Breastfeeding may protect against childhood asthma and allergic
disease, but this is controversial. Breastfeeding is critical
for optimum immune development of the infant through bioactivity
in milk and through impact on healthy establishment
of microbiota. Breast milk is best for babies because of its immunomodulatory
effects and protection against early infections.
Because early infections are a major risk factor for asthma
and allergic disease, protection through breastfeeding may
be a pathway that shields against allergic disease.
Exclusive breastfeeding for the first 6 months of life, and up to 2
years or longer, is encouraged as the “gold” standard for infant
feeding because breastfeeding has health benefits for mother
and child. Human maternal milk is uniquely suited to the human
baby with nutritional composition as well as bioactive and
immunological factors that promote healthy development.
Breastfeeding has been associated with protection against early
respiratory infections, and the observed association between
breastfeeding and asthma at early ages may be mediated by
the protection of breastfeeding on infections. Compared to formula-
fed infants, breastfed infants have a healthier microbiota
that may be linked to a reduced risk of allergic disease.
Exclusive or predominant breastfeeding to at least 6 months
of age with continued breastfeeding up to 2 years is advised
to protect against early infections and strengthen the immune
system. Infants should be introduced to “tastes” of allergenic
foods, such as egg and peanut, slowly from 4 to 6 months to
develop oral tolerance. Lactating mothers should eat a healthy
diet to ensure the quality of their breast milk and improve the
quality and diversity of their microbiota.
Scholtens S, Wijga AH, Brunekreef B, Kerkhof M, Hoekstra MO,
Gerritsen J, et al: Breastfeeding, parental allergy and asthma in
children followed for eight years: the PIAMA birth cohort study.
Breastfeeding may protect against the development
of asthma and allergic disease in children, although
this topic has been controversial for more than 8
Breastfeeding is recommended for at least the first 6
months of life and up to 2 years for immunological
development of the infant.
Breastfeeding may influence immune responses
through the bioactive, immune-modulating
properties of breast milk, or through the impact of
milk type on intestinal microbiota.
The composition of breast milk cytokines deserves
further investigation, because cytokines may provide
protection against wheeze and subsequent asthma in
The worldwide prevalence of childhood asthma has been
increasing considerably, and the protection afforded by
breastfeeding in its development has been the subject of
controversy for more than 80 years. Previous systematic reviews
have generally found a protective effect of breastfeeding
on allergic outcomes, although many studies have methodological
limitations. Although breastfeeding is protective
against lower respiratory tract infection during infancy, such
protection has not been demonstrated for asthma in all
studies. Breastfeeding has health benefits for the mother
and child. Exclusive breastfeeding for the first 6 months of
an infant’s life, with continued breastfeeding for up to 2
years or longer, is recognized as the “gold” standard for infant
feeding because human milk is uniquely suited to the
human infant, and its nutritional content and bioactivity promote
a healthy development. There is increasing concern
that the practice of delaying complementary foods until 6
months may exacerbate the risk of allergic disease. Breast
milk contains immunological components that protect
against infections and allergic disease in infancy. The composition
of human breast milk is complex, containing factors
that interact with the infant immune system and intestinal
milieu including allergens, cytokines, immunoglobulins,
polyunsaturated fatty acids, and chemokines. Transforming
growth factor β is a cytokine in human milk involved in maintaining
intestinal homeostasis, inflammation regulation, and
oral tolerance development. Modern day society, with increased
standards of hygiene, has changed the gut flora of
Western infants, potentially impacting the risk of developing
immune-mediated diseases including allergic disease and
asthma. Microbial diversity is intrinsic to healthy immune
maturation and function. Compared to breastfed infants,
formula-fed infants had lower bacterial diversity and an altered
intestinal microbiota in the first few weeks of life associated
with an increased risk of eczema and asthma. Favorable
gut colonization through continued breastfeeding may
promote tolerance as well as protection when complementary
feeding is initiated.
Breastfeeding and Childhood Illness
Breastfeeding has numerous health benefits for the
mother and child . Exclusive breastfeeding for the first
6 months of an infant’s life, with continued breastfeeding
for up to 2 years or longer, is recognized as normal and
the “gold” standard for infant feeding [2, 3]. This is because
human maternal milk is uniquely suited to the human
infant, and its nutritional composition and non-nutritive
bioactive factors promote healthy development
and ultimately survival. Breast milk contains immune
factors such as IgA antibodies protecting against many
health problems in infancy, such as necrotizing enterocolitis,
overweight and obesity, diabetes, infections, and allergic
disease [2, 4], as well as reducing the risk of diseases
later in life .
In the past 30 years, the evidence for global breastfeeding
recommendations has evolved remarkably. Epidemiological
studies combined with growing insights from
epigenetics, stem cell research, and the “developmental
origins of health and disease” hypotheses offer strong and
solid support to the concept that breast milk is best for
human infants. Never before in science history has so
much been known about the complex significance of
breastfeeding for mothers and their children.
However, the protection afforded by breastfeeding
against the development of childhood asthma and allergic
disease has been the subject of controversy in the
literature. Although breastfeeding is protective against
lower respiratory tract infection during infancy, such
protection has not been demonstrated for asthma in all
studies. Issues related to study design, analytical methods,
and confounding have greatly complicated the interpretation
and comparison of studies. Furthermore,
asthma has a complex phenotype in which numerous
genetic and environmental determinants interact. Consequently,
the effect of any single determinant is likely
to be small and the independent effects difficult to quantify.
