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Achieved oxygen saturations and retinopathy of prematurity in extreme preterms
  1. Marie G Gantz1,
  2. Waldemar A Carlo2,
  3. Neil N Finer3,
  4. Wade Rich4,
  5. Roger G Faix5,
  6. Bradley A Yoder6,
  7. Michele C Walsh7,
  8. Nancy S Newman7,
  9. Abbott Laptook8,
  10. Kurt Schibler9,10,
  11. Abhik Das11,
  12. Rosemary D Higgins12
  13. on behalf of the SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
    1. 1 Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Institute, Durham, North Carolina, USA
    2. 2 Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA
    3. 3 Department of Paediatrics Neonatology, UCFD Medical Centre, San Diego, California, USA
    4. 4 Neonatology, University of California, San Diego, California, USA
    5. 5 Pediatrics/Neonatology, University of Utah, Salt Lake City, Utah, USA
    6. 6 Pediatrics, University of Utah, Salt Lake City, Utah, USA
    7. 7 Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA
    8. 8 Department of Pediatrics, Women & Infants Hospital, Providence, Rhode Island, USA
    9. 9 Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
    10. 10 Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    11. 11 Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland, USA
    12. 12 College of Health and Human Services, George Mason University, Fairfax, Virginia, USA
    1. Correspondence to Dr Marie G Gantz, Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Institute, Research Triangle Park NC 27709, USA; mgantz{at}


    Objective To identify achieved oxygen saturations (SpO2) associated with increased risk of severe retinopathy of prematurity (ROP).

    Design This is a secondary analysis of the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)randomised controlled trial. SpO2 was recorded up to 36 weeks’ postmenstrual age. Saturations through 9 postnatal weeks were explored graphically, and logistic regression models were created to predict severe ROP.

    Setting 20 centres of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.

    Patients 984 surviving infants of 24–27 weeks’ gestational age born in 2005–2009.

    Interventions SUPPORT targeted SpO2 to a lower (85%–89%) or higher (91%–95%) range through 36 weeks’ postmenstrual age or off respiratory support.

    Main outcome measures Severe ROP defined as threshold ROP, ophthalmological surgery or bevacizumab treatment.

    Results There were statistically significant interactions between duration of oxygen supplementation and percentage of time in certain achieved saturation ranges. Specifically, for infants who spent at least 2 weeks on oxygen in postnatal weeks 1–5, a higher percentage of time at 91%–96% SpO2 was associated with increased odds of severe ROP. For infants who spent at least 3 weeks on oxygen in postnatal weeks 6–9, a higher percentage of time at 97%–100% SpO2 was associated with increased odds of severe ROP. Other significant risk factors were lower gestational age and birth weight, non-Hispanic white versus black race, prospectively defined severe illness, late-onset sepsis or meningitis, and clinical centre.

    Conclusions Among extremely preterm survivors to discharge, the association between SpO2 and severe ROP depended on the timing and duration of oxygen supplementation.

    • neonatology
    • ophthalmology
    • respiratory

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    • Contributors Conception and design: MGG, WAC, AD. Acquisition, analysis or interpretation of the data: all authors. Drafting of the manuscript: MGG, WAC. Critical revision of the manuscript: all authors. Statistical analysis: MGG, AD. On behalf of the NRN, AD (DCC Principal Investigator) and MGG (DCC Alternate Principal Investigator and Senior Statistician) had full access to all of the data in the study, and with the NRN principal investigators, take responsibility for the integrity of the data and accuracy of the data analysis.

    • Funding The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung, and Blood Institute (NHLBI) provided grant support for the Neonatal Research Network’s SUPPORT trial. While NICHD staff did have input into the study design, conduct, analysis and manuscript drafting, the comments and views of the authors do not necessarily represent the views of the NICHD. Grant numbers are

    • Competing interests None declared.

