Aggarwal Shikha, Sunderland Neroli, Thornton Charlene, Xu Bei, Hennessy Annemarie, Makris Angela
School of Medicine, Western Sydney University, Sydney, Australia; Heart Research Institute, Sydney, Australia.
Royal Prince Alfred Hospital, Sydney, Australia.
Am J Obstet Gynecol. 2017 Feb;216(2):170.e1-170.e8. doi: 10.1016/j.ajog.2016.10.028. Epub 2016 Oct 26.
Preeclampsia can be caused by shallow trophoblast invasion and results in endothelial dysfunction. Angiotensin II type 1 receptor antibodies may have a role in both processes. Other angiogenic markers (placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin) have been shown to alter before clinically evident preeclampsia.
The aim of this study is to assess the longitudinal changes and utility of biomarker angiotensin II type 1 receptor antibodies and angiogenic markers in hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia.
A longitudinal prospective cohort observational study of angiogenic markers and a secondary retrospective case-control study of angiotensin II type 1 receptor antibody changes were conducted. The studies were conducted in a large tertiary metropolitan teaching hospital (Sydney, Australia). Sequential recruitment of women with a singleton pregnancy (N = 351) was undertaken. Plasma concentrations of angiotensin II type 1 receptor antibodies, placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin were measured using validated enzyme-linked immunosorbent assays at 12, 18, 28, 36, and 40 weeks' gestation and 6 weeks' postpartum. Clinical, demographic, and pregnancy data were prospectively collected. Pregnancy outcomes were classified as normotensive, gestational hypertension, or preeclampsia. Analyses were carried out using software and significance set at P < .05.
In all, 351 women were recruited, 17 developed gestational hypertension, and 18 developed preeclampsia. Women with preeclampsia at baseline were heavier (P = .015), were taller (P = .046), and had higher systolic (P = .029) and diastolic (P = .006) blood pressure. The preeclampsia group had higher soluble fms-like tyrosine kinase-1 from ≥28 weeks (P = .003) and lower placental growth factor from 18 weeks (P = .004). Soluble endoglin and angiotensin II type 1 receptor antibodies did not vary over time or between groups. Angiotensin II type 1 receptor antibody (12 weeks) was positively correlated with serum pregnancy associated plasma protein A (P = .008) and human chorionic gonadotrophin (P = .04).
Angiogenic markers vary longitudinally during pregnancy and placental growth factor and soluble fms-like tyrosine kinase-1 have a role for predicting and diagnosing preeclampsia later in disease. Our data show that angiotensin II type 1 receptor antibodies are not sensitive for disease and hence not useful as a biomarker. Larger studies are required to describe the role and functionality of angiotensin II type 1 receptor antibodies in preeclampsia.
子痫前期可由滋养细胞浸润过浅引起，并导致内皮功能障碍。血管紧张素II 1型受体抗体可能在这两个过程中起作用。其他血管生成标志物（胎盘生长因子、可溶性fms样酪氨酸激酶-1和可溶性内皮糖蛋白）已证实在临床明显的子痫前期出现之前会发生变化。
本研究旨在评估生物标志物血管紧张素II 1型受体抗体和血管生成标志物在妊娠高血压疾病、妊娠期高血压和子痫前期中的纵向变化及效用。
进行了一项关于血管生成标志物的纵向前瞻性队列观察研究以及一项关于血管紧张素II 1型受体抗体变化的二次回顾性病例对照研究。研究在一家大型三级城市教学医院（澳大利亚悉尼）进行。连续招募了单胎妊娠女性（N = 351）。在妊娠12、18、28、36和40周以及产后6周时，使用经过验证的酶联免疫吸附测定法测量血管紧张素II 1型受体抗体、胎盘生长因子、可溶性fms样酪氨酸激酶-1和可溶性内皮糖蛋白的血浆浓度。前瞻性收集临床、人口统计学和妊娠数据。妊娠结局分为血压正常、妊娠期高血压或子痫前期。使用软件进行分析，显著性设定为P <.05。
总共招募了351名女性，其中17名发生妊娠期高血压，18名发生子痫前期。基线时患有子痫前期的女性体重更重（P = .015）、身高更高（P = .046），收缩压（P = .029）和舒张压（P = .006）更高。子痫前期组从≥28周起可溶性fms样酪氨酸激酶-1水平更高（P = .003），从18周起胎盘生长因子水平更低（P = .004）。可溶性内皮糖蛋白和血管紧张素II 1型受体抗体在不同时间或不同组之间没有变化。血管紧张素II 1型受体抗体（12周时）与血清妊娠相关血浆蛋白A呈正相关（P = .008），与人绒毛膜促性腺激素呈正相关（P = .04）。
血管生成标志物在妊娠期间呈纵向变化，胎盘生长因子和可溶性fms样酪氨酸激酶-1在疾病后期预测和诊断子痫前期中起作用。我们的数据表明，血管紧张素II 1型受体抗体对疾病不敏感，因此作为生物标志物没有用处。需要更大规模的研究来描述血管紧张素II 1型受体抗体在子痫前期中的作用和功能。