Asthma is common at a population level, and breastfeeding
is amenable to intervention, so a small effect
may have implications for public health. For this reason,
it is important to establish whether breastfeeding modifies
the risk of childhood asthma, even if the effect is
Against this background of breast milk significance,
there is evidence that breastfeeding may protect against
the development of asthma and allergic disease in children
although this has been controversial since it was first
observed more than eight decades ago [6, 7].
Definition of Infant Feeding
The World Health Organization  defines “exclusive
breastfeeding” as feeding with breast milk “only” with no
other liquid, solids, or vitamin drops. An infant who receives
water or juice but not formula is considered “predominantly
breastfed,” whereas an infant who receives
formula milk, if only for one feed, is considered “partially
breastfed,” and “never breastfed” refers to a situation
where breastfeeding was never initiated. Thereafter, to
meet their evolving nutritional requirements, infants
should receive nutritionally adequate and safe complementary
foods while breastfeeding continues for up to 2
years of age or beyond .
Definition of Allergic Disease
The definitions of allergic disease are varied and inconsistent
across studies. For example, different studies
have used allergen sensitization, self-report, or doctor diagnosis
to define presence of food allergy, with the first
two definitions correlating poorly with food challenge for
diagnosis of food allergy (the gold standard). Similarly,
diverse outcome definitions have been applied in studies
evaluating the impact of breastfeeding on eczema, asthma,
and allergic rhinitis .
To limit the scope of this review, the focus is largely on
asthma. Asthma represents a chronic, complex, polygenic
interaction in individuals with varying environmental
exposures . Asthma is the most chronic disease of
childhood and the leading cause of morbidity in children
globally as measured by emergency department visits,
hospitalizations, and days of missed school [11, 12].
Childhood asthma prevalence worldwide has been increasing
over decades, and a number of theories are proposed
to explain this startling trend. An overview of current
thinking in relation to the breastfeeding, asthma, and
allergic disease debate is given – from epidemiological,
nutritional, immunological, and gut microbial colonization
Determinants of Childhood Asthma and Allergic Disease
The disease has a broad spectrum of possible determinants
extending from genetics to lifestyle to environmental
factors. Environmental allergens such as smoking in
the household, house dust mite, grasses, or pollens may
be implicated. Lifestyle and environmental factors including
obesity, living in an urban environment, dietary
patterns including fast food and poor diet quality, formula
milk feeding, gut flora imbalance, smoking, pollution,
and infection (viral) have been associated with asthma
exacerbations in childhood
. Susceptibility to
asthma may be increased by
early life factors including low
birthweight, preterm birth,
young maternal age, and male
gender. On the other hand,
early exposure to respiratory infections may protect, although
certain infections may increase the risk .
Breastfeeding is implicated because it has been shown to
protect against early respiratory and other infections .
Epidemiological Studies on Breastfeeding, Asthma,
and Allergic Disease
Epidemiological studies in the debate as to whether
breastfeeding can have a role in protecting against allergic
disease and asthma in early childhood provide conflicting
results. While breastfeeding is recommended for all infants
irrespective of allergic heredity , with protective
effects of breastfeeding on asthma reported in young children
[16–18], other studies of children at high [19, 20] or
low risk  or adults [22, 23] show no protective effects.
Previous systematic reviews have found a protective
effect of breastfeeding on allergic outcomes, although
most studies have methodological limitations, such as
heterogeneity or noncompliant standards. A recent review
and meta-analysis aimed to identify and summarize
publications on breastfeeding and childhood asthma risk
in the general population as well as stratify analyses and
meta-regression to explore sources of heterogeneity .
Compared with other reviews, this review includes a large
number of studies, restricts search and study selection
minimally, and includes studies of different methodologies,
operational definitions for breastfeeding and asthma,
and sets of confounders . These criteria may have
increased the variability of effect estimates. Limitations
were overcome by performing meta-analyses in standardized
subgroups and meta-regressions with a broad
array of predictors. An assessment of the methodological
quality of the studies using criteria based on Kramer’s
standards  was made and a score based on these criteria
was included in the analyses, which addressed heterogeneity
between studies. The authors of this review
found evidence that children breastfed longer have a lower
risk for developing asthma (Fig. 1). Risk reduction was
pronounced in children 0–2 years of age, decreasing with
age, but still evident at school age with greater effects in
early life supporting the theory of protection from early
infection. Studies were highly
heterogeneous, and results
were similar when only longitudinal
cohort studies or
studies of high methodological
quality were included.
