血清BNP、VEGF、TGF-β1与新生儿持续性肺动脉高压病情严重程度的相关性及对预后的评估价值*

Relationship between BNP, VEGF, TGF-β1 and the severity of persistent pulmonary hypertension in neonates and its evaluation value of prognosis*

摘要:

目的 探讨新生儿持续性肺动脉高压（PPHN） 患儿血清脑钠肽（BNP）、血管内皮生长因子 （VEGF）及转化生长因子-β1（TGF-β1）水平与病情严重程度之间的关系以及对患儿预后评估的意义。方法 选 取2017年3月—2019年6月于荆州市第一人民医院就诊的PPHN患儿71例，根据肺动脉收缩压与体循环收缩压的 比值将将患儿分成轻中度PPHN组和重度PPHN组。另选取同期于该院就诊的无PPHN患儿35例作为对照组。根 据患儿预后分为死亡组和生存组。通过测定各组新生儿血清BNP、VEGF及TGF-β1水平分析其与PPHN病情严 重程度以及对预后评估的意义。结果 轻中度PPHN组和重度PPHN组血清BNP、TGF-β1以及VEGF水平较对 照组高（P <0.05），重度PPHN 组血清BNP、TGF-β1以及VEGF 水平较轻中度PPHN 组高（P <0.05）。经 Spearman 分析显示，血清BNP、TGF-β1、VEGF 水平均与PPHN 病情严重程度呈正相关（rs =0.908、0.697 和 0.835，P <0.05）。生存组BNP、TGF-β1、VEGF水平较死亡组低（P <0.05）。血清BNP最佳临界值为1 991.57 ng/L，敏感性为0.714（95%CI：0.579，0.849），特异性为0.922（95%CI：0.868，0.976）；TGF-β1最佳临界值为 1270.39 μg/L，敏感性为0.857 （95%CI：0.743，0.971），特异性为0.734 （95%CI：0.566，0.902））；VEGF最佳 临界值为665.27 ng/L，敏感性为0.815 （95%CI：0.724，0.906），特异性为0.594 （95%CI：0.401，0.787）。联合 预测因子1 最佳临界值为1979.09，敏感性为0.853 （95%CI：0.736，0.970），特异性为0.938 （95%CI：0.877， 0.999））；联合预测因子2 最佳临界值为2 050.40，敏感性为0.717 （95%CI：0.551，0.883），特异性为0.906 （95%CI：0.835，0.977）；联合预测因子3最佳临界值为3 086.47，敏感性为0.716（95%CI：0.572，0.860），特异 性为0.875（95%CI：0.764，0.986）。结论 血清BNP、VEGF及TGF-β1水平与PPHN病情严重程度相关，同时 根据BNP、TGF-β1水平建立的联合预测因子1预测患儿死亡的敏感性和特异性均较高，对患儿病情以及预后评估 具有较高的价值。

Abstract:

Objective To investigate the relationship between serum BNP, VEGF, TGF-β1 levels and severity of pulmonary hypertension in neonates, and to evaluate the prognosis of the patients. Methods 71 cases of neonatal persistent pulmonary hypertension (PPHN) and 35 cases of neonatal asphyxia without PPHN treated in our hospital from March 2017 to June 2019 were selected for control study. 71 cases of PPHN were divided into mild to moderate PPHN group and severe PPHN group according to the level of pulmonary systolic pressure. The control group was similar to the observation group in terms of gestational age, age, sex, delivery mode, basic diseases, serum sample retention time, and 35 hospitalized newborns without pulmonary hypertension. The levels of BNP, VEGF and TGF-β1 in the serum of each group were measured to analyze the relationship between BNP, PPHN and prognosis. Results The levels of serum BNP, TGF-β1 and VEGF in the mild and moderate PPHN group and the severe PPHN group were higher than those in the control group (P < 0.05), and the levels of serum BNP, TGF-β1 and VEGF in the severe PPHN group were higher than those in the mild and moderate PPHN group (P < 0.05); correlation analysis showed that serum BNP (rs = 0.908), TGF-β1 (rs = 0.697), VEGF levels (rs = 0.835) were positively correlated with the severity of PPHN disease (P < 0.05); The levels of serum BNP, TGF-β1 and VEGF in children were lower than those in the death group. Compared between the two groups, the difference was statistically significant, P < 0.05; Serum BNP, TGF-β1, VEGF levels predict the mortality of children with ROC curve to determine the optimal cutoff values of serum BNP, TGF-β1, VEGF were 1 991.57 ng / L [sensitivity 0.714 (95% CI: 0.579, 0.849)], Specificity is 0.922 (95% CI: 0.868, 0.976), 1 270.39 ug/L [sensitivity is 0.857 (95% CI: 0.743, 0.971)], specificity is 0.734 (95% CI: 0.566, 0.902), 665.265 ng/L [sensitivity 0.815 (95% CI: 0.724, 0.906)], specificity 0.594 (95% CI: 0.401, 0.787), indicating that the three serum markers have good predictive value for the prognosis of PPHN; combined The best cut-off values for predictor 1, combined predictor 2, and combined predictor 3 were 1 979.09 sensitivity 0.853 (95% CI: 0.736, 0.970), specificity 0.938 (95% CI: 0.877, 0.999), 2 050.40 sensitivity 0.717 (95% CI: 0.551, 0.883), specificity 0.906 (95% CI: 0.835, 0.977), 3 086.47 sensitivity 0.716 (95% CI: 0.572, 0.860), specificity 0.875 (95% CI: 0.764, 0.986), indicating that the combined predictor 1 established by BNP and TGF-β1 has a good predictive value for the prognosis of PPHN, which is significantly better than the results of the three serum markers alone. Conclusion The levels of BNP, VEGF and TGF-β1 in serum were correlated with the severity of PPHN, and the combined predictive factor 1 established according to the BNP and TGF- β1 levels has higher sensitivity and specificity in predicting the death of the child, and has higher value for the patient's condition and prognosis evaluation.