基于超声造影联合胎盘生长因子的早发型子痫前期预警模型构建与评估

Construction and evaluation of an early-onset preeclampsia prediction model based on contrast-enhanced ultrasound combined with placental growth factor

  • 摘要:
    目的 基于超声造影联合胎盘生长因子(PlGF)构建早发型子痫前期(EOSP)预警模型并评估其效能。
    方法 选取86例EOSP患者作为病例组(严格定义为孕周 < 34周时首次出现症状并确诊, 且检查时未达紧急终止妊娠状态),另选取同期100例健康晚期妊娠孕妇作为对照组。2组孕妇均接受胎盘超声造影检查,获取造影剂到达时间(AT)、达峰时间(TTP)、峰值强度(PI)、曲线下面积(AUC)等灌注参数; 采用酶联免疫吸附试验(ELISA)检测血清PlGF水平。采用单因素分析及多因素Logistic回归分析筛选独立影响因素,构建2种联合预警模型(模型1: 仅纳入潜在早期指标TTP、PI、PlGF; 模型2: 纳入所有差异有统计学意义的变量)。采用受试者工作特征(ROC)曲线、校准曲线、Hosmer-Lemeshow检验及Bootstrap内部验证(1 000次重复抽样)评估模型性能,通过决策曲线分析(DCA)验证模型的临床实用性。
    结果 病例组从检查到确诊的中位时间间隔为4.2(2.8, 5.6)周。病例组孕妇收缩压、舒张压高于对照组,胎儿双顶径、股骨长及胎盘厚度小于对照组, AT、TTP长于对照组, PI、AUC低于对照组,血清PlGF水平低于对照组,差异均有统计学意义(P < 0.05)。模型1公式为Logit(P)=-4.218+0.758×TTP-0.888×PI-0.954×PlGF, 经Bootstrap内部验证后AUC为0.897(95%CI: 0.852~0.932), 模型2验证后AUC为0.903(95%CI: 0.860~0.938), 两者无显著差异(P=0.621)。模型1校准度良好(Hosmer-Lemeshow检验: χ2=6.325, P=0.619), 以预测概率0.35为截断值,灵敏度为87.2%, 特异度为89.0%。DCA显示,当风险阈值在0.15~0.80时,模型1的临床净获益显著高于“全干预”或“全不干预”策略。
    结论 基于超声造影胎盘灌注参数(TTP、PI)联合血清PlGF的预警模型(模型1)具有良好的区分度、校准度及临床实用性,可在EOSP临床症状出现前实现有效预警,效能优于单一指标,且预警时间窗达4.2周,为EOSP的早期筛查、风险分层及临床干预提供了可靠依据。

     

    Abstract:
    Objective To construct an early-onset preeclampsia (EOSP) prediction model based on contrast-enhanced ultrasound combined with placental growth factor (PlGF) and evaluate its efficacy.
    Methods Eighty-six patients with EOSP were selected as case group (strictly defined as those who first presented with symptoms and were diagnosed at a gestational age of less than 34 weeks and had not reached the state of emergency termination of pregnancy at the time of examination). Another 100 healthy late-pregnancy pregnant women during the same period were selected as control group. Pregnant women in both groups underwent placental contrast-enhanced ultrasound examination to obtain perfusion parameters such as arrival time (AT), time to peak (TTP), peak intensity (PI), and area under the curve (AUC). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum PlGF levels. Univariate and multivariate logistic regression analyses were used to screen independent influencing factors, and two combined prediction models were constructed (Model 1: only included potential early indicators TTP, PI, and PlGF; Model 2: included all variables with statistically significant differences). Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, the Hosmer-Lemeshow test, and Bootstrap internal validation (1 000 repeated samplings). The clinical utility of the models was verified through decision curve analysis (DCA).
    Results The median time interval from examination to diagnosis in the case group was 4.2 (2.8, 5.6) weeks. The systolic and diastolic blood pressures of pregnant women in the case group were higher than those in the control group, while the fetal biparietal diameter, femoral length, and placental thickness were smaller than those in the control group; the AT and TTP were longer, and the PI and AUC were lower in the case group compared with the control group; the serum PlGF level in the case group was also lower than that in the control group, and all differences above were statistically significant (P < 0.05). The formula for Model 1 was Logit(P)=-4.218+0.758×TTP-0.888×PI-0.954×PlGF. After Bootstrap internal validation, the AUC of Model 1 was 0.897 (95%CI, 0.852 to 0.932), and the AUC of Model 2 after validation was 0.903 (95%CI, 0.860 to 0.938), with no significant difference between the two (P=0.621). Model 1 had good calibration (Hosmer-Lemeshow test: χ2=6.325, P=0.619). Using a predicted probability of 0.35 as the cut-off value, the sensitivity was 87.2%, and the specificity was 89.0%. DCA showed that when the risk threshold was between 0.15 and 0.80, the clinical net benefit of Model 1 was significantly higher than that of the "full-intervention" or "no-intervention" strategies.
    Conclusion The prediction model (Model 1) based on placental perfusion parameters (TTP, PI) from contrast-enhanced ultrasound combined with serum PlGF has good discrimination, calibration, and clinical utility. It can effectively provide early warning before the clinical symptoms of EOSP appear, with better efficacy than single indicators, and the early-warning time window is up to 4.2 weeks, providing a reliable basis for early screening, risk stratification, and clinical intervention of EOSP.

     

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