Antenatal Corticosteroids for Pregnant Women at High Risk of Preterm Delivery with COVID-19 Infection: A Decision Analysis

Abstract

Objective Antenatal corticosteroids given prior to preterm deliveries reduce the risk of adverse neonatal outcomes. However, steroid administration in the setting of a viral respiratory infection can worsen maternal outcomes. Therefore, the decision to administer corticosteroids must balance the neonatal benefits with the potential harm to the mother if she is infected with the novel coronavirus disease 2019 (COVID-19). This study aimed to determine the gestational ages for which administering antenatal corticosteroids to women at high risk of preterm labor with concurrent COVID-19 infection results in improved combined maternal and infant outcomes.

Study Design A decision-analytic model using TreeAge (2020) software was constructed for a theoretical cohort of hospitalized women with COVID-19 in the United States. All model inputs were derived from the literature. Outcomes included maternal intensive care unit (ICU) admission and death, along with infant outcomes of death, respiratory distress syndrome, intraventricular hemorrhage, and neurodevelopmental delay. Quality-adjusted life years (QALYs) were assessed from the maternal and infant perspectives. Sensitivity analyses were performed to determine if the results were robust over a range of assumptions.

Results In our theoretical cohort of 10,000 women delivering between 24 and 33 weeks of gestation with COVID-19, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths. Overall, we found that corticosteroid administration resulted in higher combined QALYs up to 31 weeks of gestation in all hospitalized patients, and up to 29 weeks of gestation in ICU patients.

Conclusion Administration of antenatal corticosteroids at less than 32 weeks of gestation for hospitalized patients and less than 30 weeks of gestation for patients admitted to the ICU resulted in higher combined maternal and infant outcomes compared with expectant management for women at high risk of preterm birth with COVID-19 infection. These results can guide clinicians in their counseling and management of these pregnant women.

Key Points

• Antenatal steroids reduce adverse neonatal outcomes.

• Steroids worsen maternal outcomes in COVID-19.

• Steroids given < 32 weeks result in improved outcomes.

