The effects of breastfeeding versus formula-feeding on cerebral cortex maturation in infant rhesus macaques

Abstract

Breastfeeding is positively associated with several outcomes reflecting early brain development and cognitive functioning. Brain neuroimaging studies have shown that exclusively breastfed children have increased white matter and subcortical gray matter volume compared to formula-fed children. However, it is difficult to disentangle the effects of nutrition in breast milk from other confounding factors that affect brain development, particularly in studies of human subjects. Among the nutrients provided by human breast milk are the carotenoid lutein and the natural form of tocopherol, both of which are selectively deposited in brain. Lutein is the predominant carotenoid in breast milk but not in most infant formulas, whereas infant formulas are supplemented with the synthetic form of tocopherol. In this study, a non-human primate model was used to investigate the effects of breastfeeding versus formula-feeding, as well as lutein and natural RRR-α-tocopherol supplementation of infant formula, on brain maturation under controlled experimental conditions. Infant rhesus macaques (Macaca mulatta) were exclusively breastfed, or were fed infant formulas with different levels and sources of lutein and α-tocopherol. Of note, the breastfed group were mother-reared whereas the formula-fed infants were nursery-reared. Brain structural and diffusion MR images were collected, and brain T was measured, at two, four and six months of age. The mother-reared breastfed group was observed to differ from the formula-fed groups by possessing higher diffusion fractional anisotropy (FA) in the corpus callosum, and lower FA in the cerebral cortex at four and six months of age. Cortical regions exhibiting the largest differences include primary motor, premotor, lateral prefrontal, and inferior temporal cortices. No differences were found between the formula groups. Although this study did not identify a nutritional component of breast milk that could be provided to infant formula to facilitate brain maturation consistent with that observed in breastfed animals, our findings indicate that breastfeeding promoted maturation of the corpus callosum and cerebral cortical gray matter in the absence of several confounding factors that affect studies in human infants. However, differences in rearing experience remain as a potential contributor to brain structural differences between breastfed and formula fed infants.

Breastfeeding Duration Is Associated with Regional, but Not Global, Differences in White Matter Tracts

“…There are a number of reasons why we may not have replicated the finding associating breastfeeding duration and CC volume or FA scores, as has been found by others [3,8,10,11]. First, the growth and maturation of both grey and white matter in early development is dynamic and quite different from in an adult brain [11].…”

“…Cumulatively, these studies suggest that nutritional and development factors-among other influences present early in neurodevelopment-may have significant, long-lasting consequences. Breastfed children are shown to have greater grey matter than non-breastfed children, an effect that has been reported in both humans and macaques [4,10]. A previous study supported the notion that total white matter volume was correlated with increased consumption of breastmilk [3], but did not identify individual tracts or pathways.…”

“…Despite the numerous reported neurocognitive benefits of breastfeeding, the neurobiological underpinnings of how these effects may be conferred remains largely unknown. A few neuroimaging studies underscore the idea that brain grey matter and white matter tract maturation may reflect a mechanistic outcome, 2 of 12 including increased global grey [4,10] and white matter [3], and, enhanced white matter microstructure in a variety of specific pathways in the brain [8,11].…”

Late weaning and maternal closeness, associated with advanced motor and visual maturation, reinforce autonomy in healthy, 2-year-old children

“…Human milk components are likely to be contributing to these maturational processes: for example, carotenoids and luteins accumulate in the infant retina and brain, and have a beneficial effect on visual function 40,41 . In infant rhesus macaques, breastfeeding was better than formula feeding at promoting the maturation of the corpus callosum and cerebral cortical gray matter, measured at 2, 4 and 6 months of age 42 . A similar longitudinal neuroimaging study in children from 3 months to 9 years of age showed significantly improved overall myelination accompanied by increased general, verbal, and non-verbal cognitive abilities in those who were breastfed compared to children who were exclusively formula fed 43 .…”

Neonatal diet impacts liver mitochondrial bioenergetics in piglets fed formula or human milk

“…Recent studies have reported that milk formula-fed (MF) infants present more rapid weight gain during the first weeks of life compared to breastfed infants, and this appears to be associated with weight gain later in life [3][4][5]. The nutrient composition of human milk (HM) in comparison to milk formulas may play a significant role in the observed metabolic outcomes and the reported health differences when comparing these two neonatal diets [6][7][8][9][10][11]. Mitochondrial function and energy homeostasis impinge on all of these systems, but the role of infant diet and programming of cellular bioenergetics remains largely unexplored.…”