Human milk feeding and cognitive outcome in preterm infants: the role of infection and NEC reduction

Pediatr Res. 2022 Apr;91(5):1207-1214. doi: 10.1038/s41390-021-01367-z. Epub 2021 Jun 24.


Background: Breast milk has been associated with lower risk of infection and necrotising enterocolitis (NEC) and improved long-term cognitive outcomes in preterm infants but, if unsupplemented, does not meet the nutritional requirements of preterm infants.

Methods: Preterm infants were randomised to receive a high nutrient intervention diet: preterm formula (PTF) or the standard diet: term formula (TF) or banked donor breast milk (BBM), either as their sole diet or as supplement to maternal breast milk (MBM). IQ tests were performed at ages 7, 15, 20, and 30 years.

Results: An increase in MBM and BBM intake was associated with a lower chance of neonatal infection/NEC. Neonatal infection/NEC was associated with lower Full Scale IQ (FSIQ) and Performance IQ (PIQ) score at ages 7 and 30 years. The relationship between higher intake of MBM and PIQ at age 7 years was partly mediated by neonatal infection/NEC. The intervention diet was associated with higher Verbal IQ (VIQ) scores compared to the standard diet. There was no evidence that these effects changed from childhood through to adulthood.

Conclusions: Neonatal diet is an important modifiable factor that can affect long-term cognitive outcome through a 'human milk' factor, protecting against infection/NEC, and a 'nutrient content' factor.

Impact: This is the first study to demonstrate the effects of neonatal infection/necrotising enterocolitis (NEC) on IQ in the same cohort in childhood and adulthood. Diet can be a key factor in long-term cognitive outcome in people born preterm by preventing neonatal infection/NEC and providing adequate nutrients. Human milk, whether MBM or BBM, is associated with a reduced risk of infection/NEC. A higher nutrient diet is associated with better cognitive outcome in childhood. Performance IQ is particularly vulnerable to the effects of infection/NEC and verbal IQ to the quantity of (macro)nutrients in the diet.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cognition
  • Enterocolitis, Necrotizing* / prevention & control
  • Female
  • Humans
  • Infant
  • Infant Nutritional Physiological Phenomena
  • Infant, Newborn
  • Infant, Newborn, Diseases*
  • Infant, Premature
  • Milk, Human
  • Young Adult