Few studies have attempted
to assess the association of breastfeeding over the
spectrum of allergic conditions: asthma, eczema, allergic
rhinitis, and food allergy, which is important because of
the substantial overlap in allergic diseases with shared
phenotypes. The systematic review of Lodge et al. 
aimed to analyze current evidence through proven
search methods, investigate the heterogeneity and quality
of included studies, and contextualize results with
respect to the findings related to breastfeeding and allergic
outcomes. In this review of various study types,
weak evidence that breastfeeding is protective for allergic
disease is evident. In spite of heterogeneity in the
studies of this review, there is strong evidence that
breastfeeding is associated with a reduced risk of asthma
Studies were further grouped into those reporting eczema
up to or beyond 2 years  (Fig. 3). A reduced risk
of eczema below 2 years was observed after pooling 6 cohort
study estimates comparing exclusive breastfeeding
for more than 3–4 months with other feeding types (re
OR 0.74, 95% CI 0.57–0.97, I2 62%). Weak evidence that
breastfeeding reduced the risk of eczema up to 2 years was
A review that included all study types published in
2011 considering breastfeeding and wheezing illness beyond
5 years of age only showed no association, highlighting
an enormous controversy in this area  . The authors
of this review recommend that further studies
should aim to be of the highest quality and specific diagnostic
criteria for asthma to be included.
A Birth Cohort “Case” Study
One cohort study assessed the association between
breastfeeding and asthma from 1 to 8 years and found that
breastfeeding for more than 4 months was associated with
significantly reduced asthma prevalence regardless of family
history and without evidence of attenuation . The
study population, 3,963 Dutch children born in 1996/1997
participating in the PIAMA birth cohort study, was followed
for 8 years. Asthma was defined as at least one attack
of wheeze and/or dyspnoea and/or prescription of inhalation
steroids in the previous 12 months. Chronic asthma
was defined as asthma diagnosis at 8 years with asthma
diagnosis in at least 2 other years. Specific IgE to common
airborne allergens and bronchial hyperresponsiveness
were measured according to a standard protocol .
Breastfeeding was defined as the duration of any breastfeeding
(no breastfeeding, breastfeeding for 1–16 weeks,
breastfeeding for more than 16 weeks). “Generalized estimating
equation” modelling was applied to test for associations
between breastfeeding and repeated respiratory
outcomes until 8 years adjusting for gender, maternal education,
smoking during pregnancy, and current smoking
and stratified by parental allergy. Because 10% of baseline
data were missing, missing data were imputed. Final imputation,
however, made no difference to the study findings.
In this study, asthma risk was shown to be lower in
children breastfed for more than 16 weeks compared to
those not breastfed . Children breastfed for the longer
duration had significantly fewer chronic asthma
symptoms. Having an allergic or nonallergic mother did
not change these associations. Breastfeeding for more
than 16 weeks was inversely associated with sensitization
to airborne allergens at 8 years with no association
observed for bronchial hyperresponsiveness. Breastfeeding
was associated with a lower asthma risk at all
years regardless of parental history. Repeated measures
analysis showed a lower risk of wheeze and asthma from
1 to 8 years in babies breastfed for a longer duration,
suggesting that breastfeeding affects long-term outcomes.
Strengths of the study include longitudinal design,
follow-up until 8 years, repeated measures of data
collection, a large study population, low attrition rate,
and multiple imputation. The birth cohort design with
longitudinal analysis allowed demonstration that breastfeeding
protects against asthma throughout childhood
both with and without a family history and contributing
significantly to the breastfeeding and childhood asthma
How May Breastfeeding Protect against Allergic Disease?
Timing of Introduction of Solids
There is increasing concern that the current practice
of delaying complementary foods to 6 months of age may
exacerbate the risk of immune disorders such as eczema
and allergic disease. In addition, evidence suggests that
favorable gut colonization through continued breastfeeding
may promote tolerance as well as protection when
complementary feeding is initiated. Conflict exists between
some allergy prevention guidelines that currently
recommend delaying the introduction of allergenic foods
until at least >12 months, whereas the new recommendations
are for the introduction of allergenic foods between
4 and 6 months  and not before 6 months . Prescott
et al.  suggested that early introduction of certain allergenic
foods is safe and may build tolerance. Other researchers
support the hypothesis that later introduction
of foods increases allergenic responses . Koplin et al.
 showed, following adjustment for confounding, that
a later introduction to egg increased rates of egg allergy
(OR 3.4, 95% CI 1.8–6.5, at >12 months) compared to introducing
egg between 4 and 6 months. These results have
major implications for practice and future research as
they suggest that the introduction of cooked egg at 4–6
months of age may protect against egg allergy and that
delaying introduction to egg may exacerbate it. Confirmation
of these findings may result in strong changes to
infant feeding guidelines, which currently recommend
delaying the introduction of allergenic foods until at least
The prevalence of peanut allergy among children in
Western countries has doubled in the past 10 years, and
therefore a study to evaluate strategies in preventing the
development of peanut allergy in infants at high risk for
the allergy was conducted  . The early introduction of
peanut significantly decreased peanut allergy development
among high-risk children and modulated immune
responses to peanuts. In response to these findings, guidelines
have recently changed in relation to peanut allergy
in the United States .
Bioactive Components in Milk
Breastfeeding protects against wheeze in infancy ,
and several components of human milk have been postulated
as conferring this protective effect . Protection
may be through a myriad of factors in milk including bioactive
enzymes, hormones, growth factors, cytokines, and
immunological agents. These findings augment and stimulate
host defense development [36, 37], suggesting that
bioactive components of milk are important in neonatal
development and biologically plausible mechanisms
through breastfeeding may impact asthma etiology.
Breastfeeding has been associated with protection against
early respiratory infections , and the observed association
between breastfeeding and asthma at early ages
may be mediated by the protection of breastfeeding
against infections. Breastfeeding may provide an immediate
line of defense against infectious agents, compensating
directly for immaturity of the newborn immune system
in its ability to resist infection . However, it is not
clear which components of this complex biological fluid
account for any potential protective effect.
