Jobe Alan H, Goldenberg Robert L, Kemp Matthew W
Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH.
Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY.
Am J Obstet Gynecol. 2024 Mar;230(3):330-339. doi: 10.1016/j.ajog.2023.09.013. Epub 2023 Sep 19.
Antenatal steroid therapy is increasingly central to the obstetrical management of women at imminent risk of preterm birth. For women likely to deliver between 24 and 34 weeks' gestation, antenatal steroid therapy is the standard of care, conferring sizable benefits and few risks in high-resource environments when appropriately targeted. Recent studies have focused on antenatal steroid use in periviable and late preterm populations, and in term cesarean deliveries. As a result, antenatal steroid therapy has now been applied from 22 to 39 weeks of estimated gestational age. There is also an increased appreciation that the vast majority of randomized control data informing the use of antenatal steroids are derived from predominantly high-resource, White populations. Accordingly, a sizable amount of work has recently been undertaken to test how to safely use antenatal steroids in low- and middle-resource environments, wherein the often high rates of preterm birth make these low-cost, easily administered interventions an attractive proposition. It is likely underappreciated by the obstetrical and neonatal communities that the overall efficacy of antenatal steroid therapy is highly variable (including when preterm risk is accurately assessed), the treatment regimens used are largely arbitrary, dosing is suprapharmacologic for effect, and the benefit-risk balance is significantly and differentially modified by gestation. It is also very likely that the patients consenting to receive these treatments are similarly unaware of the complex balance of potential benefits and harms. Although a small number of follow-up studies present a generally benign picture of long-term antenatal steroid risk, several large, population-based retrospective studies have identified associations between antenatal steroid use, childhood mental disease, and newborn infections that warrant urgent attention. Of particular contemporary importance are emergent efforts to optimize antenatal steroid regimens on the basis of the pharmacokinetics and pharmacodynamics of the agents themselves, the need for better targeting of these potent drugs, and clear articulation of the potential benefits and harms of antenatal steroid use at differing stages of pregnancy and in different delivery contexts.
产前类固醇疗法在即将面临早产风险的女性产科管理中日益重要。对于妊娠24至34周可能分娩的女性,产前类固醇疗法是标准治疗方法,在资源丰富的环境中若使用得当,能带来可观益处且风险极小。近期研究聚焦于在接近可存活孕周和晚期早产人群以及足月剖宫产中使用产前类固醇。因此,目前产前类固醇疗法已应用于估计孕周22至39周的情况。人们也越来越认识到,为产前类固醇使用提供依据的绝大多数随机对照数据主要来自资源丰富的白人人群。相应地,最近开展了大量工作来测试如何在资源匮乏的环境中安全使用产前类固醇,在这些环境中早产率往往较高,使得这些低成本、易于实施的干预措施颇具吸引力。产科和新生儿领域可能并未充分认识到,产前类固醇疗法的总体疗效差异很大(包括在准确评估早产风险时),所采用的治疗方案很大程度上是随意的,给药剂量为超药理效应剂量,且效益风险平衡会因孕周而显著不同。同样很有可能的是,同意接受这些治疗的患者同样未意识到潜在益处和危害之间的复杂平衡。尽管少数随访研究呈现出产前类固醇长期风险总体较为良性的情况,但几项基于人群的大型回顾性研究已发现产前类固醇使用与儿童期精神疾病以及新生儿感染之间存在关联,这值得紧急关注。当前特别重要的是,基于药物本身的药代动力学和药效学来优化产前类固醇方案的新努力,更好地靶向这些强效药物的需求,以及明确阐述在不同孕期阶段和不同分娩情况下使用产前类固醇的潜在益处和危害。