Use of term reference infants in assessing the developmental outcome of extremely preterm infants: lessons learned in a multicenter study
Authors: Green Charles E. , Tyson Jon E. , Heyne Roy J. , Hintz Susan R. , Vohr Betty R. , Bann Carla M. , Das Abhik , Bell Edward F. , Debsareea Sana Boral , Stephens Emily , Gantz Marie G. , Petrie Huitema Carolyn M. , Johnson Karen J. , Watterberg Kristi L. , Mosquera Ricardo , Peralta-Carcelen Myriam , Wilson-Costello Deanne E. , Colaizy Tarah T. , Maitre Nathalie L. , Merhar Stephanie L. , Adams-Chapman Ira , Fuller Janell , Hartley-McAndrew Michelle E. , Malcolm William F. , Winter Sarah , Duncan Andrea F. , Myer Gary J. , Kicklighter Stephen D. , Wyckoff Myra H. , DeMauro Sara B. , Hibbs Anna Maria , Stoll Barbara J. , Carlo Waldemar A. , Van Meurs Krisa P. , Rysavy Matthew A. , Patel Ravi M. , Sánchez Pablo J. , Laptook Abbot R. , Cotten C. Michael , D’Angio Carl T. , Walsh Michele C. ,   Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Polin Richard A. , Keszler Martin , Hensman Angelita M. , Vieira Elisa , Pierre Lucille St. , Burke Robert T. , Alksninis Barbara , Knoll Andrea , Keszler Mary L. , Leach Teresa M. , McGowan Elisabeth C. , Watson Victoria E. , Newman Nancy S. , Siner Bonnie S. , Roth Elizabeth , Williams Angelia , Poindexter Brenda B. , Schibler Kurt , Cahill K. Tanya E. , Grisby Cathy , Kirker Kristin , Stacey Sara , Wuertz Sandra , Goldberg Ronald N. , Goldstein Ricki F. , Ashley Patricia L. , Mago-Shah Deesha , Finkle Joanne , Fisher Kimberley A. , Gustafson Kathryn E. , Stone Caitlin , Laughon Matthew M. , Bernhardt Janice , Wereszczak Janice , Talbert Jennifer , Bentley Alexandra , Edwards Laura , Rhodes-Ryan Ginger , White Donna , Carlton David P. , Loggins Yvonne , Bottcher Diane , Carter Sheena L. , Kendrick-Allwood Salathiel , LaRossa Maureen Mulligan , Laursen Judith , Mackie Colleen , Sanders Amy , Smikle Gloria , Wineski Lynn , Bremer Andrew A. , Higgins Rosemary D. , Archer Stephanie Wilson , Khan Amir M. , Kennedy Kathleen A. , Duncan Andrea F. , Allain Elizabeth , Arldt-McAlister Julie , Boricha Fatima , Dempsey Allison G. , Garcia Carmen , Hall Donna J. , John Janice , Lillie M. Layne , Martin Karen , McDavid Georgia E. , McKee Shannon L. , Poe Michelle , Rennie Kimberly , Reddy Tina , Rodgers Shawna , Sperry Daniel K. , Wright Sharon L. , Nelin Leif D. , Slaughter Jonathan L. , Jadcherla Sudarshan R. , Timan Christopher , Luzader Patricia , Stein Melanie , Sullivan Rox Ann , Carey Helen , Burkhardt Stephanie , Nelin Mary Ann , Clark Erna , Small Kristi , McCool Jacqueline , Pietruszewski Lindsay , Purnell Jessica , Warnimont Kyrstin , Marzec Laura , Miller Bethany , Beckford Demi R. , Baugher Hallie , Levengood Katelyn , Batterson Nancy , Tonneman Jill , Hay Krystal , DeSantis Brittany , Wallace Dennis , Auman Jeanette O’ Donnell , Crawford Margaret , Gabrio Jenna , Newman Jamie E. , Parlberg Lindsay , Zaterka-Baxter Kristin M. , Stevenson David K. , Ball M. Bethany , Chock Valerie , Bahmani Dona , Bentley Barbara , DeAnda Maria Elena , DeBattista Anne M. , Earhart Beth , Huffman Lynne C. , Krueger Casey E. , Lucash Ryan E. , Taylor Heather , Weiss Hali E. , Ambalavanan Namasivayam , Bailey Kirstin J. , Biasini Fred J. , Chopko Stephanie A. , Collins Monica V. , Cosby Shirley S. , Domnanovich Kristy A. , Jno-Finn Chantel J. , Ladinsky Morissa , Moses Mary Beth , McNair Tara E. , Phillips Vivien A. , Preskitt Julie , Rector Richard V. , Stringer Kimberlly , Whitley Sally , Chapman Sheree York , Harmon Heidi M. , Johnson Karen J. , Schmelzel Mendi L. , Walker Jacky R. , Goeke Claire A. , Faruqui Sarah E. , Eastman Diane L. , Baack Michelle L. , Hogden Laurie A. , Henning Megan M. , Elenkiwich Chelsey , Broadbent Megan , Van Muyden Sarah , Ohls Robin K. , Lacy Conra Backstrom , Beauman Sandra Sundquist , Hanson Mary Ruffner , Lowe Jean R. , Kuan Elizabeth , Eichenwald Eric C. , Schmidt Barbara , Kirpalani Haresh , Abbasi Soraya , Chaudhary Aasma S. , Mancini Toni , Snyder Jonathan , Ziolkowski Kristina , Guillet Ronnie , Lakshminrusimha Satyan , Reynolds Anne Marie , Jensen Rosemary L. , Merzbach Joan , Zorn William , Farooq Osman , Myers Gary J. , Rowan Mary , Prinzing Diane , Bowman Melissa , Scorsone Ann Marie , Binion Kyle , Orme Constance , Sabaratnam Premini , Kent Alison , Jones Rachel , Boylin Elizabeth , Li Emily , Kachelmeyer Jennifer , McKee Kimberly G. , Coleman Kelly R. , Cavanaugh Brenna , Brion Luc P. , Vasil Diana M. , Adams Sally S. , Eubanks Frances , McDougald E. Rebecca , Pavageau Lara , Sepulveda Pollieanna , Guzman Alicia , Heyne Elizabeth , Lee Lizette E. , Vera Azucena , Waterbury Jillian , Boatman Cathy Twell , Yoder Bradley A. , Baserga Mariana , Faix Roger G. , Minton Stephen D. , Sheffield Mark J. , Rau Carrie A. , Baker Shawna , Christensen Susan , Cunningham Sean D. , Elmont Jennifer O. , Hall Becky , Jensen Erika R. , Loertscher Manndi C. , Marchant Trisha , McGrath Kandace M. , Mickelsen Hena G. , Morshedzadeh Galina , Parry D. Melody , Stout Kelly , Stuart Ashley L. , Weaver-Lewis Kimberlee 
Published: August 2023

Abstract
Objective
Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

Study design
Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

Results
We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56–2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001).
Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics.

Conclusion
Impairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers.

ClinicalTrials.gov ID
Term Reference (under the Generic Database Study): NCT00063063