The role of breast-feeding in the development of allergies and asthma

doi:10.1016/j.jaci.2005.01.069

Journal of Allergy and Clinical Immunology

Volume 115, Issue 6, June 2005, Pages 1238-1248

https://doi.org/10.1016/j.jaci.2005.01.069 Get rights and content

Breast-feeding is the preferred method of infant nutrition for numerous reasons. However, its role in the prevention of allergic disease remains controversial. Reasons for this controversy include methodological differences and flaws in the studies performed to date, the immunologic complexity of breast milk itself and, possibly, genetic differences among patients that would affect whether breast-feeding is protective against the development of allergies or is in fact sensitizing. The preponderance of evidence does suggest, however, that there would be much to lose by not recommending breast-feeding. In general, studies reveal that infants fed formulas of intact cow's milk or soy protein compared with breast milk have a higher incidence of atopic dermatitis and wheezing illnesses in early childhood. Consistent with these findings, exclusive breast-feeding should be encouraged for at least 4 to 6 months in infants at both high and low risk of atopy and irrespective of a history of maternal asthma.

Section snippets

Immunologic complexity of breast milk

One of the major reasons that studies into the effect of breast-feeding with regard to the development of allergies remain so inconclusive may be the complexity of the interaction between breast milk and an infant's intestinal milieu and immune system. Some elements in breast milk are thought to act to protect the infant from developing allergies, whereas others might act in the opposite fashion (Table I).

It has long been known that secretory IgA (s-IgA) is passed from mother to infant via

Allergy genes

Although a full review of the current state of knowledge of allergy genes is beyond the scope of this article, the future of the predictability of any measures instituted in an allergy prevention program, including breast-feeding, might depend on such information. Many polymorphic genetic markers have been linked to an atopic phenotype.¹³ Although some loci appear to be associated with allergy in the population at large, others seem to be predictors of susceptibility only within certain ethnic

Exposure to infection

Infection in early childhood may have a dual effect. Early infection with respiratory syncytial virus and other viruses predispose susceptible infants to wheezing episodes. Breast milk may provide antiviral antibodies and other factors that reduce the incidence of these infections and subsequent wheezing. On the other hand, certain infections may be protective for allergy development by stimulating the T_H1 immune pathway. An important variable in assessing the role of breast-feeding in the

Allergens in breast milk

Food antigens have long been known to be detectable in breast milk. β-Lactoglobulin, casein, and bovine γ-globulin have been detected in nanogram concentrations in the breast milk of women not specifically avoiding cow's milk products during lactation.²⁷ Egg²⁸ and wheat²⁹ allergens have been detected in breast milk as little as 2 to 6 hours after maternal ingestion and can be detected as long as 4 days later. Peanut proteins have been measured in breast milk by both ELISA and immunoblot

Studies evaluating the role of breast-feeding in the development of atopy

Spawned by the work of Grulee and Sanford¹ in 1939, whose nonrandomized study of 20,000 infants suggested that breast-feeding reduces the incidence of eczema, numerous studies have attempted to examine further the role of breast-feeding in the development of allergy. Differences in methodology and inevitable flaws in design make these studies difficult to compare, and no single definitive study has yet been published. Methodological differences include whether a study is prospective or

Studies showing that breast-feeding protects against the development of atopy

In the late 1970s and 1980s, several studies comparing breast-fed to cow's milk formula-fed infants demonstrated a decreased incidence of atopic dermatitis,³² fewer episodes of wheezing,³² and lower serum IgE³³ in infants who were nursed. These studies varied in their conclusions whether this protective effect was relevant for all infants³⁴ or for high-risk infants only.³² One of these cohorts was the subject of a 17-year follow-up suggesting that the protective effect of breast-feeding could

Studies showing a neutral effect or that breast-feeding may induce the development of atopy

Other studies in the 1970s and 1980s showed no protective effect could be demonstrated vis-à-vis the development of food allergy in breast-fed infants compared with their cow's milk formula-fed counterparts.43, 44, 45, 46 One of these studies was limited by the lack of supporting immunologic data.⁴⁵

Some studies performed over the last decade have suggested that breast-fed infants have an increased risk of developing allergies compared with those fed cow's milk formula, particularly high-risk

Breast-feeding by mothers with asthma

In recent years, a new concern has been raised regarding breast-feeding by atopic mothers. Breast milk from atopic women has been noted to contain higher levels of IL-4, IL-8, RANTES, IgE, and n6/n3 polyunsaturated fatty acids, all thought to induce sensitization to allergens in the infant recipient. On the other hand, TGF-β1 and TGF-β2 levels, which are thought to protect against the development of allergies, are no higher in these mothers.⁵

Clinical concerns were raised by Wright et al⁵¹ as

Critical evaluations and meta-analyses of published data

A large, critical review of the literature from 1966 to 2001 by van Odjik et al⁵⁷ was published in 2003. A total of 4323 articles were reviewed, and more than 90% were excluded as noninformative. Fifty-six were considered conclusive and were analyzed. Retrospective and prospective studies were included in the analysis, but exposures and health effects had to be recorded and relevant, cohort selection had to be satisfactory, and the statistics had to be adequate. The studies were reviewed by

Duration of breast-feeding

If not breast-feeding is associated with an increase in the development of atopic disease, then how long should exclusive breast-feeding be continued to mitigate this consequence? In 1983, Kajosaari and Saarinen⁶¹ demonstrated a clear benefit of withholding solid foods in solely breast-fed infants for 6 months as opposed to only 3 months as measured by 1 year cumulative prevalence of eczema. This benefit appeared to be lost by 5 years of age.

