Randomized Controlled Trial

. 2017 Jul:186:49-56.e1.

doi: 10.1016/j.jpeds.2017.01.057. Epub 2017 Mar 6.

Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort

Juliann M Di Fiore¹, Richard J Martin², Hong Li³, Nathan Morris³, Waldemar A Carlo⁴, Neil Finer⁵, Michele Walsh²; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health, and Human Development Neonatal Research Network

Collaborators, Affiliations

Collaborators

SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health, and Human Development Neonatal Research Network:
Alan H Jobe⁶, Michael S Caplan⁷, Richard A Polin⁸, Abbot R Laptook⁹, William Oh⁹, Angelita M Hensman⁹, Dan Gingras⁹, Susan Barnett⁹, Sarah Lillie⁹, Kim Francis⁹, Dawn Andrews⁹, Kristen Angela⁹, Avroy A Fanaroff¹⁰, Nancy S Newman¹⁰, Bonnie S Siner¹⁰, Arlene Zadell¹⁰, Kurt Schibler¹¹, Edward F Donovan¹¹, Kate Bridges¹¹, Barbara Alexander¹¹, Cathy Grisby¹¹, Marcia Worley Mersmann¹¹, Holly L Mincey¹¹, Jody Hessling¹¹, Ronald N Goldberg¹², C Michael Cotten¹², David K Wallace¹², Sharon F Freedman¹², Kathy J Auten¹², Kimberly A Fisher¹², Katherine A Foy¹², Barbara J Stoll¹³, Anthony J Piazza¹³, Susie Buchter¹³, David P Carlton¹³, Amy K Hutchinson¹³, Ellen C Hale¹³, Rosemary D Higgins¹⁴, Stephanie Wilson Archer¹⁴, Brenda B Poindexter¹⁵, James A Lemons¹⁵, Faithe Hamer¹⁵, Dianne E Herron¹⁵, Lucy C Miller¹⁵, Leslie D Wilson¹⁵, Mary Anne Berberich¹⁶, Carol J Blaisdell¹⁶, Dorothy B Gail¹⁶, James P Kiley¹⁶, Marie G Gantz¹⁷, Abhik Das¹⁷, Margaret M Crawford¹⁷, Betty K Hastings¹⁷, Amanda R Irene¹⁷, Jeanette O'Donnell Auman¹⁷, Carolyn Petrie Huitema¹⁷, James W Pickett 2nd¹⁷, Dennis Wallace¹⁷, Kristin M Zaterka-Baxter¹⁷, Krisa P Van Meurs¹⁸, David K Stevenson¹⁸, M Bethany Ball¹⁸, Melinda S Proud¹⁸, Ivan D Frantz 3rd¹⁹, John M Fiascone¹⁹, Anne Furey¹⁹, Brenda L MacKinnon¹⁹, Ellen Nylen¹⁹, Namasivayam Ambalavanan²⁰, Monica V Collins²⁰, Shirley S Cosby²⁰, Vivien A Phillips²⁰, Maynard R Rasmussen²¹, Paul R Wozniak²¹, Wade Rich²¹, Kathy Arnell²¹, Renee Bridge²¹, Clarence Demetrio²¹, Edward F Bell²², John A Widness²², Jonathan M Klein²², Karen J Johnson²², Shahnaz Duara²³, Ruth Everett-Thomas²³, Kristi L Watterberg²⁴, Robin K Ohls²⁴, Julie Rohr²⁴, Conra Backstrom Lacy²⁴, Dale L Phelps²⁵, Nirupama Laroia²⁵, Gary David Markowitz²⁵, Linda J Reubens²⁵, Erica Burnell²⁵, Pablo J Sánchez²⁶, Charles R Rosenfeld²⁶, Walid A Salhab²⁶, James Allen²⁶, Laura Grau²⁶, Alicia Guzman²⁶, Gaynelle Hensley²⁶, Melissa H Lepps²⁶, Melissa Martin²⁶, Nancy A Miller²⁶, Araceli Solis²⁶, Diana M Vasil²⁶, Kerry Wilder²⁶, Kathleen A Kennedy²⁷, Jon E Tyson²⁷, Brenda H Morris²⁷, Beverly Foley Harris²⁷, Anna E Lis²⁷, Sarah Martin²⁷, Georgia E McDavid²⁷, Patti L Tate²⁷, Sharon L Wright²⁷, Bradley A Yoder²⁸, Roger G Faix²⁸, Jill Burnett²⁸, Jennifer J Jensen²⁸, Karen A Osborne²⁸, Cynthia Spencer²⁸, Kimberlee Weaver-Lewis²⁸, T Michael O'Shea²⁹, Nancy J Peters²⁹, Seetha Shankaran³⁰, Beena G Sood³⁰, Rebecca Bara³⁰, Elizabeth Billian³⁰, Mary Johnson³⁰, Richard A Ehrenkranz³¹, Vivek Narendran³¹, Vineet Bhandari³¹, Harris C Jacobs³¹, Pat Cervone³¹, Patricia Gettner³¹, Monica Konstantino³¹, JoAnn Poulsen³¹, Janet Taft³¹

