Early versus late fortification of breast milk in preterm infants: a systematic review and meta-analysis

This systematic review and meta-analysis assessed the effects of early fortification (EF) versus late fortification (LF) of breast milk (BM) on growth of preterm infants. Randomized and quasi-randomized controlled trials (RCTs) dealing with the effects of EF versus LF on growth parameters, incidence of adverse events, and duration of hospital stay in preterm infants were included. Data were pooled using the RevMan 5.3 software. Quality of evidence for predefined outcomes was analyzed by GRADE. Available evidence (3 RCTs, 309 preterm infants) showed no statistically significant difference between EF and LF of BM for any of the growth parameters—weight (standardized mean difference (SMD) 0.13; 95% confidence interval (CI) − 0.09, 0.36); length (SMD 0.02; 95% CI − 0.20, 0.25); and head circumference (SMD − 0.10; 95% CI − 0.33, 0.12). Total parenteral nutrition days were similar. Duration of hospital stay was significantly higher with EF (MD 4.29; 95% CI 0.84, 7.75) with a trend of non-significant increase in feed intolerance and necrotizing enterocolitis (NEC).