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血清血管生成因子与支气管肺发育不良的关系。ANGIODYS 队列研究。

Association of serum angiogenic factors with bronchopulmonary dysplasia. The ANGIODYS cohort study.

机构信息

Service de Médecine et Réanimation néonatales de Port Royal, 53 avenue de l'Observatoire, 75014 Paris, France; Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM, INRA, F-75004 Paris, France.

Assistance Publique - Hopitaux de Paris, Service d'hormonologie, Paris, Île-de-France, France.

出版信息

Pregnancy Hypertens. 2019 Oct;18:82-87. doi: 10.1016/j.preghy.2019.09.015. Epub 2019 Sep 29.

Abstract

OBJECTIVES

Angiogenic factors may be involved in lung development. To evaluate the relations between maternal and cord blood angiogenic factors (sFlt-1, placental growth factor [PlGF], soluble endogline [sEng], transforming growth factor β [TGF-beta]) and their association with moderate and severe bronchopulmonary dysplasia (BPD) in very preterm growth-restricted infants.

STUDY DESIGN

Prospective monocentric cohort study. Twenty-four mother-child dyads featuring antepartum preeclampsia, intra-uterine growth restriction (IUGR) and birth before 30 weeks' gestation were included. This ensured a 80% power to test whether sFlt-1 maternal levels would be twice as high in cases of BPD as in the absence of BPD.

MAIN OUTCOME MEASURES

Four pro/anti-angiogenic factors from two pathways (sFlt-1, PlGF and sEng, TGF-beta) were measured in maternal serum before delivery (at the time of hospitalization or the day of birth) and in neonates' cord blood. Neonatal outcome was moderate to severe BPD, defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks' postmenstrual age.

RESULTS

sFlt-1 levels were positively correlated in maternal serum and cord blood (r = 0.83, p < .001) but levels of PlGF and TGF-beta and its receptor sEng were not. Among all the factors studied in cord and maternal blood, none was associated with BPD.

CONCLUSIONS

In IUGR preterm babies born before 30 weeks' gestation from preeclamptic mothers, serum sFlt-1, PlGF and sEng, TGF-β levels were not correlated with BPD. The increased BPD risk in preterm neonates born from preeclamptic mothers cannot be related to high sFlt-1 levels.

摘要

目的

血管生成因子可能参与肺发育。评估母血和脐血血管生成因子(可溶性血管内皮生长因子受体 1[sFlt-1]、胎盘生长因子[PlGF]、可溶性内皮因子[sEng]、转化生长因子β[TGF-β])与中重度支气管肺发育不良(BPD)之间的关系,并分析它们与极早产儿生长受限合并子痫前期时发生 BPD 的关系。

研究设计

前瞻性单中心队列研究。共纳入 24 对母子,均为产前子痫前期、子宫内生长受限(IUGR)和妊娠 30 周前分娩。该研究的目的是检验假设,即当存在 BPD 时,sFlt-1 母体水平是不存在 BPD 时的两倍,其检验效能为 80%。

主要观察指标

检测母血(分娩前[住院或分娩当天])和新生儿脐血中两种途径(sFlt-1、PlGF 和 sEng、TGF-β)的 4 种促/抗血管生成因子。新生儿结局为中重度 BPD,定义为需要至少 28 天吸氧,或在矫正月龄 36 周时仍需要吸氧或通气支持。

结果

sFlt-1 水平在母血和脐血中呈正相关(r=0.83,p<0.001),而 PlGF 和 TGF-β及其受体 sEng 则无相关性。在所有研究的母血和脐血因子中,均与 BPD 无关。

结论

在子痫前期母亲妊娠 30 周前早产的 IUGR 婴儿中,母血和脐血 sFlt-1、PlGF 和 sEng、TGF-β水平与 BPD 无关。子痫前期母亲所生早产儿发生 BPD 的风险增加不能归因于 sFlt-1 水平升高。

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