Causes and timing of death in extremely premature infants from 2000 through 2011

doi:10.1056/NEJMoa1403489

. 2015 Jan 22;372(4):331-40.

doi: 10.1056/NEJMoa1403489.

Causes and timing of death in extremely premature infants from 2000 through 2011

Ravi M Patel¹, Sarah Kandefer, Michele C Walsh, Edward F Bell, Waldemar A Carlo, Abbot R Laptook, Pablo J Sánchez, Seetha Shankaran, Krisa P Van Meurs, M Bethany Ball, Ellen C Hale, Nancy S Newman, Abhik Das, Rosemary D Higgins, Barbara J Stoll; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

Collaborators, Affiliations

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network:
Alan H Jobe, Michael S Caplan, William Oh, Angelita M Hensman, Kristin Basso, Avroy A Fanaroff, William E Truog, Cheri Gauldin, Kurt Schibler, Edward F Donovan, Barbara Alexander, Kate Bridges, Cathy Grisby, Marcia Worley Mersmann, Holly L Mincey, Jody Hessling, Lenora Jackson, Kristin Kirker, Estelle E Fischer, Greg Muthig, Ronald N Goldberg, C Michael Cotten, Kathy J Auten, Kimberley A Fisher, Melody B Lohmeyer, Sandra Grimes, Katherine A Foy, David P Carlton, Linda L Wright, Elizabeth M McClure, Stephanie Wilson Archer, Brenda B Poindexter, James A Lemons, Dianne E Herron, Lucy C Miller, Leslie Dawn Wilson, Leif D Nelin, Sudarshan R Jadcherla, Christine A Fortney, Nehal A Parikh, Bronte Clifford, Amanda Daubenmire, Karen Leonhart, Melanie Stein, Erin Wishloff, Marie G Gantz, W Kenneth Poole, Dennis Wallace, Jeanette O'Donnell Auman, Margaret Crawford, Betty K Hastings, Carolyn M Petrie Huitema, Kristin M Zaterka-Baxter, David K Stevenson, Marian M Adams, Charles E Ahlfors, Andrew W Palmquist, Melinda S Proud, Robert D Stebbins, Ivan D Frantz 3rd, Brenda L MacKinnon, Ellen Nylen, Anne Furey, Namasivayam Ambalavanan, Monica V Collins, Shirley S Cosby, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Neil N Finer, Maynard R Rasmussen, Paul R Wozniak, Kathy Arnell, Renee Bridge, Clarence Demetrio, Wade Rich, Karen J Johnson, Donia B Campbell, John A Widness, Dan L Ellsbury, Tarah T Colaizy, Charles R Bauer, Shahnaz Duara, Ruth Everett-Thomas, Amy Mur Worth, Kristi L Watterberg, Lu-Ann Papile, Robin K Ohls, Conra Backstrom Lacy, Rebecca A Montman, Barbara Schmidt, Haresh Kirpalani, Sara B DeMauro, Aasma S Chaudhary, Soraya Abbasi, Toni Mancini, Dara Cucinotta, Carl T D'Angio, Dale L Phelps, Ronnie Guillet, Satyan Lakshminrusimha, Linda J Reubens, Erica Burnell, Mary Rowan, Cassandra A Horihan, Holly I M Wadkins, Ann Marie Reynolds, Karen Wynn, Sheldon B Korones, Tina Hudson, Charles R Rosenfeld, Walid A Salhab, Luc P Brion, P Jeannette Burchfield, Alicia Guzman, Gaynelle Hensley, Melissa H Leps, Susie Madison, Nancy A Miller, Diana M Vasil, Lizette E Torres, Lijun Chen, Jon E Tyson, Kathleen A Kennedy, Esther G Akpa, Patricia Ann Orekoya, Beverly Foley Harris, Claudia I Franco, Anna E Lis, Sara Martin, Georgia E McDavid, Patti L Pierce Tate, Maegan C Simmons, Roger G Faix, Bradley A Yoder, Karie Bird, Jill Burnett, Jennifer J Jensen, Karen A Osborne, Cynthia Spencer, Kimberlee Weaver-Lewis, T Michael O'Shea, Nancy J Peters, Rebecca Bara, Mary E Johnson, Kara Sawaya, Richard A Ehrenkranz, Harris Jacobs, Patricia Cervone, Patricia Gettner, Monica Konstantino, JoAnn Poulsen, Janet Taft

