To the Editors:
In a recent article, Rasmussen et al1 recommend against the routine use of antenatal corticosteroids for fetal lung maturity in pregnant women with coronavirus disease 2019 (COVID-19). We believe this recommendation warrants further discussion. First, we would like to highlight that the impact of corticosteroid treatment in nonpregnant patients with COVID-19 is currently unclear, precluding conclusions about likely maternal harm in the context of COVID-19. Second, we argue that in these unique circumstances, decision-making about the use of antenatal corticosteroids should keep in mind that the absolute benefits of antenatal corticosteroids for fetal lung maturity changes on a week-by-week basis during pregnancy.
Rasmussen et al1 supported their recommendation against routine administration of corticosteroids for fetal lung maturation by citing evidence that outside of pregnancy, corticosteroids were not beneficial for the treatment of the Middle East respiratory syndrome (MERS) and may have led to decreased MERS coronavirus clearance.2 We believe it is important to better acknowledge the evolving state of evidence regarding corticosteroids in the treatment of COVID-19. A metaanalysis of observational data examining patients with viral pneumonia and acute respiratory distress syndrome (ARDS) before this pandemic suggests corticosteroids may increase mortality3; however, these findings are likely due to confounding by indication (sicker patients were more likely to receive corticosteroids). In contrast, among 201 patients who tested positive for COVID-19 with ARDS in China, of whom approximately 40% (n=84) received corticosteroids, treatment was associated with lower mortality (hazard ratio, 0.38; 95% confidence interval [CI], 0.20–0.72).4 A randomized trial investigating corticosteroid use in patients with severe COVID-19 is currently ongoing, suggesting there is still equipoise in this issue.5
As the evidence regarding corticosteroid treatment for COVID-19 evolves, decision-making on the use of antenatal corticosteroids for fetal lung maturation in the context of COVID-19 will be aided by clear information on the fetal benefits it is being weighed against. It is important to recognize that the absolute benefits of antenatal corticosteroids differ on a week-by-week basis as gestational age advances and the baseline risks of neonatal morbidity decrease. In births of <34 weeks’ gestation, the absolute risk reduction of neonatal respiratory distress syndrome associated with antenatal corticosteroids is 128 fewer cases per 1000, from a baseline risk of 310 per 1000.6 In contrast, we recently estimated that the absolute risk reduction of neonatal ventilation of >6 hours associated with antenatal corticosteroids in those born at 34 weeks’ gestation is 24 fewer cases per 1000 (95% CI, 14–35), from a US population baseline risk of 64 per 1000, and at 36 weeks’ gestation, it is 7 fewer cases per 1000 (95% CI, 4–9), from a baseline risk of 17 per 1000.7 , 8
As obstetrical care providers strive to provide the best care in these unique circumstances, considering week-by-week absolute benefits of antenatal corticosteroids allows us to best weigh potential harms and benefits of this treatment alongside our critical care colleagues. These conversations will be crucial to minimizing maternal harm while reducing the burden of neonatal respiratory morbidity in a time when ventilation resources are of paramount importance.
Footnotes
J.A.H. is supported by a Canada Research Chair in Perinatal Population Health. This organization had no involvement in the writing of this letter or in the decision to submit the manuscript. The authors report no conflict of interest.
This letter cites research that was presented in a poster at the Society for Maternal-Fetal Medicine 40th Annual Pregnancy Meeting, Grapevine, TX, February 3–8, 2020.
References
- 1.Rasmussen S.A., Smulian J.C., Lednicky J.A., Wen T.S., Jamieson D.J. Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol. 2020;222:415–426. doi: 10.1016/j.ajog.2020.02.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Arabi Y.M., Mandourah Y., Al-Hameed F. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197:757–767. doi: 10.1164/rccm.201706-1172OC. [DOI] [PubMed] [Google Scholar]
- 3.Ni Y.N., Chen G., Sun J., Liang B.M., Liang Z.A. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019;23:99. doi: 10.1186/s13054-019-2395-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Wu C., Chen X., Cai Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020 doi: 10.1001/jamainternmed.2020.0994. [Epub ahead of print] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Qin Y.Y., Zhou Y.H., Lu Y.Q. Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: protocol of a randomized controlled trial. Chin Med J (Engl) 2020;133:1080–1086. doi: 10.1097/CM9.0000000000000791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Roberts D., Brown J., Medley N., Dalziel S.R. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;3:CD004454. doi: 10.1002/14651858.CD004454.pub2. [DOI] [PubMed] [Google Scholar]
- 7.Foggin H., Liauw J., Hutcheon J.A. 841: late preterm antenatal corticosteroids and neonatal morbidity and mortality: estimating population-level absolute risk measures. Obstet Gynecol. 2020;222:S527–S528. [Google Scholar]
- 8.Birth cohort linked-infant death data files: 2012 and 2013 [Internet]: Centers for Disease Control and Prevention; 2020. Available at: https://www.cdc.gov/nchs/data_access/vitalstatsonline.htm. Accessed March 3, 2020.