Keywords

preterm birth - COVID-19 - antenatal steroids - respiratory infection

• References

• 1 CDC. If You Are Pregnant, Breastfeeding, or Caring for Young Children. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/pregnant-women-faq.html#pregnant . Accessed May 20, 2020
• 2 World Health Organization. Clinical management of severe acute respiratory infection when COVID-19 disease is suspected. Available at: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected . Accessed May 20, 2020
• 3 Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ. Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol 2020; 222 (05) 415-426
• 4 Guan W-J, Ni Z-Y, Hu Y. , et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720 . Doi: 10.1056/NEJMoa2002032
• 5 Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Available at: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004454.pub2/pdf . Accessed May 20, 2020
• 6 Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395 (10223): 473-475
• 7 Arabi YM, Mandourah Y, Al-Hameed F. , et al; Saudi Critical Care Trial Group. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med 2018; 197 (06) 757-767
• 8 Longman RE, Johnson TRB. Viral respiratory disease in pregnancy. Curr Opin Obstet Gynecol 2007; 19 (02) 120-125
• 9 Lee N, Allen Chan KC, Hui DS. , et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol 2004; 31 (04) 304-309
• 10 Auyeung TW, Lee JSW, Lai WK. , et al. The use of corticosteroid as treatment in SARS was associated with adverse outcomes: a retrospective cohort study. J Infect 2005; 51 (02) 98-102
• 11 CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19) - United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (12) 343-346
• 12 Lansbury LE, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Shen Lim W. Corticosteroids as adjunctive therapy in the treatment of influenza: an updated cochrane systematic review and meta-analysis. Crit Care Med 2020; 48 (02) e98-e106
• 13 Travers CP, Clark RH, Spitzer AR, Das A, Garite TJ, Carlo WA. Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study. BMJ 2017; 356 (j1039): j1039
• 14 Larroque B, Ancel P-Y, Marret S. , et al; EPIPAGE Study group. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet 2008; 371 (9615): 813-820
• 15 Mukerji A, Shah V, Shah PS. Periventricular/intraventricular hemorrhage and neurodevelopmental outcomes: a meta-analysis. Pediatrics 2015; 136 (06) 1132-1143
• 16 Sanders GD, Neumann PJ, Basu A. , et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: Second panel on cost-effectiveness in health and medicine. JAMA 2016; 316 (10) 1093-1103
• 17 Team IS. ; InterLACE Study Team. Variations in reproductive events across life: a pooled analysis of data from 505 147 women across 10 countries. Hum Reprod 2019; 34 (05) 881-893
• 18 Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: final data for 2017. Natl Vital Stat Rep 2018; 67 (08) 1-50
• 19 Blair E, Watson L, Badawi N, Stanley FJ. Life expectancy among people with cerebral palsy in Western Australia. Dev Med Child Neurol 2001; 43 (08) 508-515
• 20 WHO. Annex 2: tables of health statistics by country, WHO region and globally. Available at: https://www.who.int/gho/publications/world_health_statistics/2019/EN_WHS_2019_Annex2.pdf?ua=1 . Accessed May 20, 2020
• 21 Day SM, Reynolds RJ, Kush SJ. Extrapolating published survival curves to obtain evidence-based estimates of life expectancy in cerebral palsy. Dev Med Child Neurol 2015; 57 (12) 1105-1118
• 22 Cuthbertson BH, Roughton S, Jenkinson D, Maclennan G, Vale L. Quality of life in the five years after intensive care: a cohort study. Crit Care 2010; 14 (01) R6
• 23 Carroll AE, Downs SM. Improving decision analyses: parent preferences (utility values) for pediatric health outcomes. J Pediatr 2009; 155 (01) 21-25 , 25.e1–25.e5
• 24 Kuppermann M, Nease RF, Learman LA, Gates E, Blumberg B, Washington AE. Procedure-related miscarriages and Down syndrome-affected births: implications for prenatal testing based on women's preferences. Obstet Gynecol 2000; 96 (04) 511-516
• 25 Saigal S, Stoskopf B, Pinelli J. , et al. Self-perceived health-related quality of life of former extremely low birth weight infants at young adulthood. Pediatrics 2006; 118 (03) 1140-1148
• 26 Phibbs CS, Schmitt SK. Estimates of the cost and length of stay changes that can be attributed to one-week increases in gestational age for premature infants. Early Hum Dev 2006; 82 (02) 85-95
• 27 Tsai TC, Jacobson BH, Jha AK. American hospital capacity and projected need for COVID-19 patient care. Available at: https://www.healthaffairs.org/do/10.1377/hblog20200317.457910/full/. Accessed May 20, 2020
• 28 Hui DSC, Chan PKS. Severe acute respiratory syndrome and coronavirus. Infect Dis Clin North Am 2010; 24 (03) 619-638
• 29 McIntosh JJ. Corticosteroid guidance for pregnancy during COVID-19 pandemic. Am J Perinatol 2020; 2019: 1-4
• 30 Dotters-Katz S, Hughes B. ; Society for Maternal fetal medicine. Coronavirus (COVID-19) and pregnancy: what maternal-fetal medicine subspecialists need to know. Available at: https://s3.amazonaws.com/cdn.smfm.org/media/2262/COVID19_PDF.pdf . Accessed May 20, 2020
• 31 Moore LE, Martin Jr JN. When betamethasone and dexamethasone are unavailable: hydrocortisone. J Perinatol 2001; 21 (07) 456-458
• 32 Practice Bulletin No. Practice bulletin no. 171: management of preterm labor. Obstet Gynecol 2016; 128 (04) e155-e164
• 33 Sutton D, Fuchs K, D'Alton M, Goffman D. Universal screening for SARS-CoV-2 in women admitted for delivery. N Engl J Med 2020; 382 (22) 2163-2164