Growth and Clinical Outcomes of Very Low‐Birth‐Weight Infants Receiving Acidified vs Nonacidified Liquid Human Milk Fortifiers

Abstract

Background Liquid human milk fortifiers are used commonly in neonatal intensive care. Use of an acidified HMF (A‐HMF) is associated with transient metabolic acidosis, but whether growth outcomes differ between infants fed A‐HMF vs nonacidified HMF (NA‐HMF) remains unknown. Methods Retrospective cohort study of 255 infants born at <33 weeks' gestation and ≤1500 g who were receiving ≥75% fortified human milk on day of life 14, in a level III neonatal intensive care unit (NICU) from May 2015 to December 2018. Infants born before October 2017 (n = 165) received A‐HMF, whereas infants born after October 2017 (n = 90) received NA‐HMF. We used logistic regression to estimate odds of metabolic acidosis (serum bicarbonate <16 mEq/L in the first 21 days of life) in infants receiving A‐HMF vs NA‐HMF and linear mixed models to compare the mean size at discharge (weight, length, head z‐scores) by HMF type. We adjusted models for confounders and accounted for the nonindependence of multiple births. Results Median gestational age was 28.7 weeks (range, 22.6–32.9) and birth weight 1.1 kg (range, 0.4–1.5). Infants receiving A‐HMF had higher adjusted odds of metabolic acidosis than infants receiving NA–HMF (adjusted odds ratio, 2.7; 95% CI, 1.2–6.2). There were no differences between groups in size z‐scores at discharge. Conclusions In human‐milkfed, very‐low‐birthweight infants, fortification with liquid A‐HMF may contribute to metabolic acidosis in the first month of life, but this practice does not appear to impair growth through NICU discharge, compared with fortification with NA‐HMF.

Promoting Human Milk and Breastfeeding for the Very Low Birth Weight Infant

“…A trial comparing acidified to nonacidified liquid HMFs showed similar growth but increased transient metabolic acidosis among VLBW infants receiving acidified liquid HMFs. 85 Optimal timing of fortification remains unclear, but several recent RCTs of fortification at feeding volumes less than 80 mL/kg per day showed no associations with feeding intolerance or NEC. 15,86,87 Adjustable fortification algorithms based on markers such as serum urea nitrogen may improve growth.…”

Acidified Feedings in Preterm Infants: A Historical and Physiological Perspective

“…ALHMF is acidified by the addition of citric acid and has a pH of 4.0 to 4.6. 2,36 Although aseptic filling and acidification both effectively produce commercially sterile products, since the marketing of ALHMF, there have been at least nine published reports in [37][38][39][40][41][42][43][44][45] the literature indicating that its use echoes the research of Goldman 14,37-45 that using an acidified feeding for preterm infants significantly increases biochemical markers of acidic physiology and further, significantly increases the incidence of frank MA.…”

“…The bicarbonate buffering system is a series of reactions that lead to the production of carbon dioxide 53 This response leads to the hyperventilation typically seen with MA and contributes to the significant decreases in [HCO 3 À ] and/or [CO 2 ] as seen in several of these studies (►Table 2). [37][38][39][40][41][43][44][45] Another major buffering system that eliminates [H þ ] is through the excretion of urea following a series of transamination and deamination reactions in the kidneys between amino acids and α-ketogluterate. 53 The source of the amino acids required for this latter process comes from protein catabolism as shown in studies where acidosis is induced experimentally.…”

“…47 48 49 50 51 As seen in Table 1 , in all of the aforementioned studies, infants in the ALHMF group consumed significantly more protein but showed no improved growth 37 42 or significantly decreased growth. 38 39 40 41 43 44 Cordova et al 45 adjusted protein intake to be equivalent. Perhaps even more striking is that in seven of the nine studies, 38 39 40 41 42 43 44 45 52 infants fed ALHMF had significantly more MA ( Table 1 ).…”

“…60 A disequilibrium across cellular membranes may occur between carbon dioxide and bicarbonate ions, leading to intracellular acidosis in the face of seemingly resolving the acidic pH. 60 61 In that regard, a recently published study 45 that compared infants fed ALHMF versus NALHMF reported that infants who received the ALHMF had significantly more MA than infants receiving NALHMF (42% vs. 20%; p = 0.001. ), and not surprisingly almost all infants who received sodium bicarbonate treatment were in the ALHMF group compared with the NALHMF group (34 vs. 1.0%; p = 0.001) ( Table 1 ).…”