    • Ethics approval Institutional review board approval was obtained for SUPPORT at all sites.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data reported in this paper may be requested through a data use agreement. Further details are available at

    • Collaborators The following investigators, in addition to those listed as authors, participated in this study: NRN Steering Committee Chairs: Alan H Jobe, MD PhD, University of Cincinnati (2003–2006); Michael S Caplan, MD, University of Chicago, Pritzker School of Medicine (2006–2011). Alpert Medical School of Brown University and Women & Infants Hospital of Rhode Island (U10 HD27904): William Oh, MD; Betty R Vohr, MD; Angelita M Hensman, RN BSN; Bonnie E Stephens, MD; Barbara Alksninis, PNP; Dawn Andrews, RN; Kristen Angela, RN; Susan Barnett, RRT; Bill Cashore, MD; Melinda Caskey, MD; Kim Francis, RN; Dan Gingras, RRT; Regina A Gargus, MD FAAP; Katharine Johnson, MD; Shabnam Lainwala, MD; Theresa M Leach, MEd CAES; Martha R Leonard, BA BS; Sarah Lillie, RRT; Kalida Mehta; James R Moore, MD; Lucy Noel; Suzy Ventura; Rachel V Walden; Victoria E Watson, MS CAS. Case Western Reserve University and Rainbow Babies & Children’s Hospital (U10 HD21364, M01 RR80): Avroy A Fanaroff, MD; Deanne E Wilson-Costello, MD; Bonnie S Siner, RN; Arlene Zadell RN; Julie DiFiore, BS; Monika Bhola, MD; Harriet G Friedman, MA; Gulgun Yalcinkaya, MD. Cincinnati Children’s Hospital Medical Center, University of Cincinnati Hospital and Good Samaritan Hospital (U10 HD27853, M01 RR8084): Edward F Donovan, MD; Vivek Narendran, MD MRCP; Kimberly Yolton, PhD; Kate Bridges, MD; Barbara Alexander, RN; Cathy Grisby, BSN CCRC; Marcia Worley Mersmann, RN CCRC; Holly L Mincey, RN BSN; Jody Hessling, RN; Teresa L Gratton, PA. Duke University School of Medicine, University Hospital, Alamance Regional Medical Center and Durham Regional Hospital (U10 HD40492, M01 RR30): Ronald N Goldberg, MD; C Michael Cotten, MD MHS; Ricki F Goldstein, MD; Patricia Ashley, MD; Kathy J Auten, MSHS; Kimberley A Fisher, PhD FNP-BC IBCLC; Katherine A Foy, RN; Sharon F Freedman, MD; Kathryn E Gustafson, PhD; Melody B Lohmeyer, RN MSN; William F Malcolm, MD; David K Wallace, MD MPH. Emory University, Children’s Healthcare of Atlanta, Grady Memorial Hospital and Emory Crawford Long Hospital (U10 HD27851, UL1 RR25008, M01 RR39): Barbara J Stoll, MD; Susie Buchter, MD; Anthony J Piazza, MD; David P Carlton, MD; Ira Adams-Chapman, MD; Linda Black, MD; Ann M Blackwelder, RNC BS MS; Sheena Carter, PhD; Elisabeth Dinkins, PNP; Sobha Fritz, PhD; Ellen C Hale, RN BS CCRC; Amy K Hutchinson, MD; Maureen Mulligan LaRossa, RN; Gloria V Smikle, PNP MSN. Eunice Kennedy Shriver National Institute of Child Health and Human Development: Stephanie Wilson Archer, MA. Indiana University, University Hospital, Methodist Hospital, Riley Hospital for Children and Wishard Health Services (U10 HD27856, M01 RR750): Brenda B Poindexter, MD MS; Anna M Dusick, MD FAAP; James A Lemons, MD; Leslie D Wilson, BSN CCRC; Faithe Hamer, BS; Ann B Cook, MS; Dianne E Herron, RN; Carolyn Lytle, MD MPH; Heike M Minnich, PsyD