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己酮可可碱治疗严重早发型胎儿生长受限的有效性:一项随机双盲临床试验。

Effectiveness of pentoxifylline in severe early-onset fetal growth restriction: A randomized double-blinded clinical trial.

机构信息

Maternal-fetal medicine Research Center, Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Taiwan J Obstet Gynecol. 2022 Jul;61(4):612-619. doi: 10.1016/j.tjog.2021.12.003.

Abstract

OBJECTIVE

Management of pregnancy complicated by severe early-onset fetal growth restriction (FGR) is one of the most challenging obstetrical issues. So far, there has not been a proven option for the treatment or improvement of this condition. Improper immune response during placentation leads to inadequate trophoblast invasion and impaired utero-placental perfusion. Pentoxifylline improves the endothelial function and induces vasodilation by reducing the inflammatory-mediated cytokines. We have evaluated the effect of Pentoxifylline on fetal-placental perfusion, neonatal outcome, and the level of oxidative stress markers before and after the intervention in the setting of severe early-onset FGR.

MATERIALS AND METHODS

This study is a pilot randomized clinical trial on 40 pregnant women who had developed early-onset growth restricted fetus. Pentoxifylline and placebo were given with a dose of 400 mg per os two times daily until delivery. Serial ultrasound examination regarding fetal weight, amniotic fluid and also utero-placenta-fetal Doppler's were done. For the assessment of serum Antioxidant level, blood sampling was done once at the beginning of the study and again, at least, three weeks after the investigation. After delivery, umbilical-cord blood gas analysis, APGAR score at 1 and 5 min, NICU admission, and neonatal death were recorded and compared between the two groups.

RESULTS

Utero-placenta-fetal Doppler's in the Pentoxifylline group did not significantly change compared to the control group. Fetal weight gain was significantly higher in the Pentoxifylline group before (996.33 ± 317.41) and after (1616.89 ± 527.90) treatment (P = 0.002). Total serum antioxidant capacity significantly increased in the Pentoxifylline group (p < 0.036). Average 5 min Apgar score was significantly higher (P < 0.036) and the percentage of babies admitted to NICU was significantly lower (P < 0.030) in the treated group.

CONCLUSION

Using Pentoxifylline in pregnancy affected by FGR might show promising effects. In this study, Pentoxifylline improved the neonatal outcome, increased fetal weight gain, and reduced neonatal mortality by decreasing the level of oxidative stress markers and cutting down the inflammatory cascade.

摘要

目的

妊娠合并严重早发型胎儿生长受限(FGR)的管理是产科最具挑战性的问题之一。到目前为止,还没有一种被证实的治疗或改善这种情况的方法。胎盘形成过程中免疫反应不当会导致滋养细胞侵袭不足和子宫胎盘灌注受损。己酮可可碱通过减少炎症介导的细胞因子来改善内皮功能并诱导血管扩张。我们评估了在严重早发型 FGR 背景下,己酮可可碱对胎儿-胎盘灌注、新生儿结局以及干预前后氧化应激标志物水平的影响。

材料和方法

这是一项针对 40 名早发型生长受限胎儿孕妇的随机临床试验。己酮可可碱和安慰剂的剂量均为 400mg,每天口服两次,直至分娩。对胎儿体重、羊水以及子宫胎盘-胎儿多普勒进行连续超声检查。为了评估血清抗氧化水平,在研究开始时和至少在研究结束后 3 周进行一次采血。分娩后,记录脐动脉血气分析、1 分钟和 5 分钟时的 Apgar 评分、NICU 入院和新生儿死亡情况,并比较两组之间的差异。

结果

与对照组相比,己酮可可碱组子宫胎盘-胎儿多普勒没有显著变化。与治疗前(996.33±317.41)相比,治疗后(1616.89±527.90)胎儿体重增加明显(P=0.002)。己酮可可碱组血清总抗氧化能力明显增加(P<0.036)。治疗组平均 5 分钟 Apgar 评分明显较高(P<0.036),新生儿入住 NICU 的比例明显较低(P<0.030)。

结论

在 FGR 孕妇中使用己酮可可碱可能会显示出良好的效果。在本研究中,己酮可可碱通过降低氧化应激标志物水平和阻断炎症级联反应,改善了新生儿结局,增加了胎儿体重增加,降低了新生儿死亡率。

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