Does the Rate of Increasing Milk Volume Matter in Preterm Infants?

Published - Written by Ken Wu, MBBS, MRCPCH

The essence of neonatal care is to enable infants to grow and develop and stay healthy while doing so. In fact, the phrase “feeding and growing” is ubiquitously used by neonatologists when referring to preterm infants who are otherwise well in the neonatal intensive care unit (NICU). As a pediatric resident on my NICU rotations, I regularly faced decisions about feeding tiny preterm neonates, some of whom were born as early as 27 weeks’ gestation and weighed only one kilogram. After initial resuscitation and stabilization, the questions of when, what, and how much to start and subsequently increase enteral feeds all have debatable answers.

The initial goal of feeding in preterm infants is to establish full enteral feeding. Approaches to achieving this goal strike a delicate balance between speed and safety, with attendings and fellows influenced by local practices in NICUs where they have worked and trained as well as evidence-based medicine. Case-control studies have shown that faster rates of advancement of feeding volumes increase the risk of necrotizing enterocolitis. However,  a meta-analysis showed that slower rates increase the risk of late-onset sepsis.

The multicenter, parallel-group, randomized-controlled Speed of Increasing Milk Feeds Trial (SIFT) further explored this issue in very preterm (<32 weeks’ gestation) or very low birth weight (<1500 g) infants. The results of the SIFT trial, recently published in NEJM, showed no significant difference in 24-month survival without moderate or severe neurodevelopmental disability in very preterm or very low birth weight infants between daily increases in milk volume of 30 mL/kg/day versus 18 mL/kg/day. Secondary outcomes, including rates of necrotizing enterocolitis and late-onset sepsis, also did not differ significantly between the two feeding strategies. These results bring into question the importance of a preferred rate of increasing milk volume to mitigate the risks of necrotizing enterocolitis, late-onset sepsis, and neurodevelopmental disability in preterm infants.

The following NEJM Journal Watch summary explains the study and results in more detail.


Feeding Rates and Developmental Outcomes in Very Preterm Neonates

Bruder Stapleton, MD reviewing Dorling J et al. N Engl J Med 2019 Oct 10

Neurodevelopmental outcomes at 24 months did not differ between neonates randomized to rapid or slow increases in milk volumes.

The effects of rapidly versus slowly increasing milk volumes to reach full feeding in very premature neonates remains unclear. In a multinational study of 2470 preterm neonates (gestational age <32 weeks or birth weight <1500 g), researchers compared 24-month neurocognitive outcomes between neonates randomized to daily increases in milk volume of either 30 or 18 mL/kg. Most children received breast milk, alone or with formula; only 70 received formula alone.

Median gestational age was 29 weeks. Approximately 95% of participants in each group survived to 24 months (corrected for gestational age). There was no significant difference in the rate of moderate or severe neurodevelopmental disability between the rapid- and slow-increment groups (31% and 28%). In the small subset that received formula alone, neurodevelopmental outcomes were worse in the rapid-increment group. Secondary outcomes of cerebral palsy, late-onset sepsis, necrotizing enterocolitis, weight change at discharge, and length of hospital stay were not statistically different between the two groups. Few adverse events occurred.

Comment: Although this important study does not help define a preferred feeding protocol for very premature infants, it offers reassurance that careful feeding with daily increases of either 30 or 18 mL/kg has comparable outcomes. The study included too few infants fed with formula alone to determine whether outcomes differ with breast milk or formula feeds.


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 Ken is a 2019-2020 NEJM Editorial Fellow and a paediatrician working in the National Health Service of the United Kingdom. He graduated from Imperial College School of Medicine and is training in general paediatrics in London.