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The Complex Challenge of Antenatal Steroid Therapy Non-Responsiveness

  • Tsukasa Takahashi
    Affiliations
    Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia

    Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
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  • Alan H. Jobe
    Affiliations
    Cincinnati Children’s Hospital Medical Centre, University of Cincinnati School of Medicine, Cincinnati, OH, USA
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  • Erin L. Fee
    Affiliations
    Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia
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  • John P. Newnham
    Affiliations
    Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia
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  • Augusto F. Schmidt
    Affiliations
    Miller School of Medicine, University of Miami, FL, USA
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  • Haruo Usuda
    Affiliations
    Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia

    Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
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  • Matthew W. Kemp
    Correspondence
    CORRESPONDING AUTHOR: Matthew W. Kemp, PhD, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore. TEL: +65-6772-4285.
    Affiliations
    Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia

    Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan

    School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia

    Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Open AccessPublished:August 03, 2022DOI:https://doi.org/10.1016/j.ajog.2022.07.030
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      [ABSTRACT]

      Antenatal steroid (ANS) therapy is standard care for women at imminent risk of preterm delivery. When deliveries occur within seven days of treatment, ANS 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 ANS treatment efficacy, and an important percentage of fetuses exposed to ANS therapy do not respond sufficiently to derive benefit. Respiratory distress syndrome (RDS), for example, is a central metric of clinical trials to assess ANS outcomes. In the present analysis, we addressed the concept of ANS non-responsiveness, and defined a failed or sub-optimal response to ANS as being death or a diagnosis of RDS following treatment. For deliveries 24-35 weeks’ gestation, the number needed to treat (NNT) to prevent one case of RDS is 19 (95% CI, 14-28). Reflecting gestation-dependent risk, for deliveries >34 weeks’ gestation the NNT is 55 (95% CI, 30-304), whereas for elective surgical deliveries at term the NNT is 106 (95% CI, 61-421).
      We reviewed data from clinical and animal studies investigating ANS therapy to highlight the significant incidence of ANS therapy non-responsiveness (i.e. residual mortality or RDS after treatment), and the potential mechanisms underpinning this outcome variability. Origins of this variability may relate both to the manner in which the therapy is applied (i.e. the treatment regimen itself) and factors specific to the individual (i.e. genetic variation, stress, infection). The primary aims of this review were: i) to emphasise to the obstetric and neonatal communities the extent of ANS response variability and potential impact; ii) to propose approaches by which ANS therapy may be better applied to improve overall benefit; and iii) to stimulate further research towards the empirical optimisation of this important antenatal therapy.