Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula

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

Preterm nutrition and brain development

“…The most recent studies, including an important randomised controlled trial (RCT) published in JAMA and including 483 extremely preterm infants, have shown that fortified donated milk does not confer better neurodevelopmental outcomes at 22 and 26 months of corrected age when compared with formula for preterm infants (cognitive, language and motor scores on the Bayley Scales of Infant and Toddler Development, neurodevelopmental impairment and cerebral palsy incidence were the same in the two groups). 25 The same result was obtained by the 2018 Cochrane systematic review, which concluded with moderate evidence that the data did not show an effect of donor milk on neurodevelopment. 26…”

Response to “Repeating the errors of the past: the hazards of a commercial human milk industry” Modi (2024) from the Global Alliance of Milk Banks and Associations

“…[8][9][10][11][12] Additionally, a recently published RCT of a study conducted in the US (the MILK trial) has confirmed this evidence. 13 3. The belief by Modi that "mothers are faced with having to express milk for a prolonged period which is difficult and stressful" is a context-specific statement.…”

Melatonin in Human Breast Milk and Its Potential Role in Circadian Entrainment: A Nod towards Chrononutrition?

“…Only recently was it reported that among extremely preterm infants, donor human milk feeding did not result in different 2-year neurodevelopmental outcomes compared with preterm formula feeding [115]. However, no information was provided as to whether matched milk according to the stage of lactation was used or whether mistimed feeding was undertaken, which seems probable since this was not otherwise mentioned.…”