Improved Growth Velocity Using a New Liquid Human Milk Fortifier in Very Low Birth Weight Infants: A Multicenter, Retrospective Study

Abstract

This study aimed to compare growth outcomes and tolerance among very low birth weight (VLBW) infants receiving a new, liquid human milk fortifier (LHMF-NEW) or a human milk fortifier-acidified liquid (HMF-AL).Retrospective, multicenter study of 515 VLBW infants in three regional neonatal intensive care units. The primary objective was to compare growth velocity (g/kg/d) during fortification between groups by repeated measures regression. Secondary outcomes of interest were feeding tolerance and the incidence of late-onset sepsis, necrotizing enterocolitis, and metabolic acidosis. Student's t, analysis of variance, Wilcoxon, and Kruskal-Wallis tests were used for numeric variables, or chi-squared and Fisher's exact test for categorical variables.No demographic differences were identified between the groups (HMF-AL, n = 242; LHMF-NEW, n = 273). Growth velocity during fortification was significantly higher in the group receiving LHMF-NEW, despite relatively similar total fluid, calorie, or protein intake (p = 0.001). Feeding intolerance was comparable between fortifiers. Necrotizing enterocolitis and late-onset sepsis did not differ between groups and metabolic acidosis was diagnosed less frequently with the LHMF-NEW. Anthropometric measures at discharge and length of stay were comparable.Infants receiving human milk fortified with the LHMF-NEW had faster growth velocity during fortification, similar tolerance, and less metabolic acidosis compared with an earlier cohort of infants who received human milk fortified with an HMF-AL. · Among VLBW infants, using an LHMF-NEW resulted in a faster growth velocity in weight during several weeks of fortification than using the previous HMF-AL.. · The incidence of feeding intolerance (stopping feeds >8 hour) in any given week of fortification was low and not different between groups. Also, late-onset sepsis and necrotizing enterocolitis were uncommon with no differences between groups, whereas the incidence of metabolic acidosis was lower in infants receiving the LHMF-NEW.. · No differences in length of stay or anthropometrics at discharge were identified..

Fig. 1

( A ) Total fluid intake over the first 4 weeks of fortification for the groups receiving HMF-AL (blue) or LHMF-NEW (light blue) shown as median and 25 to 75 IQR, vertical lines represent the range. The total N per week of fortification is shown in the x -axis. There were no significant differences. ( B ) Total protein intake over the first 4 weeks of fortification for the groups receiving HMF-AL (blue) or LHMF-NEW (light blue) is shown as median and 25 to 75 IQR, vertical lines represent the range. The total N per week of fortification is shown in the x -axis. Significant differences in HMF-AL versus LHMF-NEW (median [IQR]): Week 1, 3.80 [3.53, 4.08] versus 3.63 [3.38, 3.90], p  < 0.001; Week 2, 4.22 [3.95, 4.43] versus 4.10 [3.75, 4.40], p  = 0.015; Week 3, 4.30 [4.00, 4.50] versus 4.16 [3.80, 4.40], p  = 0.006. ( C ) Total calorie intake over the first 4 weeks of fortification for the groups receiving HMF-AL (blue) or LHMF-NEW (light blue), shown as median and 25 to 75 IQR, vertical lines represent the range. The total N per week of fortification is shown in the x -axis. Significant differences in HMF-AL versus LHMF-NEW (median [IQR]): before fortification, 97.0 [89.00, 106.2] versus 99.05 [92.12, 108.77], p  = 0.017. HMF-AL, human milk fortifier-acidified liquid; IQR, interquartile range; LHMF-NEW, new, liquid human milk fortifier.

Fig. 2

( A ) Growth rate over the study period calculated with the exponential method. Comparisons of the growth velocity regression lines for the HMF-AL (blue) and LHMF-NEW (light blue) groups were done using a repeated measures regression (see Methods) only including infants who received either fortifier throughout the first 4 weeks of treatment ( N  = 308). Gestational age, fortifier group, location, and gender were incorporated into the model. ( B ) Changes in weight Z-score over time for the groups receiving HMF-AL (blue) or LHMF-NEW (light blue) are shown as median and 25 to 75 IQR; vertical lines represent the range. No significant differences were identified. HMF-AL, human milk fortifier-acidified liquid; IQR, interquartile range; LHMF-NEW, new, liquid human milk fortifier; SOF, start of fortification.