The complex challenge of antenatal steroid therapy nonresponsiveness

Tsukasa Takahashi; Alan H Jobe; Erin L Fee; John P Newnham; Augusto F Schmidt; Haruo Usuda; Matthew W Kemp

doi:10.1016/j.ajog.2022.07.030

The complex challenge of antenatal steroid therapy nonresponsiveness

Am J Obstet Gynecol. 2022 Nov;227(5):696-704. doi: 10.1016/j.ajog.2022.07.030. Epub 2022 Aug 3.

Authors

Tsukasa Takahashi¹, Alan H Jobe², Erin L Fee³, John P Newnham³, Augusto F Schmidt⁴, Haruo Usuda¹, Matthew W Kemp⁵

Affiliations

¹ Division of Obstetrics and Gynaecology, University of Western Australia, Perth, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.
² Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH.
³ Division of Obstetrics and Gynaecology, University of Western Australia, Perth, Australia.
⁴ Miller School of Medicine, University of Miami, Miami, FL.
⁵ Division of Obstetrics and Gynaecology, University of Western Australia, Perth, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan; School of Veterinary and Life Sciences, Murdoch University, Perth, Australia; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: kemma@nus.edu.sg.

PMID: 35932879
DOI: 10.1016/j.ajog.2022.07.030

Abstract

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.

Keywords: betamethasone; dexamethasone; fetus; glucocorticoid; lung maturation; nonresponsiveness; preterm birth; variability.

Publication types

Review