Nutrient Enrichment of Human Milk with Human and Bovine Milk-Based Fortifiers for Infants Born <1250 g: 18-month Neurodevelopment Follow-up of a Randomized Clinical Trial

Abstract

Abstract Background Bovine milk-based fortifiers (BMBF) have been standard of care for nutrient fortification of feeds for very low birthweight (VLBW) infants, however there is increasing use of human milk-based fortifiers (HMBF) in neonatal care despite additional costs and limited supporting data. No randomized clinical trial has followed infants fed these fortifiers after initial hospitalization. Objective To compare neurodevelopment in infants born weighing <1250 g fed mother's milk with supplemental donor milk and either a HMBF or BMBF. Methods This is a follow-up of a completed pragmatic, triple-blind, parallel randomized clinical trial conducted in Southern Ontario between August 2014 and March 2016 (NCT02137473) with feeding tolerance as the primary outcome. Infants weighing <1250 g at birth were block randomized by an online third-party service to receive either HMBF (n = 64) or BMBF (n = 63) added to mother's milk with supplemental donor milk during hospitalization. Neurodevelopment was assessed at 18-months corrected age using the Bayley Scales of Infant and Toddler Development, Third Edition. Follow-up was completed October 2017. Results Of the 127 infants randomized, 109 returned for neurodevelopmental assessment. No statistically significant differences between fortifiers were identified for cognitive composite scores (adjusted scores 94.7 in the HMBF group and 95.9 in the BMBF group; fully adjusted mean difference, −1.1 [95% CI: −6.5 to 4.4]), language composite scores (adjusted scores 92.4 in the HMBF group and 93.1 in the BMBF; fully adjusted mean difference, −1.2 [−7.5 to 5.1]), or motor composite scores (adjusted scores 95.6 in the HMBF group and 97.7 in the BMBF; fully adjusted mean difference, −1.1 [−6.3 to 4.2]). There was no difference in the proportion of participants that died or had neurodevelopmental impairment or disability between groups. Conclusions Providing HMBF compared to BMBF does not improve neurodevelopment scores at 18-months corrected age in infants born <1250 g otherwise fed a human milk diet. Trial Registration: NCT02137473, clinicaltrials.gov.