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产前皮质类固醇治疗以减少早产导致的新生儿呼吸系统并发症发病率和死亡率

Authors
Men-Jean Lee, MD
Debra Guinn, MD, FACOG
Section Editors
Charles J Lockwood, MD, MHCM
Richard Martin, MD
Deputy Editor
Vanessa A Barss, MD, FACOG
Translators
汤泽中, 副主任医师，副教授

引言

Liggins和Howie在一篇里程碑式的论文中发现，对有早产(preterm delivery, PTD)风险的女性，产前给予单疗程皮质类固醇治疗可以降低新生儿呼吸窘迫综合征(respiratory distress syndrome, RDS)的发病率和严重程度，并降低新生儿死亡率[1]。超过12项随机试验已证实这些发现[2]。随后的试验还显示，产前皮质类固醇治疗可以改善早产儿的循环稳定性；与未接受治疗女性的早产儿相比，可以减少脑室内出血(intraventricular hemorrhage, IVH)和坏死性小肠结肠炎(necrotizing enterocolitis, NEC)的发生率。

本文将总结支持有早产风险的妊娠女性产前使用皮质类固醇以改善早产新生儿结局的证据、药理学问题以及使用该治疗相关的临床问题。

背景

作用机制 — 由皮质类固醇刺激发育调控基因以及生理机能会引起肺成熟及一些其他问题[3]。产前给予类固醇使Ⅰ型和Ⅱ型肺泡上皮细胞加速发育，可引起结构和生化改变，这能改善肺力学(最大肺容积、顺应性)和气体交换[4-8]。诱导Ⅱ型肺泡上皮细胞能增加表面活性物质的产生，其是通过诱导产生表面活性物质蛋白和磷脂合成所需酶。产前给予皮质类固醇的其他影响包括：诱导肺β受体，受刺激时肺β受体对表面活性物质释放和肺泡液吸收起到一定作用[5]；诱导胎儿肺抗氧化酶[9]；以及上调上皮Na+通道的基因表达，其对出生后肺液的吸收很重要[10]。然而，为了实现这些变化，需要肺已达到能对皮质类固醇产生生物学反应的发育阶段。 (参见下文‘给药时的孕龄’)

重复进行产前皮质类固醇治疗的生物学原理是基于：在细胞培养模型中观察到引起表面活性物质产生的生化刺激似乎是可逆的，例如，在去除皮质醇后，表面活性物质蛋白的mRNA水平下降到对照水平[5,11]。然而，其他有益影响(如细胞结构成熟)，在停止类固醇暴露后仍然持续存在(在恒河猴模型中)[12]。 (参见下文‘应用重复疗程治疗’)

短期临床有效性的证据

RDS的减少 — 世界范围内的随机试验一致报道称：暴露于产前皮质类固醇治疗的婴儿，RDS的发病率显著降低。一篇2006年系统评价纳入一些随机试验，这些试验在有早产风险的女性中比较了产前皮质类固醇治疗与安慰剂/无治疗，发现产前皮质类固醇治疗有如下结果[2]：

                                      

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