BACKGROUND The use of antenatal steroid therapy is common in pregnancy. In early pregnancy, steroids may be used in women for the treatment of recurrent miscarriage or fetal abnormalities such as congenital adrenal hyperplasia. In mid-late pregnancy, the antenatal administration of corticosteroids to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; antenatal corticosteroids are now standard care for pregnancies at risk of premature delivery in high- and middle-income countries. The widespread uptake of this therapy is due to a compelling body of evidence demonstrating improved neonatal outcomes following antenatal corticosteroid exposure, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function. As we approach the 50th anniversary of landmark work in this area by Liggins and Howie, it is apparent that much remains to be understood with regards to how we might best apply antenatal corticosteroid therapy to improve pregnancy outcomes at both early and mid to late gestation. METHODS Drawing on advances in laboratory science, pre-clinical and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the benefits, risks and uncertainties regarding antenatal corticosteroid use in pregnancy. Three, well-established therapeutic uses of antenatal steroids, namely recurrent miscarriage, congenital adrenal hyperplasia and preterm birth, were selected to frame the review. RESULTS Even the most well-established antenatal steroid therapies lack the comprehensive pharmacokinetic and dose-response data necessary to optimize dosing regimens. New insights into complex, tissue-specific corticosteroid signalling by genomic-dependent and independent mechanisms have not been used to inform corticosteroid treatment strategies. There is growing evidence that some fetal corticosteroid treatments are either ineffective, or may result in adverse outcomes, in addition to lasting epigenetic changes in a variety of homeostatic mechanisms. Nowhere is the need to better understand the intricacies of corticosteroid therapy better conveyed than in the findings of Althabe and colleagues who recently reported an increase in overall neonatal mortality and maternal morbidity in association with antenatal corticosteroid administration in low-resource settings. CONCLUSIONS New research to clarify the benefits and potential risks of antenatal corticosteroid therapy is urgently needed, especially with regard to corticosteroid use in low-resource environments. We conclude that there is both significant scope and an urgent need for further research-informed refinement to the use of antenatal corticosteroids in pregnancy.

中文翻译：

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怀孕期间皮质类固醇的临床使用。

背景技术在孕妇中通常使用产前类固醇疗法。在怀孕初期，类固醇可用于女性，以治疗反复流产或胎儿异常，如先天性肾上腺皮质增生。在中晚期妊娠中，预期早产对孕妇准产前给予皮质类固醇激素是围产期医学最重要的进步之一。在高收入和中等收入国家，产前皮质类固醇现在已成为具有早产风险的怀孕的标准护理。该疗法的广泛采用是由于大量证据表明，在产前服用皮质类固醇激素后，新生儿结局得到了改善，其中最明显的原因是皮质类固醇激素驱动的胎儿肺功能成熟。当我们接近Liggins和Howie在这一领域具有里程碑意义的工作50周年之际，关于如何最好地应用产前皮质类固醇疗法来改善妊娠早期和中期至晚期的妊娠结局，显然还有很多尚待理解。方法利用实验室科学，临床前和临床研究的进展，我们对科学文献进行了叙述性回顾，以提供有关妊娠前使用皮质类固醇在妊娠中的益处，风险和不确定性的及时更新。选择了三项行之有效的产前类固醇治疗用途，即反复流产，先天性肾上腺皮质增生和早产。结果即使最完善的产前类固醇疗法也缺乏优化剂量方案所需的全面药代动力学和剂量反应数据。通过基因组依赖性和独立机制对复杂的，组织特异性的皮质类固醇信号传导的新见解尚未用于告知皮质类固醇治疗策略。越来越多的证据表明，除了在各种体内平衡机制中持续的表观遗传学改变之外，某些胎儿皮质类固醇激素治疗无效或可能导致不良后果。Althabe和他的同事的发现最近更好地了解了皮质类固醇疗法的复杂性，在最近的报道中指出，在资源贫乏地区，新生儿的整体死亡率和产妇发病率与产前服用皮质类固醇激素有关会增加。结论迫切需要开展新的研究来阐明产前皮质类固醇治疗的益处和潜在风险，尤其是在资源贫乏的环境中使用皮质类固醇方面。我们得出的结论是，在妊娠中使用产前皮质类固醇激素进行进一步的研究知情化既有很大的范围，也迫切需要。尤其是在资源匮乏的环境中使用皮质类固醇。我们得出的结论是，在妊娠中使用产前皮质类固醇激素进行进一步的研究知情化既有很大的范围，也迫切需要。尤其是在资源匮乏的环境中使用皮质类固醇。我们得出的结论是，在妊娠中使用产前皮质类固醇激素进行进一步的研究知情化既有很大的范围，也迫切需要。