fib、PLT、Hb、ISTH显性DIC评分均明显低于存活组。ROC曲线联合Logistic回归分析结果显示,D-二聚体预测新生儿早期脓毒症患儿预后的AUC为0.967,95%可信区间(95%CI)为0.793~0.971,截断值为4.98 mg/L,敏感度为88.70%,特异度为81.20%;Kaplan-Meier生存曲线显示,随着D-二聚体水平升高,患儿的死亡风险也随之增加。D-二聚体≥4.98 mg/L组7 d病死率明显高于D-二聚体<4.98 mg/L组〔48.98%(21/49)比15.00%(21/140),P<0.05〕。结论D-二聚体水平升高对新生儿早发脓毒症的不良预后具有较好的预测价值。

Objective To explore the predictive value of serum D-dimer in the prognosis of neonate with early-onset sepsis.Methods The 189 neonates with early-onset sepsis admitted to Neonatal Intensive Care Unit of the Children's Hospital Affiliated to Xi'an Jiaotong University from April 2015 to April 2020 were enrolled and their demographic data and clinical laboratory results within 8 hours after admission were collected;7-day death after admission was taken as end event.According to the different levels of D-dimer,the patients with D-dimer≥0.50 mg/L were assigned in the observation group(61 cases)and those with D-dimer<0.50 mg/L were allowed in the control group(128 cases).The white blood cell count(WBC),C-reactive protein(CRP),serum procalcitonin(PCT),blood lactic acid(Lac),prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),platelet count(PLT),hemoglobin(Hb),pediatric risk mortalityⅢscore(PRISMⅢ)and International Society of Thrombosis and Hemostasis(ISTH)dominant disseminated intravascular coagulation(DIC)score were compared between the observation and control groups and in patients with different prognoses in each group.The predictive value of D-dimer for the prognosis of neonate with early-onset sepsis was verified by the receiver operater characteristic curve(ROC),area under ROC curve(AUC)combined with Logistic regression analysis.According to the best cut-off value,the 7-day Kaplan-Meier survival curve was performed.Results Among the 189 newborns with early-onset sepsis,42 died in 7 days and 7-day mortality was 22.22%.The incidence of maternal infection,history of asphyxia,amniotic fluid pollution,umbilical cord/placenta lesions,premature rupture of membranes and the positive rate of Gram negative(G^(-))bacteria in the observation group were higher than those in the control group,the differences being statistically significant between the two groups[maternal infection:34.43%(21/61)vs.9.38%(12/128),history of asphyxia:34.43%(21/61)vs.11.72%(15/128),amniotic fluid pollution:26.23%(16/61)vs.8.59%(11/128),umbilical cord/placenta lesions:24.59%(15/61)vs.10.94%(14/128),premature rupture of membranes:29.51%(18/61)vs.9.38%(12/128),positive rate of G-bacteria:27.87%(17/61)vs.9.38%(12/128),all P<0.05].Compared with the control group,the levels of WBC,PCT,Lac,PT,APTT,ISTH dominant DIC score,CRP and PRISMⅢscore in observation group were higher[WBC(×10^(9)/L):24.2(4.4,29.4)vs.21.2(19.1,28.4),PCT(ng/L):67.3±40.4 vs.37.8±25.1,Lac(mmol/L):8.7±7.2 vs.2.3±1.1,PT(s):47.5±12.2 vs.36.6±32.0,APTT(s):85.1±49.6 vs.64.3±29.8,CRP(mg/L):67.8±23.1 vs.41.4±19.6,PRISMⅢscore:19.5±6.3 vs.10.6±2.1,all P<0.05];the levels of Fib,PLT,Hb and ISTH dominant DIC score were significantly lower than those of the control group[Fib(g/L):1.5±1.2 vs.2.4±0.8,PLT(×10^(9)/L):154.4±57.9 vs.189.1±29.4,Hb(g/L):168.9±49.4 vs.181.5±52.3,ISTH dominant DIC score:5.1±1.6 vs.6.1±2.7,all P<0.05].Compared between the two groups with different prognosis,the levels of APTT,PT,PCT,Lac,PRISMⅢscore,D-dimer and CPR in death group were higher than those in the survival group,while the levels of WBC,Fib,PLT,Hb and ISTH dominant DIC score were lower than those in the survival group.The results of ROC curve combined with Logistic regression analysis showed that the AUC in D-dimer predicting prognosis of sepsis was 0.967,95%confidence interval(95%CI)was 0.793-0.971,the cut-off value was 4.98 mg/L,the sensitivity and specificity were 88.70%and 81.20%respectively;Logistic regression curve analysis showed that the risk of death was positively correlated with the D-dimer level.The 7-day mortality of the D-dimer≥4.98 mg/L group was higher than that in the D-dimer<4.98 mg/L group[42.86%(21/49)vs.15.00%(21/140),P<0.05].Conclusion The elevation of D-dimer level has a predictive value of poor prognosis for neonate with early-onset sepsis.