Design: Systematic review and meta-analysis of randomised trials
Population: Preterm or very low birthweight infants fed human milk, nine trials
Primary outcome: Mortality and necrotising enterocolitis
Effect: Fortifier alone: NEC RR 0.83 (95% CI 0.39–1.78); with donor milk replacing formula: RR 0.45 (0.20–0.99)

A meta-analysis of nine randomised trials compared human milk-derived with bovine protein-based fortifiers for preterm or very low birthweight infants fed human milk. The authors separated trials that changed only the fortifier from those that also replaced any shortfall in mother's milk with donor milk in one arm and preterm formula in the other.

When only the fortifier differed, there was no clear effect on mortality (RR 0.60, 95% CI 0.29 to 1.23) or necrotising enterocolitis (RR 0.83, 0.39 to 1.78). Necrotising enterocolitis fell (RR 0.45) only in the dual-intervention trials, where donor milk also replaced formula.

The practical reading is that the exclusive human milk diet, not the fortifier itself, is what appears to protect the gut. That matters for cost: human milk-derived fortifiers are expensive and scarce, whereas supporting mother's own milk and access to donor milk banks is achievable in many Indian neonatal units.

Prioritise mother's own milk for preterm infants, with lactation support from the first hours.
Use pasteurised donor milk rather than preterm formula when mother's milk is insufficient, where a milk bank is available.
Continue bovine fortifier where human milk-derived fortifier is unavailable or unaffordable.
Monitor growth on fortified feeds and adjust fortification to targets.

Why it matters

It redirects spending from an expensive product to the milk supply that actually seems to matter.

The statistics, in plain English

The mortality and NEC intervals for fortifier type alone cross 1.0 and are wide, so an effect cannot be confirmed or excluded. The NEC reduction of 0.45 came from trials where two things changed at once, so it cannot be credited to the fortifier.