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Infant Food Allergy: Where Are We Now?

  • Vickerstaff Health Services Inc


For many years, the prevailing maxim for prevention of food allergy in at-risk infants was to reduce allergic sensitization by avoiding exposure to highly allergenic foods until the baby's immune and digestive systems were sufficiently developed to cope with the allergen. Current thinking is completely different: exposure to food in the early stages of development may be the way to induce tolerance. Exclusive breastfeeding until 4-6 months, followed by introduction of complementary foods individually, is recommended. Any restrictions on mother's diet, other than avoidance of her own allergens during pregnancy and breastfeeding, are contraindicated. If a baby at high risk for allergy (defined as having 1 first-degree relative with diagnosed allergy) cannot be exclusively breastfed to 4-6 months of age, the preferred method of feeding for the prevention of atopic disease is an extensively hydrolyzed formula. There appears to be no value in delaying the introduction of any food beyond 6 months of age. Most food allergy is outgrown in childhood, but allergy to some foods tends to persist. Induction of tolerance to foods to which a child is allergic may be achieved by low-dose exposure in a process known as specific oral tolerance induction (SOTI). Early results indicate that some probiotic strains of bacteria, such as Lactobacillus rhamnosus GG or Lactobacillus F19, may reduce allergic sensitization.
Journal of Parenteral and Enteral
The online version of this article can be found at:
DOI: 10.1177/0148607111420155
2012 36: 49SJPEN J Parenter Enteral Nutr
Janice M. Joneja
Infant Food Allergy : Where Are We Now?
Published by:
On behalf of:
The American Society for Parenteral & Enteral Nutrition
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hosted at
For many years, the prevailing maxim for prevention of food allergy
in at-risk infants was to reduce allergic sensitization by avoiding
exposure to highly allergenic foods until the baby’s immune and
digestive systems were sufficiently developed to cope with the aller-
gen. Current thinking is completely different: exposure to food in
the early stages of development may be the way to induce toler-
ance. Exclusive breastfeeding until 4–6 months, followed by intro-
duction of complementary foods individually, is recommended. Any
restrictions on mother’s diet, other than avoidance of her own
allergens during pregnancy and breastfeeding, are contraindicated.
If a baby at high risk for allergy (defined as having 1 first-degree
relative with diagnosed allergy) cannot be exclusively breastfed to
4–6 months of age, the preferred method of feeding for the preven-
tion of atopic disease is an extensively hydrolyzed formula. There
appears to be no value in delaying the introduction of any food
beyond 6 months of age. Most food allergy is outgrown in child-
hood, but allergy to some foods tends to persist. Induction of toler-
ance to foods to which a child is allergic may be achieved by
low-dose exposure in a process known as specific oral tolerance
induction (SOTI). Early results indicate that some probiotic strains
of bacteria, such as Lactobacillus rhamnosus GG or Lactobacillus
F19, may reduce allergic sensitization. (JPEN J Parenter Enteral
Nutr. 2012;36:49S-55S)
Keywords: food allergy prevention; pediatric food allergy
management; probiotics in food allergy prevention; allergy
nutrition; specific oral tolerance induction (SOTI)
Infant Food Allergy:
Where Are We Now?
Janice M. Joneja, PhD
Financial disclosure: The publication of the supplement in which this article appears is sponsored by Nestlé Nutrition Institute.
high-risk infants have been used; the prevailing definition,
published as a joint statement of the European Society of
Paediatric Allergology and Clinical Immunology (ESPACI)
and the European Society for Paediatric Gastroenterology,
Hepatology and Nutrition (ESPGHAN)1 and the American
Academy of Pediatrics,2 defines high-risk infants as those
with at least 1 first-degree relative (parent or sibling) with
documented allergic disease, and most authorities rely on
this definition as the basis of their assessment of the at-
risk-for-allergy pediatric population.
Sensitization to food allergens occurs mainly in the
first year of life, and cow’s milk allergy is often the first
food allergy to appear in susceptible infants. The inci-
dence of allergy in children of allergic parents is signifi-
cantly greater than in children of nonatopics; it is
estimated that genetic factors account for 50%–70% of
asthma and allergy.3 However, many children who develop
atopic diseases during the first years of life come from
families without any history of allergy.
The potential to develop allergy is thought to be
inheritance of the Th2 response to allergens, not inherit-
ance of allergy to a specific allergen. Allergic sensitization
One of the most significant changes in pediatric
food allergy management in recent years has
been in strategies to prevent food allergy in early
infancy. Previously, the idea prevailed that if the most
highly allergenic foods are withheld from the infant until
the immune and digestive systems were more mature,
allergic sensitization would be prevented or significantly
reduced. Frequently, the advice regarding introduction of
the most highly allergenic foods was “the later the better.”
