背景:妊娠合并先兆子痫分娩后的胎盘病理评估,胎儿生长受限,早剥,死产揭示了一系列潜在的疾病。最常见的病理是母体血管灌注不良,表现为高阻力子宫动脉多普勒波形和循环母体血管生成生长因子的异常表达。据报道,罕见的胎盘疾病(大量绒毛周围的纤维蛋白样沉积和慢性组织细胞性阴道炎)具有很高的复发风险,但它们与子宫动脉多普勒波形和血管生成生长因子的关系目前尚不明确。
目的:探讨在形成特定类型胎盘病理的妊娠中,胎盘生长因子连续测量和子宫动脉多普勒波形评估的模式,以深入了解它们与疾病发病时间和妊娠结局的关系。
方法:2017年1月至2021年11月进行的一项回顾性队列研究包括所有单胎妊娠,在妊娠16至36周期间至少进行1次母体循环胎盘生长因子测量,在我们的机构交付,和胎盘病理分析显示母体血管灌注不良的诊断特征,胎儿血管灌注不良,不明病因的绒毛炎,慢性组织细胞夹带炎,或大量绒毛周围纤维蛋白样沉积。比较了这些胎盘病理之间循环胎盘生长因子随着胎龄提前的概况。记录产妇和围产期结局。
结果:来自329名个体的337例妊娠符合我们的纳入标准。这些包括母体血管灌注不良的胎盘病理学诊断(n=109),胎儿血管灌注不良(n=87),不明病因的绒毛炎(n=96),慢性组织细胞性阴道炎(n=16),和大量绒毛周围纤维蛋白样沉积(n=29)。在发生母体血管灌注不良的患者中,胎盘生长因子水平随着妊娠进展而逐渐下降(妊娠16-20周胎盘生长因子<10百分位数,占42.9%;20-24周,占61.9%;24-28周,占77%;28-32周,占81.4%),并伴有平均子宫动脉多普勒搏动指数>95百分位数的71.6%病例。发生胎儿血管灌注不良或病因不明的绒毛炎的患者大多表现出与正常子宫动脉多普勒波形相关的正常循环胎盘生长因子值(平均[标准偏差]搏动指数值:胎儿血管灌注不良,1.14[0.49];病因不明的绒毛炎,1.13[0.45])。发生慢性组织细胞间粘膜炎或大量绒毛周围纤维蛋白样沉积的患者在孕中期早期表现出持续低的胎盘生长因子水平(妊娠16-20周时胎盘生长因子<10百分位数,分别占80%和77.8%,分别;20-24周为88.9%和63.6%;24-28周为85.7%和75%),全部与正常子宫动脉多普勒波形(平均搏动指数>95分:慢性组织细胞性颌间炎,25%;大量绒毛周围纤维蛋白样沉积,37.9%)。337例患者中有83例(24.6%)发生了先兆子痫,在发生母体血管灌注不良的患者中最常见(54/109,49.5%),其次是慢性组织细胞性阴道炎(7/16,43.8%)。队列中有29例死胎(母体血管灌注不良,n=10[9.2%];胎儿血管灌注不良,n=5[5.7%];病因不明的绒毛炎,n=1[1.0%];慢性组织细胞夹带炎,n=7[43.8%];大量绒毛周围纤维蛋白样沉积,n=6[20.7%])。大多数死胎患者表现出正常的子宫动脉多普勒波形(21/29,72.4%)和非母体血管灌注不良病理(19/29,65.5%)。相比之下,29例死产患者中有28例(96.5%)在胎儿死亡前胎盘生长因子值≥1。
结论:系列循环母体胎盘生长因子测试,结合妊娠中期子宫动脉多普勒波形评估,可能表明潜在类型的胎盘病理介导严重不良围产期事件。这种方法具有测试疾病特异性治疗策略以改善临床结果的潜力。系列胎盘生长因子检测,与子宫动脉多普勒研究相比,由于母体血管灌注不良以外的疾病以正常的子宫胎盘循环为特征,因此确定了更大比例的注定围产期结局不良的患者。
BACKGROUND: Placental pathology assessment following delivery in pregnancies complicated by preeclampsia, fetal growth restriction, abruption, and stillbirth reveals a range of underlying diseases. The most common pathology is maternal vascular malperfusion, characterized by high-resistance uterine artery Doppler waveforms and abnormal expression of circulating maternal angiogenic growth factors. Rare placental diseases (massive perivillous fibrinoid deposition and chronic histiocytic intervillositis) are reported to have high recurrence risks, but their associations with uterine artery Doppler waveforms and angiogenic growth factors are presently ill-defined.