The Composition of Breast Milk
One of the reasons that studies of breastfeeding and allergic
disease remain inconclusive could be the complexity
of interaction between breast milk, the infant intestinal milieu,
and the developing immune system. Some elements in
breast milk may protect the infant from developing allergies,
whereas others may act in an opposing way (Table 1).
The components of breast milk have immunomodulatory
activity, including antigens (allergens), cytokines, immunoglobulins,
polyunsaturated fatty acids, and chemokines
. It is known that secretory IgA (s-IgA) is passed
from mother to infant through breast milk or colostrum.
s-IgA may confer passive protection to the infant immune
system. Low levels of s-IgA in breast milk are associated
with an increased risk of cow’s milk allergy in infants. Lower
s-IgA levels to ovalbumin have been shown in colostrum
and mature milk of allergic mothers compared to mothers
without allergy, although the presence of these antibodies
was not predictive of allergies in their infants .
Cytokines are small soluble glycoproteins acting in an
autocrine-paracrine fashion by binding to specific cellular
receptors, operating in networks, and orchestrating
immune system development and function . Human
milk was revealed to contain cytokines more than 20
years ago , and early milk has an abundance of cytokines
at a time when neonatal organ systems are immature.
Cytokine concentrations may play a role in breast milk
immunogenicity. IL-4, IL-5, and IL-13 cytokines intimately
involved with IgE production and eosinophil induction
exist in higher concentrations in breast milk of
atopic mothers compared with nonatopic mothers. Soluble
CD-14 may protect against allergy development due
to its high concentrations in breast milk and importance
in the TH1 induction response to bacteria .
Transforming Growth Factor-β
Transforming growth factor-β (TGF-β) is a cytokine
identified in human milk , containing TGF-β1,
TGF-β2, and other isoforms at mRNA and protein levels
with TGF-β2 being the major isoform (95%) . The
immunoactive factors in breast milk may influence the
development and maturation of the mucosal immune
system of the infant [45–50], and mounting evidence suggests
that TGF-β, a multifunctional polypeptide, may be
a key immunoregulatory factor for the establishment of
this response, by promoting IgA production as well as induction
of oral tolerance [44, 49, 51–54]. TGF-β increases
the infant’s ability to produce IgA against β-lactoglobulin,
casein, gliadin, and ovalbumin . In an infant
prone to cow’s milk allergy, an increased TGF-β content
of mother’s milk may be beneficial by promoting IgG-IgA
antibody production and inhibiting IgE- and cell-mediated
reactions to cow’s milk [39, 54].
Original work [55, 56] showed that TGF-β1 was a
growth factor exhibiting pleiotropic regulatory effects on
developmental and physiological pathways. Disruption
of the TGF-β1 gene by homologous recombination in
murine embryonic stem cells generated mice that carry
the disrupted allele. Homozygotic animals for the mutated
TGF-β1 allele showed no gross developmental abnormalities
about 20 days after birth, but they then succumbed
to a wasting syndrome with a multifocal, mixed
inflammatory cell response and tissue necrosis leading to
organ failure and death . Letterio et al.  observed
that TGF-β-deficient mice survived while breastfeeding
(i.e., TGF-β1 gene knockout), indicating that maternal
sources of TGF-β1 via both placental transfer and milk
are essential for normal development and postnatal survival.
The role of milk-borne TGF-β in exposed lactating
mice to an airborne allergen assessed the development of
asthma in progeny. Breastfeeding-induced tolerance relied
on the presence of TGF-β during lactation, was mediated
by regulatory CD4+ T lymphocytes, and was dependent
on TGF-β signaling in T cells . Airborne allergens
transferred from mother to newborn through breast
milk induced antigen-specific tolerance in the offspring
resulting in protection against allergic disease. Breast
milk-mediated transfer of an antigen and TGF-β to the
neonate resulted in oral tolerance induction and antigenspecific
protection from allergic disease. Further, oral administration
of TGF-β in vivo in animal studies results in
biological activity sufficient to promote oral tolerance
New insights into the mechanisms underlying tolerance
induction in neonates pinpoint maternal influence
through “breast milk-mediated antigen transfer” as crucial
in the process. Because the amount of TGF-β in maternal
milk is less in mothers with atopic disease [59–61],
these and other findings  suggest that this milk cytokine
may influence the development of allergic disease
The publication of these reviews relating to TGF-β
regulation to immune responses [62, 63] and other studies
highlight the importance of milk TGF-β , although
the mechanistic pathways by which TGF-β modulates development
and maintenance of the immune system and
its role in regulation of tolerance and immunity has not
yet been fully described.
The administration of probiotics may increase human
milk TGF-β concentration depending on the probiotic
strain. Inverse effects have been seen with Lactobacillus
reuteri , and because concentrations of human milk
TGF-β may be critical in determining immune function,
more work is needed in this area.
