Both Types of Liquid Human Milk Fortifier Promote Growth of Very-Low-Birthweight Infants

Newborn baby in NICU

Adding liquid human milk fortifier (HMF) to expressed human milk is now standard clinical practice for hospitalized infants with very-low-birthweight because human milk alone is insufficient to meet the high nutritional needs of preterm infants.

HMFs are sterilized by either acidification or heat treatment, and a few observational studies have reported an increased incidence of metabolic acidosis in infants given acidified HMF compared with the nonacidified product. These studies haven’t addressed, though, whether this transient metabolic acidosis has clinically meaningful effects.

Mandy Brown Belfort, MD, MPH, a neonatologist and epidemiologist in the Department of Pediatric Newborn Medicine at Brigham and Women’s Hospital, and colleagues recently confirmed that administration of acidified HMF is associated with a higher incidence of metabolic acidosis in the first weeks of life. However, the type of fortifier was not an important determinant of growth during the NICU stay. The team’s report appears in Nutrition in Clinical Practice.


The researchers retrospectively studied 255 infants who were admitted to the NICU at the Brigham between May 2015 and December 2018. The infants were born at <33 weeks’ gestation and <1,500 grams, received at least 75% of their enteral feedings as human milk on day of life 14, and stayed in the NICU for at least 21 days.

165 infants were initiated on acidified HMF between May 2015 and September 2017. The other 90 were initiated on nonacidified HMF between October 2017 and December 2018.

Nonacidified HMF provides less protein than acidified HMF, so a protein modular was administered to infants receiving nonacidified HMF when they reached full-volume feedings.

Metabolic Acidosis

The incidence of metabolic acidosis, defined as any serum bicarbonate level <16 mEg/L in the first 21 days of life, was higher in the acidified HMF group (42% vs. 20% of the nonacidified HMF group; P<0.001).

The median lowest serum bicarbonate level was 16 versus 17, respectively (P<0.001), and the proportion of infants who needed sodium bicarbonate treatment was 34% versus 1% (P<0.001).

After adjustment for covariates, infants receiving acidified HMF remained at higher odds of metabolic acidosis (aOR, 2.7).

Infant Size

Infant size at discharge from the NCU was similar between fortifier groups:

  • Weight z-score: mean −1.03 in the acidified HMF group vs. 1.04 in the nonacidified HMF group (P=0.97)
  • Length z-score: −1.42 vs. −1.41 (P=0.99)
  • Head circumference z-score: −0.58 vs. −0.74 (P=0.21)

Similarly, the z-scores for change from birth to discharge and the growth velocity during NICU admission were similar between groups for all three growth parameters.

The Role of Protein Modular

The lack of growth advantage among infants fed acidified HMF–fortified milk in this study might result from the provision of protein modular to infants receiving nonacidified HMF. Once hospitalized infants with very-low-birthweight reach full-volume feedings, the recommended energy and protein requirements are ∼120 kcal/kg/day and 4 g/kg/day, respectively.

At the Brigham, infants receiving nonacidified HMF are given liquid protein-containing casein hydrolysate, 1 mL per 60 mL fortified human milk.

Leave a Reply