Affiliations

¹ Division of Neonatology, Rainbow Babies & Children's Hospital, Department of Pediatrics, Case Western Reserve University, Cleveland, OH. Electronic address: jmd3@case.edu.
² Division of Neonatology, Rainbow Babies & Children's Hospital, Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
³ Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, OH.
⁴ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
⁵ Department of Pediatrics, University of California, San Diego, CA.
⁶ University of Cincinnati.
⁷ University of Chicago, Pritzker School of Medicine.
⁸ Division of Neonatology, College of Physicians and Surgeons, Columbia University.
⁹ Alpert Medical School of Brown University, Women & Infants Hospital in Rhode Island.
¹⁰ Case Western Reserve University, Rainbow Babies & Children's Hospital.
¹¹ Cincinnati Children's Hospital Medical Center, University of Cincinnati Hospital, Good Samaritan Hospital.
¹² Duke University School of Medicine, University Hospital, Alamance Regional Medical Center, Durham Regional Hospital.
¹³ Emory University, Children's Healthcare of Atlanta, Grady Memorial Hospital, Emory Crawford Long Hospital.
¹⁴ Eunice Kennedy Shriver National Institute of Child Health and Human Development.
¹⁵ Indiana University, University Hospital, Methodist Hospital, Riley Hospital for Children, Wishard Health Services.
¹⁶ National Heart, Lung, and Blood Institute.
¹⁷ RTI International.
¹⁸ Stanford University, Lucile Packard Children's Hospital.
¹⁹ Tufts Medical Center, Floating Hospital for Children.
²⁰ University of Alabama at Birmingham Health System, The Children's Hospital of Alabama.
²¹ University of California-San Diego Medical Center, Sharp Mary Birch Hospital for Women & Newborns.
²² University of Iowa.
²³ University of Miami, Holtz Children's Hospital.
²⁴ University of New Mexico Health Sciences Center.
²⁵ University of Rochester Medical Center, Golisano Children's Hospital.
²⁶ University of Texas Southwestern Medical Center at Dallas, Parkland Health & Hospital System, Children's Medical Center.
²⁷ University of Texas Health Science Center at Houston, Medical School, Children's Memorial Hermann Hospital.
²⁸ University of Utah Medical Center, Intermountain Medical Center, LDS Hospital, Primary Children's Medical Center.
²⁹ Wake Forest University Baptist Medical Center, Brenner Children's Hospital, Forsyth Medical Center.
³⁰ Wayne State University, Hutzel Women's Hospital, Children's Hospital of Michigan.
³¹ Yale University, Yale New Haven Children's Hospital, Bridgeport Hospital.

PMID: 28279433
PMCID: PMC5484739
DOI: 10.1016/j.jpeds.2017.01.057

Randomized Controlled Trial

Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort

Juliann M Di Fiore et al. J Pediatr. 2017 Jul.

. 2017 Jul:186:49-56.e1.

doi: 10.1016/j.jpeds.2017.01.057. Epub 2017 Mar 6.

