Sequential plasma angiogenic factors levels in women with suspected preeclampsia
Sequential plasma angiogenic factors levels in women with suspected preeclampsia
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DOI：
10.1016/j.ajog.2016.01.168
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发表时间：
2016-07-01
影响因子：
9.8
通讯作者：
Rana, Sarosh
中科院分区：
文献类型：
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作者：
Baltajian, Kedak;Bajracharya, Surichhya;Rana, Sarosh
背景技术背景：循环血管生成因子的改变与先兆子痫的诊断相关，并与妊娠晚期不良围产期结局相关。我们对马萨诸塞州波士顿贝斯以色列女执事医疗中心收治的单胎妊娠妇女进行了一项观察性研究，用于评估妊娠37周以下的先兆子痫。在入院时和前3天每天收集血浆样本，然后每周收集一次，直到分娩。入院时（48小时内）和每周（采血后24小时内）进行多普勒超声检查，以评估子宫胎盘和脐带血流量。记录产妇人口统计学资料、住院过程、分娩方式、高血压疾病诊断、不良产妇结局（肝功能酶升高、血小板计数低、肺水肿、脑出血、惊厥、急性肾功能不全或产妇死亡）和不良胎儿/新生儿结局（小于胎龄儿、脐动脉多普勒异常、胎儿死亡和新生儿死亡）。循环血管生成因子（可溶性fms样酪氨酸激酶和胎盘生长因子）在分娩后以单批和盲法在自动化平台上测量。数据呈现为中位数（第25至第75百分位数），平均值，或比例为appropriates.RESULTS：在研究期间，从100名妇女的数据进行了分析的研究，43有不良后果。有不良结局的妇女分娩胎龄较低，住院期间收缩压和舒张压较高，出生体重和胎盘重量较低（均P <0.01）。这些患者入院时可溶性fms样酪氨酸激酶和可溶性fms样酪氨酸激酶/胎盘生长因子比值较高，并且在整个住院过程中水平持续升高。有不良结局的患者中可溶性fms样酪氨酸激酶/胎盘生长因子比值的中位数（第25位至第75位）为205.9（72.5，453.1），而无不良结局的女性为47.5（9.7，87.0）（P <0.001）。在有不良结局的女性中，可溶性fms样酪氨酸激酶水平（pg/mL）每天绝对变化的中位数（第25 - 75位）为491.0 pg/mL（120.3，1587.2），而在无不良结局的女性中为81.3 pg/mL（-177.9，449.0）（P = 0.01）。同样，两组间可溶性fms样酪氨酸激酶/胎盘生长因子比值每天的绝对变化分别为15.1（1.8，58.1）和2.7（-0.6，8.3）（P = 0.004）。可溶性fms样酪氨酸激酶/胎盘生长因子比值>= 85的受试者从入院到分娩的平均（范围）天数为6（0-35）天，比值低于85的受试者为14（0-39）天（P= 85），入院时2周内分娩的受试者为91%（83-99%）。入院血浆可溶性fms样酪氨酸激酶/胎盘生长因子比值与分娩前子宫动脉阻力指数呈正相关（r = 0.35; P = .004）。结论：在因评估先兆子痫而入院的妇女中，有不良妊娠结局风险的妇女入院时可溶性fms样酪氨酸激酶/胎盘生长因子比值较高，持续升高直至分娩。可溶性fms样酪氨酸激酶/胎盘生长因子比值高的妇女比可溶性fms样酪氨酸激酶/胎盘生长因子水平低的妇女分娩早。这些数据支持这一假设，即针对血管生成的不平衡先兆子痫可能会导致延长妊娠。
BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester.OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia.STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate.RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio >= 85 and 14 (0-39) below a ratio of 85 (P= 85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004).CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.