OBJECTIVE: To characterize the patterns of serial placental growth factor measurements and uterine artery Doppler waveform assessments in pregnancies that develop specific types of placental pathology to gain insight into their relationships with the timing of disease onset and pregnancy outcomes.
METHODS: A retrospective cohort study conducted between January 2017 and November 2021 included all singleton pregnancies with at least 1 measurement of maternal circulating placental growth factor between 16 and 36 weeks\' gestation, delivery at our institution, and placental pathology analysis demonstrating diagnostic features of maternal vascular malperfusion, fetal vascular malperfusion, villitis of unknown etiology, chronic histiocytic intervillositis, or massive perivillous fibrinoid deposition. Profiles of circulating placental growth factor as gestational age advanced were compared between these placental pathologies. Maternal and perinatal outcomes were recorded.
RESULTS: A total of 337 pregnancies from 329 individuals met our inclusion criteria. These comprised placental pathology diagnoses of maternal vascular malperfusion (n=109), fetal vascular malperfusion (n=87), villitis of unknown etiology (n=96), chronic histiocytic intervillositis (n=16), and massive perivillous fibrinoid deposition (n=29). Among patients who developed maternal vascular malperfusion, placental growth factor levels gradually declined as pregnancy progressed (placental growth factor <10th percentile at 16-20 weeks\' gestation in 42.9%; 20-24 weeks in 61.9%; 24-28 weeks in 77%; and 28-32 weeks in 81.4%) accompanied by mean uterine artery Doppler pulsatility index >95th percentile in 71.6% cases. Patients who developed either fetal vascular malperfusion or villitis of unknown etiology mostly exhibited normal circulating placental growth factor values in association with normal uterine artery Doppler waveforms (mean [standard deviation] pulsatility index values: fetal vascular malperfusion, 1.14 [0.49]; villitis of unknown etiology, 1.13 [0.45]). Patients who developed either chronic histiocytic intervillositis or massive perivillous fibrinoid deposition exhibited persistently low placental growth factor levels from the early second trimester (placental growth factor <10th centile at 16-20 weeks\' gestation in 80% and 77.8%, respectively; 20-24 weeks in 88.9% and 63.6%; 24-28 weeks in 85.7% and 75%), all in combination with normal uterine artery Doppler waveforms (mean pulsatility index >95th centile: chronic histiocytic intervillositis, 25%; massive perivillous fibrinoid deposition, 37.9%). Preeclampsia developed in 83 of 337 (24.6%) patients and was most common in those developing maternal vascular malperfusion (54/109, 49.5%) followed by chronic histiocytic intervillositis (7/16, 43.8%). There were 29 stillbirths in the cohort (maternal vascular malperfusion, n=10 [9.2%]; fetal vascular malperfusion, n=5 [5.7%]; villitis of unknown etiology, n=1 [1.0%]; chronic histiocytic intervillositis, n=7 [43.8%]; massive perivillous fibrinoid deposition, n=6 [20.7%]). Most patients experiencing stillbirth exhibited normal uterine artery Doppler waveforms (21/29, 72.4%) and had nonmaternal vascular malperfusion pathologies (19/29, 65.5%). By contrast, 28 of 29 (96.5%) patients experiencing stillbirth had ≥1 low placental growth factor values before fetal death.
CONCLUSIONS: Serial circulating maternal placental growth factor tests, in combination with uterine artery Doppler waveform assessments in the second trimester, may indicate the likely underlying type of placental pathology mediating severe adverse perinatal events. This approach has the potential to test disease-specific therapeutic strategies to improve clinical outcomes. Serial placental growth factor testing, compared with uterine artery Doppler studies, identifies a greater proportion of patients destined to have a poor perinatal outcome because diseases other than maternal vascular malperfusion are characterized by normal uteroplacental circulation.