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Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis

Abstract

Objective:

To determine if extremely low birth weight infants with surgical necrotizing enterocolitis have a higher risk of death or neurodevelopmental impairment and neurodevelopmental impairment among survivors (secondary outcome) at 18–22 months corrected age compared with infants with spontaneous intestinal perforation and infants without necrotizing enterocolitis or spontaneous intestinal perforation.

Study Design:

Retrospective analysis of the Neonatal Research Network very low birth weight registry, evaluating extremely low birth weight infants born between 2000 and 2005. The study infants were designated into three groups: (1) spontaneous intestinal perforation without necrotizing enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3) neither spontaneous intestinal perforation nor necrotizing enterocolitis. Multivariate logistic regression analysis was performed to evaluate the association between the clinical group and death or neurodevelopmental impairment, controlling for multiple confounding factors including center.

Result:

Infants with surgical necrotizing enterocolitis had the highest rate of death before hospital discharge (53.5%) and death or neurodevelopmental impairment (82.3%) compared with infants in the spontaneous intestinal perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar results were observed for neurodevelopmental impairment among survivors. On logistic regression analysis, both spontaneous intestinal perforation and surgical necrotizing enterocolitis were associated with increased risk of death or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2 and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively).

Conclusion:

Spontaneous intestinal perforation and surgical necrotizing enterocolitis are associated with a similar increase in the risk of death or neurodevelopmental impairment and neurodevelopmental impairment among extremely low birth weight survivors at 18–22 months corrected age.

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Abbreviations

ELBW:

extremely low birth weight

MDI:

mental developmental index

NEC:

necrotizing enterocolitis

NDI:

neurodevelopmental impairment

NRN:

Neonatal Research Network

PDI:

psychomotor developmental index

SIP:

spontaneous intestinal perforation

SurgNEC:

