Hormone Laboratory, 2nd Department of Obstetrics & Gynecology, Medical School, University of Athens, "Aretaieio" Hospital, Athens, Greece.
Eur J Obstet Gynecol Reprod Biol. 2013 Dec;171(2):225-30. doi: 10.1016/j.ejogrb.2013.08.040. Epub 2013 Sep 4.
To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia.
In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy.
In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284) (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%.
Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia.
在正常妊娠、发生子痫前期的妊娠和分娩小于胎龄儿（SGA）的妊娠中，纵向测定胎盘生长因子（PlGF）和可溶性 fms 样酪氨酸激酶-1（sFlt-1）的母血清浓度，以评估它们作为预测子痫前期的标志物。
在这项病例对照研究中，我们纳入了 12 例发生子痫前期的单胎妊娠和 104 例随机选择的正常单胎妊娠。正常妊娠中有 14 例分娩的婴儿为 SGA。在妊娠第 1、2 和 3 个三个月收集血样和超声数据。
在子痫前期孕妇中，第 2 个月（208；84-339）（p=0.035）和第 3 个月（202；109-284）（p=0.002）的 PlGF（pg/mL）（中位数；四分位距）显著降低，而 sFlt-1 仅在第 3 个月显著升高（2521；2101-3041）（p=0.011），与正常妊娠相比。第 2 个月 PlGF（202；109-284）（p=0.002）和第 3 个月 PlGF（780；472-1037）（p=0.002）（2 个月 PlGF 为 311；243-440，3 个月 PlGF 为 780；472-1037，sFlt-1 为 3 个月为 1616；1186-2220）。在 SGA 婴儿的妊娠中，PlGF 和 sFlt-1 在任何三个月均与正常妊娠无显著差异。第 2 和第 3 个月子痫前期孕妇的 sFlt-1 与 PlGF 比值均显著高于正常妊娠。与正常妊娠相比，子痫前期孕妇第 1 至第 2 个月 PlGF 浓度的相对差异和斜率明显降低。预测因子 BMI、第 2 个月多普勒 PI 和第 1 至第 2 个月 PlGF 相对差异的逻辑回归模型对子痫前期的预测具有 46%的敏感性和 99%的特异性，其阴性预测值非常高，为 98.3%。
我们的研究证实，在发生子痫前期的妊娠中，母体血清 PlGF 浓度至少在第 20 周后明显降低，而 sFlt-1 浓度在第 3 个月明显升高。分娩 SGA 婴儿的妊娠在整个妊娠期间没有改变血管生成因子浓度。第 1 至第 2 个月 PlGF 的相对差异、第 2 个月的子宫动脉多普勒 PI 和 BMI 是预测子痫前期的最有力标志物。
