Department of Pediatrics, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Pediatr Res. 2013 Sep;74(3):290-8. doi: 10.1038/pr.2013.98. Epub 2013 Jun 14.
Congenital diaphragmatic hernia (CDH) represents a spectrum of lung hypoplasia, and consequent pulmonary hypertension (PH) is an important cause of postnatal morbidity and mortality. We studied biomarkers at the maternal-fetal interface to understand factors associated with the persistence of PH.
Maternal and cord blood samples from fetuses with CDH and unaffected controls were analyzed using a human 39plex immunoassay kit. Cellular trafficking between the mother and the fetus was quantified using quantitative real-time PCR for nonshared alleles. Biomarker profiles were then correlated with CDH severity on the basis of the degree of PH.
Cord blood levels of epidermal growth factor, platelet-derived growth factor, and several inflammatory mediators increased significantly as the severity of CDH increased, whereas maternal levels of growth factors and mediators decreased significantly with CDH severity. Maternal cells were increased in fetuses with severe CDH as compared with controls, with elevated levels of the CXC chemokine ligand-10 in patients with the highest trafficking.
Patients with CDH demonstrate proinflammatory and chemotactic signals in fetal blood at the time of birth. Because some of these molecules have been implicated in the development of PH, prenatal strategies targeting specific molecular pathways may be useful adjuncts to current fetal therapies.
先天性膈疝 (CDH) 代表了肺发育不全的一系列表现，而随之而来的肺动脉高压 (PH) 是导致新生儿发病率和死亡率的重要原因。我们研究了母体-胎儿界面的生物标志物，以了解与 PH 持续存在相关的因素。
使用人 39 plex 免疫分析试剂盒分析了患有 CDH 和无影响对照组的胎儿的母血和脐血样本。使用定量实时 PCR 检测非共享等位基因来量化母亲和胎儿之间的细胞迁移。然后根据 PH 的严重程度将生物标志物谱与 CDH 的严重程度相关联。
随着 CDH 严重程度的增加，脐血中表皮生长因子、血小板衍生生长因子和几种炎症介质的水平显著升高，而生长因子和介质的母血水平随着 CDH 严重程度的增加而显著降低。与对照组相比，严重 CDH 胎儿中的母体细胞增加，在迁移水平最高的患者中 CXC 趋化因子配体-10 水平升高。
出生时 CDH 患者的胎儿血液中存在促炎和趋化信号。由于其中一些分子与 PH 的发展有关，因此针对特定分子途径的产前策略可能是当前胎儿治疗的有用辅助手段。
