P2.I167: Impact of Human-milk based Fortifier Usage and Metabolic Acidosis in Premature Infants

Background: Human milk is an optimal source of nutrition; however, fortification with Human-milk-based human milk fortifier (HM-HMF) is often necessary to provide additional calories, proteins, and minerals to achieve adequate growth in premature infants. Fortification is the only way to ensure these medically fragile infants receive an exclusive human milk diet. Using HM-HMF (e.g., Prolacta) is occasionally associated with metabolic acidosis, but no studies have been published yet. The purpose of this study was to evaluate the impact of HM-HMF on metabolic acidosis compared to bovine-milk-based human milk fortifiers (BM-HMF) in extremely premature infants.

Methods: We included all infants who received HM-HMF and were admitted between 08/01/2023 to 01/31/24 to our tertiary neonatal intensive care unit (NICU) at the University of Florida Health, Jacksonville. Per our unit guidelines, all infants < 30 weeks gestational age (GA) or birthweight < 1000 grams are eligible for fortification with HM-HMF. Infants who died or were transferred out of the NICU before reaching full feeding volume were excluded. We matched all infants who received BM-HMF based on their birthweight or GA. Trends in serum bicarbonate level and base deficit were compared between HM-HMF and the BM-HMF groups. Clinical and demographic data were collected in both groups by chart reviews. Data are presented as counts (percentage) or median (IQR) and compared using a chi-square test, 2-sided paired t-test or Wilcoxon rank-sum test, as appropriate.

Results: 48 infants were eligible for review in the study period. Of 48 infants, 9 (18.7%) developed metabolic acidosis while on HM-HMF. No infant in the BM-HMF group developed metabolic acidosis. Serum Bicarbonate level was significantly lower [13 (13,16.5) vs 26.5 (25.25,27), P = 0.006], and the base deficit was significantly higher [-10.3(-8.8, -13.1) vs -1 (-2.25,0), p = 0.01] in the HM-HMF. The difference in bicarbonate level was noted despite no difference in gestational age and birthweight between the two groups (Table 1). Infants developed metabolic acidosis at a median corrected gestational age of 28.6 weeks and 27 days of life in the HM-HMF group. Serum bicarbonate and base deficit values were promptly restored to normal values after removing HM-HMF from the diet in all infants.

Conclusion: Bicarbonate and base deficit were significantly abnormal in about 20% of extremely premature infants who received HM-HMF. Although the exact mechanism remains unclear, hypotheses suggest that differences in protein and mineral content of the HM-HMF may contribute to acid production, overwhelming the immature renal function of extremely premature infants. Early recognition and management of metabolic acidosis is essential to prevent associated complications. We further hypothesize that an unknown factor unique to HM-HMF may contribute to metabolic acidosis in these infants. Further research to study the proteomic and metabolomic profiles of HM-HMF may be of interest.