Case Study: Infant Immune Study
Data on breastfeeding and infant wheeze were collected
from birth to 1 year from 243 mothers as part of the
Infant Immune Study in Tucson, AZ, USA . Breast
milk samples obtained at 11 days postpartum (mean age)
and assayed by ELISA for concentrations of TGF-β1, IL-
10, TNF-α, and soluble form of CD14 as well as cytokine
dose and its relationship with wheeze were assessed. An
increasing duration of breastfeeding was associated with
decreased prevalence of wheeze (p = 0.039). A higher
TGF-β1 dose was associated with less wheeze (p = 0.017)
at 1 year, showing a linear trend with wheeze (χ2 p =
0.006) when considered as a dose ( Fig. 4 ). The risk of
wheeze decreased (OR 0.22, 95%CI 0.05–0.89, p = 0.034)
with increasing dose of TGF-β1 (identified from longer
duration of breastfeeding and TGF-β1 concentration level,
as compared to short duration of breastfeeding and
low TGF-β1 concentration level) when adjusted for sex,
gestational age, maternal smoking, exposure to other
children, maternal education, and maternal asthma. The
dose of TGF-β1 from breast milk had a significant relationship
with infant wheeze at 1 year. Because wheeze is
a risk factor for asthma in childhood, this relationship is
The authors concluded that TGF-β from human milk
is a family of growth factors involved in maintaining intestinal
homeostasis, inflammation regulation, allergy
development, and promotion of oral tolerance development.
The dose of human milk TGF-β1 and TGF-β2 may
modulate or regulate immunological responses of infants
in early postnatal life. The composition of breast milk cytokines
deserves further investigation, because cytokines
may provide protection against wheeze and subsequent
asthma in childhood.
Polyunsaturated Fatty Acids and Polyamines
Polyunsaturated fatty acids and polyamines may impact
on the allergenicity and/ or immune protectiveness
of breast milk. A high arachidonic acid to eicosapentaenoic
acid ratio in breast milk may be associated with a
higher risk of allergic disease and atopy, although this is
controversial . How these various mechanisms of immunomodulation
are expressed in mother-infant pairs is
not known. Genetic factors may allow better predictability
but require future investigation to determine the complex
interaction effects of immunomodulatory factors in
milk and development of allergic disease .
Modern day society, with increased standards of hygiene,
has changed the gut flora of Western infants, potentially
impacting the risk of developing immune-mediated
diseases including allergic disease and asthma .
In adults, intestinal microbiota consists of several hundred,
mostly anaerobic, bacterial species. Formed through
successive establishment of different bacteria in infancy
and early childhood, this system is complex. Facultative
and aerotolerant bacteria establish first, followed by more
and more strict anaerobes, and commensal microbes provide
major incentive for immune system maturation.
The microbial colonization of the newborn intestine is
influenced by delivery and feeding mode, family structure,
and other lifestyle behaviors. Gut microbiota are required
for normal immune development, regulation of
gut inflammatory responses, and oral tolerance induction
to new foods . The specific microbial changes associated
with protection against allergic disease remain uncertain,
and more recent data suggest that microbial diversity
may be of relevance [69, 71, 72]. Altered intestinal
microbiota in the first few weeks of life is associated with
increased risk of eczema and asthma in infancy [7, 73–
75]. Mice raised in a germ-free environment failed to develop
oral tolerance and had persistent Th2-dependent
responses . This immune deviation may be experimentally
corrected by Bacteroides fragilis seeding, but
only during the neonatal period.
Breastfeeding for 4–6 months may assist in the development
of a healthy gut microbiota by providing bifidobacteria
and lactic acid bacteria that reinforce colonization
 and by supplying galacto-oligosaccharides that
promote a healthy microbiota composition. A wide variety
of galacto-oligosaccharides are found in breast milk,
exhibiting bifidogenic effects in the infant gut. Breast
milk also contains nucleotides, IgA, and antimicrobial
factors such as lactoferrin, which can modulate the infant
gut microbiota composition.
Breastfeeding facilitates the exchange of microbes between
mother and infant, and bacterial diversity could be
intrinsic to healthy immune maturation and function.
Minor differences are seen in microbial content between
breast- and formula-fed infants, reflecting improved infant
formulas in the past 30 years . Bifidobacteria and
lactobacillus are found in both breast- and formula-fed
babies, although formula-fed babies have more prevalent
and higher counts of Clostridium difficile, Bacteroides, enterococci,
and Enterobacteriaceae, while staphylococci
are more numerous in breastfed infants. Generally, formula-
fed infants had lower bacterial diversity. Further research
is required to define the microbial stimulus for
normal development, investigate the mechanisms involved,
and confirm the role of microbiota in protection
for allergic disease.
The Debate Continues
The debate whether breastfeeding protects against allergic
disease and asthma in children continues, and it is
still not possible to make a definitive conclusion regarding
this relationship. Much of the difficulty is in the various
study designs applied to ask the question. In addition,
other factors impact breast milk and its link to allergic
disease, such as the mother’s diet, the infant’s diet, maternal
microbiota and exposure to allergens in the environment,
timing of introduction to other foods, and composition
of the mother’s milk (nutritional, immunomodulatory,
bioactive). Many of these factors have not been
assessed in studies considering the research question
“does breastfeeding impact allergic disease?” Research
needs to consider confounding, effect modification, and
interactions. More research into the bioactive factors
within breast milk (such as TGF-β) is required to identify
possible effect modifiers. Finally, exclusive breastfeeding
for 6 months continues to be the keystone for the promotion
of allergy health and continues to be recommended
by international pediatric societies and academies [78,
The author has no conflict of interest to disclose. The writing
of this article was supported by Nestlé Nutrition Institute.
