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Antenatal corticosteroids for the late preterm infant and agnotology

Journal of Perinatology volume 37, pages 1265–1267 (2017)Cite this article

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In 2002, then Secretary of Defense Donald Rumsfeld answered inquiries about possible weapons of mass destruction—‘There are known knowns,…there are known unknowns,…but there are also unknown unknowns – the ones we don’t know we don’t know,…it is the latter category that tend to be the difficult ones.’ This prescient observation provides an epistemological framework to discuss antenatal corticosteroids (ACS) for pregnant women at risk for delivering late preterm infants (LPIs) at 34 to 36 weeks' gestation, an emerging practice recently recommended by the American College of Obstetricians and Gynecologists (ACOG).1 We suggest there is a consequential fourth category of uncertainty and risk imbedded within decision-making that is conspicuously unappreciated—unknown knowns. Obstetricians and neonatologists have partaken in therapeutic misadventures related to uncritical adoption of many partially studied but enthusiastically employed treatments.2, 3, 4, 5, 6 Have we forgotten the distinction between uncertainty (not knowing what will happen) and risk (the product of harm and the chance it will occur)? Is the recent ACOG ACS recommendation for 34- to 36-week pregnancies a precarious amalgam of ‘unknown unknowns’ and ‘unknown knowns’, and the very peradventure of doubt requiring thoughtful discussion? We contend that while ACS therapy has a decidedly favorable risk/benefit ratio at less than 34 weeks' gestation, the troubling dearth of meaningful advantages and the real possibility of long-term side effects suggest we be most cautious before endorsing this intervention for potential 34- to 36-week births.

ACS are a highly efficacious therapy in pregnant women delivering 23- to 33-week gestation infants with clear reductions in mortality, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC).7, 8 Because LPIs comprise ~70% of all premature births (three infants are born between 34 and 36 weeks for every one born 33 weeks or less) a relatively straightforward and inexpensive therapy like ACS that might reduce morbidity is understandably attractive.9 The Antenatal Late Preterm Steroids (ALPS) trial randomized pregnant women at risk for premature birth between 34 0/7 and 36 5/7 weeks to a two-dose regimen of betamethasone or placebo.10 The primary outcome (need for respiratory support, extracorporeal membrane oxygenation or mechanical ventilation) was reduced from 14.4% in the placebo group to 11.6% in the ACS group, the number needed to treat (NNT) was 35 women given ACS to prevent one case of the composite end point. ‘Need for respiratory support’ was generously defined as any infant requiring just 2 or more hours of nasal continuous positive airway pressure or high flow nasal cannula, or a FiO2 requirement of 30% for just 4 h or more (with no pre-specified saturation target). ‘Severe RDS’, broadly defined as any infant who required nasal continuous positive airway pressure or high flow nasal cannula for only 12 continuous hours or more, or a FiO2 of 30% or more for 24 consecutive hours, was reduced in the ACS group from 12.1% to 8.1% (NNT 25). Transient tachypnea of the newborn (TTN) (NNT 31), surfactant use (NNT 77), need for delivery room resuscitation (NNT 24) and bronchopulmonary dysplasia (NNT 200) were also reduced in the ACS treated infants.

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Acknowledgements

This investigation was supported by the Providence Health and Services Foundation (Portland, OR, USA). The sponsor had no role in the conduct of this analysis and commentary.

Author contributions

Both authors take responsibility for the integrity and accuracy of this analysis and commentary and shared equally in its’ conception and draft. Both authors critically reviewed the manuscript at each step, all data analysis and participated in the formulation and final revision.

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Authors and Affiliations

  1. Department of Neonatology, Women and Children’s Program, Providence St. Vincent Medical Center, Portland, OR, USA

    J W Kaempf

  2. Department of Pediatrics, Baylor College of Medicine, Section Head and Service Chief of Neonatology, Texas Children’s Hospital, Houston, TX, USA

    G Suresh

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Correspondence to J W Kaempf.

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Kaempf, J., Suresh, G. Antenatal corticosteroids for the late preterm infant and agnotology. J Perinatol 37, 1265–1267 (2017). https://doi.org/10.1038/jp.2017.76

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