Science Update: Fortified human milk may promote growth of preterm infants, according to NIH-funded study

An infant in a neonatal intensive care unit.
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Extremely preterm infants fed fortified human milk grew longer and more rapidly and had larger head circumferences than infants fed unfortified human milk, according to a study funded by the National Institutes of Health. The findings provide support for future studies on the potential benefits of human milk fortification in preventing malnutrition among infants born at 28 weeks or younger.

The study was conducted by Ariel A. Salas, M.D., M.S.P.H., and colleagues at the University of Alabama at Birmingham. It appears in Pediatrics. Funding was provided by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).


Extremely preterm infants are at high risk of malnutrition, which may lead to poor growth. Previous studies have shown that preterm infants have less fat-free mass—total muscle, bone, and lean mass—when they reach the equivalent age of an infant born at full term. Other studies have shown that infants with less fat-free mass are at higher risk for neurodevelopmental impairment, obesity, and other health problems.

Because fat-free mass is formed largely of protein, researchers have theorized that increasing the protein content of human milk fed to preterm infants might increase their fat-free mass.

For the current study, researchers conducted a randomized trial. A total of 105 infants born from 23 to 28 weeks completed the study. Half were fed human milk alone and half were fed human milk with a human milk-based fortifier—a nutritional supplement made from heated, concentrated, donor human milk and additional vitamins and minerals. When the infants reached the 36 weeks postmenstrual age (the stage of pregnancy they would have reached had they not been born preterm), the researchers measured their fat-free mass z scores—their fat-free mass in relation to a growth chart of average fat-free mass for infants of the same length and age.


Fat-free mass z scores for age did not differ between the two groups. However, infants fed fortified human milk had grown longer at 36 weeks postmenstrual age than those fed human milk alone. Infants born before 28 weeks generally have lower head circumference z scores compared to the averages. However, declines in head circumference z scores were less for infants fed human milk with human milk fortifier than for those fed human milk alone.


The authors concluded that although fortified human milk did not appear to increase the fat-free mass of extremely preterm infants, it did appear to increase the rate at which they grew and to reduce the decline in their head circumference z scores.

Next Steps

The authors called for larger studies that could detect any uncommon adverse effects of human milk fortification and studies to determine if extremely preterm infants initially fed fortified human milk experience any neurological benefits by the time they reach age 2.


Salas, AA et al. Early Human Milk Fortification in Infants Born Extremely Preterm: A Randomized Trial. Pediatrics. 2023. DOI: 10.1542/peds.2023-061603 external link

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