LÅ Hanson

Abstract

Breastfeeding has been clearly shown to significantly reduce morbidity and mortality in diarrhoea and pneumonia. Furthermore, it protects against neonatal septicemia, necrotising enterocolitis, urinary tract infections and otitis media. There is also good evidence the protection remains at a higher level than in non-breastfed for years after the termination of breastfeeding. This has been demonstrated for otitis media, respiratory tract infections, wheezing bronchitis, diarrhoea and Haemophilus influenzae type b infections. Vaccine responses also seem to be enhanced by breastfeeding. This suggests that mother's milk can actively stimulate the immune system of the infant via its cytokines, anti-idiotypic antibodies and T and B lymphocytes. Such active stimulation of the infant's immune system may explain why breastfeeding protects against coeliac disease, most likely against allergies and possibly against autoimmune diseases.

Man is the only mammal which interferes with breastfeeding. There is evidence that this has taken place far back in time, even thousands of years.¹ Today we know that breastfeeding is an ideal source of nutrient for infants, which for instance seems to enhance neurological development with faster development of vision and increased IQ as a result.^2-3

It was debated for a long time whether or not breastfeeding prevents infections. This has now been clearly proven, but data is also appearing that breastfeeding has more long lasting effects by actively influencing the infant's own immune system. As a result there is improved protection against infections also after the termination of breastfeeding. This editorial will review the data supporting these concepts.

Breastfeeding Protects Against Infections

The protection against infections during breastfeeding has been studied repeatedly. With good epidemiological techniques several investigators have now settled old controversies demonstrating a significant decrease in morbidity and mortality in several infectious diseases.⁴ Thus the risk of dying from diarrhoea in poor countries is 25 times higher among non-breastfed compared to exclusively breastfed.⁵ It is notable that breastfeeding protects against acute as well as prolonged diarrhoea.^6-7 This is important since the risk of dying is 5 times higher in prolonged than acute diarrhoea.⁸

The mortality in pneumonia was 3.6 times higher among non-breastfed Brazilian children than among breastfed. Partially breastfed had 1.6 times lower risk than nonbreastfed.⁹ These effects of breastfeeding are so strong that WHO evaluates that an increase in breastfeeding by 40% would reduce respiratory deaths by 50% and diarrhoea, deaths by 66% world wide in children <18 months of age.¹⁰

Significant protection against diarrhoea, respiratory tract infections, otitis media, necrotizing enterocolitis and urinary tract infections has been confirmed in several studies in developed countries.^4,11-14

Modes of protection of the infant by the mother

The presented results give a good basis for promotion of breastfeeding, which provides the infant with high doses of protective secretory IgA antibodies that are especially resistant to proteolysis and pH changes making it possible for them to function on mucosal membranes such as in the gut. Without inducing inflammation they prevent infections just by blocking the attachment of microbes to mucosal membranes, which is the initial step in all infections taking place via mucosae. That is the great majority of infections, especially in the child.

Such non-inflammatogenic host defence via the milk is in contrast to the tissue defence provided via the maternal IgG antibodies obtained via the placenta. These protect tissues and always cause energy- consuming inflammation when acting. Such inflammation is a major cause of the undernutrition following upon repeated or chronic infections. This is the background to the fact that milk-mediated protection of the infant is so effective by preventing infections in an energy-saving non-inflammatogenic way.

The secretory IgA antibodies are produced in the mammary glands by lymphocytes which have migrated there primarily from the Peyer's patches in the gut. There they have been exposed to all the microbes, foods etc., which pass through the mother's gut. As a consequence the mother's milk contains secretory IgA antibodies against all the microbes the infant might be exposed to, since these lymphocytes do not only originate from recent antigen exposure in the gut of the mother, but also include memory cells representing previous encounters with microbial and other antigens in the mother's life.

Human milk contains numerous other defence factors like IgG and IgM antibodies, the strongly bactericidal and anti-inflammatory lactoferrin, multiple T and B lymphocytes, macrophages and granulocytes.

