Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula
Author:
Colaizy Tarah T.1, Poindexter Brenda B.2, McDonald Scott A.3, Bell Edward F.1, Carlo Waldemar A.4, Carlson Susan J.1, DeMauro Sara B.5, Kennedy Kathleen A.6, Nelin Leif D.7, Sánchez Pablo J.7, Vohr Betty R.8, Johnson Karen J.1, Herron Dianne E.9, Das Abhik10, Crawford Margaret M.10, Walsh Michele C.11, Higgins Rosemary D.1112, Stoll Barbara J.26, Polin Richard A13, Keszler Martin13, Hensman Angelita M13, Viera Elisa13, St. Pierre Lucille13, Burke Robert T13, Alksninis Barbara13, Knoll Andrea13, Keszler Mary L13, Leach Teresa M13, McGowan Elisabeth C13, Watson Victoria E13, Newman Nancy S13, Siner Bonny S13, Williams Angelia13, Roth Elizabeth13, Truog William E13, Pallotto Eugenia K13, Gauldin Cheri13, Holmes Anne13, Johnson Kathy13, Scott Allison13, Gaetano Lisa13, Cotten C Michael13, Goldberg Ronald N13, Goldstein Ricki F13, Ashley Patricia L13, Mago-Shah Deena13, Finkle Joanne13, Gustafson Kathryn E13, Bose Carl L13, Bernhardt Janice13, Bose Gennie13, Wereszczak Janice13, Warner Diane13, Talbert Jennifer13, Patel Ravi13, Carlton David P13, Stoll Barbara J13, Loggins Yvonne13, Bottcher Diane13, Carter Sheena L13, Hale Ellen C13, Kendrick-Allwood Salathiel13, Laursen Judith13, Mulligan LaRossa Maureen13, Mackie Colleen13, Sanders Amy13, Smile Gloria13, Wineski Lynn13, Bremer Andrew A13, Wilson Archer Stephanie13, Papile Lu Ann13, Lytle Carolyn13, Smiley Lucy13, Wilson Leslie Dawn13, Watkins Donna13, Gunn Susan13, Joyce Jeff13, Tyson Jon E13, Khan Amir M13, Mosquera Ricardo A13, Stephens Emily13, Allain Elizabeth13, Arldt-McAlister Julie13, Boricha Fatima13, Burson Katrina13, Dempsey Allison G13, Garcia Carmen13, Hall Donna J13, John Janice13, Jones Patrick M13, Lillie M Layne13, Martin Karen13, Martin Sara C13, Mason Carrie M13, McDavid Georgia E13, McKee Shannon L13, Poe Michelle13, Rennie Kimberly13, Reddy Tina13, Rodgers Shawna13, Khan Siddiki Saba13, Sperry Daniel13, Pierce Tate Patti L13, Wright Sharon L13, Slaughter Jonathan L13, Timan Christopher13, Yeates Keith O13, Luzader Patricia13, Batterson Nancy13, Baugher Hallie13, Beckford Demi R13, Burkhardt Stephanie13, Carey Helen13, Chao Michelle13, Cira Courtney13, Clark Erna13, DeSantis Brittany13, Fearns Erin13, Fortney Christine A13, Fowler Aubrey13, Gutentag Juie13, Grothause Jennifer L13, Hague Cole D13, Keim Sarah A13, Levengood Katelyn13, Marzec Laura13, McCool Jacqueline13, Miller Bethany13, Morehead Pamela13, Nelin Mary Ann13, Newton Julia13, Park Courtney13, Pietruszewski Lindsay13, Purnell Jessica13, Shadd Julie C13, Small Kristi L13, Stein Melanie13, Sullivan Margaret13, Sullivan Rox Ann13, Warnimont Kyrstin13, Yossef-Salameh Lina13, Bann Carla M13, Gantz Marie G13, Wallace Dennis13, O’Donnell Auman Jeanette13, Bayard Annie13, Gabrio Jenna13, Leblond David13, Newman Jamie E13, Parlberg Lindsay13, Petrie Huitema Carolyn M13, Zaterka-Baxter Kristin M13, Collins Monica V13, Cosby Shirley S13, Bailey Kirstin J13, Biasini Fred J13, Chopko Stephanie A13, Domnanovich Kristy A13, Jno-Finn Chantel J13, Ladinsky Morissa13, Moses Mary Beth13, McNair Tara E13, Phillips Vivien A13, Preskitt Julie13, Rector Richard V13, Stringer Kimberlly13, Whitley Sally13, York Chapman Sheree13, Widness John13, Brumbaugh Jane E13, Schmelzel Mendi L13, Walker Jacky R13, Goeke Claire A13, Eastman Diane L13, Baack Michelle L13, Henning Megan M13, Elenkiwich Chelsey13, Broadbent Megan13, Van Muyden Sarah13, Watterberg Kristi L13, Backstrom Lacy Conra13, Hartenberger Carol13, Sundquist Beauman Sandra13, Hanson Mary13, Lowe Jean R13, Kuan Elizabeth13, Eichenwald Eric C13, Kirpalani Haresh13, Chaudhary Aasma S13, Mancini Toni13, Berenbaum Judy C13, Gerdes Marsha13, Hurt Hallam13, Snyder Jonathan13, Vangala Saritha13, Ziolkowski Kristina13, Guillet Ronnie13, Myers Gary J13, Lakshminrusimha Satyan13, Wadkins Holly I M13, Sacilowski Michael G13, Carmen Melissa F13, Jensen Rosemary L13, Merzbach Joan13, Zorn William13, Farooq Osman13, Williams Ashley13, Guilford Stephanie13, Yost Kelley13, Bowman Melissa13, Scorsone Ann Marie13, Fallone Caitlin13, Binion Kyle13, Orme Constance13, Sabaratnam Premini13, Kent Alison13, Jones Rachel13, Boylin Elizabeth13, Roches Daisy13, Lillie