血管生成标志物与胎儿性别之间的关联：对子痫前期研究的启示。

The association between angiogenic markers and fetal sex: Implications for preeclampsia research.

作者信息

Andersen L B, Jørgensen J S, Herse F, Andersen M S, Christesen H T, Dechend R

机构信息

HCA Research, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.

Institute for Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark; Department of Obstetrics and Gynecology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Odense Patient data Explorative Network (OPEN), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.

出版信息

J Reprod Immunol. 2016 Sep;117:24-9. doi: 10.1016/j.jri.2016.05.005. Epub 2016 Jun 23.

DOI:10.1016/j.jri.2016.05.005

PMID:27359072

Abstract

OBJECTIVE

Current research suggests sexual dimorphism between the male and female fetoplacental units, but with unknown relevance for preeclampsia. We investigated the association between fetal sex and concentrations of the angiogenic markers soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in first and second-third trimester in women with/without preeclampsia, and the impact of fetal sex on the prognostic value of angiogenic markers for preeclampsia.

STUDY DESIGN

Observational study in a prospective, population-based cohort of 2110 singleton pregnancies with 150 preeclampsia cases.

RESULTS

Higher sFlt-1 concentrations were observed for women carrying female fetuses in first trimester (all, 1107.65 vs. 992.27pg/ml; preeclampsia cases, 1118.79 vs. 934.49pg/ml, p<0.05) and in second-third trimester (all, 1130.03 vs. 1043.15pg/ml; preeclampsia, 1480.30 vs. 1152.86pg/ml, p<0.05), with similar findings for the sFlt-1/PlGF ratio concentrations in first (29.67 vs. 27.39 p<0.05) and second-third trimester (3.56 vs. 3.22, p<0.05). In first trimester, log transformed concentrations of PlGF, sFlt-1 and sFlt-1/PlGF (all participants) and sFlt-1 (preeclampsia cases) associated with fetal sex in adjusted analyses (p<0.05). In second-third trimester, only log(sFlt-1) associated with fetal sex (all, p=0.028; preeclampsia, p=0.067) In receiver operating curve analysis, prediction of early-onset preeclampsia by sFlt-1/PlGF tended to be superior in pregnancies with female vs. male fetuses (p=0.06).

CONCLUSION

Sexual dimorphism was observed for concentrations of angiogenic markers. Female fetal sex was associated to higher sFlt-1 and sFlt-1/PlGF ratio concentrations in both healthy pregnancies and women developing preeclampsia. Fetal sex should be considered in research and clinical use of angiogenic markers.

摘要

目的

当前研究提示男女胎儿 - 胎盘单位之间存在性别差异，但与子痫前期的相关性尚不清楚。我们调查了有无子痫前期女性在孕早期和孕中晚期胎儿性别与血管生成标志物可溶性Fms样酪氨酸激酶1（sFlt - 1）、胎盘生长因子（PlGF）浓度及sFlt - 1/PlGF比值之间的关联，以及胎儿性别对子痫前期血管生成标志物预后价值的影响。

研究设计

对一个基于人群的前瞻性队列中2110例单胎妊娠（其中150例为子痫前期病例）进行观察性研究。

结果

孕早期，怀有女胎的女性sFlt - 1浓度较高（所有孕妇，1107.65 vs. 992.27pg/ml；子痫前期病例，1118.79 vs. 934.49pg/ml, p<0.05）；孕中晚期同样如此（所有孕妇，1130.03 vs. 1043.15pg/ml；子痫前期患者，1480.30 vs. 1152.86pg/ml, p<0.05），sFlt - 1/PlGF比值浓度在孕早期（29.67 vs. 27.39 p<0.05）和孕中晚期（3.56 vs. 3.22, p<0.05）也有类似结果。在孕早期，经校正分析，PlGF、sFlt - 1和sFlt - 1/PlGF（所有参与者）以及sFlt - 1（子痫前期病例）的对数转换浓度与胎儿性别相关（p<0.05）。在孕中晚期，只有log(sFlt - 1)与胎儿性别相关（所有孕妇，p = 0.028；子痫前期患者，p = 0.067）。在受试者工作特征曲线分析中，sFlt - 1/PlGF对早发型子痫前期的预测在怀有女胎的妊娠中往往优于怀有男胎的妊娠（p = 0.06）。