Mechanisms of the active stimulation of the infant's immune system by breastfeeding

Recent studies have shown that the milk normally contains not only antibodies but also anti-antibodies (anti-idiotypes). Such antibodies are specific for the antigen binding site of the first antibody and may function as a stimulator of the immune system like an antigen. We have shown that Swedish mothers' milk contain anti-idiotypic antibodies to poliovirus and may possibly stimulate the breast-fed infant's immune system.¹⁵ Two experimental studies in mice have actually shown that transfer of anti-idiotypic antibodies via milk actively primes antibody responses in the neonate.^16-17

There is also interesting evidence of transfer of leucocytes, especially lymphocytes, from the milk to the offspring in several models. Labelled milk lymphocytes were demonstrated in the intestinal mucosa, the spleen, mesenteric lymph nodes and lungs of the recipient.^18-20 Transfer of B lymphocytes via milk to B cell deficient animals resulted in antibody production in the recipients.²¹

This cell transfer might explain the fact that breastfed individuals seem to be tolerized to maternal HLA antigens. As a result renal transplants do much better from mothers to offsprings who have been breastfed than not breastfed.²² The same result is seen for renal transplants between breastfed siblings.²³ A transplant from the father does worse. Breastfed infants have fewer lymphocytes reacting with maternal HLA.²⁴ The fact that the thymus is much larger among breastfed than non breastfed infants may be another sign of effects on the infant's immune system by breastfeeding.²⁵

Possible consequences of the active effects on the infant's immune system by breastfeeding

Careful epidemiological studies have shown that breastfed infants are better protected against certain infections than not breastfed for years after the termination of lactation.⁴ Thus Swedish infants remained better protected against Haemophilus influenzae type b infection still 10 years later.^26,27 Such data were also collected for diarrhoea, respiratory tract infections and otitis media.^11,28,29 The occurrence of wheezing bronchitis was less common still 6-7 years after the termination of breastfeeding.³⁰ This could be an anti-allergy effect, but could also be due to prevention of the viral infections which are known to initiate some 85 % of attacks of wheezing bronchitis. The protective effect was mainly seen among non-atopic children.^31,32

Certain studies suggest that breastfeeding enhances vaccine responses against tetanus, diphtheria, polio virus, Haemophilus influenzae type B and BCG vaccines.^33-36 Other studies have not confirmed all of these observations. Further work is important.

It has long been debated whether or not breastfeeding prevents allergy and asthma. There are reports showing an effect, or a temporary effect and others which show no effect.⁴ Recently an interesting study by Saarinen and Kajosaari from Finland indicated that there was significant protection against food allergy at 2-3 years of age followed by significant protection against inhalant allergy up to the age of 17 when the follow up was completed.³⁷

There are several publications suggesting that breastfeeding may decrease the risk of certain autoimmune diseases like type 1 diabetes,⁴ but that has been questioned.³⁸ Single studies indicate that there may be protection by breastfeeding against rheumatoid arthritis, multiple sclerosis, lymphoma, appendicitis, tonsillitis, pyloric stenosis.⁴ All these investigations need to be confirmed. This is also true for the observations that breastfeeding may decrease the risk of Crohn's disease and ulcerative colitis,^39,40 whereas the data showing protection against coeliac disease seem quite convincing.⁴¹ The risk of developing disease seems to be diminished if gluten is introduced during breastfeeding.^42,43

The background to these effects might be that the stimulated immune system of the breastfed infant might give better vaccine responses and better protection against infection. Such a stimulated immune system might possibly also be better controlled and more ready to respond with immunological tolerance to allergens and autoantigens.

In conclusion, it seems that scientific evidence give strong arguments for breastfeeding. It protects efficiently in developing as well as developed counties against numerous infections not only during breastfeeding, but in several instances also for years afterwards.

In addition it might be that the immune system of the breastfed infant after active stimulation by immune components in the mothers' milk is in better control with a deceased risk of immunological diseases like allergy, autoimmune diseases and inflammatory bowel diseases as a result. This, however, must be further studied.

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