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Am J Perinatol 2024; 41(04): 395-404
DOI: 10.1055/s-0042-1760386
Review Article

Long-Term Outcomes of Multiple versus a Single Course of Antenatal Steroids: A Systematic Review

Kiran Ninan 
1   Department of Obstetrics and Gynecology, McMaster University, Ontario, Canada
2   Department of Health Research Methods, Evidence, and Impact, McMaster University, Ontario, Canada
,
Sugee K. Liyanage
1   Department of Obstetrics and Gynecology, McMaster University, Ontario, Canada
,
Kellie E. Murphy
3   Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Toronto, Toronto, Ontario, Canada
,
Elizabeth V. Asztalos 
4   Division of Neonatology, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
,
Sarah D. McDonald 
1   Department of Obstetrics and Gynecology, McMaster University, Ontario, Canada
2   Department of Health Research Methods, Evidence, and Impact, McMaster University, Ontario, Canada
5   Department of Radiology, McMaster University, Ontario, Canada
6   Division of Maternal-Fetal Medicine, McMaster University, Ontario, Canada
› Author Affiliations
Funding S.D.M. is supported by a Tier II Canadian Institutes of Health Research (CIHR) Canada Research Chair (grant number: 950-229920). CIHR was not involved in any aspect of this study and the authors declare no sources of financial support or competing interests for this project.
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Abstract

Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57–8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms.

Key Points

  • We systematically reviewed the long-term impact of multiple versus a single course of ACS.

  • Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS.

  • In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms.

  • In children born at term, multiple courses of ACS were associated with neurosensory impairment.

  • Preterm administration of multiple courses of ACS should be considered cautiously.

Keywords

antenatal corticosteroids - long-term outcomes - neurodevelopment - systematic review

Supplementary Material



Publication History

Received: 24 March 2022

Accepted: 25 October 2022

Article published online:
01 February 2023

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