Antenatal steroid therapy is standard care for women at imminent risk of preterm delivery. When deliveries occur within 7 days of treatment, antenatal steroid therapy reduces the risk of neonatal death and improves preterm outcomes by exerting diverse developmental effects on the fetal organs, in particular the preterm lung and cardiovascular system. There is, however, sizable variability in antenatal steroid treatment efficacy, and an important percentage of fetuses exposed to antenatal steroid therapy do not respond sufficiently to derive benefit. Respiratory distress syndrome, for example, is a central metric of clinical trials to assess antenatal steroid outcomes. In the present analysis, we addressed the concept of antenatal steroid nonresponsiveness, and defined a failed or suboptimal response to antenatal steroids as death or a diagnosis of respiratory distress syndrome following treatment. For deliveries at 24 to 35 weeks’ gestation, the number needed to treat to prevent 1 case of respiratory distress syndrome was 19 (95% confidence interval, 14–28). Reflecting gestation-dependent risk, for deliveries at >34 weeks’ gestation the number needed to treat was 55 (95% confidence interval, 30–304), whereas for elective surgical deliveries at term this number was 106 (95% confidence interval, 61–421).

We reviewed data from clinical and animal studies investigating antenatal steroid therapy to highlight the significant incidence of antenatal steroid therapy nonresponsiveness (ie, residual mortality or respiratory distress syndrome after treatment), and the potential mechanisms underpinning this outcome variability. The origins of this variability may be related to both the manner in which the therapy is applied (ie, the treatment regimen itself) and factors specific to the individual (ie, genetic variation, stress, infection). The primary aims of this review were: (1) to emphasize to the obstetrical and neonatal communities the extent of antenatal steroid response variability and its potential impact; (2) to propose approaches by which antenatal steroid therapy may be better applied to improve overall benefit; and (3) to stimulate further research toward the empirical optimization of this important antenatal therapy.

产前类固醇治疗是针对即将面临早产风险的女性的标准护理。当治疗后 7 天内分娩时，产前类固醇治疗可通过对胎儿器官（特别是早产肺和心血管系统）产生多种发育影响，降低新生儿死亡风险并改善早产结局。然而，产前类固醇治疗的功效存在很大差异，并且接受产前类固醇治疗的胎儿中有很大一部分没有充分反应而无法获益。例如，呼吸窘迫综合征是评估产前类固醇结局的临床试验的一个核心指标。在本分析中，我们讨论了产前类固醇无反应的概念，并将对产前类固醇的失败或次优反应定义为死亡或治疗后诊断为呼吸窘迫综合征。对于妊娠 24 至 35 周的分娩，预防 1 例呼吸窘迫综合征所需治疗的人数为 19 例（95% 置信区间，14-28）。反映妊娠依赖性风险，对于妊娠 > 34 周的分娩，需要治疗的人数为 55（95% 置信区间，30-304），而对于足月选择性手术分娩，该数字为 106（95% 置信区间，61） –421）。

我们回顾了调查产前类固醇治疗的临床和动物研究的数据，以强调产前类固醇治疗无反应的显着发生率（即治疗后的残余死亡率或呼吸窘迫综合征），以及支撑这种结果变异性的潜在机制。这种变异性的根源可能与治疗的应用方式（即治疗方案本身）和个体特有的因素（即遗传变异、压力、感染）有关。本次审查的主要目的是：（1）向产科和新生儿社区强调产前类固醇反应变异的程度及其潜在影响；(2) 提出更好地应用产前类固醇治疗以提高总体效益的方法；(3) 促进进一步研究以实证优化这一重要的产前治疗。