HSPP. McGovern Medical School at The University of Texas Health Science Center at Houston and Children’s Memorial Hermann Hospital (U10 HD21373): Kathleen A Kennedy, MD MPH; Jon E Tyson, MD MPH; Patricia W Evans, MD; Nora I Alaniz, BS; Patricia Evans, MD; Beverly Foley Harris, RN BSN; Charles Green, PhD; Margarita Jiminez, MD MPH; Anna E Lis, RN BSN; Sarah Martin, RN BSN; Georgia E McDavid, RN; Brenda H Morris, MD; Margaret L Poundstone, RN BSN; Stacy Reddoch, BA; Saba Siddiki, MD; Patti L Pierce Tate, RCP; Laura L Whitely, MD; Sharon L Wright, MT (ASCP). National Heart, Lung, and Blood Institute: Mary Anne Berberich, PhD; Carol J Blaisdell, MD; Dorothy B Gail, PhD; James P Kiley, PhD. RTI International (U10 HD36790): W Kenneth Poole, PhD; Lisa A Wrage, MPH; Jamie E Newman, PhD MPH; Betty K Hastings; Jeanette O’Donnell Auman, BS; Carolyn Petrie Huitema, MS; James W Pickett II, BS; Dennis Wallace, PhD; Kristin M Zaterka-Baxter, RN BSN. Stanford University and Lucile Packard Children’s Hospital (U10 HD27880, UL1 RR25744, M01 RR70): Krisa P Van Meurs, MD; David K Stevenson, MD; Susan R Hintz, MD MS Epi; M Bethany Ball, BS CCRC; Barbara Bentley, PsychD MSEd; Elizabeth F Bruno, PhD; Alexis S Davis, MD MS; Maria Elena DeAnda, PhD; Anne M DeBattista, RN, PNP; Jean G Kohn, MD MPH; Melinda S Proud, RCP; Renee P Pyle, PhD; Nicholas H St John, PhD; Hali E Weiss, MD. Tufts Medical Center, Floating Hospital for Children (U10 HD53119, M01 RR54): Ivan D Frantz III, MD; Elisabeth C McGowan, MD; John M Fiascone, MD; Anne Furey, MPH; Brenda L MacKinnon, RNC; Ellen Nylen, RN BSN; Ana Brussa, MS OTR/L; Cecelia Sibley, PT MHA. University of Alabama at Birmingham Health System and Children’s Hospital of Alabama (U10 HD34216, M01 RR32): Namasivayam Ambalavanan, MD; Myriam Peralta-Carcelen, MD MPH; Monica V Collins, RN BSN MaEd; Shirley S Cosby, RN BSN; Vivien A Phillips, RN BSN; Kirstin J Bailey, PhD; Fred J Biasini, PhD; Maria Hopkins, PhD; Kristen C Johnston, MSN CRNP; Sara Krzywanski, MS; Kathleen G Nelson, MD; Cryshelle S Patterson, PhD; Richard V Rector, PhD; Leslie Rodriguez, PhD; Amanda Soong, MD; Sally Whitley, MA OTR-L FAOTA; Sheree York, PT DPT MS PCS. University of California San Diego Medical Center and Sharp Mary Birch Hospital for Women (U10 HD40461): Maynard R Rasmussen, MD; Paul R Wozniak, MD; Yvonne E Vaucher, MD MPH; Kathy Arnell, RNC; Rene Barbieri-Welge; Ayala Ben-Tall; Renee Bridge, RN; Clarence Demetrio, RN; Martha G Fuller, RN MSN; Elaine Ito; Meghan Lukasik; Deborah Pontillo; Donna Posin, OTR/L MPA; Cheryl Runyan; James Wilkes; Paul Zlotnik. University of Iowa Children’s Hospital (U10 HD53109, UL1 RR24979, M01 RR59): Edward F Bell, MD; John A Widness, MD; Michael J Acarregui, MD; Jonathan M Klein, MD; Tarah T Colaizy, MD MPH; Karen J Johnson, RN BSN; Diane L Eastman, RN CPNP MA. University of Miami and Holtz Children’s Hospital (U10 HD21397, M01 RR16587): Shahnaz Duara, MD; Charles R Bauer, MD; Ruth Everett-Thomas, RN MSN; Maria Calejo, MEd; Alexis N Diaz, BA; Silvia M Frade Eguaras, BA; Andrea Garcia, MA; Kasey Hamlin-Smith, PhD; Michelle Harwood Berkowits, PhD; Sylvia