Authors

Erik A. Jensen, Division of Neonatology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia
Laura Elizabeth Wiener, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina
Matthew A. Rysavy, Department of Pediatrics, University of Texas McGovern Medical School, Houston
Kevin C. Dysart, Neonatal/Perinatal Medicine, Nemours Children's Hospital, Wilmington, Delaware
Marie G. Gantz, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina
Eric C. Eichenwald, Division of Neonatology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia
Rachel G. Greenberg, Department of Pediatrics and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
Heidi M. Harmon, Stead Family Department of Pediatrics, University of Iowa, Iowa City
Matthew M. Laughon, Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill
Kristi L. Watterberg, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
Michele C. Walsh, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Bradley A. Yoder, Division of Neonatology, University of Utah, Salt Lake City
Scott A. Lorch, Division of Neonatology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia
Sara B. DeMauro, Division of Neonatology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia
Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

Document Type

Article

Publication Date

5-1-2023

Abstract

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022.

EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age.

RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%).

CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

Publication Title

JAMA Netw Open

ISSN

2574-3805

Volume

6

Issue

5

First Page

2312277

Last Page

2312277

DOI

10.1001/jamanetworkopen.2023.12277

Share

COinS