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Relevance of the antenatal corticosteroids-to-delivery interval in the prevention of neonatal respiratory distress syndrome through the eyes of causal inference: a review and target trial

  • Maternal-Fetal Medicine
  • Published:
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Abstract

Purpose

To critically analyse the literature on the antenatal corticosteroids (ACS)-to-birth interval from a causal point of view and to present a solution to the problem of bias caused by post hoc analysis.

Methods

Due to the post hoc nature of the ACS-to-birth interval, a randomised controlled trial (RCT) of ACS versus placebo is not able to examine the importance of the interval. When an RCT is not feasible, for whatsoever reason, a target trial can be set up and an attempt can be made to answer the causal question of interest using observational data. An attempt was made to set up a target trial which could enable to examine the causal effect of the ACS-to-birth interval on neonatal outcomes. An analysis of current literature on the ACS-to-birth interval was done.

Results

The majority of studies aimed to examine the causal effect of the interval, but their study design only permitted to find associations between the interval and neonatal outcomes. Barriers for setting up a target trial are highlighted.

Conclusion

Evidence on the superiority of any ACS-to-birth interval is lacking and the question can only be addressed causally and become clinically relevant if baseline randomisation to ACS-to-birth intervals is made possible.

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Acknowledgements

This article is part of the PhD project of Isabelle Dehaene, called “PREdiction tool for preTerm laboUr and Neonatal outcome” (PRETURN). We would like to thank all other researchers involved in PRETURN, in particular Johan Steen, statistician at Ghent University and Ghent University Hospital, Belgium. He is a specialist in causal inference with a special interest in time-varying treatments. This work would not have been possible without his input.

Funding

Isabelle Dehaene is funded by a scholarship of FWO (1700520N). The funding body played no role in the creation of this manuscript.

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Authors and Affiliations

  1. Obstetrics and Gynaecology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium

    Isabelle Dehaene & Kristien Roelens

  2. Neonatal Intensive Care Unit, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium

    Koenraad Smets

  3. Intensive Care Unit, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium

    Johan Decruyenaere

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  1. Isabelle Dehaene
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  2. Kristien Roelens
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  3. Koenraad Smets
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  4. Johan Decruyenaere
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Contributions

ID: conceptualization, writing—original draft, writing—review and editing; KR: writing—review and editing, supervision; KS: writing—review and editing, supervision; JD: writing—review and editing, supervision.

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Correspondence to Isabelle Dehaene.

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Dehaene, I., Roelens, K., Smets, K. et al. Relevance of the antenatal corticosteroids-to-delivery interval in the prevention of neonatal respiratory distress syndrome through the eyes of causal inference: a review and target trial. Arch Gynecol Obstet 305, 885–892 (2022). https://doi.org/10.1007/s00404-021-06213-5

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  • DOI: https://doi.org/10.1007/s00404-021-06213-5

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