Ballard O, Morrow AL: Human milk composition:
nutrients and bioactive factors. Pediatr
Clin North Am 2013; 60: 49–74.
American Academy of Pediatrics: Policy
Statement: breastfeeding and the use of human
milk. Pediatrics 2012; 129:e827–e841.
World Health Organization Recommendations
on Postnatal Care of the Mother and
Newborn. Geneva, World Health Organization,
Matheson M, Allen KJ, Tang MLK: Understanding
the evidence for and against the
role of breastfeeding in allergy prevention.
Clin Exp Allergy 2012; 42: 827–851.
León-Cava N, Lutter C, Ross J, Martin L:
Quantifying the Benefits of Breastfeeding: A
Summary of the Evidence. Washington, Pan
American Health Organization, 2002.
Grulee CG, Sanford HN, Herron PH: Breast
and artificial feeding. JAMA 1934; 103: 735.
Grulee CG, Sanford HN: The influence of
breast and artificial feeding on infantile eczema.
J Pediatr 1936; 9: 223–225.
World Health Organization: Indicators for
Assessing Infant and Young Child Feeding
Practices: Conclusions of a Consensus Meeting
Held 6–8 November 2007 in Washington
D.C., USA. Geneva, 2008.
World Health Organization: Global Strategy
for Infant and Young Child Feeding. Geneva,
Becker A, Chan-Yeung M: Primary asthma
prevention: is it possible? Curr Allergy Asthma
Rep 2008; 8: 255–261.
Masoli M, Fabian D, Holt S, Beasley R; Global
Initiative for Asthma (GINA) Program:
The global burden of asthma: executive summary
of the GINA Dissemination Committee
report. Allergy 2004; 59: 469–478.
Ding G, Ji R, Bao Y: Risk and protective factors
for the development of childhood asthma.
Paediatr Resp Rev 2015; 16: 133–139.
Oddy WH, de Klerk NH, Sly PD, Holt PG:
The effects of respiratory infections, atopy
and breastfeeding on childhood asthma. Eur
Respir J 2002; 19: 899–905.
Oddy WH, Sly PD, de Klerk NH, Landau LI,
Kendall GE, Holt PG, et al: Breast feeding
and respiratory morbidity in infancy: a birth
cohort study. Arch Dis Child 2003; 88: 224–
Høst A, Halken S, Muraro A, Dreborg S,
Niggemann B, Aalberse R, et al: Dietary prevention of allergic diseases in infants and
small children. Pediatr Allergy Immunol
2008; 19: 1–4.
Oddy WH, Holt PG, Sly PD, Read AW, Landau
LI, Stanley FJ, et al: Association between
breastfeeding and asthma in 6 year old children:
findings of a prospective birth cohort
study. BMJ 1999; 319: 815–819.
Gdalevich M, Mimouni D, Mimouni M:
Breast-feeding and the risk of bronchial
asthma in childhood: a systematic review
with meta-analysis of prospective studies. J
Pediatr 2001; 139: 261–266.
Friedman NJ, Zeiger RS: The role of breastfeeding
in the development of allergies and
asthma. J Allergy Clin Immunol 2005; 115:
Wright AL, Holberg CJ, Taussig LM, Martinez
FD: Factors influencing the relation of
infant feeding to asthma and recurrent
wheeze in childhood. Thorax 2001; 56: 192–
Mihrshahi S, Ampon R, Webb K, Almqvist
C, Kemp AS, Hector D, et al: The association
between infant feeding practices and subsequent
atopy among children with a family
history of asthma. Clin Exp Allergy 2007; 37:
Kramer MS, Matush L, Vanilovich I, Platt R,
Bogdanovich N, Sevkovskaya Z, et al: Effect
of prolonged and exclusive breast feeding on
risk of allergy and asthma: cluster randomised
trial. BMJ 2007; 335: 815.
Sears MR, Greene JM, Willan AR, Taylor
DR, Flannery EM, Cowan JO, et al: Longterm
relation between breastfeeding and development
of atopy and asthma in children
and young adults: a longitudinal study. Lancet
2002; 360: 901–907.
Matheson MC, Erbas B, Balasuriya A, Jenkins
MA, Wharton CL, Tang ML, et al:
Breast-feeding and atopic disease: a cohort
study from childhood to middle age. J Allergy
Clin Immunol 2007; 120: 1051–1057.
Dogaru CM, Nyffenegger D, Pescatore AM,
Spycher BD, Kuehni CE: Breastfeeding and
childhood asthma: systematic review and
meta-analysis. Am J Epidemiol 2014; 179:
Kramer MS: Does breastfeeding help protect
against atopic disease? Biology, methodology,
and a golden jubilee of controversy. J Pediatr
1988; 112: 181–190.
Lodge CJ, Tan DJ, Lau MXZ, Dai X, Tham R,
Lowe AJ, et al: Breastfeeding and asthma and
allergies: a systematic review and meta-analysis.
Acta Paediatrica 2015; 104: 38–53.
Brew BK, Allen CW, Toelle BG, Marks GB:
Systematic review and meta-analysis investigating
breast feeding and childhood wheezing
illness. Paediatr Perinatal Epidemiol
2011; 25: 507–518.