surgical necrotizing enterocolitis

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Acknowledgements

The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provided grant support for the Neonatal Research Network’s Generic Database Study and Follow-up Study. Data collected at participating sites of the NICHD Neonatal Research Network (NRN) were transmitted to RTI International, the data coordinating center (DCC) for the network, which stored, managed and analyzed the data for this study. On behalf of the NRN, Drs Abhik Das (DCC Principal Investigator) and Shampa Saha (DCC Statistician) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. We are indebted to our medical and nursing colleagues. 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 (2000–2006); Michael S Caplan, MD, University of Chicago, Pritzker School of Medicine (2006-present). Alpert Medical School of Brown University and Women & Infants Hospital of Rhode Island (U10 HD27904)—Betty R Vohr, MD; Bonnie E Stephens, MD; Angelita M Hensman, RN BSN; Barbara Alksninis, PNP; Bill Cashore, MD; Theresa M Leach, MEd CAES; Martha R Leonard, BA BS; Kalida Mehta; Lucy Noel; Suzy Ventura; Victoria E Watson, MS CAS. Case Western Reserve University, Rainbow Babies & Children's Hospital (U10 HD21364, M01 RR80)—Avroy A Fanaroff, MD; Deanne E Wilson-Costello, MD; Nancy S Newman, RN; Bonnie S Siner, RN. Cincinnati Children's Hospital Medical Center, University of Cincinnati Hospital and Good Samaritan Hospital (U10 HD27853, M01 RR8084)–Kurt Schibler, MD; Edward F Donovan, MD; Jean J Steichen, MD; Kimberly Yolton, PhD; Kate Bridges, MD; Barbara Alexander, RN; Teresa L Gratton, PA; Cathy Grisby, BSN CCRC; Marcia Worley Mersmann, RN CCRC; Holly L. Mincey, RN BSN; Jody Hessling, RN. Duke University School of Medicine, University Hospital and Durham Regional Hospital (U10 HD40492, M01 RR30)—Ronald N Goldberg, MD; Ricki F Goldstein, MD; C Michael Cotten, MD MHS; Kimberley A Fisher, PhD FNP-BC IBCLC; Kathryn E Gustafson, PhD; Melody B Lohmeyer, RN MSN. Emory University, Children’s Healthcare of Atlanta, Grady Memorial Hospital and Emory Crawford Long Hospital (U10 HD27851, M01 RR39)—David P Carlton, MD; Ira Adams-Chapman, MD; Linda Black; Ann M Blackwelder, RNC BS MS; Sheena Carter, PhD; Elisabeth Dinkins, PNP; Ellen C Hale, RN BS CCRC; Judson Miller, MD; Maureen Mulligan LaRossa, RN; Irma Seabrook, RRT; Gloria V Smikle, PNP MSN. Eunice Kennedy Shriver National Institute of Child Health and Human Development—Linda L Wright, MD; Elizabeth M McClure, MEd; Stephanie 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; James A Lemons, MD; Ann B Cook, MS; Anna M Dusick, MD FAAP; Dianne E Herron, RN; Lucy C Miller, RN BSN CCRC; Heike M Minnich, PsyD HSPP; Leslie Richard, RN; Leslie Dawn Wilson, BSN CCRC; Faithe Hamer, BS. RTI International (U10 HD36790)—W Kenneth Poole, PhD; Betty K Hastings; Elizabeth M McClure, MEd; Margaret Cunningham, BS; Jeanette O’Donnell Auman, BS; Jamie E Newman, PhD MPH; Carolyn Petrie Huitema, MS; Kristin M Zaterka-Baxter, RN BSN. Stanford University, El Camino Hospital and Lucile Packard Children's Hospital (U10 HD27880, M01 RR70)—Krisa P Van Meurs, MD; David K Stevenson, MD; Marian M Adams, MD; M Bethany Ball, BS CCRC, Joan M Baran, PhD; Ginger K Brudos, PhD; Anne M DeBattista, RN PNP; Dharshi Sivakumar, MD MRCP; Nicholas H St. John, PhD. University of Alabama at Birmingham Health System and Children’s Hospital of Alabama (U10 HD34216, M01 RR32)—Waldemar A Carlo, MD; Namasivayam Ambalavanan, MD; Myriam Peralta-Carcelen, MD MPH; Amanda Soong, MD; Monica V Collins, RN BSN MaEd; Shirley S Cosby, RN BSN; Kirstin J Bailey, PhD; Fred J Biasini, PhD; Stephanie A Chopko, PhD; Mary Beth Moses, PT MS PCS; Kathleen G Nelson, MD; Vivien A Phillips, RN BSN; Julie Preskitt, MSOT MPH; Richard V Rector, PhD; Sally Whitley, MA OTR-L FAOTA. University of California—San Diego Medical Center and Sharp Mary Birch Hospital for Women and Newborns (U10 HD40461)—Neil N Finer, MD; Paul R Wozniak, MD; Maynard R Rasmussen, MD; Yvonne E Vaucher, MD MPH; Kathy Arnell, RNC; Clarence Demetrio, RN; Chris Henderson, RCP CRTT; Wade Rich, BSHS RRT; Rene Barbieri-Welge; Ayala Ben-Tall; Martha G Fuller, RN MSN; Elaine Ito; Meghan Lukasik; Deborah Pontillo; Donna Posin, OTR/L MPA; Cheryl Runyan; James Wilkes. University of Miami Holtz Children's Hospital (U10 HD21397, M01 RR16587)—Shahnaz Duara, MD; Charles R Bauer, MD; Ruth Everett-Thomas, RN MSN; Mary Allison, RN; Maria