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No Downsides to Donor Milk for Extremely Premature Infants

    An extremely premature infant next to a graphic of donor milk vs formula.

    Written by: Jyoti Madhusoodanan, Ph.D. | Issue # 120 | 2024

    • Donor human milk is currently recommended for extremely premature infants
    • Infants fed donor human milk are half as likely to experience necrotizing enterocolitis 
    • Infants fed pre-term formula gained weight more quickly than those who were fed donor milk 

    A typical human pregnancy lasts 40 weeks, and at least 37 weeks of gestation enables a baby’s lungs, heart, and other organs to form and function. Babies defined as ‘extremely premature’—being born before 29 weeks of gestation—are at high risk of disorders because their organs are immature. They are also at higher risk for sepsis, hemorrhage, and the life-threatening intestinal infection necrotizing enterocolitis, which kills up to 50 percent of affected babies.

    Studies have shown that a mother’s milk protects extremely premature infants, who often weigh less than 2 pounds at birth, against necrotizing enterocolitis and improves neurodevelopment until they are of school age [1]. But a mother’s own milk is often unavailable to these infants in part because of their early birth, as pregnancy complications or the infant’s inability to suckle, can reduce the chances of successful lactation. In the absence of a mother’s milk, the American Academy of Pediatrics and the World Health Organization both recommend donor milk over pre-term formula because of studies that suggest that the former offers greater protection against necrotizing enterocolitis. However, no studies had compared the two for their effects on neurodevelopment, weight gain, and other important markers of health in extremely pre-term infants.

    Now, results from a large randomized controlled trial reveal that approximately two years after birth, there is little difference in cognitive scores and other neurodevelopmental markers amongst infants who received donor milk and those who received pre-term formula [2]. The trial was “long awaited” and “well designed and well executed,” according to the authors of an accompanying editorial [3], who were not involved in the study. 

    To compare how infants fared on donor milk and pre-term formula, researchers at 15 hospitals enrolled more than 400 families in a clinical trial between 2012 and 2019. Infants born before 29 weeks of pregnancy and those with a birth weight of less than 1000 grams (2.2 pounds) who had no congenital heart disease, prior infections or other serious illnesses were included. The researchers only included babies who had received little to no of their birthing parents’ own milk in the first three weeks of birth. Approximately 200 received donor milk from human milk banks, and about the same number received pre-term formula, a specialized form of nutrition fortified with additional calories and dietary supplements necessary for extremely pre-term infants. Infants in the study began receiving either donor milk or formula at about 16 days after birth and received the diet for their group for approximately 56 days. The study diet was discontinued at about 37 weeks of age. 

    Babies in both groups were weighed weekly, and their length and head circumference were measured once in two weeks. Infants fed donor milk gained weight more slowly than those who received pre-term formula, but both gained in length and head circumference equally well. 

    At about 22 to 26 months after the date that these infants would have been full-term, clinicians conducted a commonly used test to gauge brain development. This test measures language development, motor skills such as a child’s ability to walk, jump or grasp objects, social and emotional development, cognitive impairment, and more. The researchers found no significant difference between the scores of infants in either group. 

    The greatest benefit of donor milk, it turned out, was reducing the odds of necrotizing enterocolitis: infants who received donor milk contracted the infection half as often as those in the pre-term formula group. 

    The study included a total of 483 children and is likely the largest to compare the benefits of donor milk and pre-term formula. The researchers stopped recruiting infants in part because it became extremely difficult. When they began the work in 2012, less than 25 percent of centers in the Neonatal Research Network, a collaboration of NICUs across the U.S., used donor milk. But just a year later, the AAP, WHO and other organizations officially began to recommend donor milk over pre-term formula. By the time the researchers stopped including infants in 2019, more than 75 percent of centers in the Neonatal Research Network were using donor milk, making it difficult to justify placing infants in the pre-term formula group of the trial. 

    The results are not the last word on the relative benefits of human milk and pre-term formula, according to the authors of the accompanying editorial. Although the study found no benefits of donor milk to cognitive scores and other measures of brain development, it also found no downsides. Considering the protection that donor milk offers against potentially lethal necrotizing enterocolitis, data from this large trial support current recommendations to use donor milk for extremely premature infants. 

    Understanding why infants gained weight more slowly on donor milk could help researchers find ways to fortify this crucial food and improve babies’ weight gain in future studies. 

    The authors of the editorial also emphasize that donor milk is not the same as a birthing parent’s milk. A mother’s own milk offers two benefits: it reduces risk of necrotizing enterocolitis and has been linked to better neurodevelopment in extremely pre-term babies. As a result, the authors write that ensuring all extremely preterm infants have access to their mother’s own milk remains crucial “to improve the short-term and long-term outcomes in preterm infants.

    References

    1. Cortez J, Makker K, Kraemer DF, Neu J, Sharma R, Hudak ML. Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants. Journal of Perinatology. 2018 Jan;38(1):71-4.
    2. Colaizy TT, Poindexter BB, McDonald SA, Bell EF, Carlo WA, Carlson SJ, DeMauro SB, Kennedy KA, Nelin LD, Sánchez PJ, Vohr BR. Neurodevelopmental outcomes of extremely preterm infants fed donor milk or preterm infant formula: a randomized clinical trial. JAMA. 2024 Feb; 331(7):582-591.
    3. Belfort MB, Perrin M. Delivering on the promise of human milk for extremely preterm infants in the NICU. JAMA. 2024 Jan; 331(7):567-569.