Affiliation

¹ From the Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta (R.M.P., E.C.H., B.J.S.); the Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, NC (S.K.); the Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland (M.C.W., N.S.N.), and Department of Pediatrics, Nationwide Children's Hospital-Ohio State University, Columbus (P.J.S.); the Department of Pediatrics, University of Iowa, Iowa City (E.F.B.); the Division of Neonatology, University of Alabama at Birmingham, Birmingham (W.A.C.); the Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI (A.R.L.); the Department of Pediatrics, Wayne State University School of Medicine, Detroit (S.S.); the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA (K.P.V.M., M.B.B.); and the Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville (A.D.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda (R.D.H.) - both in Maryland.

PMID: 25607427
PMCID: PMC4349362
DOI: 10.1056/NEJMoa1403489

Causes and timing of death in extremely premature infants from 2000 through 2011

Ravi M Patel et al. N Engl J Med. 2015.

. 2015 Jan 22;372(4):331-40.

doi: 10.1056/NEJMoa1403489.

Authors

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network:
Alan H Jobe, Michael S Caplan, William Oh, Angelita M Hensman, Kristin Basso, Avroy A Fanaroff, William E Truog, Cheri Gauldin, Kurt Schibler, Edward F Donovan, Barbara Alexander, Kate Bridges, Cathy Grisby, Marcia Worley Mersmann, Holly L Mincey, Jody Hessling, Lenora Jackson, Kristin Kirker, Estelle E Fischer, Greg Muthig, Ronald N Goldberg, C Michael Cotten, Kathy J Auten, Kimberley A Fisher, Melody B Lohmeyer, Sandra Grimes, Katherine A Foy, David P Carlton, Linda L Wright, Elizabeth M McClure, Stephanie Wilson Archer, Brenda B Poindexter, James A Lemons, Dianne E Herron, Lucy C Miller, Leslie Dawn Wilson, Leif D Nelin, Sudarshan R Jadcherla, Christine A Fortney, Nehal A Parikh, Bronte Clifford, Amanda Daubenmire, Karen Leonhart, Melanie Stein, Erin Wishloff, Marie G Gantz, W Kenneth Poole, Dennis Wallace, Jeanette O'Donnell Auman, Margaret Crawford, Betty K Hastings, Carolyn M Petrie Huitema, Kristin M Zaterka-Baxter, David K Stevenson, Marian M Adams, Charles E Ahlfors, Andrew W Palmquist, Melinda S Proud, Robert D Stebbins, Ivan D Frantz 3rd, Brenda L MacKinnon, Ellen Nylen, Anne Furey, Namasivayam Ambalavanan, Monica V Collins, Shirley S Cosby, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Neil N Finer, Maynard R Rasmussen, Paul R Wozniak, Kathy Arnell, Renee Bridge, Clarence Demetrio, Wade Rich, Karen J Johnson, Donia B Campbell, John A Widness, Dan L Ellsbury, Tarah T Colaizy, Charles R Bauer, Shahnaz Duara, Ruth Everett-Thomas, Amy Mur Worth, Kristi L Watterberg, Lu-Ann Papile, Robin K Ohls, Conra Backstrom Lacy, Rebecca A Montman, Barbara Schmidt, Haresh Kirpalani, Sara B DeMauro, Aasma S Chaudhary, Soraya Abbasi, Toni Mancini, Dara Cucinotta, Carl T D'Angio, Dale L Phelps, Ronnie Guillet, Satyan Lakshminrusimha, Linda J Reubens, Erica Burnell, Mary Rowan, Cassandra A Horihan, Holly I M Wadkins, Ann Marie Reynolds, Karen Wynn, Sheldon B Korones, Tina Hudson, Charles R Rosenfeld, Walid A Salhab, Luc P Brion, P Jeannette Burchfield, Alicia Guzman, Gaynelle Hensley, Melissa H Leps, Susie Madison, Nancy A Miller, Diana M Vasil, Lizette E Torres, Lijun Chen, Jon E Tyson, Kathleen A Kennedy, Esther G Akpa, Patricia Ann Orekoya, Beverly Foley Harris, Claudia I Franco, Anna E Lis, Sara Martin, Georgia E McDavid, Patti L Pierce Tate, Maegan C Simmons, Roger G Faix, Bradley A Yoder, Karie Bird, Jill Burnett, Jennifer J Jensen, Karen A Osborne, Cynthia Spencer, Kimberlee Weaver-Lewis, T Michael O'Shea, Nancy J Peters, Rebecca Bara, Mary E Johnson, Kara Sawaya, Richard A Ehrenkranz, Harris Jacobs, Patricia Cervone, Patricia Gettner, Monica Konstantino, JoAnn Poulsen, Janet Taft

