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Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach

Abstract

Bronchopulmonary dysplasia (BPD) is the most common respiratory consequence of premature birth and contributes to significant short- and long-term morbidity, mortality and resource utilization. Initially defined as a radiographic, clinical and histopathological entity, the chronic lung disease known as BPD has evolved as obstetrical and neonatal care have improved the survival of lower gestational age infants. Now, definitions based on the need for supplementary oxygen at 28 days and/or 36 weeks provide a useful reference point in the neonatal intensive-care unit (NICU), but are no longer based on histopathological findings, and are neither designed to predict longer term respiratory consequences nor to study the evolution of a multifactorial disease. The aims of this review are to critically examine the evolution of the diagnosis of BPD and the challenges inherent to current classifications. We found that the increasing use of respiratory support strategies that administer ambient air without supplementary oxygen confounds oxygen-based definitions of BPD. Furthermore, lack of reproducible, genetic, biochemical and physiological biomarkers limits the ability to identify an impending BPD for early intervention, quantify disease severity for standardized classification and approaches and reliably predict the long-term outcomes. More comprehensive, multidisciplinary approaches to overcome these challenges involve longitudinal observation of extremely preterm infants, not only those with BPD, using genetic, environmental, physiological and clinical data as well as large databases of patient samples. The Prematurity and Respiratory Outcomes Program (PROP) will provide such a framework to address these challenges through high-resolution characterization of both NICU and post-NICU discharge outcomes.

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Acknowledgements

Supported by U01 HL101794 to B Schmidt, U01 HL101456 to JL Aschner, U01 HL101798 to PL Ballard and RL Keller, U01 HL101813 to GS Pryhuber, R Ryan and T Mariani, U01 HL101465 to A Hamvas and T Ferkol, U01 HL101800 to AH Jobe and CA Chougnet and 5R01HL105702 to CM Cotton, SD Davis and JA Voynow. In addition to the Principal Investigators, We acknowledge the following PROP Investigators for input into the manuscript: James Kemp, MD and Clement Ren, MD. We also acknowledge Carol J. Blaisdell, MD of NHLBI for her guidance and review of the manuscript and Lynn Taussig for his contributions as Chair of the PROP Steering Committee.

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Correspondence to N L Maitre.

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Appendix 1

Appendix 1

Investigators and Research Staff

Cincinnati Children's Hospital Medical Center

Investigators

Claire Chougnet, PhD

Robert Frenk, MD

James M. Greenberg, MD

William Hardie, MD

Alan H. Jobe, MD, PhD

Karen McDowell, MD

Research Staff

Barbara Alexander, RN

Tari Gratton, PA

Cathy Grigsby, BSN, CCRC

Beth Koch, BHS, RRT, RPFT

Kelly Thornton, BS

Washington University School of Medicine site

Investigators

Thomas Ferkol, MD

Aaron Hamvas, MD2

Mark R. Holland, PhD

James Kemp, MD

Philip T. Levy, MD

Phillip Tarr, MD

Gautam K. Singh, MD

Barbara Warner, MD

Research Staff

Pamela Bates, CRT, RPFT, RPSGT

Claudia Cleveland, RRT

Julie Hoffmann, RN

Laura Linneman, RN

Jayne Sicard-Su, RN

Gina Simpson, RRT, CPFT

2Northwestern University Feinberg School of Medicine

University of California San Francisco site

Investigators

Philip L. Ballard, MD, PhD

Roberta A. Ballard, MD

David J. Durand, MD2

Eric C. Eichenwald, MD4

Roberta L. Keller, MD

Amir M. Khan, MD4

Leslie Lusk, MD

Jeffrey D. Merrill, MD3

Dennis W. Nielson, MD, PhD

Elizabeth E. Rogers, MD

Research Staff

Jeanette M. Asselin, MS RRT-NPS2

Samantha Balan

Katrina Burson, RN, BSN4

Cheryl Chapin

Erna Josiah-Davis, RN, NP3

Carmen Garcia, RN, CCRP4

Hart Horneman

Rick Hinojosa, BSRT, RRT, CPFT-NPS4

Christopher Johnson, MBA, RRT4

Susan Kelley, RRT

Karin L. Knowles

M. Layne Lillie, RN, BSN4

Karen Martin, RN4

Sarah Martin, RN, BSN;

Julie Arldt-McAlister, RN, BSN4

Georgia E. McDavid, RN4

Lori Pacello, RCP2

Shawna Rodgers, RN, BSN4

Daniel K. Sperry, RN4

2Children's Hospital and Research Center Oakland, Oakland, CA

3Alta Bates Summit Medical Center, Berkeley, CA

4University of Texas Health Science Center- Houston, Houston, TX

Vanderbilt University Medical Center site

Investigators

Judy Aschner, MD2

Candice Fike, MD

Scott Guthrie, MD3

Tina Hartert, MD

Nathalie Maitre, MD

Paul Moore, MD

Marshall Summar, MD4

Research Staff

Amy B Beller, BSN

Mark O’ Hunt

Theresa J. Rogers, RN

Odessa L. Settles, RN, MSN, CM

Steven Steele, RN

Sharon Wadley, BSN, RN, CLS3

2Albert Einstein College of Medicine, Bronx, NY

3Jackson-Madison County General Hospital, Jackson, TN

4Children’s National Health System, Washington, DC

University of Rochester Medical Center/University of Buffalo NY site

Investigators

Carl D’Angio, MD

Vasanth Kumar, MD

Tom Mariani, PhD

Gloria Pryhuber, MD

Clement Ren, MD

Anne Marie Reynolds, MD, MPH

Rita M. Ryan, MD1

Kristin Scheible, MD

Timothy Stevens, MD, MPH

Research Staff

Shannon Castiglione, RN

Aimee Horan, LPN

Deanna Maffet, RN

Jane O’Donnell, PNP

Michael Sacilowski, MAT

Tanya Scalise, RN, BSN

Elizabeth Werner, MPH

Jason Zayac, BS

Heidie Huyck, BS

Valerie Lunger, MS

Kim Bordeaux, RRT

Pam Brown, RRT

Julia Epping, AAS, RT

Lisa Flattery-Walsh, RRT

Donna Germuga, RRT, CPFT

Nancy Jenks, RN

Mary Platt, RN

Eileen Popplewell, RRT

Sandra Prentice, CRT

1Medical University of South Carolina, Charleston, SC

Duke Investigators

C. Michael Cotten, MD

Kim Fisher, PhD

Jack Sharp, MD

Judith A. Voynow, MD2Research Staff

Kim Ciccio, RN

2Virginia Commonwealth University

Indiana Investigators

Stephanie Davis, MD

Brenda Poindexter, MD, MS2Research Staff

Charles Clem, RRT

Susan Gunn, NNP, CCRC

Lauren Jewett, RN, CCRC

2Cincinnati Children's Hospital Medical Center

University of Pennsylvania, Perelman School of Medicine, DCC site

Investigators

Jonas Ellenberg, PhD

Rui Feng, PhD

Melissa Fernando, MPH

Howard Panitch, MD

Barbara Schmidt, MD, MSc

Pamela Shaw, PhD

Research Staff

Ann Tierney, BA, MS

Maria Blanco, BS

Denise Cifelli, MS

Sara DeMauro, MD

University of Denver, Steering Committee Chair

Lynn M. Taussig, MD

NHLBI Program Officer

Carol J. Blaisdell, MD

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Maitre, N., Ballard, R., Ellenberg, J. et al. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol 35, 313–321 (2015). https://doi.org/10.1038/jp.2015.19

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