TY - JOUR
T1 - Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula
T2 - A Randomized Clinical Trial
AU - MILK Trial Investigators
AU - for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
AU - Colaizy, Tarah T.
AU - Poindexter, Brenda B.
AU - McDonald, Scott A.
AU - Bell, Edward F.
AU - Carlo, Waldemar A.
AU - Carlson, Susan J.
AU - DeMauro, Sara B.
AU - Kennedy, Kathleen A.
AU - Nelin, Leif D.
AU - Sánchez, Pablo J.
AU - Vohr, Betty R.
AU - Johnson, Karen J.
AU - Herron, Dianne E.
AU - Das, Abhik
AU - Crawford, Margaret M.
AU - Walsh, Michele C.
AU - Higgins, Rosemary D.
AU - Ambalavanan, Namisavayam
AU - Wyckoff, Myra H.
AU - D'Angio, Carl T.
AU - Bugg, George W.
AU - Ohls, Robin K.
AU - Reynolds, Anne Marie
AU - Sokol, Gregory M.
AU - Laptook, Abbot R.
AU - Olsen, Steven L.
AU - White, Jessica R.
AU - Jadcherla, Sudarshan R.
AU - Bajaj, Monika
AU - Parimi, Prabhu S.
AU - Schmidt, Barbara
AU - Laughon, Matthew M.
AU - Barks, John
AU - Fisher, Kimberley A.
AU - Hibbs, Anna Maria
AU - Peralta-Carcelen, Myriam
AU - Cook, Noah
AU - Heyne, Roy J.
AU - Cavanaugh, Brenna
AU - Adams-Chapman, Ira
AU - Fuller, Janell
AU - Hartley-McAndrew, Michelle E.
AU - Harmon, Heidi M.
AU - Duncan, Andrea F.
AU - Hines, Abbey C.
AU - Kilbride, Howard W.
AU - Richards, Laurie A.
AU - Maitre, Nathalie L.
AU - Natarajan, Girija
AU - Chopko, Stephanie A.
N1 - Publisher Copyright:
© 2024 American Medical Association. All rights reserved.
PY - 2024/2/20
Y1 - 2024/2/20
N2 - 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.
AB - 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.
KW - Birth Weight
KW - Child
KW - Double-Blind Method
KW - Enterocolitis, Necrotizing/epidemiology
KW - Female
KW - Humans
KW - Infant
KW - Infant Formula
KW - Infant, Extremely Premature
KW - Infant, Newborn
KW - Intensive Care Units, Neonatal
KW - Male
KW - Milk, Human
UR - https://www.scopus.com/pages/publications/85183986660
U2 - 10.1001/jama.2023.27693
DO - 10.1001/jama.2023.27693
M3 - Article
C2 - 38497706
AN - SCOPUS:85183986660
SN - 0098-7484
VL - 331
SP - 582
EP - 591
JO - JAMA
JF - JAMA
IS - 7
ER -