Grzych Hayley, Fee Erin, Kemp Matthew W, Royse Emily, Usada Haruo, Ikeda Hideyuki, Takahashi Yuki, Takahashi Tsukasa, Jobe Alan H, Hillman Noah H
Division of Neonatology, Cardinal Glennon Children's Hospital, Saint Louis University, Saint Louis, MO, USA.
School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia.
Pediatr Res. 2025 Jun 10. doi: 10.1038/s41390-025-04172-0.
Both the addition of budesonide to surfactant and prophylactic hydrocortisone show promise for decreasing lung inflammation without increasing neurodevelopmental changes in preterm infants. Determining if combining these postnatal steroid therapies with antenatal steroids is safe is essential.
Utilizing preterm sheep (n = 7-8/group) combining antenatal betamethasone (0.25 mg/kg) and brief injurious ventilation, lambs were randomized to endotracheal surfactant with budesonide (0.25 mg/kg) or saline and either hydrocortisone (1 mg/kg) or saline IV at 15 min. Lambs were then ventilated for 4 h to evaluate physiology and effects on the lungs, liver, and brain.
The addition of budesonide to surfactant, even after antenatal steroids, improved ventilation physiology, decreased lung inflammation, acute phase mRNA, and pro-inflammatory changes in the liver and the brain compared with mechanical ventilation with surfactant alone. Hydrocortisone had minimal effects on physiology, other than blood pressure, and decreased some of the anti-inflammatory effects seen with budesonide. Mechanical ventilation, with or without budesonide, activated GFAP+ astrocytes in the cortical tissue and white matter, and hydrocortisone further increased activation. Only hydrocortisone also activated Iba1+ microglial cells in the brain.
Combining hydrocortisone with budesonide may decrease the anti-inflammatory effects of budesonide and hydrocortisone may induce astrocyte and microglial activation.
Even after antenatal steroids, the addition of budesonide to surfactant improved ventilation physiology and markers of injury in the lung, liver, and brain. Hydrocortisone IV had minimal effects on physiology, other than blood pressure, and decreased some of the beneficial effects seen with budesonide in the lung and liver. Mechanical ventilation activated GFAP+ astrocytes in the cortical tissue and white matter, and hydrocortisone further increased this activation. Hydrocortisone also activated Iba1+ microglial cells, whereas neither mechanical ventilation or budesonide increased Iba1. The medications were given at same time, and clinical timing may differ in premature infants affecting the results.
在表面活性剂中添加布地奈德和预防性使用氢化可的松，在不增加早产儿神经发育变化的情况下，均有望减轻肺部炎症。确定将这些产后类固醇疗法与产前类固醇联合使用是否安全至关重要。
利用早产绵羊（每组7 - 8只），联合产前倍他米松（0.25mg/kg）和短暂的损伤性通气，羔羊在15分钟时被随机分为接受含布地奈德（0.25mg/kg）的气管内表面活性剂或生理盐水，以及静脉注射氢化可的松（1mg/kg）或生理盐水。然后羔羊通气4小时，以评估生理功能以及对肺、肝和脑的影响。
与单独使用表面活性剂进行机械通气相比，即使在产前使用类固醇后，在表面活性剂中添加布地奈德仍可改善通气生理功能，减轻肺部炎症、急性期mRNA以及肝脏和大脑中的促炎变化。氢化可的松除了对血压有影响外，对生理功能的影响极小，并且减弱了布地奈德所见的一些抗炎作用。无论有无布地奈德，机械通气都会激活皮质组织和白质中的GFAP +星形胶质细胞，而氢化可的松会进一步增加这种激活。只有氢化可的松还会激活大脑中的Iba1 +小胶质细胞。
氢化可的松与布地奈德联合使用可能会降低布地奈德的抗炎作用，并且氢化可的松可能会诱导星形胶质细胞和小胶质细胞激活。
即使在产前使用类固醇后，在表面活性剂中添加布地奈德仍可改善通气生理功能以及肺、肝和脑的损伤标志物。静脉注射氢化可的松除了对血压有影响外，对生理功能的影响极小，并且减弱了布地奈德在肺和肝中所见的一些有益作用。机械通气会激活皮质组织和白质中的GFAP +星形胶质细胞，而氢化可的松会进一步增加这种激活。氢化可的松还会激活Iba1 +小胶质细胞，而机械通气和布地奈德均不会增加Iba1。这些药物是同时给药的，而临床给药时间在早产儿中可能有所不同，这会影响结果。
