Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula
Authors: Tarah T. Colaizy, Brenda B. Poindexter, Scott A. McDonald, Edward F. Bell, Waldemar A. Carlo, Susan J. Carlson, Sara B. DeMauro, Kathleen A. Kennedy, Leif D. Nelin, Pablo J. Sánchez, Betty R. Vohr, Karen J. Johnson, Dianne E. Herron, Abhik Das, Margaret M. Crawford, Michele C. Walsh, Rosemary D. Higgins, Barbara J. Stoll, Richard A Polin, Martin Keszler, Angelita M Hensman, Elisa Viera, Lucille St. Pierre, Robert T Burke, Barbara Alksninis, Andrea Knoll, Mary L Keszler, Teresa M Leach, Elisabeth C McGowan, Victoria E Watson, Nancy S Newman, Bonny S Siner, Angelia Williams, Elizabeth Roth, William E Truog, Eugenia K Pallotto, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Scott, Lisa Gaetano, C Michael Cotten, Ronald N Goldberg, Ricki F Goldstein, Patricia L Ashley, Deena Mago-Shah, Joanne Finkle, Kathryn E Gustafson, Carl L Bose, Janice Bernhardt, Gennie Bose, Janice Wereszczak, Diane Warner, Jennifer Talbert, Ravi Patel, David P Carlton, Barbara J Stoll, Yvonne Loggins, Diane Bottcher, Sheena L Carter, Ellen C Hale, Salathiel Kendrick-Allwood, Judith Laursen, Maureen Mulligan LaRossa, Colleen Mackie, Amy Sanders, Gloria Smile, Lynn Wineski, Andrew A Bremer, Stephanie Wilson Archer, Lu Ann Papile, Carolyn Lytle, Lucy Smiley, Leslie Dawn Wilson, Donna Watkins, Susan Gunn, Jeff Joyce, Jon E Tyson, Amir M Khan, Ricardo A Mosquera, Emily Stephens, Elizabeth Allain, Julie Arldt-McAlister, Fatima Boricha, Katrina Burson, Allison G Dempsey, Carmen Garcia, Donna J Hall, Janice John, Patrick M Jones, M Layne Lillie, Karen Martin, Sara C Martin, Carrie M Mason, Georgia E McDavid, Shannon L McKee, Michelle Poe, Kimberly Rennie, Tina Reddy, Shawna Rodgers, Saba Khan Siddiki, Daniel Sperry, Patti L Pierce Tate, Sharon L Wright, Jonathan L Slaughter, Christopher Timan, Keith O Yeates, Patricia Luzader, Nancy Batterson, Hallie Baugher, Demi R Beckford, Stephanie Burkhardt, Helen Carey, Michelle Chao, Courtney Cira, Erna Clark, Brittany DeSantis, Erin Fearns, Christine A Fortney, Aubrey Fowler, Juie Gutentag, Jennifer L Grothause, Cole D Hague, Sarah A Keim, Katelyn Levengood, Laura Marzec, Jacqueline McCool, Bethany Miller, Pamela Morehead, Mary Ann Nelin, Julia Newton, Courtney Park, Lindsay Pietruszewski, Jessica Purnell, Julie C Shadd, Kristi L Small, Melanie Stein, Margaret Sullivan, Rox Ann Sullivan, Kyrstin Warnimont, Lina Yossef-Salameh, Carla M Bann, Marie G Gantz, Dennis Wallace, Jeanette O’Donnell Auman, Annie Bayard, Jenna Gabrio, David Leblond, Jamie E Newman, Lindsay Parlberg, Carolyn M Petrie Huitema, Kristin M Zaterka-Baxter, Monica V Collins, Shirley S Cosby, Kirstin J Bailey, Fred J Biasini, Stephanie A Chopko, Kristy A Domnanovich, Chantel J Jno-Finn, Morissa Ladinsky, Mary Beth Moses, Tara E McNair, Vivien A Phillips, Julie Preskitt, Richard V Rector, Kimberlly Stringer, Sally Whitley, Sheree York Chapman, John Widness, Jane E Brumbaugh, Mendi L Schmelzel, Jacky R Walker, Claire A Goeke, Diane L Eastman, Michelle L Baack, Megan M Henning, Chelsey Elenkiwich, Megan Broadbent, Sarah Van Muyden, Kristi L Watterberg, Conra Backstrom Lacy, Carol Hartenberger, Sandra Sundquist Beauman, Mary Hanson, Jean R Lowe, Elizabeth Kuan, Eric C Eichenwald, Haresh Kirpalani, Aasma S Chaudhary, Toni Mancini, Judy C Berenbaum, Marsha Gerdes, Hallam Hurt, Jonathan Snyder, Saritha Vangala, Kristina Ziolkowski, Ronnie Guillet, Gary J Myers, Satyan Lakshminrusimha, Holly I M Wadkins, Michael G Sacilowski, Melissa F Carmen, Rosemary L Jensen, Joan Merzbach, William Zorn, Osman Farooq, Ashley Williams, Stephanie Guilford, Kelley Yost, Melissa Bowman, Ann Marie Scorsone, Caitlin Fallone, Kyle Binion, Constance Orme, Premini Sabaratnam, Alison Kent, Rachel Jones, Elizabeth Boylin, Daisy Roches, Emily Lillie, Jennifer Kachelmeyer, Kimberly G McKee, Kelly R Coleman, Karen Wynn, Michelle Hartley-McAndrew, Nirupama Laroia, Jeffrey Meyers, Luc P Brion, Diana M Vasil, Sally S Adams, Lijun Chen, Maria M De Leon, Frances Eubanks, Rebecca McDougald, Lara Pavageau, Pollieanna Sepulveda, Alicia Guzman, Elizabeth Heyne, Linda A Madden, Lizette E Lee, Kristine Tolentino-Plata, Cathy Twell Boatman, Azucena Vera, Jillian Waterbury, Amy Atok, Denise Weuhausen, Elizabeth Brammer, Cheryl Laird, Seetha Shankaran, Athina Pappas, Beena G Sood, Melissa 44958, Prashant Agarwal, Sanjay Chawla, Rebecca Bara, Kirsten Childs, Eunice Woldt, Laura Goldston, Stephanie A Wiggins, Mary K Christensen, Diane F White, Namisavayam Ambalavanan, Myra H. Wyckoff, Carl T. D’Angio, George W. Bugg, Robin K. Ohls, Anne Marie Reynolds, Gregory M. Sokol, Abbot R. Laptook, Steven L. Olsen, Jessica R. White, Sudarshan R. Jadcherla, Monika Bajaj, Prabhu S. Parimi, Barbara Schmidt, Matthew M. Laughon, John Barks, Kimberley A. Fisher, Anna Maria Hibbs, Myriam Peralta-Carcelen, Noah Cook, Roy J. Heyne, Brenna Cavanaugh, Ira Adams-Chapman, Janell Fuller, Michelle E. Hartley-McAndrew, Heidi M. Harmon, Andrea F. Duncan, Abbey C. Hines, Howard W. Kilbride, Laurie A. Richards, Nathalie L. Maitre, Girija Natarajan, Andrea N. Trembath, Martha D. Carlson, William F. Malcolm, Deanne E. Wilson-Costello
Journal: JAMA (2024)

Importance Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months’ corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days’ gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months’ corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months’ corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent’s race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months’ corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, −0.77 [95% CI, −3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, −1% [95% CI, −4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, −5% [95% CI, −9% to −2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months’ corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration ClinicalTrials.gov Identifier: NCT01534481