Scholtens S, Wijga AH, Brunekreef B, Kerkhof
M, Hoekstra MO, Gerritsen J, et al:
Breastfeeding, parental allergy and asthma
in children followed for eight years: the PIAMA
birth cohort study. Thorax 2009; 64:
Burney PG, Luczynska C, Chinn S, Jarvis D:
The European Community Respiratory
Health Survey. Eur Respir J 1994; 7: 954–960.
Prescott SL, Tang MLK: The Australasian
Society of Clinical Immunology and Allergy
position statement: summary of allergy prevention
in children. Med J Aust 2005; 182:
Prescott SL, Smith P, Tang M, Palmer DJ,
Sinn J, Huntley SJ, et al: The importance of
early complementary feeding in the development
of oral tolerance: concerns and controversies.
Pediatr Allergy Immunol 2008; 19:
Koplin JJ, Osborne NJ, Wake M, Martin PE,
Gurrin LC, Robinson MN, et al: Can early
introduction of egg prevent egg allergy in infants?
A population-based study. J Allergy
Clin Immunol 2010; 126: 807–813.
Du Toit G, Roberts G, Sayre PH, Bahnson
HT, Radulovic S, Santos AF, et al: Randomized
trial of peanut consumption in infants
at risk for peanut allergy. N Engl J Med 2015;
Togias A, Cooper SF, Acebal ML, Assa’ad A,
Baker JR Jr, Beck LA, et al: Addendum guidelines
for the prevention of peanut allergy in
the United States: report of the National Institute
of Allergy and Infectious Diseases –
sponsored expert panel. J Allergy Clin Immunol
2017; 139: 29–44.
Field CJ: The immunological components of
human milk and their effect on immune development
in infants. J Nutr 2005; 135: 1–4.
Newburg DS, Walker WA: Protection of the
neonate by the innate immune system of developing
gut and of human milk. Pediatr Res
2007; 61: 2–8.
Garofalo RP, Goldman AS: Expression of
functional immunomodulatory and anti-inflammatory
factors in human milk. Clin
Perinatol 1999; 26: 361–378.
Hanson LÅ: Breastfeeding provides passive
and likely longlasting active immunity.
Ann Allergy Asthma Immunol 1998; 81:
Saarinen KM, Vaarala O, Klemetti P, Savilahti
E: Transforming growth factor-β1 in
mothers’ colostrum and immune responses
to cows’ milk proteins in infants with cows’
milk allergy. J Allergy Clin Immunol 1999;
Srivastava MD, Srivastava A, Brouhard B,
Saneto R, Groh-Wargo S, Kubit J: Cytokines
in human milk. Res Commun Mol Pathol
Pharmacol 1996; 93: 263–287.
Goldman AS, Rudloff HE: Are cytokines in
human milk? Adv Exp Med Biol 1991; 310:
Labéta MO, Vidal K, Rey Nores JE, Arias M,
Vita N, Morgan P, et al: Innate recognition of
bacteria in human milk is mediated by a
milk-derived highly expressed pattern recognition
receptor, soluble CD14. J Exp Med
2000; 5: 1807.
Böttcher MF, Jenmalm MC, Garofalo RP,
Björkstén B: Cytokines in breast milk from
allergic and nonallergic mothers. Pediatr Res
2000; 47: 157–162.
Kalliomaki M, Ouwehand A, Arvilommi H,
Kero P, Isolauri E: Transforming growth factor-
beta in breast milk: a potential regulator
of atopic disease at an early age. J Allergy
Clin Immunol 1999; 104: 1251–1257.
Goldman AS: Modulation of the gastrointestinal
tract of infants by human milk. Interfaces
and interactions. An evolutionary perspective.
J Nutr 2000; 130: 426S–431S.
Goldman AS, Chheda S, Garofalo R: Evolution
of immunologic functions of the mammary
gland and the postnatal development
of immunity. Pediatr Res 1998; 43: 155–162.
Noda K, Umeda M, Ono T: Transforming
growth factor activity in human colostrum.
Gann 1984; 75: 109–112.
Ogawa J, Sasahara A, Yoshida T, Sira MM,
Futatani T, Kanegane H, et al: Role of transforming
growth factor-beta in breast milk
for initiation of IgA production in newborn
infants. Early Hum Dev 2004; 77: 67–75.
Savilahti E, Siltanen M, Kajosaari M, Vaarala
O, Saarinen KM: IgA antibodies, TGF-beta1
and -beta2, and soluble CD14 in the colostrum
and development of atopy by age 4.
Pediatr Res 2005; 58: 1300–1305.
Donnet-Hughes A, Duc N, Serrant P, Vidal
K, Schiffrin EJ: Bioactive molecules in milk
and their role in health and disease: the role
of transforming growth factor-beta. Immunol
Cell Biol 2000; 78: 74–79.
Saarinen KM, Juntunen-Backman K, Jarvenpaa
AL, Klemetti P, Kuitunen P, Lope L,
et al: Breast-feeding and the development of
cows’ milk protein allergy. Adv Exp Med Biol
2000; 478: 121–130.
