Fortification of Breast Milk With Preterm Formula Powder vs Human Milk Fortifier in Preterm Neonates

Abstract

breast milk (EBM) using commercially available human milk fortifiers (HMF) increases short-term weight and length in preterm very low-birth-weight (VLBW) neonates. However, the high cost and increased risk of feed intolerance limit their widespread use. Preterm formula powder fortification (PTF) might be a better alternative in resource-limited settings.OBJECTIVE To demonstrate that fortification of EBM by preterm formula powder is noninferior to fortification by HMF, in terms of short-term weight gain, in VLBW neonates.DESIGN, SETTING, AND PARTICIPANTS Open-label, noninferiority, randomized trial conducted from December 2017 to June 2019 at a level 3 neonatal unit in India. The trial enrolled preterm (born at or before 34 weeks of gestation) VLBW neonates receiving at least 100 mL/kg/d of feeds and consuming 75% of milk or more as EBM.INTERVENTIONS Neonates were randomly assigned to receive fortification by either PTF or HMF. Calcium, phosphorus, iron, vitamin D, and multivitamins were supplemented in PTF and only vitamin D in the HMF group to meet the recommended dietary allowances. MAIN OUTCOMES AND MEASURESThe primary outcome was the weight gain until discharge from the hospital or 40 weeks' postmenstrual age, whichever was earlier; the prespecified noninferiority margin was 2 g/kg/d. Secondary outcomes included morbidities such as necrotizing enterocolitis, feed intolerance, and extrauterine growth restriction (<10th percentile on the Fenton chart at 40 weeks' postmenstrual age). RESULTSOf the 123 neonates enrolled, 60 and 63 were randomized to the PTF and HMF groups, respectively. The mean gestation (30.5 vs 29.9 weeks) and birth weight (1161 vs 1119 g) were comparable between the groups. There was no difference in the mean (SD) weight gain between the PTF and HMF groups (15.7 [3.9] vs 16.3 [4.0] g/kg/d; mean difference, −0.5 g/kg/d; 95% CI, −1.9 to 0.7). The lower bound of 95% CI did not cross the noninferiority margin. The incidence of feed intolerance was lower in the PTF group (1.4 vs 6.8 per 1000 patient-days; incidence rate ratio 0.19; 95% CI, 0.04 to 0.95), and fewer neonates required withholding of fortification for 24 hours or more (5% vs 22%; risk ratio, 0.22; 95% CI, 0.07 to 0.75). The incidence of necrotizing enterocolitis stage II or more (0 vs 5%) and extrauterine growth restriction (73% vs 81%) was comparable between the groups.CONCLUSIONS AND RELEVANCE Fortification with preterm formula powder is not inferior to fortification with human milk fortifiers in preterm neonates. Given the possible reduction in feed intolerance and lower costs, preterm formula might be a better option for fortification, especially in resource-restricted settings.

Human Milk Fortification for Preterm Infants

“…Oft-villainized infant formula has been invited back into the neonatal intensive care unit (NICU) by Chinnappan et al, who demonstrate the role of preterm formula (PTF) to supplement, rather than supplant, human milk (HM).…”

“…Chinnappan et al present a randomized noninferiority study designed to determine whether this practice is not only cost-effective but also clinically effective compared with standard HMF. The primary outcome is short-term weight gain measured at time of discharge or at 40 weeks’ corrected gestational age.…”

“…A more detailed understanding of micronutrient and macronutrient intake as well as formula supplementation/replacement after discharge would lend added real-world credibility. One of the potential benefits uncovered in this study is the cost savings that could be realized by the hospital and the families using PTF rather than HMF to fortify feeds. A cost-effectiveness analysis is an important future step to fully understand the impact of this work.…”

“…The trial by Chinnappan et al has revealed that PTF supplementation may be safely used in hospital to achieve similar growth to the more expensive HMF fortification. Postdischarge follow-up is needed to determine the long-term outcomes of these infants.…”

Additional Insights Into the Use of Preterm Formula Among Neonates

“…To the Editor We read with great interest the study by Chinnappan et al on the fortification of breast milk with preterm formula powder vs human milk fortifier in preterm infants. This trial addressed the pertinent clinical dilemma regarding optimal fortifier composition for preterm infants, particularly in low- and middle-income countries.…”