The first 1,000 days in the life of a human being are a vulnerable stage where early stimuli may program adverse health outcomes in future life. Proper maternal nutrition before and during pregnancy modulates the development of the fetus, a physiological process known as fetal programming. Defective programming promotes non-communicable chronic diseases in the newborn which might be prevented by postnatal interventions such as breastfeeding. Breast milk provides distinct bioactive molecules that contribute to immune maturation, organ development, and healthy microbial gut colonization, and also secures a proper immunological response that protects against infection and inflammation in the newborn. The gut microbiome provides the most critical immune microbial stimulation in the newborn in early life, allowing a well-trained immune system and efficient metabolic settings in healthy subjects. Conversely, negative fetal programming by exposing mothers to diets rich in fat and sugar has profound effects on breast milk composition and alters the immune profiles in the newborn. At this new stage, newborns become vulnerable to immune compromise, favoring susceptibility to defective microbial gut colonization and immune response. This review will focus on the importance of breastfeeding and its immunological biocomponents that allow physiological immune programming in the newborn. We will highlight the importance of immunological settings by breastfeeding, allowing proper microbial gut colonization in the newborn as a window of opportunity to secure effective immunological response.
Infant formulas have been conventionally prepared with an excess of total protein in order to provide sufficient amounts of essential amino acids to the rapidly growing infant. However, this practice leads to higher than necessary protein intake during early infant development, inducing accelerated growth patterns correlated with the development of chronic diseases later in life. This study was aimed at assessing the safety of an infant formula enriched with bovine alpha-lactalbumin containing a total protein concentration very close to that of human milk, and determining its efficacy in the support of healthy infant growth from the first month to the fourth month of age. Healthy full-term infants ≤40 days of age were randomized in this controlled single blind trial to one of the following infant formulas: IF 1 (containing 1.0 g protein/dL; n = 30), IF 2 (containing 1.3 g protein/dL; n = 24), and IF 3 (containing 1.5 g protein/dL; n = 42). A control group consisting of exclusively breastfed infants (HM; n = 212) was included in the study. Anthropometric measurements and Z-scores were evaluated at baseline, at 1 month of age, and at 4 months of age. Weight gain (g/day) was similar in the IF 1 and the HM groups (p = 0.644), and it was significantly greater in the IF 2 and IF 3 groups than in the HM group. Growth patterns in both breastfed or IF-fed infants were in accordance with the World Health Organization (WHO) growth standards. At four months of age, the mean weight-for-age Z-score (WAZ) adjusted for initial value in the IF 1 group was similar to that of the HM group and significantly lower than that of the IF 2 and IF 3 groups (p = 0.031 and p = 0.014 for IF 2 and IF 3, respectively). Length-for-age (LAZ) adjusted for initial value was similar among all groups at four months of age. From 1 to 4 months of life, IF 1 containing 1.0 g protein/dL promotes growth and weight gain similar to those observed in exclusively breastfed infants. As this is a first approach to studying an IF containing total protein in a level below that recommended by international committees on nutrition, further investigations are needed to support these findings evaluating infant’s metabolic profile and growth in the long term.
During pregnancy the human fetus receives timed cues from the circadian rhythms of temperature, metabolites, and hormones from the mother. This influence is interrupted after parturition, the infant does not secrete melatonin and their circadian rhythms are still immature. However, evolution provided the solution to this problem. The newborn can continue receiving the mother's timed cues through breastmilk. Colostrum, transitional, and mature human milk are extraordinary complex biofluids that besides nutrients, contain an array of other non-nutritive components. Upon birth the first milk, colostrum, is rich in bioactive, immunological factors, and in complex oligosaccharides which help the proper establishment of the microbiome in the gut, which is crucial for the infants' health. Hormones, such as glucocorticoids and melatonin, transfer from the mother's plasma to milk, and then the infant is exposed to circadian cues from their mother. Also, milk components of fat, proteins, amino acids, and endogenous cannabinoids, among others, have a markedly different concentration between day and night. In the present review, we give an overview of nutritive and non-nutritive components and their daily rhythms in human milk and explore their physiological importance for the infant. Finally, we highlight some interventions with a circadian approach that emphasize the importance of circadian rhythms in the newborn for their survival, proper growth, and development. It is estimated that ~600,000 deaths/year are due to suboptimal breastfeeding. It is advisable to increase the rate of exclusive breastfeeding, during the day and night, as was established by the evolution of our species.
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