It was hoped that this would in turn prevent allergy not
only to food but to inhalant and contact allergies in later
life. However, new research seems to indicate the very
opposite—that exposure to allergens in early life may
actually tolerize the infant’s immune system and prevent
allergic sensitization to food.*
Early Allergy Predictors
Allergic diseases result from a strong relationship between
genetic and environmental factors. Various definitions of
From Vickerstaff Health Services, Inc, Kamloops, Canada.
Received for publication May 24, 2011; accepted for publica-
tion July 13, 2011.
Address correspondence to: Janice M. Joneja, PhD, Vickerstaff
Health Services, Inc, 2016 High Canada Place, Kamloops, V2E
2E3, Canada; e-mail:
*Allergic sensitization involves an immunological response to
the allergen with the production of allergen-specific IgE;
Immunological tolerance indicates that consumption of the
allergenic food does not result in an allergic response.
Symposium Report
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50S Journal of Parenteral and Enteral Nutrition / Vol. 36, Suppl. 1, January 2012
depends on the baby’s exposure to the allergen and the
response of his or her immune system at the time of expo-
sure, although some foods are more likely than others to
lead to allergy.
Food Allergy and Other Allergic Diseases
For many years, it was assumed that if the early onset of
allergy could be prevented or delayed, the child might avoid
what allergists like to call the “allergic march”—the pro-
gression from food allergy to inhalant-triggered respiratory
allergy and asthma, which usually have their onset at a
later age. It was assumed that the early expression of
allergy in the form of allergic reaction to foods “primed”
the immune system to take the Th2 route, and once
started, like a train starting from a station along a track, the
Th2 response would progress to respiratory allergy and
asthma. However, newer research has demonstrated that
this is not necessarily the case. Prevention of food allergy
in early infancy prevents or reduces food allergy; the direct
effect of food allergy in the development of allergy to air-
borne and environmental allergens has yet to be identified
by scientific studies. Nevertheless, it is extremely impor-
tant to prevent, reduce, or relieve food allergy as early as
possible because of the central role of allergy to foods in
many allergic diseases (particularly eczema), its contribu-
tion to asthma and allergic rhinitis, and the real danger of
life-threatening anaphylactic reactions.
This leads to an extremely important question: how
can we implement strategies to promote tolerance and
avoid sensitization of the baby to allergens? Clearly, the
first difficulty is in determining exactly when allergic sen-
sitization is likely to occur.
Does Atopic Disease Start in Fetal Life?
During pregnancy, immune responses in the uterus are
skewed to the Th2 (allergic) rather than the Th1 (protec-
tive) response because the fetus must be protected from
rejection by the mother’s system.4 The fetus, having
inheritance from both father and mother, has a different
cellular composition from its mother. Therefore, the
developing baby might be at risk of rejection by the
mother’s immune system, which would be a Th1 response.
To avoid this rejection, the fetal environment is thought
to develop a predominantly Th2 milieu, which suppresses
the mother’s protection/rejection response. This effec-
tively bathes the fetus in Th2-type cytokines that keep it
safe in its environment.
Because the fetus is enveloped by Th2-type cytokines
in the womb, it is logical to question whether allergens
from the mother’s diet might gain access to the developing
baby’s system and thereby start allergic sensitization even
before birth. Allergens have been detected in amniotic
fluid, indicating that allergenic material to which the
mother has been exposed can cross the placenta.5 However,
there is no real evidence to suggest that the fetal immune
system is primed to respond to these allergens.6 In fact,
some authorities suggest that exposure to food antigens in
utero may promote fetal tolerance7—that is, the immune
system is “educated” to recognize the food as “foreign but
safe” and not to mount a defensive action against it when
the food is encountered at any time in the future. So, in
utero exposure to food molecules may mark the beginning
of the ability to consume food with impunity.
At birth, all neonates have low levels of interferon
(INF)–γ and produce the cytokines associated with the
Th2 response, especially interleukin (IL)–4, and new-
borns of both atopic and nonatopic inheritance have a
predominantly Th2 response to antigens. As the baby
matures, there is a switch from the Th2 to the “protec-
tive” Th1 response, except in atopic babies, where the
Th2 response continues to predominate and sets the
stage for allergen sensitization and allergy.8 So here the
important question is, why do all neonates not have
allergy? New research is indicating that the answer may
lie with the immune system of the mother, which plays a
significant role in the expression of allergy in her baby.9
The only antibody that crosses the placenta from
mother to fetus is IgG. There are 4 subtypes of IgG, des-
ignated IgG1, IgG2, IgG3, and IgG4. IgG4 is frequently
associated with IgE in allergy. The nonatopic mother pro-
duces abundant IgG1 and IgG3, which cross the placenta
to protect her fetus in utero. Because food proteins can
cross the placenta, it is thought that fetal exposure to
these antigens in the environment of the uterus protected
by the mother’s IgG1 and IgG3 may promote fetal toler-
ance to these foods, and this continues in the neonatal
period. In contrast, the allergic mother tends to produce
IgE and IgG4; IgG4 is very poor at crossing the placenta,
and it is thought that the IgE/IgG ratio of the mother has
the greatest consequences for the offspring.9 In allergic
mothers, there is likely to be insufficient IgG1 and IgG3
to downregulate fetal IgE, and thus at birth, her baby may
be primed to become sensitized to allergens and to
develop allergic symptoms very early.
