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Objective: Amidst a high prevalence of prematurity, limited research on the growth of very low birth weight (VLBW) preterm infants and the availability of a reformulated fortifier c(RF), the study aimed to compare in-hospital growth of such infants receiving exclusively human milk fortified with either of 2 different formulations in a tertiary South African hospital. Methods: In a prospective comparative effectiveness design, intakes and growth of VLBW infants on the Original Fortifier (OF; 2016–2017) were compared with those receiving RF (2017–2018). Daily intake was calculated using published composition of preterm and mature milk with fortifier (OF: 0.2 g protein, 3.5kcal/g powder; RF: 0.4 g protein, 4.4 kcal/g powder). Change in z scores from start to end of fortification for weight (WFAZ), length (LFAZ), and head circumference (HCFAZ) for age was the primary outcome. Additionally, weight gain velocity (g · kg−1 · day−1) and gain in length and head circumference (HC) (cm/week) were calculated. Results: Fifty-eight infants (52% girls; gestational age: 30 ± 2 weeks; birth weight: 1215 ± 187 g) received OF for 16 days and 59 infants (56% girls; gestational age: 29 ± 2 weeks; birth weight 1202 ± 167 g) received RF for 15 days. Protein intake of RF (3.7 ± 0.4 g · kg−1 · day−1) was significantly higher (P < 0.001) than of OF (3.4 ± 0.2 g · kg−1 · day−1). Protein-to-energy ratio of RF (2.6 ± 0.2 g/100 kcal) was significantly higher (P < 0.001) than of OF (2.3 ± 0.1 g/100 kcal). In both groups, WFAZ and LFAZ decreased; HCFAZ improved slightly. No significant differences (P > 0.05) were noted between the 2 groups for change in z scores, weight gain velocity, length or HC gain. Conclusions: Despite a modest increase in protein intake and protein-to-energy ratio, the growth of VLBW infants on RF was not better than on OF during their hospital stay.

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