Calejo, MS; Alexis N Diaz, BA; Silvia M Frade Eguaras, MA; Yamiley C Gideon, BA; Kasey Hamlin-Smith, PhD; Sylvia Hiriart-Fajardo, MD; Lisa Jean-Gilles, BA; Ann Londono, MD; Elaine O Mathews, RN. University of New Mexico Health Sciences Center (U10 HD53089, M01 RR997)—Kristi L Watterberg, MD; Lu-Ann Papile, MD; Janell Fuller, MD Conra Backstrom Lacy, RN; Debra V Long, BSN; Jean Lowe, PhD; Rebecca Montman, BSN; Julie Rohr, MSN RNC CNS. University of Rochester Medical Center, Golisano Children's Hospital (U10 HD40521, M01 RR44)—Dale L Phelps, MD; Gary J Myers, MD; Linda J Reubens, RN CCRC; Erica Burnell, RN; Julie Babish Johnson, MSW; Diane Hust, MS RN CS; Rosemary L Jensen; Emily Kushner, MA; Joan Merzbach, LMSW; Kelley Yost, PhD. University of Tennessee (U10 HD21415)—Sheldon B Korones, MD; Henrietta S Bada, MD; Tina Hudson, RN BSN; Marilyn Williams, LCSW; Kimberly Yolton, 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; R Sue Broyles, MD; Roy J Heyne, MD; Sally S Adams, MS RN CPNP; Cristin Dooley, MS LSSP; Gaynelle Hensley, RN; Elizabeth Heyne, PA-C; Jackie F Hickman, RN; Linda A Madden, BSN RN CPNP; Susie Madison, RN; Nancy A Miller, RN; Janet S Morgan, RN; Alicia Guzman; Catherine Twell Boatman, MS. University of Texas Health Science Center at Houston Medical School, Children's Memorial Hermann Hospital and Lyndon Baines Johnson General Hospital/Harris County Hospital District (U10 HD21373)—Kathleen A Kennedy, MD MPH; Jon E Tyson, MD MPH; Pamela J Bradt, MD MPH; Patricia W Evans, MD; Esther G Akpa, RN BSN; Nora Alaniz, BS; Patty A Cluff, RN; Susan Dieterich, PhD; Claudia I Franco, RNC MSN; Anna E Lis, RN BSN; Terri Major-Kincade, MD MPH; Georgia E McDavid, RN; Brenda H Morris, MD; Maegan C Simmons, RN; Patti Pierce Tate, RCP; Stacey Reddoch, BA; Laura L Whitely, MD; Sharon Wright, MT. Wake Forest University, Baptist Medical Center, Forsyth Medical Center, and Brenner Children’s Hospital (GCRC M01 RR7122, U10 HD40498)—T Michael O’Shea, MD MPH; Robert G Dillard, MD; Nancy J Peters, RN CCRP; Korinne Chiu, MA; Deborah Evans Allred, MA LPA; Donald J Goldstein, PhD; Raquel Halfond, MA; Barbara G Jackson, RN BSN; Carroll Peterson, MA; Ellen L Waldrep, MS; Melissa Whalen Morris, MA; Gail Wiley Hounshell, PhD. Wayne State University, Hutzel Women’s Hospital and Children’s Hospital of Michigan (U10 HD21385)—Virginia Delaney-Black, MD MPH; Yvette R Johnson, MD MPH; Rebecca Bara, RN BSN; Geraldine Muran, RN BSN; Deborah Kennedy, RN BSN; Laura Goldston, MA. Yale University Yale-New Haven Children’s Hospital (U10 HD27871, M01 RR125, M01 RR6022, UL1 RR24139)–Richard A Ehrenkranz, MD; Patricia Gettner, RN; Monica Konstantino, RN BSN; JoAnn Poulsen, RN; Janet Taft, RN BSN; Nancy Close, PhD; Elaine Romano, MSN; Joanne Poulsen, RN.

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Correspondence to R Wadhawan.

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RW conceptualized the study, performed data analysis and interpretation, drafted and approved the final manuscript. WO conceptualized the study, guided data analysis and interpretation, edited and approved the final manuscript. SH provided input into the study design and data interpretation, edited and approved the final manuscript. MLB provided input into the study design and data interpretation, edited and approved the final manuscript. AD provided input into the study design and data interpretation, edited and approved the final manuscript. EFB provided input into data interpretation and presentation, edited and approved the final manuscript. SS performed statistical analyses, provided input into data analysis and interpretation, edited and approved the final manuscript. ARL provided input into data interpretation and presentation, edited and approved the final manuscript. SS provided input into data interpretation and presentation, edited and approved the final manuscript. BJS provided input into data interpretation and presentation, edited and approved the final manuscript. MCW provided input into data interpretation and presentation, edited and approved the final manuscript. RDH provided input into data interpretation and presentation, edited and approved the final manuscript.

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Wadhawan, R., Oh, W., Hintz, S. et al. Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis. J Perinatol 34, 64–70 (2014). https://doi.org/10.1038/jp.2013.128

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