Therapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Reproduction. 2022 Dec 2;165(1):R9-R23. doi: 10.1530/REP-22-0226. Print 2023 Jan 1.
Preterm birth is the leading cause of perinatal morbidity and mortality; however, current therapies offer limited efficacy to delay birth and improve neonatal outcomes. This review explores the potential of repurposing drugs with known safety profiles to quench uterine contractions and inflammation, identifying promising agents for clinical trials.
Preterm birth is the leading cause of neonatal morbidity and mortality globally. Despite extensive research into the underlying pathophysiology, rates of preterm birth have not significantly reduced. Currently, preterm labour management is based on optimising neonatal outcomes. Treatment involves administering drugs (tocolytics) to suppress uterine contractions to allow sufficient time for transfer to an appropriate facility and administration of antenatal corticosteroids for fetal lung maturation. Current tocolytics are limited as they are associated with adverse maternal and fetal effects and only delay delivery for a short period. There has been a serious lack of therapeutic development for preterm birth, and new approaches to protect against or delay preterm birth are urgently needed. Repurposing drugs for the prevention of preterm birth presents as a promising approach by reducing the time and costs associated with pharmaceutical drug development. In this review, we explore the evidence for the potential of therapies, specifically proton pump inhibitors, tumour necrosis factor inhibitors, prostaglandin receptor antagonists, aspirin, and statins, to be repurposed as preventatives and/or treatments for preterm birth. Importantly, many of these innovative approaches being explored have good safety profiles in pregnancy. We also review how delivery of these drugs can be enhanced, either through targeted delivery systems or via combination therapy approaches. We aim to present innovative strategies capable of targeting multiple aspects of the complex pathophysiology that underlie preterm birth. There is an urgent unmet need for preterm birth therapeutic development, and these strategies hold great promise for improving neonatal outcomes.
早产是围产期发病率和死亡率的主要原因；然而，目前的治疗方法在延迟分娩和改善新生儿结局方面效果有限。本综述探讨了将具有已知安全性的药物重新用于抑制子宫收缩和炎症的潜力，确定了有希望用于临床试验的药物。
早产是全球新生儿发病率和死亡率的主要原因。尽管对潜在的病理生理学进行了广泛的研究，但早产率并没有显著降低。目前，早产的管理基于优化新生儿结局。治疗包括使用药物（宫缩抑制剂）抑制子宫收缩，以便有足够的时间转移到适当的医疗机构，并给予产前皮质激素促进胎儿肺成熟。目前的宫缩抑制剂存在局限性，因为它们会对母婴产生不良影响，并且只能短时间延迟分娩。早产的治疗方法严重缺乏，迫切需要新的方法来预防或延迟早产。重新利用药物预防早产是一种很有前途的方法，可以减少与药物开发相关的时间和成本。在本综述中，我们探讨了质子泵抑制剂、肿瘤坏死因子抑制剂、前列腺素受体拮抗剂、阿司匹林和他汀类药物等治疗方法在预防和/或治疗早产方面的潜在应用。重要的是，许多正在探索的创新方法在怀孕期间具有良好的安全性。我们还回顾了如何通过靶向递送系统或联合治疗方法来增强这些药物的递送。我们的目标是提出能够靶向早产复杂病理生理学多个方面的创新策略。早产治疗方法的发展迫切需要创新，这些策略为改善新生儿结局带来了巨大的希望。
