Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, South Africa.
Women's Health and HIV Research Group, Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, South Africa.
PLoS One. 2019 Apr 25;14(4):e0215807. doi: 10.1371/journal.pone.0215807. eCollection 2019.
The imbalance between circulating concentrations of anti- and pro-angiogenic factors is usually intense in preeclampsia with severe features (sPE). It is possible that pre-delivery circulating levels of angiogenic factors in sPE may be associated with postpartum antihypertensive drug requirements.
To determine the predictive association between maternal pre-delivery serum concentrations of angiogenic factors and the use of ≥3 slow- and/or a rapid-acting antihypertensive drug therapy in sPE on postpartum days zero to three following caesarean delivery.
Women with sPE (n = 50) and normotensive pregnancies (n = 90) were recruited prior to childbirth. Serum samples were obtained from each participant < 48 hours before delivery to assess the concentrations of placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the Roche Elecsys platform. Each participant was followed up on postpartum days zero, one, two and three to monitor BP and confirm antihypertensive treatment. The optimal cut-off thresholds of sFlt-1/PIGF ratio from receiver operating characteristic curve predictive of the antihypertensive therapy were subjected to diagnostic accuracy assessment.
The majority 58% (29/50) of sPE had multiple severe features of preeclampsia in the antenatal period with the commonest presentation being severe hypertension in 88% (44/50) of this group, followed by features of impending eclampsia which occurred in 42% (21/50). The median gestational age at delivery was 38 (Interquartile range, IQR 1) vs 36 (IQR 6) weeks, p < 0.001 in normotensive and sPE groups respectively. Notably, the median sFlt-1/PIGF ratio in normotensive and sPE groups were 7.3 (IQR 17.9) and 179.1 (IQR 271.2) respectively, p < 0.001. Of the 50 sPE participants, 34% (17/50) had early-onset preeclampsia. The median (IQR) of sFlt-1/PIGF in the early- and late-onset preeclampsia groups were 313.52 (502.25), and 166.59(195.37) respectively, p = 0.006. From postpartum days zero to three, 48% (24/50) of sPE received ≥ 3 slow- and/or a rapid-acting antihypertensive drug. However, the daily administration of ≥ 3 slow- and/or a rapid-acting antihypertensive drug in sPE were pre-delivery 26% (13/50), postpartum day zero 18% (9/50), postpartum day one 34% (17/50), postpartum day two 24% (12/50) and postpartum day three 20% (10/50). In sPE, the pre-delivery sFlt-1/PIGF ratio was predictive of administration of ≥3 slow- and/or a rapid-acting antihypertensive drug on postpartum days zero, one and two with the optimal cut-off ratio being ≥315.0, ≥181.5 and ≥ 267.8 respectively (sensitivity 72.7-75.0%, specificity 64.7-78.6%, positive predictive value 40.0-50.0% and negative predictive value 84.6% - 94.3%). The predictive performance of sFlt-1/PIG ratio on postpartum day 3 among the sPE was not statistically significant (area under receiver operating characteristic curve, 0.6; 95% CI, 0.3-0.8).
A pre-delivery sFlt-1/PIGF ratio (< 181.5) is a promising predictor for excluding the need for ≥3 slow- and/or a rapid-acting antihypertensive drug therapy in the immediate postpartum period in sPE.
子痫前期严重特征(sPE)患者的循环中抗血管生成和促血管生成因子的平衡通常会受到强烈影响。sPE 患者分娩前循环中血管生成因子的水平可能与产后降压药物的需求有关。
确定 sPE 患者分娩前血清中血管生成因子水平与剖宫产术后 0 至 3 天内使用≥3 种慢作用和/或快作用降压药物治疗之间的预测关联。
在分娩前招募了 50 例 sPE 患者(n=50)和 90 例正常妊娠患者(n=90)。在分娩前 <48 小时从每位参与者中获取血清样本,使用罗氏 Elecsys 平台评估胎盘生长因子(PIGF)和可溶性 fms 样酪氨酸激酶-1(sFlt-1)的浓度。在产后第 0、1、2 和 3 天监测每位参与者的血压并确认降压治疗。使用受试者工作特征曲线评估预测降压治疗的 sFlt-1/PIGF 比值的最佳截断阈值的诊断准确性。
大多数 sPE 患者(58%,29/50)在产前具有多种子痫前期严重特征,最常见的表现为 88%(44/50)的严重高血压,其次为 42%(21/50)的即将发生子痫的特征。分娩时的中位胎龄分别为 38(四分位距 IQR 1)和 36(IQR 6)周,正常妊娠和 sPE 组分别差异有统计学意义(p<0.001)。值得注意的是,正常妊娠和 sPE 组的中位 sFlt-1/PIGF 比值分别为 7.3(IQR 17.9)和 179.1(IQR 271.2),差异有统计学意义(p<0.001)。在 50 例 sPE 患者中,34%(17/50)为早发型子痫前期。早发型和晚发型子痫前期患者的 sFlt-1/PIGF 中位数(IQR)分别为 313.52(502.25)和 166.59(195.37),差异有统计学意义(p=0.006)。从产后第 0 天到第 3 天,48%(24/50)的 sPE 患者接受了≥3 种慢作用和/或快作用降压药物。然而,sPE 患者产后第 0 天、第 1 天、第 2 天和第 3 天需要≥3 种慢作用和/或快作用降压药物的每日给药率分别为 26%(13/50)、18%(9/50)、34%(17/50)、24%(12/50)和 20%(10/50)。在 sPE 中,分娩前 sFlt-1/PIGF 比值可以预测产后第 0、1 和 2 天使用≥3 种慢作用和/或快作用降压药物治疗,最佳截断比值分别为≥315.0、≥181.5 和≥267.8(敏感性 72.7-75.0%,特异性 64.7-78.6%,阳性预测值 40.0-50.0%,阴性预测值 84.6%-94.3%)。sPE 患者产后第 3 天 sFlt-1/PIG 比值的预测性能没有统计学意义(受试者工作特征曲线下面积,0.6;95%CI,0.3-0.8)。
分娩前 sFlt-1/PIGF 比值(<181.5)是 sPE 患者排除产后立即使用≥3 种慢作用和/或快作用降压药物治疗的有前途的预测指标。