Comparison of the effect of two human milk fortifiers on clinical outcomes in premature infants

Abstract

The use of human milk fortifiers (HMF) helps to meet the high nutritional requirements of the human milk-fed premature infant. Previously available powdered products have not met the protein requirements of the preterm infant population and many neonatologists add powder protein modulars to help meet protein needs. The use of powdered products is discouraged in neonatal intensive care units (NICU) due to concern for invasive infection. The use of a commercially available acidified liquid product with higher protein content was implemented to address these two concerns. During the course of this implementation, poor growth and clinically significant acidosis of infants on Acidified Liquid HMF (ALHMF) was observed. The purpose of this study was to quantify those observations by comparing infant outcomes between groups receiving the ALHMF vs. infants receiving powdered HMF (PHMF). A retrospective chart review compared outcomes of human milk-fed premature infants<2000 g receiving the ALHMF (n=23) and the PHMF (n=46). Infant growth, enteral feeding tolerance and provision, and incidence of necrotizing enterocolitis (NEC), metabolic acidosis, and diaper dermatitis were compared between the two groups. No infants were excluded from this study based on acuity. Use of ALHMF resulted in a higher incidence of metabolic acidosis (p=0.002). Growth while on HMF as measured in both g/kg/day (10.59 vs. 15.37, p<0.0001) and in g/day (23.66 vs. 31.27, p=0.0001) was slower in the ALHMF group, on increased mean cal/kg/day (128.7 vs. 117.3, p=0.13) with nearly twice as many infants on the ALHMF requiring increased fortification of enteral feedings beyond 24 cal/ounce to promote adequate growth (48% vs. 26%, p=0.10). Although we were not powered to study NEC as a primary outcome, NEC was significantly increased in the ALHMF group. (13% vs. 0%, p=0.03). Use of a LHMF in an unrestricted NICU population resulted in an increase in clinical complications within a high-acuity NICU, including metabolic acidosis and poor growth. Although further research is needed to assess outcomes among infants with a variety of clinical acuities, gestational ages, and weights to confirm these findings, based on this experience, caution is urged to avoid potential risks.

Figure 1

CO2 levels between groups after Day of Life 14. The lowest CO2 levels after DOL 14 were collected from metabolic panels. The mean level in the powder group was 23, the mean level in the liquid group was 18.5. Laboratory clinical reference range 22–32 mmol/L. The difference is statistically significant (p = 0.002).

Figure 2

CO2 levels between groups after Day of Life 30. The lowest CO2 levels after DOL 30 were collected from metabolic panels. The mean level in the powder group was 25, the mean level in the liquid group was 20. Laboratory Clinical reference range 22–32 mmol/L. The difference is statistically significant (p = 0.002).

Figure 3

The growth pattern of infants receiving powder differs from the growth pattern of infants receiving liquid on fortified feed days. The plot shows the growth pattern for each infant and the fitted line by group. Based on the plot, infants on powder grow at a faster rate than infants receiving liquid. Evaluation of growth in gm/kg/day for the days infants were fed fortified breast milk, based on the mixed effects model, shows a significant interaction between day and group (p = 0.0022). Truncating the analysis at 45 days did not attenuate the results.