Nutrition may:

be the source of antigens to which the immune system must become tolerant

provide factors, including nutrients, that themselves might modulate immune maturation and responses

provide factors that influence the intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses.

Nutrition in early in life may affect later immune competence, protection against infection, the development of tolerance to “self” and to benign environmental antigens, and the development of immunologic disorders. Evidence has accumulated for a large number of interactions between early nutrition and immune outcomes, but here we focus on the possible impact of malnutrition and of infant feeding.

Malnutrition and the immune response

Paediatricians have long known that severe underweight induces a secondary immunodeficiency, with increased infection rates, morbidity and mortality. These serious sequelae of malnutrition affect also children in affluent countries, including children with primary malnutrition due to neglect or abuse, infants compromised by preterm birth², and children suffering from diseases inducing secondary malnutrition³.

The degree of underweight or stunting has been associated with mortality, both in primary malnutrition and in childhood disease, although underlying mechanisms and the role of altered substrate metabolism are not fully understood^4,5. Deficiency of some individual nutrients such as vitamin A and zinc has adverse effects on infectious disease risk and child mortality, and marked health benefits are achieved with supplementation of depleted populations^4,6,7.

Malnutrition in early life also appears to have lasting long-term effects on immune function, i.e. an early metabolic programming of a later immune response⁸. Individuals born in Gambia, West Africa, during the annual hungry season suffer from a markedly increased occurrence of severe infectious diseases not in infancy and childhood, but rather after puberty, resulting in a ten fold higher risk for infection-related mortality in adulthood⁹. Thus, early nutrient supply appears to have long term immunomodulatory effects.

Mode of infant feeding

About one century ago in Europe, breastfed infants had a seven fold lower mortality than those who were not. With improvements in both hygiene and of the quality of breastmilk substitutes, this difference has fortunately disappeared, at least in affluent populations. How the infant’s immune response. In addition to providing nutrients, human milk contains a variety of compounds with anti-infectious properties (Table 1).

A large number of epidemiological studies have reported lower rates of infectious disease in fully and partially breast-fed than in formula-fed populations. In many studies these differences persist after adjusting for confounding factors such as socio-economic status.

Table 1. Selected humoral and cellular components of human milk with anti-infectious properties. Modified from¹⁰

Humoral compounds	Cellular compounds
Bile salt stimulated lipase	Epithelial cell membranes
Fibronectin	Lymphocytes
Immunoglobulins: sIgA, IgG, IgM, IgD	Milk fat globule membranes
Lactoferrin	Neutrophil granulocytes, macrophages
Lysozyme
Monoglycerides, non-esterified fatty acids
Mucines
Nucleotides
Oligo- and polysaccharides, glycoconjugates

The authors of a recent, detailed systematic review concluded that there is convincing evidence for a protective effect of breastfeeding against gastrointestinal infections, diarrhoea, and otitis media¹¹.

Possible protective effects were found for respiratory infections and urinary tract infections, whereas no evidence was found for protection against Haemophilus influenza infections, occurrence of fever, and of hospitalisation¹¹. The evidence from epidemiological studies is limited by possible residual confounding by factors associated with breastfeeding, which could be overcome by randomised controlled studies. Although it is generally not possible to randomise healthy infants to breast or formula feeding, two studies using a randomised approach are available.

In Belarus some 31 maternity departments were cluster-randomised in 1996-1997 to enhanced breastfeeding promotion or to a control intervention¹². The intervention achieved a longer duration of total breastfeeding and a higher incidence of exclusive breastfeeding at three months (43.3% vs 6.4%; p<.001) and at six months (7.9% vs 0.6%; p =.01), and was associated with a reduction of gastrointestinal infections (9.1% vs 13.2%; adj. OR, 0.60; 95% CI, 0.40-0.91) but not of other infections. It is noteworthy that in this study, non breastfed infants did not always receive high quality infant formulas.

In another trial in Nairobi, Kenya, pregnant women infected by the human immunodeficiency virus type 1 (HIV-1) who agreed to participate in the trial were randomly assigned at ~32 weeks of gestation to breastfeed their infant after birth (n=212), or to feed a powdered infant formula prepared with boiled water from a cup (n=213). Up to the age of 24 months, there was a significantly higher cumulative rate of HIV-1 infection in the breastfed population, but there was no difference either in mortality or in the incidence of acute or chronic diarrhoea. Thus, the extent of anti-infectious protection by breastfeeding may depend on the circumstances of the formula-fed population. Around the world the prevalence of different chronic inflammatory diseases,including allergies, asthma, atopy, and inflammatory bowel diseases has markedly increased¹. Although there are genetic predispositions to these diseases, the presence of certain polymorphisms alone is unlikely to explain the shift in disease prevalence. Thus, in addition to genetics, environmental factors must be considered. Epidemiological studies identified early exposure to microbes as an important protective factor for chronic inflammatory diseases, a concept referred to as the “hygiene hypothesis”^14,15. Also breastfeeding may furnish protective effects. In the above-mentioned clusterrandomised study in Belarus, the higher rates and longer duration of breastfeeding achieved with the intervention were associated with a significant reduction of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31- 0.95)¹². The systematic review of van Rossum et al found a probable protective effect against wheezing, asthma and eczema and a possible effect with atopy¹¹. Recent results from the Danish National Birth Cohort Study and from the German Infant Nutrition Intervention Trial suggest that the possible effects of breastfeeding may differ in infants with or without familial allergy risk. There is also evidence to link breast feeding with a reduced risk of later inflammatory bowel disease and childhood malignancies. Some recent data suggest that the introduction of gluten containing Beikost at a time when the infant is still breastfed may be related to a reduced risk of later celiac disease, a hypothesis which is now being tested in a controlled intervention trial.






Conclusions


Early feeding has a major impact both on immediate and long-term immune function. Prevention of inadequate nutrient supply as well as breastfeeding contributes to enhancing child health. Progress in the elucidation of the underlying physiology may provide the basis for further improvements of infant feeding concepts.

References

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