Hiriart-Fajardo, MD; Elaine O Mathews, RN; Helina Pierre, BA; Arielle Riguard, MD; Alexandra Stroerger, BA. University of New Mexico Health Sciences Center (U10 HD53089, M01 RR997): Kristi L Watterberg, MD; Robin K Ohls, MD; Janell Fuller, MD; Julie Rohr, MSN RNC CNS; Conra Backstrom Lacy, RN; Jean Lowe, PhD; Rebecca Montman, BSN. University of Rochester Medical Center and Golisano Children’s Hospital (U10 HD40521, M01 RR44): Dale L Phelps, MD; Nirupama Laroia, MD; Gary David Markowitz, MD; Gary J Myers, MD; Linda J Reubens, RN CCRC; Diane Hust, MS RN CS; Lisa Augostino; Julie Babish Johnson, MSW; Erica Burnell, RN; Rosemary L Jensen; Emily Kushner, MA; Joan Merzbach, LMSW; Kelley Yost, PhD. University of Texas Southwestern Medical Center at Dallas, Parkland Health & Hospital System, and Children’s Medical Center Dallas (U10 HD40689, M01 RR633): Pablo J Sánchez, MD; Charles R Rosenfeld, MD; Walid A Salhab, MD; Roy J Heyne, MD; Sally S Adams, MS RN CPNP; James Allen, RRT; Laura Grau, RN; Alicia Guzman; Gaynelle Hensley, RN; Elizabeth T Heyne, PsyD PA-C; Melissa H Lepps, RN; Linda A Madden, RN CPNP; Melissa Martin, RN; Nancy A Miller, RN; Janet S Morgan, RN; Araceli Solis, RRT; Lizette E Torres, RN; Catherine Twell Boatman, MS CIMI; Diana M Vasil, RNC-NIC; Kerry Wilder, RN. University of Utah Medical Center, Intermountain Medical Center, LDS Hospital and Primary Children’s Medical Center (U10 HD53124, M01 RR64): Anna Bodnar, MD; Shawna Baker, RN; Karie Bird, RN; Jill Burnett, RN; Laura Cole, RN; Karen A Osborne, RN BSN CCRC; Cynthia Spencer, RNC; Mike Steffens, PhD; Kimberlee Weaver-Lewis, RN BSN; Karen Zanetti, RN. Wake Forest University, Baptist Medical Center, Brenner Children’s Hospital and Forsyth Medical Center (U10 HD40498, M01 RR7122): T Michael O’Shea, MD MPH; Robert G Dillard, MD; Lisa K Washburn, MD; Nancy J Peters, RN CCRP; Barbara G Jackson, RN BSN; Korinne Chiu, MA; Deborah Evans Allred, MA LPA; Donald J Goldstein, PhD; Raquel Halfond, MA; Carroll Peterson, MA; Ellen L Waldrep, MS; Cherrie D Welch, MD MPH; Melissa Whalen Morris, MA; Gail Wiley Hounshell, PhD. Wayne State University, Hutzel Women’s Hospital and Children’s Hospital of Michigan (U10 HD21385): Seetha Shankaran, MD; Beena G Sood, MD MS; Athina Pappas, MD; Rebecca Bara, RN BSN; Elizabeth Billian, RN MBA; Laura A Goldston, MA; Mary Johnson, RN BSN. Yale University, Yale-New Haven Children’s Hospital and Bridgeport Hospital (U10 HD27871, UL1 RR24139, M01 RR125): Richard A Ehrenkranz, MD; Vineet Bhandari, MD DM; Harris C Jacobs, MD; Pat Cervone, RN; Patricia Gettner, RN; Monica Konstantino, RN BSN; JoAnn Poulsen, RN; Janet Taft, RN BSN; Christine G Butler, MD; Nancy Close, PhD; Walter Gilliam, PhD; Sheila Greisman, RN; Elaine Romano, MSN; Joanne Williams, RN BSN. Retinopathy of Prematurity Adjudication Committee: Gary David Markowitz, MD, University of Rochester; Amy K Hutchinson, MD, Emory University; David K Wallace, MD MPH, Duke University; Sharon F Freedman, MD, Duke University.

    • Patient consent for publication Parental/guardian consent obtained.

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