Human vs. cow's milk fortifier in preterm infants: No significant outcome difference, study finds

By Dr. Liji Thomas, MDJan 3 2024

Extremely preterm infants remain a very high-risk category for illness and mortality. Prior research indicates this may be mitigated by feeding preterm infants with human milk fortified with a human milk-based fortifier (HMBF). A new research paper in The Lancet’s eClinical Medicine journal explores the effects of such feeding vs. fortifiers produced from cow’s milk.

Study: Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial. Image Credit: LullaBEE / Shutterstock

Introduction

Preterm birth is linked to many complications that lead to approximately 1 million deaths among under-5 children each year. Extremely preterm babies (born before they complete 28 weeks of gestation) are at greatest risk, and about a quarter of them die before one year, even in highly developed countries like Sweden.

Among the most severe of these complications is necrotizing enterocolitis (NEC), where the baby’s gut is deprived of blood supply and rots away. Up to one in seven babies born with a weight below 1500 g suffer from this illness. Late-onset sepsis is another common and life-threatening illness in this group, affecting up to a third of extremely preterm babies.

Breast milk, preferably the mother’s own, is the feed of choice for these babies, but donor milk or preterm formula is used if not available. Human milk reduces the risk of both these complications, while NEC risk increases with formula use.

However, human milk is insufficient to supply all the nourishment extremely preterm babies require, making fortification with protein imperative. While bovine milk-based fortifier (BMBF) has been the norm, increasing the rate of growth and the weight of the infant may increase the risk of NEC/sepsis and death. This has led to the development of HMBF.

However, there is little data based on a direct comparison of HMBF as fortification for extremely preterm babies.

The current paper describes the findings of a randomized controlled trial (RCT) from Sweden, carried out over 24 neonatal units. All babies involved were between 22 and ~28 weeks of gestation when born. All were given only human breast milk.

However, they were randomly assigned to be fed milk fortified with either HMBF or BMBF. Such fortification was begun before they began to take in 100 mL/kg/day by mouth. The aim was to investigate the effect of such fortification on the incidence of necrotizing enterocolitis (NEC), sepsis, and death by the 44^th week from the last menstrual period.

What does the study show?

The study included 228 babies. After randomization, 115 babies were given HBMF vs 113 on BMBF.

In both groups, the incidence of these complications was comparable. About a third of babies in each group had either NEC or sepsis or died.

Feeding intolerance occurred at the same rate in both groups, with babies taking a median of 10 days to reach full enteral feed volumes. There were no significant differences in adverse events between groups.

What are the implications?

This is the largest RCT conducted on HMBF in a group of babies born extremely preterm without previous formula feeding. Significantly, it was powered to detect differences in the incidence of severe outcomes between groups.

The researchers chose to club NEC, sepsis, and death together as the primary outcome of interest since NEC and sepsis often stem from common pathways and share the same clinical profile. Moreover, prior work suggested that HMBF benefited the risk of both conditions.

In the absence of any improvement in outcomes with HMBF supplementation, the scientists say, “Our results do not support routine supplementation with HMBF as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants exclusively fed human milk.”

HMBF could cost between €10,000 to €12,000 if continued up to 32 weeks from the LMP, making it unlikely to be a cost-effective intervention. In contrast, BMBF has been suggested to increase the cost of tertiary neonatal intensive care unit (NICU) care by 1.55-fold vs. HMBF.

These findings must be validated by more extensive trials to rule out differences in the rates of major complications or death. The effects may also vary with gestational age.