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