Absence of Evidence of Beneficial Effects of Human Milk‐Based Fortifier: A Bayesian Model‐Averaged Meta‐Analysis

Aim: Human milk-based fortifiers (HMBFs) have been adopted in neonatal care despite limited efficacy data. Our objective was to conduct a Bayesian re-analysis of the current evidence on the protective effect of HMBF against necrotising enterocolitis (NEC, stage II-III). Methods: We searched for randomised controlled trials (RCTs) comparing HMBF versus bovine milk-based fortifier (BMBF) in infants with gestational age < 32 weeks or birthweight < 1500 g. Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1, presence of effect) over the probability of the data under the null hypothesis (H0, absence of effect). Results: We included 3 RCTs (405 infants). The BMA analysis did not show conclusive evidence in favour of H1 (BF10 > 3) or in favour of H0 (BF10 < 1/3) for NEC (BF10 = 0.86), mortality (BF10 = 1.07), late onset sepsis (BF10 = 0.69), bronchopulmonary dysplasia (BPD, BF10 = 0.92), or severe retinopathy of prematurity (ROP, BF10 = 0.75). Conclusions: The extant corpus of RCTs does not provide sufficient evidence to either confirm or exclude a potential effect of HMBF compared with BMBF on the risk of NEC, mortality, sepsis, BPD, or severe ROP.