Short Duration of Antenatal Corticosteroid Exposure and Outcomes in Extremely Preterm Infants
Authors: Chawla Sanjay , Wyckoff Myra H. , Lakshminrusimha Satyan , Rysavy Matthew A. , Patel Ravi Mangal , Chowdhury Dhuly , Das Abhik , Greenberg Rachel G. , Natarajan Girija , Shankaran Seetha , Bell Edward F. , Ambalavanan Namasivayam , Younge Noelle E. , Laptook Abbot R. , Pavlek Leeann R. , Backes Carl H. , Van Meurs Krisa P. , Werner Erika F. , Carlo Waldemar A. ,   National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), Ambalavanan Namasivayam , Carlo Waldemar A. , Collins Monica V. , Cosby Shirley S. , Gentle Samuel J. , McNair Tara E. , Travers Colm P. , Hensman Angelita M. , Keszler Martin , Laptook Abbot R. , St. Pierre Lucille , Vieira Elisa , Werner Erika F. , Lakshminrusimha Satyan , Li Emily , Reynolds Anne Marie , Sacilowski Michael G. , Hibbs Anna Maria , Newman Nancy S. , Walsh Michele C. , Beiersdorfer Traci , Dudley Juanita , Grisby Cathy , Jackson Lenora Denise , Kim Jae , Kirker Kristin , Merhar Stephanie L. , Muthig Greg , Poindexter Brenda B. , Russell David , Schibler Kurt , Thompson Julia , Wuertz Sandra , Polin Richard A. , Brion Luc P. , De Leon Maria M. , Duran Joanne , Eubanks Frances , Sepulveda Pollieanna , Vasil Diana M. , Webbon Michelle , Wyckoff Myra H. , Cotten C. Michael , Fisher Kimberley A. , Goldberg Ronald N. , Greenberg Rachel G. , Mago-Shah Deesha , Probst Joanne , Warren Mollie , Younge Noelle E. , Bergstedt Vicki , Moore Ryan , Moseley Sherry , Bottcher Diane I. , Carlton David P. , Laursen Judith , Loggins Yvonne C. , Mackie Colleen , Patel Ravi M. , Sanders Amy , Hall Donna J. , Kennedy Kathleen A. , Khan Amir M. , Martin Karen , McDavid Georgia Elaine , Rysavy Matthew A. , Stephens Emily K. , Stoll Barbara J. , Tyson Jon E. , White Michelle , Wright Sharon L. , Bell Edward F. , Colaizy Tarah T. , Goeke Claire A. , Johnson Karen J. , Schmelzel Mendi L. , Walker Jacky R. , Ellsbury Dan L. , Tud Tracy L. , Backes Carl H. , Batterson Nancy , Baugher Hallie , Beckford Demi R. , Burkhardt Stephanie , Carey Helen , Chao Michelle , Cira Courtney , Clark Erna , DeSantis Brittany , Fathi Omid , Fortney Christine A. , Fowler Aubry , Grothause Jennifer L. , Gutentag Julie , Hague Cole D. , Jadcherla Sudarshan R. , Keim Sarah A. , Levengood Katelyn , Luzader Patricia , Marzec Laura , McCool Jacqueline , Miller Bethany , Nelin Leif D. , Newton Julia , Park Courtney , Pavlek Leeann R. , Pietruszewski Lindsay , Purnell Jessica , Sánchez Pablo J. , Shadd Julie C. , Slaughter Jonathan L. , Stein Melanie , Sullivan Margaret , Sullivan Rox Ann , Timan Christopher J. , Warnimont Kyrstin , Yossef-Salameh Lina , Bremer Andrew A. , Higgins Rosemary D. , Wilson Archer Stephanie , Abbasi Soraya , Catts Christine , Chaudhary Aasma S. , DeMauro Sara B. , Dhawan Megan A. , Eichenwald Eric C. , Ghavam Sarvin , Kirpalani Haresh , Mancini Toni , Puopolo Karen M. , Schmidt Barbara , Snyder Jonathan M. , Binion Kyle , Boylin Elizabeth , D'Angio Carl T. , Guillet Ronnie , Jones Rachel , Kachelmeyer Jennifer , Kent Alison , Orme Constance , Prinzing Diane M. , Rochez Daisy , Rowan Mary , Sabaratnam Premini , Scorsone Ann Marie , Wadkins Holly I.M. , Bayard Annie M. , Chowdhury Dhuly , Das Abhik , Gabrio Jenna , Leblond David , Lewis Amanda , O’Donnell Auman Jeanette , Petrie Huitema Carolyn M. , Zaterka-Baxter Kristin M. , Baack Michelle L. , Broadbent Megan , Elenkiwich Chelsey , Henning Megan M. , Hogden Laurie A. , Van Muyden Sarah , Adams Marian M. , Bahmani Dona , Ball M. Bethany , Chock Valerie Y. , Chuck Jennifer E. , Earhart Beth A. , Huffman Lynne C. , Proud Melinda S. , Recine Barbara P. , Reichert Elizabeth N. , Rutkowska Lilia , Stevenson David K. , Van Meurs Krisa P. , Weiss Hali E. , Williams R. Jordan , Bernhardt Janice , Bose Carl L. , Bose Gennie , Laughon Matthew Maxwell , Talbert Jennifer , Backstrom Lacy Conra , Fuller Janell , Kuan Elizabeth , Ruffner Hanson Mary , Sundquist Beauman Sandra , Watterberg Kristi L. , Baserga Mariana , Burnett Jill , Christensen Susan , Coleman Kathleen , Davis Brandy , Elmont Jennifer O. , Faix Roger G. , Francom Barbara L. , Gerday Erick B. , Jordan Jamie , Loertscher Manndi C. , Marchant Trisha , Maxson Earl , McGrath Kandace M. , Mickelsen Hena G. , Minton Stephen D. , Ohls Robin K. , Parry D. Melody , Rau Carrie A. , Schaefer Susan T. , Sheffield Mark J. , Tice Katherine , Weaver-Lewis Kimberlee , Woodbury Kathryn D. , Yoder Bradley A. , Kicklighter Stephen D. , Rhodes-Ryan Ginger , White Donna , Chawla Sanjay , Natarajan Girija , Shankaran Seetha 
Published: February 2025