More recently, the results of a Swedish prospective

Maternal avoidance diets during lactation

In searching for an explanation for the wide variety of results demonstrated in decades of studies evaluating the role of breast-feeding in the development of atopy, a logical suggestion has been that the presence of food antigens in breast milk might sensitize the infant if the mother does not avoid these foodstuffs in her diet during lactation. It is also invoked as a potential exposure route responsible for the development of atopic disease and sensitization in approximately 6% of

Probiotics in breast-feeding

In recent years, immunomodulation is being explored as a means of preventing atopy. The administration of probiotics or lactobacilli, nonpathogenic organisms which have been known to protect the gut against colonization with pathogens, is being evaluated as a means to encourage a T_H1-predominant immune system. Kalliomaki et al⁷¹ have reported a decrease in atopic dermatitis in infants whose mothers were given probiotics 4 weeks prepartum and during lactation. A concomitant decrease in total

Supplemental hypoallergenic formulas

In evaluating the role of breast-feeding in the prevention of atopy, it is necessary also to examine the role of formulas that are so frequently used in supplemental infant feeding. Extensively hydrolyzed formulas were first developed 60 years ago and have been an extremely important way of feeding infants with malabsorption, milk intolerance, and milk allergy. An ideal hydrolyzed formula should contain no peptides larger than 1.5 kd and no intact proteins, and should show protein determinate

Conclusion

It is widely accepted that breast-feeding is the ideal form of infant nutrition. Breast milk is highly nutritious, and the psychological benefits of mother-infant bonding that occur through nursing are myriad. However, despite decades of research and the fact that the AAP² and ESPACI/ESPGHAN³ recommend breast-feeding as part of an allergy prevention program, one can still not make a definitive statement that breast-feeding will help prevent sensitization to allergens in infants or later

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Seventy-three infants developed atopy. Forty-one were diagnosed with AD (25%), 33 developed food allergy (20%), and 10 had wheezing (6%). Eleven developed >1 condition (7%). Infants who did not develop atopy consumed higher concentrations of miR-375–3p (d = 0.18, P = 0.022, adj P = 0.044) and miR-148b-3p (d = 0.23, P = 0.007, adj P = 0.028). The consumption of miR-375–3p (X² = 5.7, P = 0.017, OR: 0.92, 95% CI: 0.86, 0.99) was associated with reduced atopy risk. Concentrations of miR-375–3p increased throughout lactation (r = 0.46, F = 132.3, P = 8.4 × 10⁻³⁴) and were inversely associated with maternal body mass (r = –0.11, t = –2.1, P = 0.032).
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: Disclosure of potential conflict of interest: N. Friedman, none disclosed; R. Zeiger received honoraria for lectures at scientific advisory board meetings for Ross Laboratories and Nestle USA, Nutrition Division.

View full text

Food allergy, dermatologic diseases, and anaphylaxisThe role of breast-feeding in the development of allergies and asthma

Section snippets

Immunologic complexity of breast milk

Allergy genes

Exposure to infection

Allergens in breast milk

Studies evaluating the role of breast-feeding in the development of atopy

Studies showing that breast-feeding protects against the development of atopy

Studies showing a neutral effect or that breast-feeding may induce the development of atopy

Breast-feeding by mothers with asthma

Critical evaluations and meta-analyses of published data

Duration of breast-feeding

Maternal avoidance diets during lactation

Probiotics in breast-feeding

Supplemental hypoallergenic formulas

Conclusion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Pediatr

Lancet

Int J Hyg Environ Health

Lancet

J Am Acad Dermatol

J Pediatr

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Pediatr

J Allergy Clin Immunol

The influence of breast and artificial feeding on infantile eczema

J Pediatr

Hypoallergenic infant formulas

Pediatrics

Arch Dis Child

Human milk polyunsaturated longchain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy

Pediatr Allergy Immunol

Cytokines in breast milk from allergic and nonallergic mothers

Pediatr Res

Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14

J Exp Med

A polymorphism∗ in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E

Am J Respir Cell Mol Biol

Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants

Clin Exp Allergy

Are milk polyamines preventive agents against food allergy?

Proc Nutr Soc

Eosinophil cationic protein in human milk is associated with development of cow's milk allergy and atopic eczema in breast-fed infants

Pediatr Res

Atopy and asthma genes—where do we stand?

Allergy

Genetic susceptibility to asthma and atopy among Chinese in Singapore—linkage to markers on chromosome 5q31-33

Allergy

A genome-wide search for quantitative trait loci underlying asthma

Nature

Association between atopy and variants of the subunit of the high-affinity immunoglobulin E receptor

Nat Genet

Protective and harmful effects of viral infections in childhood on wheezing disorders and asthma

Am J Respir Crit Care Med

Puzzling associations between childhood infections and the later occurrence of asthma and atopy

Ann Med

The causes of the increasing prevalence of allergy: is atopy a microbial deprivation disorder?

Allergy

Siblings, day-care attendance, and the risk of asthma and wheezing during childhood

N Engl J Med

Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods

J Pediatr Gastroenterol Nutr

Antibiotic use in early childhood and the development of asthma

Clin Exp Allergy

The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database

Am J Respir Crit Care Med

Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years

Am J Respir Crit Care Med

Passage of cows' milk protein in breast milk

Clin Allergy

Food allergy, dermatologic diseases, and anaphylaxis
The role of breast-feeding in the development of allergies and asthma

A polymorphism^∗ in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E