Authors

Collaborators

SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health, and Human Development Neonatal Research Network:
Alan H Jobe⁶, Michael S Caplan⁷, Richard A Polin⁸, Abbot R Laptook⁹, William Oh⁹, Angelita M Hensman⁹, Dan Gingras⁹, Susan Barnett⁹, Sarah Lillie⁹, Kim Francis⁹, Dawn Andrews⁹, Kristen Angela⁹, Avroy A Fanaroff¹⁰, Nancy S Newman¹⁰, Bonnie S Siner¹⁰, Arlene Zadell¹⁰, Kurt Schibler¹¹, Edward F Donovan¹¹, Kate Bridges¹¹, Barbara Alexander¹¹, Cathy Grisby¹¹, Marcia Worley Mersmann¹¹, Holly L Mincey¹¹, Jody Hessling¹¹, Ronald N Goldberg¹², C Michael Cotten¹², David K Wallace¹², Sharon F Freedman¹², Kathy J Auten¹², Kimberly A Fisher¹², Katherine A Foy¹², Barbara J Stoll¹³, Anthony J Piazza¹³, Susie Buchter¹³, David P Carlton¹³, Amy K Hutchinson¹³, Ellen C Hale¹³, Rosemary D Higgins¹⁴, Stephanie Wilson Archer¹⁴, Brenda B Poindexter¹⁵, James A Lemons¹⁵, Faithe Hamer¹⁵, Dianne E Herron¹⁵, Lucy C Miller¹⁵, Leslie D Wilson¹⁵, Mary Anne Berberich¹⁶, Carol J Blaisdell¹⁶, Dorothy B Gail¹⁶, James P Kiley¹⁶, Marie G Gantz¹⁷, Abhik Das¹⁷, Margaret M Crawford¹⁷, Betty K Hastings¹⁷, Amanda R Irene¹⁷, Jeanette O'Donnell Auman¹⁷, Carolyn Petrie Huitema¹⁷, James W Pickett 2nd¹⁷, Dennis Wallace¹⁷, Kristin M Zaterka-Baxter¹⁷, Krisa P Van Meurs¹⁸, David K Stevenson¹⁸, M Bethany Ball¹⁸, Melinda S Proud¹⁸, Ivan D Frantz 3rd¹⁹, John M Fiascone¹⁹, Anne Furey¹⁹, Brenda L MacKinnon¹⁹, Ellen Nylen¹⁹, Namasivayam Ambalavanan²⁰, Monica V Collins²⁰, Shirley S Cosby²⁰, Vivien A Phillips²⁰, Maynard R Rasmussen²¹, Paul R Wozniak²¹, Wade Rich²¹, Kathy Arnell²¹, Renee Bridge²¹, Clarence Demetrio²¹, Edward F Bell²², John A Widness²², Jonathan M Klein²², Karen J Johnson²², Shahnaz Duara²³, Ruth Everett-Thomas²³, Kristi L Watterberg²⁴, Robin K Ohls²⁴, Julie Rohr²⁴, Conra Backstrom Lacy²⁴, Dale L Phelps²⁵, Nirupama Laroia²⁵, Gary David Markowitz²⁵, Linda J Reubens²⁵, Erica Burnell²⁵, Pablo J Sánchez²⁶, Charles R Rosenfeld²⁶, Walid A Salhab²⁶, James Allen²⁶, Laura Grau²⁶, Alicia Guzman²⁶, Gaynelle Hensley²⁶, Melissa H Lepps²⁶, Melissa Martin²⁶, Nancy A Miller²⁶, Araceli Solis²⁶, Diana M Vasil²⁶, Kerry Wilder²⁶, Kathleen A Kennedy²⁷, Jon E Tyson²⁷, Brenda H Morris²⁷, Beverly Foley Harris²⁷, Anna E Lis²⁷, Sarah Martin²⁷, Georgia E McDavid²⁷, Patti L Tate²⁷, Sharon L Wright²⁷, Bradley A Yoder²⁸, Roger G Faix²⁸, Jill Burnett²⁸, Jennifer J Jensen²⁸, Karen A Osborne²⁸, Cynthia Spencer²⁸, Kimberlee Weaver-Lewis²⁸, T Michael O'Shea²⁹, Nancy J Peters²⁹, Seetha Shankaran³⁰, Beena G Sood³⁰, Rebecca Bara³⁰, Elizabeth Billian³⁰, Mary Johnson³⁰, Richard A Ehrenkranz³¹, Vivek Narendran³¹, Vineet Bhandari³¹, Harris C Jacobs³¹, Pat Cervone³¹, Patricia Gettner³¹, Monica Konstantino³¹, JoAnn Poulsen³¹, Janet Taft³¹

Affiliations

¹ Division of Neonatology, Rainbow Babies & Children's Hospital, Department of Pediatrics, Case Western Reserve University, Cleveland, OH. Electronic address: jmd3@case.edu.
² Division of Neonatology, Rainbow Babies & Children's Hospital, Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
³ Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, OH.
⁴ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
⁵ Department of Pediatrics, University of California, San Diego, CA.
⁶ University of Cincinnati.
⁷ University of Chicago, Pritzker School of Medicine.
⁸ Division of Neonatology, College of Physicians and Surgeons, Columbia University.
⁹ Alpert Medical School of Brown University, Women & Infants Hospital in Rhode Island.
¹⁰ Case Western Reserve University, Rainbow Babies & Children's Hospital.
¹¹ Cincinnati Children's Hospital Medical Center, University of Cincinnati Hospital, Good Samaritan Hospital.
¹² Duke University School of Medicine, University Hospital, Alamance Regional Medical Center, Durham Regional Hospital.
¹³ Emory University, Children's Healthcare of Atlanta, Grady Memorial Hospital, Emory Crawford Long Hospital.
¹⁴ Eunice Kennedy Shriver National Institute of Child Health and Human Development.
¹⁵ Indiana University, University Hospital, Methodist Hospital, Riley Hospital for Children, Wishard Health Services.
¹⁶ National Heart, Lung, and Blood Institute.
¹⁷ RTI International.
¹⁸ Stanford University, Lucile Packard Children's Hospital.
¹⁹ Tufts Medical Center, Floating Hospital for Children.
²⁰ University of Alabama at Birmingham Health System, The Children's Hospital of Alabama.
²¹ University of California-San Diego Medical Center, Sharp Mary Birch Hospital for Women & Newborns.
²² University of Iowa.
²³ University of Miami, Holtz Children's Hospital.
²⁴ University of New Mexico Health Sciences Center.
²⁵ University of Rochester Medical Center, Golisano Children's Hospital.
²⁶ University of Texas Southwestern Medical Center at Dallas, Parkland Health & Hospital System, Children's Medical Center.
²⁷ University of Texas Health Science Center at Houston, Medical School, Children's Memorial Hermann Hospital.
²⁸ University of Utah Medical Center, Intermountain Medical Center, LDS Hospital, Primary Children's Medical Center.
²⁹ Wake Forest University Baptist Medical Center, Brenner Children's Hospital, Forsyth Medical Center.
³⁰ Wayne State University, Hutzel Women's Hospital, Children's Hospital of Michigan.
³¹ Yale University, Yale New Haven Children's Hospital, Bridgeport Hospital.

