Acidified Feedings in Preterm Infants: A Historical and Physiological Perspective.

The use of acidified milk for feeding infants has a long, interesting history that appears to have developed from the use of buttermilk in Holland as early as the late 19th century for feeding infants with diarrhea. Physicians in the early 20th century assumed that the observed benefits were from buttermilk's acidity leading to the practice of acidifying infant formula. The historical and physiological perspective on the use of acidified infant formula is now especially relevant with the emergence of an acidified liquid human milk fortifier for preterm infants. Here, we review that history, with a deeper dive into the contemporary research on the use of acidified human milk fortifiers, the consequences for preterm infants, and the underlying physiological mechanisms. KEY POINTS: · In the late 19th and early 20th century acidified feedings were in common use for sick infants.. · By the mid-20th century, acidified feedings tested in preterm infants resulted in acidic physiology and poor growth.. · The current practice of acidifying feedings in preterm infants has been associated with metabolic acidosis, poor tolerance, and delayed growth..

Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical Trial.

OBJECTIVE: To compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. STUDY DESIGN: This prospective, controlled, parallel, multicenter growth and tolerance study included 164 preterm infants (≤32 weeks of gestation, birth weight 700-1500 g) who were randomized to acidified or nonacidified liquid human milk fortifier from study day 1, the first day of fortification, through study day 29 or until hospital discharge. RESULTS: There was no difference in the primary outcome of weight gain from study days 1 to 29 (acidified liquid human milk fortifier, 16.4 ± 0.4 g/kg/day; nonacidified liquid human milk fortifier, 16.9 ± 0.4 g/kg/day). However, in both the intention-to-treat and the protocol evaluable analyses, infants fed nonacidified liquid human milk fortifier had significantly greater weight gain from study days 1 to 15 (17.9 g/kg/day vs 15.2 g/kg/day; P = .001). Infants fed with acidified liquid human milk fortifier received more protein (4.26 vs g/kg/day 4.11 g/kg/day, P = .0099) yet had lower blood urea nitrogen values (P = .010). The group fed acidified liquid human milk fortifier had more vomiting (10.3% vs 2.4%; P = .018), gastric residuals (12.8% vs 3.7%; P = .022), and metabolic acidosis (27% vs 5%; P < .001) in the intention-to-treat analysis and more abdominal distension (14.0% vs 1.7%; P = .015) in the protocol evaluable analysis. CONCLUSIONS: Infants fed an acidified liquid human milk fortifier had higher rates of metabolic acidosis and poor feeding tolerance compared with infants fed a nonacidified liquid human milk fortifier. Initial weight gain was poorer with the acidified liquid human milk fortifier. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02307760.

Growth and Tolerance of Preterm Infants Fed a New Extensively Hydrolyzed Liquid Human Milk Fortifier.

OBJECTIVES: This study was a comparison of growth and tolerance in premature infants fed either standard powdered human milk fortifier (HMF) or a newly formulated concentrated liquid that contained extensively hydrolyzed protein. METHODS: This was an unblinded randomized controlled multicenter noninferiority study on preterm infants receiving human milk (HM) supplemented with 2 randomly assigned HMFs, either concentrated liquid HMF containing extensively hydrolyzed protein (LE-HMF) or a powdered intact protein HMF (PI-HMF) as the control. The study population consisted of preterm infants ≤33 weeks who were enterally fed HM. Infants were studied from the first day of HM fortification until day 29 or hospital discharge, whichever came first. RESULTS: A total of 147 preterm infants were enrolled. Noninferiority was observed in weight gain reported in the intent-to-treat (ITT) analysis was 18.2 and 17.5 g · kg(-1) · day(-1) for the LE-HMF and PI-HMF groups, respectively. In an a priori defined subgroup of strict protocol followers (n = 75), the infants fed LE-HMF achieved greater weight over time than those fed PI-HMF (P = 0.036). The LE-HMF group achieved greater linear growth over time compared to the PI-HMF (P = 0.029). The protein intake from fortified HM was significantly higher in the LE-HMF group compared with the PI-HMF group (3.9 vs 3.3 g · kg(-1) · day(-1), P < 0.0001). Both fortifiers were well tolerated with no significant differences in overall morbidity. CONCLUSIONS: Both fortifiers showed excellent weight gain (grams per kilograms per day), tolerance, and low incidence of morbidity outcomes with the infants who were strict protocol followers fed LE-HMF having improved growth during the study. These data point to the safety and suitability of this new concentrated liquid HMF (LE-HMF) in preterm infants. Growth with this fortifier closely matches the recent recommendations for a weight gain of >18 g · kg(-1) · day(-1).

Metabolic Acidosis in Preterm Infants is Associated with a Longer Length of Stay in the Neonatal Intensive Care Unit.

INTRODUCTION: Preterm births account for disproportionately high healthcare costs, in large part due to expenses related to length of stay in the hospital neonatal intensive care unit (NICU). It is common for preterm infants to receive human milk fortifier (HMF) while in the NICU. Liquid HMF is available in both acidified and non-acidified formulations. A recent randomized clinical trial found that acidified HMF is associated with an increased incidence of metabolic acidosis, which may contribute to increased costs and longer NICU length of stay. OBJECTIVE: The present study is a secondary analysis of these data, seeking to determine whether additional factors contribute to metabolic acidosis, whether metabolic acidosis is associated with longer hospital length of stay, and whether these associations contribute to the burden of hospital costs. METHODS: The study sample consisted of 152 infants who were hospitalized in US NICUs. Multiple logistic regression was used to model the NICU length of stay. Data from the 2012 Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) were used to calculate the average cost (charge) per day in a NICU. Costs (charges) were adjusted to $US, year 2018 values, using the health Consumer Price Index. RESULT: Results indicated that acidified HMF was a strong predictor of metabolic acidosis, more so than gestational age or birth weight. Furthermore, metabolic acidosis was associated with incremental NICU costs (charges) of $US19,002 ($US65,462) per infant and longer NICU LOS. CONCLUSION: Future studies should further investigate factors that contribute to NICU length of stay and associated costs of care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02307760.

Growth of healthy term infants fed ready-to-feed and powdered forms of an extensively hydrolyzed casein-based infant formula: a randomized, blinded, controlled trial.

Extensively hydrolyzed formulas present a complex matrix subject to adverse conditions during manufacture that could influence growth and tolerance of infants fed these formulas. A masked, randomized, parallel growth study was conducted in infants fed a ready-to-feed (RTF) or powdered (PWD) form of an extensively hydrolyzed casein-based formula. Infants were enrolled between 0 and 9 days and studied to 112 days of age. Growth, formula intake, and stool patterns were assessed. There were no significant differences between groups in weight, length, head circumference, or their respective gains. Tolerance was similar between groups except that the RTF group had greater formula intakes and passed more stools/day compared to the PWD group. This study demonstrates that the PWD formulation of this RTF formula supports similar growth and tolerance in infants during the first 4 months of life.