A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy.
A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy.
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DOI：
10.1007/s43032-023-01264-2
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发表时间：
2023-11
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尽管广泛使用，但产前皮质类固醇（ACS）治疗的剂量方案很差，尚未优化。ACS治疗对胎儿发育具有编程效应，这可能与心血管疾病风险增加有关。已经证明低剂量类固醇治疗是成熟早产儿肺的有效手段，我们假设低剂量类固醇暴露会对胎儿心脏产生较少的不良功能和转录变化。我们使用低剂量类固醇治疗（通过持续输注给母羊10毫克，持续36小时）验证了这一假设，并比较了高剂量治疗（通过肌肉注射给母羊30毫克，持续24小时，模拟目前临床使用的ACS方案）对心脏的影响。在ACS治疗开始当天通过超声评估胎儿心功能。对胎儿心肌组织进行转录组学分析。与生理盐水对照组相比，高剂量临床治疗组胎儿舒张期早期心室充盈与心房收缩期心室充盈比例明显降低，心肌肥大相关转录物βMHC、GADD45γ、PPARγ表达差异。这些变化的长期影响仍未得到研究。无论如何，优化ACS给药方案，以最大限度地提高呼吸益处，同时最大限度地减少对心脏等关键器官系统的不良影响，为改善与这一重要产科治疗相关的急性和长期结果提供了一种手段。在线版本包含补充材料，下载地址：10.1007/s43032-023-01264-2。
Despite widespread use, dosing regimens for antenatal corticosteroid (ACS) therapy are poorly unoptimized. ACS therapy exerts a programming effect on fetal development, which may be associated with an increased risk of cardiovascular disease. Having demonstrated that low-dose steroid therapy is an efficacious means of maturing the preterm lung, we hypothesized that a low-dose steroid exposure would exert fewer adverse functional and transcriptional changes on the fetal heart. We tested this hypothesis using low-dose steroid therapy (10 mg delivered to the ewe over 36 h via constant infusion) and compared cardiac effects with those of a higher dose treatment (30 mg delivered to the ewe over 24 h by intramuscular injection; simulating currently employed clinical ACS regimens). Fetal cardiac function was assessed by ultrasound on the day of ACS treatment initiation. Transcriptomic analyses were performed on fetal myocardial tissue. Relative to saline control, fetuses in the higher-dose clinical treatment group had significantly lower ratios between early diastolic ventricular filling and ventricular filling during atrial systole, and showed the differential expression of myocardial hypertrophy-associated transcripts including βMHC, GADD45γ, and PPARγ. The long-term implications of these changes remain unstudied. Irrespective, optimizing ACS dosing regimens to maximize respiratory benefit while minimizing adverse effects on key organ systems, such as the heart, offers a means of improving the acute and long-term outcomes associated with this important obstetric therapy. The online version contains supplementary material available at 10.1007/s43032-023-01264-2.
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