Affiliation

¹ From the Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta (R.M.P., E.C.H., B.J.S.); the Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, NC (S.K.); the Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland (M.C.W., N.S.N.), and Department of Pediatrics, Nationwide Children's Hospital-Ohio State University, Columbus (P.J.S.); the Department of Pediatrics, University of Iowa, Iowa City (E.F.B.); the Division of Neonatology, University of Alabama at Birmingham, Birmingham (W.A.C.); the Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI (A.R.L.); the Department of Pediatrics, Wayne State University School of Medicine, Detroit (S.S.); the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA (K.P.V.M., M.B.B.); and the Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville (A.D.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda (R.D.H.) - both in Maryland.

PMID: 25607427
PMCID: PMC4349362
DOI: 10.1056/NEJMoa1403489

Abstract

Background: Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families.

Methods: We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences.

Results: The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days.

Conclusions: We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

**Figure 1. Proportionate Mortality for Major Causes of Death, According to Postnatal Age**
CNS denotes central nervous system.

See this image and copyright information in PMC

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References

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[1] Mathews TJ, MacDorman MF. Infant mortality statistics from the 2009 period linked birth/infant death data set. Hyattsville, MD: National Centers for Health Statistics; 2013. ( http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_08.pdf) - PubMed

[2] Mathews TJ, MacDorman MF. Infant mortality statistics from the 2009 period linked birth/infant death data set. Hyattsville, MD: National Centers for Health Statistics; 2013. ( http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_08.pdf) - PubMed

[3] Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–56. - PMC - PubMed

[4] Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–56. - PMC - PubMed

[5] Lemons JA, Bauer CR, Oh W, et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. Pediatrics. 2001;107(1):E1. - PubMed

[6] Lemons JA, Bauer CR, Oh W, et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. Pediatrics. 2001;107(1):E1. - PubMed

[7] Gould JB, Benitz WE, Liu H. Mortality and time to death in very low birth weight infants: California, 1987 and 1993. Pediatrics. 2000;105(3):E37. - PubMed

[8] Gould JB, Benitz WE, Liu H. Mortality and time to death in very low birth weight infants: California, 1987 and 1993. Pediatrics. 2000;105(3):E37. - PubMed

[9] Mohamed MA, Nada A, Aly H. Day-by-day postnatal survival in very low birth weight infants. Pediatrics. 2010;126(2):e360–e366. - PubMed

[10] Mohamed MA, Nada A, Aly H. Day-by-day postnatal survival in very low birth weight infants. Pediatrics. 2010;126(2):e360–e366. - PubMed

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Causes and timing of death in extremely premature infants from 2000 through 2011

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Causes and timing of death in extremely premature infants from 2000 through 2011

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