Supplementary Material for: Early versus Delayed Fortification of Human Milk in Preterm Infants: A Systematic Review

Expressed breast milk (EBM) is commonly supplemented with commercially prepared human milk fortifier to meet the additional nutritional needs of preterm infants. The optimal milk intake at which to introduce fortification is unknown. The objective of this systematic review was to compare the effect of early fortification (EF) versus that of delayed introduction of human milk fortifier (DF) on short-term outcomes including growth, feeding intolerance, length of hospital stay, and maturity at discharge in very-low-birth-weight infants. The search was carried out until March 2019 using 5 electronic databases (PubMed, Ovid Medline, Web of Science, Ovid Embase, and the Cochrane Library). The search was supplemented with a search of the clinical trial registry and reference lists. Eligible studies involved randomized controlled trials that had been designed to compare EF against DF using multi-nutrient fortifier for infants of a birth weight of <1,500 g who were fed exclusively or predominantly EBM. Four authors independently screened the studies for eligibility. A total of 1,972 articles were screened; 2 studies met the inclusion criteria and were included with a total number of participants of 171. The definition of EF and DF was not consistent between the 2 studies. There was no significant impact of EF versus DF on all outcomes. In conclusion, current data are limited and do not provide evidence on the optimal time to start fortification. The definition of EF and DF needs to be agreed upon and further larger randomized controlled trials are required.