Shull MM, Ormsby I, Kier AB, Pawlowski
S, Diebold RJ, Yin M, et al: Targeted disruption
of the mouse transforming growth factor-
beta 1 gene results in multifocal inflammatory
disease. Nature 1992; 359: 693–
Kulkarni AB, Karlsson S: Transforming
growth factor-beta 1 knockout mice. A mutation
in one cytokine gene causes a dramatic
inflammatory disease. Am J Pathol 1993;
Verhasselt V, Milcent V, Cazareth J, Kanda
A, Fleury S, Dombrowicz D, et al: Breast
milk-mediated transfer of an antigen induces
tolerance and protection from allergic
asthma. Nature Med 2008; 14: 170–175.
Ando T, Hatsushika K, Wako M, Ohba T,
Koyama K, Ohnuma Y, et al: Orally administered
TGF-beta is biologically active in the
intestinal mucosa and enhances oral tolerance.
J Allergy Clin Immunol 2007; 120: 916–
Laiho K, Lampi AM, Hamalainen M,
Moilanen E, Piironen V, Arvola T, et al:
Breast milk fatty acids, eicosanoids, and cytokines
in mothers with and without allergic
disease. Pediatr Res 2003; 53: 642–647.
Rigotti E, Piacentini GL, Ress M, Pigozzi R,
Boner AL, Peroni DG: Transforming growth
factor-β1 and interleukin-10 in breast milk
and development of atopic diseases in infants.
Clin Exp Allergy 2006; 36: 614–618.
Oddy WH, Rosales FJ: A systematic review of
the importance of milk TGF-beta on immunological
outcomes in the infant and young
child. Pediatr Allergy Immunol 2010; 21: 47–
Li MO, Wan YY, Sanjabi S, Robertson AKL,
Flavell RA: Transforming growth factor-β
regulation of immune responses. Ann Rev
Immunol 2006; 24: 99–146.
Penttila I: Effects of transforming growth
factor-beta and formula feeding on systemic
immune responses to dietary beta-lactoglobulin
in allergy-prone rats. Pediatr Res 2006;
Rautava S: Potential uses of probiotics in the
neonate. Semin Fetal Neonatal Med 2007; 12:
Oddy WH, Halonen M, Martinez FD, Lohman
IC, Stern DA, Kurzius-Spencer M, et al:
TGF-β in human milk is associated with
wheeze in infancy. J Allergy Clin Immunol
2003; 112: 723–728.
Stoney RM, Woods RK, Hosking CS, Hill
DJ, Abramson MJ, Thien FC: Maternal
breast milk long-chain n-3 fatty acids are associated
with increased risk of atopy in
breastfed infants. Clin Exp Allergy 2004; 34:
Friedman NJ, Zeiger RS: The role of breastfeeding
in the development of allergies and
asthma. J Allergy Clin Immunol 2005; 115:
Adlerberth I, Wold AE: Establishment of the
gut microbiota in Western infants. Acta Paediatr
2009; 98: 229–238.
Tang MLK: Probiotics and prebiotics: immunological
and clinical effects in allergic
disease; in Tang MLK, Brandtzaeg P, Isolauri
E, Prescott SL (eds): Microbial-Host Interaction:
Tolerance versus Allergy. Nestlé Nutr
Inst Workshop Ser Pediatr Program. Basel,
Karger, 2009, vol 64, pp 219–238.
Adlerberth I, Strachan DP, Matricardi PM,
Ahrné S, Orfei L, Åberg N, et al: Gut microbiota
and development of atopic eczema in 3
European birth cohorts. J Allergy Clin Immunol
2007; 120: 343–350.
Wang M, Karlsson C, Olsson C, Adlerberth
I, Wold AE, Strachan DP, et al: Reduced diversity
in the early fecal microbiota of infants
with atopic eczema. J Allergy Clin Immunol
2008; 121: 129–134.
Penders J, Thijs C, van den Brandt PA, Kummeling
I, Snijders B, Stelma F, et al: Gut microbiota
composition and development of
atopic manifestations in infancy: the KOALA
Birth Cohort Study. Gut 2007; 56: 661–
Kalliomäki M, Kirjavainen P, Eerola E, Kero
P, Salminen S, Isolauri E: Distinct patterns of
neonatal gut microflora in infants in whom
atopy was and was not developing. J Allergy
Clin Immunol 2001; 107: 129–134.
Bjorksten B, Sepp E, Julge K, Voor T, Mikelsaar
M: Allergy development and the intestinal
microflora during the first year of life.
J Allergy Clin Immunol 2001; 108: 516–520.
Sudo N, Sawamura S, Tanaka K, Aiba Y,
Kubo C, Koga Y: The requirement of intestinal
bacterial flora for the development of an
IgE production system fully susceptible to
oral tolerance induction. J Immunol 1997;
Martín R, Olivares M, Marín ML, Fernández
L, Xaus J, Rodríguez JM: Probiotic potential
of 3 Lactobacilli strains isolated from breast
milk. J Hum Lact 2005; 21: 8–17.
Agostoni C, Braegger C, Decsi T, Kolacek S,
Koletzko B, Michaelsen KF, et al: Breastfeeding:
a commentary by the ESPGHAN
Committee on Nutrition. J Pediatr Gastroenterol
Nutr 2009; 49: 112–125.
Eidelman AI: Breastfeeding and the use of
human milk: an analysis of the American
Academy of Pediatrics 2012 Breastfeeding
Policy Statement. Breastfeed Med 2012; 7:
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