Hydrocortisone for Preventing Mortality and Bronchopulmonary Dysplasia in Preterm Infants with or without Chorioamnionitis Exposure: A Meta-Analysis of Randomized Trials

Abstract

Objective This study sought to assess whether infants exposed to chorioamnionitis are the optimal population to benefit the most from early postnatal hydrocortisone delivery in preventing bronchopulmonary dysplasia (BPD). This meta-analysis was conducted to discover the efficacy of hydrocortisone in preterm infants with and without chorioamnionitis.

Study Design From the earliest available date until March 2018, studies, review articles, and papers published in PubMed, Ovid, and Web of Science were reviewed. Randomized controlled trials comparing hydrocortisone with placebo/no intervention in preterm infants with a known status of chorioamnionitis exposure were included.

Results Early postpartum low-dose hydrocortisone prevents the combined outcome of neonatal BPD or death in infants weighing less than 1,000 g with chorioamnionitis exposure (odds ratio [95% confidence interval]: 0.52 [0.32–0.79]; risk difference: –0.15 [–0.24 to –0.06]; number needed to treat: 6 [4–16]) but not in infants without chorioamnionitis exposure. Further secondary analysis showed no significant difference between the hydrocortisone group and the placebo group in individual outcomes of BPD or death, regardless of infant exposure to chorioamnionitis.

Conclusion Early application of low-dose hydrocortisone could potentially prevent BPD or death in infants weighing less than 1,000 g with exposure to chorioamnionitis. This finding provides the basis for further study in this target group.

Keywords

hydrocortisone - bronchopulmonary dysplasia - mortality - meta-analysis

Publication History

Received: 26 February 2019

Accepted: 22 October 2019

Article published online:
03 January 2020

• References

• 1 Islam JY, Keller RL, Aschner JL, Hartert TV, Moore PE. Understanding the short- and long-term respiratory outcomes of prematurity and bronchopulmonary dysplasia. Am J Respir Crit Care Med 2015; 192 (02) 134-156
• 2 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314 (10) 1039-1051
• 3 Delara M, Chauhan BF, Le ML. et al. Efficacy and safety of pulmonary application of corticosteroids in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2019; 104 (02) F137-F144
• 4 Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Late (> 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017; 10: CD001145
• 5 Halliday HL, Ehrenkranz RA, Doyle LW. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2010; (01) CD001146
• 6 Onland W, Offringa M, van Kaam A. Late (≥ 7 days) inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017; 8: CD002311
• 7 Shah SS, Ohlsson A, Halliday HL, Shah VS. Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev 2017; 10: CD002058
• 8 Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017; 10: CD001146
• 9 Ofman G, Perez M, Farrow KN. Early low-dose hydrocortisone: is the neurodevelopment affected?. J Perinatol 2018; 38 (06) 636-638
• 10 Pharoah PO. Dexamethasone treatment and cerebral palsy. Arch Dis Child Fetal Neonatal Ed 2001; 84 (02) F140
• 11 Halliday HL. Early postnatal dexamethasone and cerebral palsy. Pediatrics 2002; 109 (06) 1168-1169
• 12 Metcalfe A, Lisonkova S, Sabr Y, Stritzke A, Joseph KS. Neonatal respiratory morbidity following exposure to chorioamnionitis. BMC Pediatr 2017; 17 (01) 128
• 13 Higgins JPT, Green S. eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration, 2011. Accessed December 2018 at: www.handbook.cochrane.org
• 14 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62 (10) 1006-1012
• 15 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
• 16 Baud O, Maury L, Lebail F. et al; PREMILOC trial study group. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016; 387 (10030): 1827-1836
• 17 Héneau A, Guimiot F, Mohamed D, Rideau Batista Novais A, Alberti C, Baud O. PREMILOC Trial study group. Placental findings and effect of prophylactic hydrocortisone in extremely preterm infants. Pediatrics 2018; 141 (02) e20171788
• 18 Watterberg KL, Gerdes JS, Gifford KL, Lin HM. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants. Pediatrics 1999; 104 (06) 1258-1263
• 19 Watterberg KL, Gerdes JS, Cole CH. et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics 2004; 114 (06) 1649-1657
• 20 Shaffer ML, Baud O, Lacaze-Masmonteil T, Peltoniemi OM, Bonsante F, Watterberg KL. Effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone in very preterm infants: an individual patient data meta-analysis. J Pediatr 2019; 207: 136-142
• 21 Watterberg KL. American Academy of Pediatrics. Committee on Fetus and Newborn. Policy statement--postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics 2010; 126 (04) 800-808
• 22 Baud O, Trousson C, Biran V, Leroy E, Mohamed D, Alberti C. PREMILOC Trial Group. Association between early low-dose hydrocortisone therapy in extremely preterm neonates and neurodevelopmental outcomes at 2 years of age. JAMA 2017; 317 (13) 1329-1337
• 23 Hochwald O, Palegra G, Osiovich H. Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants. Indian J Pediatr 2014; 81 (08) 808-810
• 24 Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB. DART Study Investigators. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics 2006; 117 (01) 75-83
• 25 Isayama T, Iwami H, McDonald S, Beyene J. Association of noninvasive ventilation strategies with mortality and bronchopulmonary dysplasia among preterm infants: a systematic review and meta-analysis. JAMA 2016; 316 (06) 611-624