PMID: 28279433
PMCID: PMC5484739
DOI: 10.1016/j.jpeds.2017.01.057

Abstract

Objective: To characterize actual achieved patterns of oxygenation in infants born appropriate vs small for gestational age (SGA) randomized to a lower (85-89%) vs higher (91%-95%) oxygen saturation target in the Surfactant Positive Pressure and Oxygen Trial. To determine the association between achieved oxygen saturation levels and survival in infants born appropriate vs SGA enrolled in the Surfactant Positive Pressure and Oxygen Trial.

Study design: Median oxygen saturation and intermittent hypoxemia events (<80%, 20 seconds-5 minutes) were documented in 1054 infants of 24^0/7-27^6/7 weeks of gestation while receiving supplemental oxygen during the first 3 days of life.

Results: Lower target infants who were small for gestational age had the lowest oxygen saturation and highest incidence of intermittent hypoxemia during the first 3 days of life. The lowest quartile of oxygen saturation (≤92%) during the first 3 days of life was associated with lower 90-day survival for both infants born appropriate and SGA. An increased incidence of intermittent hypoxemia events during the first 3 days of life was associated with lower 90-day survival only in infants born SGA.

Conclusion: Lower achieved oxygen saturation during the first 3 days of life was associated with lower 90-day survival in extremely preterm infants. Infants born SGA had enhanced vulnerability to lower oxygen saturation targets as evidenced by lower achieved oxygen saturation and an association between increased intermittent hypoxemia events and lower survival.

Trial registration: ClinicalTrials.gov: NCT00233324.

Keywords: hypoxia; intermittent hypoxemia; oxygen saturation; small for gestational age; supplemental oxygen.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure 1**
online. Daily Patterns of oxygenation during the first month of life in AGA and SGA infants enrolled in SUPPORT and randomized to lower (85–89%) or higher (91–95%) oxygen saturation targets including A) Median oxygen saturation, B) Time with hypoxemia (<80%), C) shorter intermittent hypoxemia events (IH) of 20s–1min and D) longer IH of 1–5min. (mean +/− SEM)

**Figure 2**
Kaplan Meier survival analysis in AGA and SGA infants based on actual achieved patterns of oxygenation during the first three days of life. Group stratifications were based on quartile cutoffs with the lowest quartile compared with all others for median oxygen saturation and the highest quartile compared with all others for time <80% and frequency of IH events. A) Median oxygen saturation, B) % time with hypoxemia (<80%) C) Short IH events of 20sec to 1 minute in duration and D) Long IH events of 1 to 5 minutes in duration.

See this image and copyright information in PMC

Comment in

Oxygen Targeting in Infants Born Extremely Preterm Who Are Small for Gestational Age: A Need for Heightened Vigilance.
Schmidt B, Whyte RK, Roberts RS. Schmidt B, et al. J Pediatr. 2017 Jul;186:9-10. doi: 10.1016/j.jpeds.2017.02.071. Epub 2017 Mar 18. J Pediatr. 2017. PMID: 28318530 No abstract available.
Is more oxygen better for our smallest babies, or maybe just our smallest babies?
Wright CJ. Wright CJ. J Pediatr. 2017 Jul;186:3. doi: 10.1016/j.jpeds.2017.05.012. J Pediatr. 2017. PMID: 28648280 No abstract available.

References

1. Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, et al. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362:1959–1969. - PMC - PubMed
1. Stenson B, Brocklehurst P, Tarnow-Mordi W. Increased 36-week survival with high oxygen saturation target in extremely preterm infants. N Engl J Med. 2011;364:1680–1682. - PubMed
1. Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, et al. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010;157:69–73. - PMC - PubMed
1. Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, et al. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015;314:595–603. - PubMed
1. Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA, et al. Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. J Pediatr. 2012;161:1047–1052. - PMC - PubMed

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Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort

Collaborators

Affiliations

Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical