Division of Obstetrics and Gynaecology, University of Western Australia , Perth , Australia.
Tohoku University Hospital, Sendai, Miyagi , Japan.
Am J Physiol Regul Integr Comp Physiol. 2018 Oct 1;315(4):R825-R839. doi: 10.1152/ajpregu.00193.2017. Epub 2018 Apr 11.
Antenatal steroids (ANS) are among the most important and widely utilized interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24-34 wk) delivered between 1 and 7 days after the administration of a single course of ANS. Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved, and treatment doses and regimens remain largely unoptimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside the 1- to 7-day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement(s) of this important therapy. Complementary approaches using nonhuman primates, sheep, and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focusing on these three major model groups, this review highlights the role of three key animal models (sheep, nonhuman primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy in an era of personalised medicine.
产前类固醇(ANS)是改善早产儿预后最重要和最广泛应用的干预措施之一。大量证据表明,在给予单疗程 ANS 后 1 至 7 天内分娩的 24-34 周早产儿中,治疗效果得到改善。此外,ANS 具有广泛应用、成本低且易于通过肌肉注射给予产妇的优势。然而,使用 ANS 使胎儿肺部成熟并非没有争议。它们在妊娠中的使用未获得美国食品和药物管理局(FDA)批准,且治疗剂量和方案仍在很大程度上未得到优化。其使用方式在各国之间差异很大,并且人们仍然担心使胎儿暴露于高剂量外源性类固醇的安全性。很大一部分女性在接受 ANS 治疗后 1-7 天的治疗窗口之外分娩,这种延迟可能与母婴不良结局的风险增加有关。如今,基于动物的研究是解决与 ANS 相关剂量和安全性的关键问题的一种手段,可进一步完善这种重要的治疗方法。使用非人类灵长类动物、绵羊和啮齿动物的补充方法为我们理解外源性类固醇暴露如何影响胎儿发育提供了宝贵的进展。本文聚焦于这三个主要模型组,重点介绍了三种关键动物模型(绵羊、非人类灵长类动物、啮齿动物)在产前类固醇治疗发展中的作用,并对在个性化医学时代完善该治疗方法的当前努力进行了最新综合。