Fetal Medicine Research Institute, Kings College Hospital, London, UK.
Fetal Medicine Research Institute, Kings College Hospital, London, UK; Kings' College London, London, UK.
Am J Obstet Gynecol. 2020 Apr;222(4):374.e1-374.e9. doi: 10.1016/j.ajog.2019.10.101. Epub 2019 Nov 6.
An imbalance between angiogenic and antiangiogenic factors is thought to be a central pathogenetic mechanism in preeclampsia. In pregnancies that subsequently experience preeclampsia, the maternal serum concentration of the angiogenic placental growth factor is decreased from as early as the first trimester of pregnancy, and the concentration of the antiangiogenic soluble fms-like tyrosine kinase-1 is increased in the last few weeks before the clinical presentation of the disease. Chronic hypertension, which complicates 1-2% of pregnancies, is the highest risk factor for the development of preeclampsia among all other factors in maternal demographic characteristics and medical history. Two previous studies in women with chronic hypertension reported that first-trimester serum placental growth factor and soluble fms-like tyrosine kinase-1 levels were not significantly different between those who experienced superimposed preeclampsia and those who did not, whereas a third study reported that concentrations of placental growth factor were decreased.
The purpose of this study was to investigate whether, in women with chronic hypertension, serum concentrations of placental growth factor and soluble fms-like tyrosine kinase-1 and soluble fms-like tyrosine kinase-1/placental growth factor ratio at 11-13 weeks gestation are different between those women who experienced superimposed preeclampsia and those who did not and to compare these values with those in normotensive control subjects.
The study population comprised 650 women with chronic hypertension, which included 202 women who experienced superimposed preeclampsia and 448 women who did not experience preeclampsia, and 142 normotensive control subjects. Maternal serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1 were measured by an automated biochemical analyzer and converted into multiples of the expected median with the use of multivariate regression analysis in the control group. Comparisons of placental growth factor and soluble fms-like tyrosine kinase-1 levels and soluble fms-like tyrosine kinase-1/placental growth factor ratio in multiples of the expected median values between the 2 groups of chronic hypertension and the control subjects were made with the analysis of variance or the Kruskal-Wallis test.
In the group of women with chronic hypertension who experienced preeclampsia compared with those women who did not experience preeclampsia, there were significantly lower median concentrations of serum placental growth factor multiples of the expected median (0.904 [interquartile range, 0.771-1.052] vs 0.948 [interquartile range, 0.814-1.093]; P=.014) and soluble fms-like tyrosine kinase-1 multiples of the expected median (0.895 [interquartile range, 0.760-1.033] vs 0.938 [interquartile range, 0.807-1.095]; P=.013); they were both lower than in the normotensive control subjects (1.009 [interquartile range, 0.901-1.111] and 0.991 [interquartile range, 0.861-1.159], respectively; P<.01 for both). There were no significant differences among the 3 groups in soluble fms-like tyrosine kinase-1/placental growth factor ratios. In women with chronic hypertension, serum placental growth factor and soluble fms-like tyrosine kinase-1 levels provided poor prediction of superimposed preeclampsia (area under the curve, 0.567 [95% confidence interval, 0.537-0.615] and 0.546 [95% confidence interval, 0.507-0.585], respectively).
Women with chronic hypertension, and particularly those who subsequently experienced preeclampsia, have reduced first-trimester concentrations of both placental growth factor and soluble fms-like tyrosine kinase-1.
血管生成和抗血管生成因子之间的失衡被认为是子痫前期的主要发病机制。在随后经历子痫前期的妊娠中，母体血清中血管生成的胎盘生长因子浓度从妊娠早期开始降低，而在疾病临床表现前的最后几周，可溶性 fms 样酪氨酸激酶-1 的浓度增加。慢性高血压是妊娠中最常见的并发症，约占 1-2%，是所有母体人口统计学特征和病史因素中发生子痫前期的最高风险因素。两项针对慢性高血压女性的研究报告称，在经历子痫前期的患者和未经历子痫前期的患者中，第一孕期血清胎盘生长因子和可溶性 fms 样酪氨酸激酶-1 水平没有显著差异，而第三项研究报告称胎盘生长因子浓度降低。
本研究旨在探讨在患有慢性高血压的女性中，11-13 周妊娠时胎盘生长因子和可溶性 fms 样酪氨酸激酶-1 以及可溶性 fms 样酪氨酸激酶-1/胎盘生长因子比值的血清浓度是否在经历子痫前期的患者和未经历子痫前期的患者之间存在差异，并与正常血压对照组进行比较。
研究人群包括 650 名患有慢性高血压的女性，其中 202 名患有子痫前期，448 名未患子痫前期，142 名正常血压对照组。通过自动生化分析仪测量母体血清中胎盘生长因子和可溶性 fms 样酪氨酸激酶-1 的浓度，并使用多元回归分析将对照组中的浓度转换为预期中位数的倍数。使用方差分析或 Kruskal-Wallis 检验比较两组慢性高血压患者和对照组之间胎盘生长因子和可溶性 fms 样酪氨酸激酶-1 水平及可溶性 fms 样酪氨酸激酶-1/胎盘生长因子比值的中位数倍数。
与未经历子痫前期的患者相比，患有子痫前期的慢性高血压女性的血清胎盘生长因子中位数倍数（0.904[四分位距，0.771-1.052]比 0.948[四分位距，0.814-1.093]；P=.014）和可溶性 fms 样酪氨酸激酶-1 中位数倍数（0.895[四分位距，0.760-1.033]比 0.938[四分位距，0.807-1.095]；P=.013）均显著降低，且均低于正常血压对照组（1.009[四分位距，0.901-1.111]和 0.991[四分位距，0.861-1.159]；两者均 P<.01）。三组间可溶性 fms 样酪氨酸激酶-1/胎盘生长因子比值无显著差异。在慢性高血压女性中，血清胎盘生长因子和可溶性 fms 样酪氨酸激酶-1 水平对子痫前期的预测效果不佳（曲线下面积，0.567[95%置信区间，0.537-0.615]和 0.546[95%置信区间，0.507-0.585]）。
患有慢性高血压的女性，尤其是随后经历子痫前期的女性，第一孕期的胎盘生长因子和可溶性 fms 样酪氨酸激酶-1 浓度均降低。
