Effects of higher protein formula with improved fat blend on growth, feeding tolerance and nutritional biomarkers in preterm infants: A double-blind, randomized, controlled clinical trial

Abstract

BACKGROUND: Preterm formulas containing greater protein:energy ratio are beneficial for non-breastfed infants, since protein is critical for promoting catch-up growth and synthesis of lean body mass. Additionally, formulas containing enriched sn-2 palmitate (sn-2) and reduced medium chain triglycerides (MCTs) may support better feeding tolerance and nutrient utilization. METHODS: The objective of this randomized, controlled, double-blinded clinical trial is to evaluate growth, feeding tolerance and nutritional biomarkers of preterm infants with birth weight ≤2000g and gestational age ≤33wks from one neonatal unit in Vietnam receiving experimental formula (EF, n = 80) containing higher protein level of 3.4 g/100 kcal and improved fat blend with enriched sn-2 and modified level of MCTs or isocaloric control formula (CF, n = 80) containing protein level of 2.9 g/100 kcal and standard fat blend. The differences in weight gain (g/d; primary endpoint) from day 1 (D1) of full enteral feeding (FEF) until D21 between groups was evaluated for non-inferiority (margin = -2.5 g/d) and superiority (margin = 0 g/d). RESULTS: Mean weight gain was 3.09 g/d greater in EF than CF; the lower limit of 95% CI (0.31 g/d) exceeded both non-inferiority and superiority margins. There was no significant difference in length-for-age and head circumference-for-age z-score. By D79, the mean change in weight-for-age z-scores from D1 in EF group (+0.76 SDs) surpassed the criteria for catch-up growth (+0.67 SDs). Infants in the EF group (vs. CF) tended to have softer stools (EF = 3.2 ± 0.59 vs. CF = 3.4 ± 0.58; P = 0.07) based on 5-point scale (1 = watery, 5 = hard). Difference in blood urea nitrogen and biomarkers for bone mineral status (i.e., plasma phosphorus, alkaline phosphatase and urinary calcium/phosphorus ratio) between EF and CF on FEF Day 21 reached statistical significance (P < 0.05) but all mean values stayed within normal clinical ranges for both groups. CONCLUSION: Preterm formula with greater protein:energy ratio and new fat blend is safe, nutritionally suitable, well-tolerated, and improves catch-up weight gain of preterm infants. Clinical trial registry identifier is NCT03055052 (ClinicalTrials.gov).