Comparison of a Powdered, Acidified Liquid, and Non-Acidified Liquid Human Milk Fortifier on Clinical Outcomes in Premature Infants

Abstract

We previously compared infant outcomes between a powdered human milk fortifier (P-HMF) vs. acidified liquid HMF (AL-HMF). A non-acidified liquid HMF (NAL-HMF) is now commercially available. The purpose of this study is to compare growth and outcomes of premature infants receiving P-HMF, AL-HMF or NAL-HMF. An Institutional Review Board (IRB) approved retrospective chart review compared infant outcomes (born < 2000 g) who received one of three HMF. Growth, enteral nutrition, laboratory and demographic data were compared. 120 infants were included (P-HMF = 46, AL-HMF = 23, NAL-HMF = 51). AL-HMF infants grew slower in g/day (median 23.66 vs. P-HMF 31.27, NAL-HMF 31.74 (p < 0.05)) and in g/kg/day, median 10.59 vs. 15.37, 14.03 (p < 0.0001). AL-HMF vs. NAL-HMF infants were smaller at 36 weeks gestational age (median 2046 vs. 2404 g, p < 0.05). However AL-HMF infants received more daily calories (p = 0.21) and protein (p < 0.0001), mean 129 cal/kg, 4.2 g protein/kg vs. P-HMF 117 cal/kg, 3.7 g protein/kg , NAL-HMF 120 cal/kg, 4.0 g protein/kg. AL-HMF infants exhibited lower carbon dioxide levels after day of life 14 and 30 (p < 0.0001, p = 0.0038). Three AL-HMF infants (13%) developed necrotizing enterocolitis (NEC) vs. no infants in the remaining groups (p = 0.0056). A NAL-HMF is the most optimal choice for premature human milk-fed infants in a high acuity neonatal intensive care unit (NICU).

Comments to Article by Thoene M et al., Nutrients 2016, 8, 451

“…These authors associated this metabolic acidosis to a much slower rate of growth with AL-HMF (10.59 g/kg/day), thereby ascribing clinical significance to such finding. This was not corroborated in the report by Cibulskis [5] showing similar rates of growth between fortifiers, which were actually higher than those reported by Thoene for a somewhat similar population of infants and approximated those reported in the Moya trial [1,2,3]. Moreover, in a recent prospective, randomized trial of timing of human milk fortification by Shah et al [6], in which the only fortifier used was AL-HMF, there was an overall 7% rate of metabolic acidosis using a far more liberal definition (base deficit ≥10 mEq/L) and the rate of growth reported at 36 weeks postmenstrual age was higher than in the Thoene and Cibulskis reports.…”

“…These authors attempted to address which human milk fortifier (HMF) is the optimal choice for preterm infants in a neonatal intensive care unit (NICU). To do this they reported again data from a previous retrospective study published in Nutrients on January 2014 [2] using a powdered HMF (P-HMF) with an acidified liquid HMF (AL-HMF), and compared it with additional retrospective data using yet a different non-acidified liquid HMF (NAL-HMF). The authors focused on relevant issues for neonatologists such as growth, impact of HMF’s in acid-base balance and the occurrence of necrotizing enterocolitis (NEC).…”

“…Both retrospective studies by Thoene [1,2] selected a population of larger preterm infants without excluding for acuity. Thus, they reported a vastly different population than in the original prospective randomized trials by Moya et al [3] evaluating the AL-HMF, which enrolled infants less than 30 3/7 weeks of gestation and <1250 g at birth, and the trial by Kim et al [4] examining the NAL-HMF, which enrolled infants <33 weeks and range 700–1500 g at birth.…”

“…These trials described in detail relevant demographic characteristics of their populations such as proportion of infants <1000 g, mode of delivery, Apgar scores, and provided descriptive statistics of the range of gestational age and birth weight. Much of this information is missing in both reports by Thoene, including ranges or standard deviations for many continuous variables, especially for the new retrospective group of infants receiving the NAL-HMF from their most recent study [2]. Moreover, there are multiple additional discrepancies in data between both studies by Thoene, which make it harder to reconcile their findings and conclude how representative is their population, i.e., “N” for AL-HMF group for gestational age, birth weight, length and head circumference at 36 weeks, death, number of infants with bronchoplumonary dysplasia.…”

“…Growth rate in all infants was calculated at 4 weeks of age and at 36 weeks [6]. In both studies by Thoene [1,2] and Cibulskis [5], it is unclear what proportion got donor milk and for how long. In addition growth rates were calculated by Thoene only among infants while they received >50% of fortified mother’s milk, but we do not know at all what proportion of the remaining nutrition came from donor milk or formula except for a brief statement in the discussion mentioning that formula was utilized equally in all groups [2].…”