Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants
Authors: Jensen Erik A. , Wiener Laura Elizabeth , Rysavy Matthew A. , Dysart Kevin C. , Gantz Marie G. , Eichenwald Eric C. , Greenberg Rachel G. , Harmon Heidi M. , Laughon Matthew M. , Watterberg Kristi L. , Walsh Michele C. , Yoder Bradley A. , Lorch Scott A. , DeMauro Sara B. ,   Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Polin Richard A. , Laptook Abbot R. , Keszler Martin , Vohr Betty R. , Hensman Angelita M. , Vieira Elisa , Pierre Lucille St. , Burke Robert T. , Alksninis Barbara , Knoll Andrea , Keszler Mary L. , Leach Teresa M. , McGowan Elisabeth C. , Watson Victoria E. , Hibbs Anna Maria , Newman Nancy S. , Wilson-Costello Deanne E. , Siner Bonnie S. , Friedman Harriet G. , Truog William E. , Pallotto Eugenia K. , Kilbride Howard W. , Gauldin Cheri , Holmes Anne , Johnson Kathy , Scott Allison , Parimi Prabhu S. , Gaetano Lisa , Merhar Stephani L. , Schibler Kurt , Poindexter Brenda B. , Yolton Kimberly , Cahill Tanya E. , Gratton Teresa L. , Grisby Cathy , Kirker Kristin , Wuertz Sandra , Cotten Michael C. , Goldberg Ronald N. , Goldstein Ricki F. , Malcolm William F. , Ashley Patricia L. , Mago-Shah Deesha , Finkle Joanne , Fisher Kimberley A. , Gustafson Kathryn E. , Bose Carl L. , Bernhardt Janice , Bose Gennie , Wereszczak Janice , Warner Diane , Talbert Jennifer , Kicklighter Stephen D. , Bentley Alexandra , Edwards Laura , Rhodes-Ryan Ginger , White Donna , Patel Ravi M. , Carlton David P. , Loggins Yvonne , Adams-Chapman (deceased) Ira , Bottcher Diane , Carter Sheena L. , Hale Ellen C. , Kendrick-Allwood Salathiel , Mulligan LaRossa Maureen , Mackie Colleen , Sanders Amy , Smikle Gloria , Wineski Lynn , Bremer Andrew A. , Higgins Rosemary D. , Wilson Archer Stephanie , Sokol Gregory M. , Harmon Heidi , Papile Lu Ann , Herron Dianne E. , Hines Abbey C. , Lytle Carolyn , Smiley Lucy , Wilson Leslie Dawn , Tyson Jon E. , Khan Amir M. , Kennedy Kathleen A. , Stoll Barbara J. , Mosquera Riciardo A. , Duncan Andrea F. , Stephens Emily , Allain Elizabeth , Arldt-McAlister Julie , Boricha Fatima , Burson Katrina , Dempsey Allison G. , Evans Patricia W. , Garcia Carmen , Hall Donna J. , Jiminez Margarita , John Janice , Jones Patrick M. , Lillie M. Layne , Martin Karen , Martin Sara C. , McDavid Georgia E. , McKee Shannon L. , Poe Michelle , Rennie Kimberly , Reddy Tina , Rodgers Shawna , Khan Siddiki Saba , Sperry Daniel , Pierce Tate Patti L. , Wright Sharon L. , Sánchez Pablo J. , Slaughter Jonathan L. , Nelin Leif D. , Jadcherla Sudarshan R. , Maitre Nathalie L. , Timan Christopher , Yeates Keith O. , Luzader Patricia , Batterson Nancy , Baugher Hallie , Beckford Demi R. , Burkhardt Stephanie , Carey Helen , Chao Michelle , Cira Courtney , Clark Erna , DeSantis Brittany , Fortney Christine A. , Fowler Aubrey , Gutentag Julie , Grothause Jennifer L. , Hague Cole D. , Keim Sarah A. , Levengood Katelyn , Marzec Laura , McCool Jacqueline , Miller Bethany , Nelin Mary Ann , Newton Julia , Park Courtney , Pietruszewski Lindsay , Purnell Jessica , Seabrook Ruth , Shadd Julie C. , Small Kristi , Stein Melanie , Sullivan Margaret , Sullivan Rox Ann , Warnimont Krystin , Yossef-Salameh Lina , Fearns Erin , Das Abhik , Gantz Marie G. , Bann Carla M. , Wallace Dennis , O'Donnell Auman Jeanette , Crawford Margaret , Gabrio Jenna , Newman Jamie E. , Parlberg Lindsay , Petrie Huitema Carolyn M. , Zaterka-Baxter Kristin M. , Van Meurs Krisa P. , Chock Valerie Y. , Stevenson David K. , Hintz Susan R. , Ball Bethany M. , Adams Marian M. , Bahmani Dona , Bentley Barbara , DeAnda Maria Elena , DeBattista Anne M. , Earhart Beth , Huffman Lynne C. , Krueger Casey E. , Lucash Ryan E. , Proud Melinda S. , Reichert Elizabeth N. , Taylor Heather , Weiss Hali E. , Williams Jordan R. , Carlo Waldemar A. , Ambalavanan Namasivayam , Peralta-Carcelen Myriam , Collins Monica V. , Cosby Shirley S. , Bailey Kirstin J. , Biasini Fred J. , Chopko Stephanie A. , Domnanovich Kristy A. , Jno-Finn Chantel J. , Ladinsky Morissa , Moses Mary Beth , McNair Tara E. , Phillips Vivien A. , Preskitt Julie , Rector Richard V. , Stringer Kimberlly , Whitley Sally , York Chapman Sheree , Devaskar Uday , Garg Meena , Purdy Isabell B. , Chanlaw Teresa , Geller Rachel , Colaizy Tarah T. , Widness John A. , Brumbaugh Jane E. , Harmon Heidi M. , Johnson Karen J. , Schmelzel Mendi L. , Walker Jacky R. , Goeke Claire A. , Eastman Diane L. , Baack Michelle L. , Hogden Laurie A. , Henning Megan M. , Elenkiwich Chelsey , Broadbent Megan , Ellsbury Dan L. , Bass Donia B. , Tud Tracy L. , Fuller Janell , Ohls Robin K. , Backstrom Lacy Conra , Hartenberger Carol , Sundquist Beauman Sandra , Hanson Mary , Lowe Jean R. , Kuan Elizabeth , Schmidt Barbara , Kirpalani Haresh , Abbasi Soraya , Chaudhary Aasma S. , Mancini Toni , Cucinotta Dara M. , Bernbaum Judy C. , Gerdes Marsha , Ghayam Sarvin , Hurt Hallam , Snyder Jonathan , Ziolkowski Kristina , D'Angio Carl T. , Guillet Ronnie , Myers Gary J. , Reynolds Anne Marie , Lakshminrusimha Satyan , Wadkins Holly I.M. , Sacilowski Michael G. , Jensen Rosemary L. , Merzbach Joan , Zorn William , Farooq Osman , Maffett Dee , Williams Ashley , Hunn Julianne , Guilford Stephanie , Yost Kelley , Rowan Mary , Prinzing Diane , Wynn Karen , Bowman Melissa , Reubens Linda J. , Scorsone Ann Marie , Hartley-McAndrew Michelle , Fallone Caitlin , Binion Kyle , Orme Constance , Sabaratnam Premini , Kent Alison , Horihan Cassandra A. , Jones Rachel , Boylin Elizabeth , Rochez Daisy , Li Emily , Kachelmeyer Jennifer , McKee Kimberly G. , Coleman Kelly R. , Wyckoff Myra H. , Brion Luc P. , Heyne Roy J. , Vasil Diana M. , Adams Sally S. , Chen Lijun , De Leon Maria M. , Eubanks Frances , McDougald Rebecca , Payageau Lara , Sepulveda Pollieanna , Guzman Alicia , Heyne Elizabeth , Madden Linda A. , Lee Lizette E. , Twell Boatman Cathy , Vera Azucena , Waterbury Jillian , Yoder Bradley A. , Baserga Mariana , Faix Roger G. , Minton Stephen D. , Sheffield Mark J. , Rau Carrie A. , Baker Shawna , Burnett Jill , Christensen Susan , Cunningham Sean D. , Davis Brandy , Elmont Jennifer O. , Hall Becky , Jensen Erika R. , Loertscher Manndi C. , Marchant Trisha , Maxson Earl , McGrath Kandace M. , Mickelsen Hena G. , Morshedzadeh Galina , Parry Melody D. , Schaefer Susan T. , Stout Kelly , Stuart Ashley L. , Weaver-Lewis Kimberlee , Winter Sarah , Woodbury Kathryn D. , Shankaran Seetha , Natarajan Girija , Pappas Athina , Sood Beena G. , Bajaj Monika , February Melissa , Agarwal Prashant , Chawla Sanjay , Bara Rebecca , Childs Kirsten , Woldt Eunice , Goldston Laura , Barks John , Wiggins Stephanie A. , Christensen Mary K. , Carlson Martha , White Diane F. 
Published: May 2023

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.