Effect of different feeding approaches on growth, neonatal morbidities, mortality and neurodevelopmental outcome in preterm infants: a systematic review and network meta-analysis

OBJECTIVE: To compare feeding strategies on preterm infants' growth during hospitalisation, neonatal morbidities, mortality and neurodevelopmental outcome (NDO) at 18-26 months corrected age. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension statement for network meta-analysis . We searched five medical databases for randomised controlled trials comparing different feeding approaches in preterm infants and their effects on growth, neonatal morbidities, mortality and NDO. The Cochrane Collaboration's tool was used to assess the risk of bias. We used a random-effects model. Pooled mean differences (MD) or risk ratios with 95% CIs were calculated. RESULTS: Ninety-five studies (9663 infants) were included.Human milk (HM) with bovine milk fortifier (BMF) (adjusted according to blood urea nitrogen) achieved the best length increment (MD=0.56 cm/week; 95% CI 0.19 to 0.93). Notably, HM+BMF (3.5 gm/kg/d protein) showed the best head circumference growth (MD 0.46 cm/week; 95% CI 0.10 to 0.81) but no significant difference in weight gain. There were no significant differences in neonatal morbidities/mortality. While MOM|+PTF (supp) displayed significantly lower NDO delay in the domain of mild cognitive delay. CONCLUSION: Overall, there is a lack of strong evidence to support a specific enteral feeding strategy and further high-quality research is required. Targeted HM fortification appears to improve head growth, while adjusted fortification enhances length. Given the significant inconsistency detected, which may compromise the reliability of the network estimates, these results must be interpreted carefully.