Importance

When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

Objective

To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

Design, Setting, and Participants

This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks’ gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive care, and infants with congenital anomalies were excluded. Data were analyzed from October 2021 to December 2024.

Exposure

Time in hours from anenatal betamethasone administration to birth.

Main Outcomes and Measures

The primary outcome was survival to discharge. Secondary outcomes included survival without major morbidity and composites of individual morbidities and death. The association of time from antenatal betamethasone administration to birth with neonatal survival and morbidity was assessed using generalized linear models, adjusting for gestational age, infant sex, maternal race, education, small for gestational age, mode of delivery, multiple birth, prolonged rupture of membranes, and center of birth.

Results

Of 7464 infants born during the study period, 1806 infants (928 [51.3%] boys) were included in the cohort: 475 with no betamethasone and 1331 with exposure to a single dose of betamethasone within 24 hours before birth. The median (IQR) administration-to-birth interval for infants born after a single dose of betamethasone was 3.8 (1.4-9.5) hours. The administration-to-birth interval was independently associated with survival (adjusted relative risk [aRR] per 1-hour increase, 1.01 [95% CI, 1.00-1.01]; aRR per 6-hour increase, 1.04 [95% CI, 1.01-1.07]) and survival without severe neonatal morbidity (aRR per 1-hour increase, 1.01 [95% CI, 1.01-1.02]; aRR per 6-hour increase, 1.09 [95% CI, 1.04-1.14].

Conclusions and Relevance

In this cohort study, for women at risk of imminent preterm birth, even short duration of exposure to antenatal betamethasone was associated with improved neonatal survival and survival without severe neonatal morbidity.