Levine Richard J, Qian Cong, Maynard Sharon E, Yu Kai F, Epstein Franklin H, Karumanchi S Ananth
Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, Bethesda, MD 20892, USA.
Am J Obstet Gynecol. 2006 Apr;194(4):1034-41. doi: 10.1016/j.ajog.2005.10.192.
The purpose of this study was to determine whether serum fms-like tyrosine kinase 1 (sFlt1) concentration during preeclampsia were associated with mid trimester blood pressure, other maternal characteristics, or pregnancy outcomes.
We performed a nested case-control study within the Calcium for Preeclampsia Prevention study cohort. Each woman with preeclampsia (case) was matched to 1 normotensive control. A total of 120 pairs of women was chosen randomly. Serum concentrations of sFlt1 and placental growth factor were measured throughout pregnancy, but before labor and delivery. We focused on data from 40 women with blood specimens that were obtained after the onset of preeclampsia. After logarithmic transformation, we determined mean serum sFlt1 concentrations of all control specimens within gestational age windows during which case specimens had been obtained after the onset of preeclampsia. Within each of these gestational age windows, we computed an upper bound for the control specimens equal to 2 standard deviations above the mean. After the onset of preeclampsia, 16 women with log-transformed serum sFlt1 values greater than the upper bound of the control specimens were considered to have high preeclampsia serum sFlt1 levels. The 24 other women were considered to have low preeclampsia serum sFlt1 levels.
Women with high or low concentrations of serum sFlt1 during preeclampsia (arithmetic means, 5746 and 3007 pg/mL, respectively) had similar pregnancy outcomes and similar maternal characteristics, except for blood pressure at Calcium for Preeclampsia Prevention study enrollment. Systolic and diastolic blood pressure at enrollment at 13 to 21 weeks of gestation were significantly higher in the 24 women with low serum sFlt1 concentrations during preeclampsia (systolic blood pressure, 114 mm Hg; diastolic blood pressure, 65 mm Hg) than in the 16 women who had preeclampsia at high serum sFlt1 concentrations (systolic blood pressure, 106 mm Hg; diastolic blood pressure, 59 mm Hg). Blood pressure at 13 to 21 weeks among the women with high preeclampsia serum sFlt1 concentrations was identical to the blood pressure among normotensive control subjects. In linear regression analyses of data from all 40 women, both systolic (P < .0001) and diastolic (P = .014) blood pressures at enrollment were correlated negatively with natural logarithm serum sFlt1 concentration after onset of preeclampsia.
Women with higher mid trimester blood pressure had preeclampsia at lower serum sFlt1 concentrations. Because higher blood pressure may reflect occult endothelial damage, these observations may explain increased susceptibility to preeclampsia among women with pre-existing vascular disease.
本研究旨在确定子痫前期患者血清中类fms样酪氨酸激酶1（sFlt1）浓度是否与孕中期血压、其他母体特征或妊娠结局相关。
我们在预防子痫前期的钙补充研究队列中进行了一项巢式病例对照研究。每例子痫前期患者（病例）与1名血压正常的对照进行匹配。总共随机选择了120对女性。在整个孕期，但在临产和分娩前，测量血清sFlt1和胎盘生长因子的浓度。我们重点关注40例在子痫前期发病后采集血标本的女性的数据。经过对数转换后，我们确定了在子痫前期发病后采集病例标本的胎龄范围内所有对照标本的平均血清sFlt1浓度。在每个胎龄范围内，我们计算出对照标本的上限，等于平均值以上2个标准差。子痫前期发病后，16例血清sFlt1值经对数转换后高于对照标本上限的女性被认为子痫前期血清sFlt1水平高。另外24例女性被认为子痫前期血清sFlt1水平低。
子痫前期血清sFlt1浓度高或低的女性（算术平均值分别为5746和3007 pg/mL）具有相似的妊娠结局和相似的母体特征，但预防子痫前期的钙补充研究入组时的血压除外。子痫前期血清sFlt1浓度低的24例女性在妊娠13至21周入组时的收缩压和舒张压（收缩压114 mmHg；舒张压65 mmHg）显著高于血清sFlt1浓度高的16例子痫前期女性（收缩压106 mmHg；舒张压59 mmHg）。子痫前期血清sFlt1浓度高的女性在13至21周时的血压与血压正常的对照受试者的血压相同。在对所有40例女性的数据进行线性回归分析时，入组时的收缩压（P < .0001）和舒张压（P = .014）均与子痫前期发病后血清sFlt1浓度的自然对数呈负相关。
孕中期血压较高的女性子痫前期的血清sFlt1浓度较低。由于较高的血压可能反映隐匿性内皮损伤，这些观察结果可能解释了已有血管疾病的女性子痫前期易感性增加的原因。
