Fortification of Human Milk With Infant Formula for Very Low Birth Weight Preterm Infants: A Systematic Review

Abstract

Background: Off-label fortification of expressed human milk (HM) with infant milk formula (IMF) is common in developing countries, though its benefits and safety are unclear.

Objective: To study the effects of IMF fortification of HM on growth of very low birth weight (VLBW) preterm infants.

Design: Systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs).

Data sources and selection criteria: MEDLINE, EMBASE, CINAHL, CENTRAL and other databases were searched for articles published in English language from inception to December 2019, evaluating the effects of HM fortified with IMF as intervention, compared to unfortified HM or HM fortified with human milk fortifier (HMF).

Participants: Five RCTs including 423 VLBW preterm infants.

Intervention: Feeding with HM fortified with IMF compared to unfortified or HMF-fortified HM.

Outcome measures: Primary outcome measure was assessment of growth as weight, length and head circumference (HC) gain velocity. Secondary outcome measures were incidences of feed intolerance (FI), necrotizing enterocolitis (NEC), time to reach full feeds, concentration of nutritional biomarkers, duration of hospital-stay and cost of intervention.

Results: Of the five studies included in the review, pooled effects regarding weight gain velocity (SMD 0.27 g/day; 95% CI 0.08 to 0.62), length gain (MD 0.07cm/week; 95% CI 0.02 to 0.16) and HC gain (MD 0.05 cm/wk; 95% CI 0.01 to 0.11), were not statistically significant. Sensitivity analysis by pooling studies using unfortified milk as comparator yielded a statistically significant result for all growth parameters. Risk of FI or NEC was comparable. Length of hospitalstay was reduced in the intervention group.

Conclusions: A very-low quality evidence suggested that IMF fortification of HM is superior to unfortified milk and may be a safe alternative for HMF for short term growth of VLBW preterm infants.