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

Abstract

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.

Role of Bifidobacteria on Infant Health

“…However, breast milk also contains commensal bacteria (staphylococci, streptococci, lactic acid bacteria, and bifidobacteria) [19][20][21][22], which may also play a role in the dominance of this microorganism observed in breastfed infants. Moreover, the fact that breast milk promotes correct neonatal microbial and immune system development, prevents several non-communicable diseases, and improves cognitive outcomes [23][24][25][26] has prompted the industry towards the supplementation of infant formulas with these microorganisms.…”

Biology of human milk oligosaccharides: From basic science to clinical evidence

“…Development of the immune system is particularly important in infants born preterm, who are at increased risk of numerous health problems such as NEC, sepsis and cerebral palsy, which are all at least partly linked to an inappropriate immune reaction. Human milk feeding strongly reduces the risk of developing these diseases, probably by its immune modulating effects through components with direct action and others that involve the development of the gut microbiome 11,118–121 . Several blends and individual HMOs have been investigated for their protective effects in preclinical NEC models.…”

“…Human milk feeding strongly reduces the risk of developing these diseases, probably by its immune modulating effects through components with direct action and others that involve the development of the gut microbiome. 11 , 118 , 119 , 120 , 121 Several blends and individual HMOs have been investigated for their protective effects in preclinical NEC models. In rodent models, not only DSLNT, 122 but also 6'‐SL and 2'‐FL, 45 , 123 , 124 showed some protection against the severity of NEC.…”

Extracellular vesicles in human milk

“…Necrotizing enterocolitis (NEC), an acute inflammatory disease, is one of the most severe gastrointestinal diseases in premature infants and develops in up to 10% of premature infants [63]. Human milk has been proved to reduce the risk of NEC [64,65]. Several in vivo and in vitro studies showed the potential of MDEVs to modulate NEC [37 ▪ ,66 ▪ ,67–69,].…”