Emily13, Kachelmeyer Jennifer13, McKee Kimberly G13, Coleman Kelly R13, Wynn Karen13, Hartley-McAndrew Michelle13, Laroia Nirupama13, Meyers Jeffrey13, Brion Luc P13, Vasil Diana M13, Adams Sally S13, Chen Lijun13, De Leon Maria M13, Eubanks Frances13, McDougald Rebecca13, Pavageau Lara13, Sepulveda Pollieanna13, Guzman Alicia13, Heyne Elizabeth13, Madden Linda A13, Lee Lizette E13, Tolentino-Plata Kristine13, Twell Boatman Cathy13, Vera Azucena13, Waterbury Jillian13, Atok Amy13, Weuhausen Denise13, Brammer Elizabeth13, Laird Cheryl13, Shankaran Seetha13, Pappas Athina13, Sood Beena G13, 44958 Melissa13, Agarwal Prashant13, Chawla Sanjay13, Bara Rebecca13, Childs Kirsten13, Woldt Eunice13, Goldston Laura13, Wiggins Stephanie A13, Christensen Mary K13, White Diane F13, Ambalavanan Namisavayam4, Wyckoff Myra H.14, D’Angio Carl T.15, Bugg George W.2, Ohls Robin K.1617, Reynolds Anne Marie18, Sokol Gregory M.9, Laptook Abbot R.8, Olsen Steven L.19, White Jessica R.20, Jadcherla Sudarshan R.7, Bajaj Monika21, Parimi Prabhu S.22, Schmidt Barbara5, Laughon Matthew M.23, Barks John24, Fisher Kimberley A.25, Hibbs Anna Maria26, Peralta-Carcelen Myriam4, Cook Noah27, Heyne Roy J.14, Cavanaugh Brenna15, Adams-Chapman Ira2, Fuller Janell16, Hartley-McAndrew Michelle E.18, Harmon Heidi M.1, Duncan Andrea F.28, Hines Abbey C.9, Kilbride Howard W.19, Richards Laurie A.20, Maitre Nathalie L.7, Natarajan Girija21, Trembath Andrea N.23, Carlson Martha D.24, Malcolm William F.25, Wilson-Costello Deanne E.26, ,
Affiliation:
1. Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City 2. Department of Pediatrics, Children’s Healthcare of Atlanta, School of Medicine, Emory University, Atlanta, Georgia 3. Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina 4. Division of Neonatology, Heersink School of Medicine, University of Alabama, Birmingham 5. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 6. Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center, Houston 7. Department of Pediatrics, Nationwide Children’s Hospital, College of Medicine, Ohio State University, Columbus 8. Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Island 9. Department of Pediatrics, School of Medicine, Indiana University, Indianapolis 10. Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland 11. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 12. College of Health and Human Services, George Mason University, Fairfax, Virginia 13. and the MILK Trial Investigators 14. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 15. University of Rochester School of Medicine and Dentistry, Rochester, New York 16. University of New Mexico Health Sciences Center, Albuquerque 17. Department of Pediatrics, Division of Neonatology, School of Medicine, University of Utah, Salt Lake City 18. Department of Pediatrics, Oishei Children’s Hospital, University at Buffalo, Buffalo, New York 19. Department of Pediatrics, Children’s Mercy Hospital, Kansas City, Missouri 20. Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls 21. Department of Pediatrics, School of Medicine, Wayne State University, Detroit, Michigan 22. Department of Pediatrics, Kansas University Medical Center, Kansas City 23. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill 24. Department of Neonatal-Perinatal Medicine, C. S. Mott Children’s Hospital, University of Michigan, Ann Arbor 25. Department of Pediatrics, School of Medicine, Duke University, Durham, North Carolina 26. Department of Pediatrics, University Hospitals Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, Ohio 27. Department of Pediatrics, Pennsylvania Hospital, Philadelphia 28. Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia
Abstract
ImportanceMaternal 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.ObjectiveTo 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 ParticipantsDouble-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.InterventionPreterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge.Main Outcomes and MeasuresThe 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.ResultsOf 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT01534481
Publisher
American Medical Association (AMA)
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