Although there is no evidence that the fetus of the aller-
gic mother can mount an IgE-mediated response to specific
allergens in utero, the potential to produce allergen-specific
IgE predominates at birth. The only defence against this at
present is to reduce the allergic mother’s exposure to her
own allergens throughout pregnancy in an attempt to
decrease her production of IgE and IgG4 and, it is hoped,
enhance production of the protective IgG1 and IgG3. The
mother should avoid foods to which she is allergic at all
times and obtain complete balanced nutrition from alternate
sources. There is no evidence to suggest that maternal avoid-
ance of any foods other than her own allergens (and not
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Infant Food Allergy / Joneja 51S
those of the baby’s father) during pregnancy will improve the
allergic status of her baby. A 1988 report10 indicated that
excluding highly allergenic foods from the mother’s diet
from week 28 to the end of pregnancy did not affect the
atopic status of the infant in any way.
Breastfeeding and Allergy
Breast milk provides the ideal nutritional, immunologic,
and physiologic nourishment for all newborns.
Components of human milk enhance the baby’s natural
defences and promote maturation of the immune sys-
tem.11 Ninety percent of antibodies in human colostrum
and milk are secretory IgA, which provide the baby with
protection at mucosal surfaces until the infant is produc-
ing adequate quantities of its own sIgA at about 6 months
of age.12 However, the effect of breastfeeding on the
development of allergic diseases in the breastfed infant
remains controversial.
Several studies report that breastfeeding is protective
against allergy, with a definite improvement in infant
eczema and associated gastrointestinal complaints, as
well as a reduced risk of asthma in the first 24 months,
when the baby is exclusively breastfed and the mother
eliminates highly allergenic foods from her diet.13 A
recent (2010) report indicates that IgG immune com-
plexes found in breast milk are potent inducers of toler-
ance to aerosolized antigens to which the mother was
sensitized, providing antigen-specific protection from
asthma in their babies.14
However, other studies seem to indicate that breast-
feeding has no effect on the infant’s symptoms of allergy
or, worse, may be associated with an increased prevalence
of atopic eczema.15,16 One of the reasons for this apparent
contradiction may be explained by data that indicate that
the breast milk of atopic mothers differs immunologically
from that of the nonallergic.17-19
Atopic mothers tend to have a higher level of the
cytokines and chemokines associated with allergy in their
breast milk and also have a lower level of the cytokine
known as transforming growth factor (TGF)–β1 that pro-
motes tolerance to food components in the intestinal
immune response. A normal level of TGF-β1 in the moth-
er’s colostrum and breast milk is likely to facilitate toler-
ance to food encountered by the infant in the mother’s
breast milk and later to formulas and solids.20 Evidence
seems to suggest that breastfeeding is protective against
allergies when the mother is nonatopic21 but that babies
of allergic mothers may be at risk of developing allergies,
especially to foods, during breastfeeding.
In view of the large amount of evidence regarding the
role of breast milk in promoting the well-being of all
babies, on the basis of careful analysis of all research data
on the topic, ESPACI and ESPGHAN strongly recom-
mend exclusive breastfeeding for 4–6 months, and the
American Academy of Pediatrics (AAP)2,22 recommends at
least 4 months, with introduction of complementary
foods no earlier than 4–6 months as the hallmark for
allergy prevention.2,23
Prevention of Food Allergic Sensitization
During the First 6 Months
From the results of epidemiological studies, it is thought
that initial sensitization to food allergens in the exclu-
sively breastfed baby occurs predominantly from external
sources, such as a single feeding of infant formula or
perhaps by accident. In an important study of 1749 new-
borns in Odense, Denmark, 39 (2.2%) were identified as
being sensitized to cow’s milk proteins soon after birth. Of
these, 9 developed symptoms of cow’s milk allergy before
3 months of age, despite being exclusively breastfed.
Review of records from the newborn nursery revealed that
all 9 infants had been exposed to cow’s milk formula in
amounts corresponding to approximately 0.4–3.0 g of
β-lactoglobulin (BLG) during the first 3 days of life.
Similar proteins were detected in their mother’s breast
milk, to which the allergic infants reacted with the devel-
opment of symptoms. The authors conclude that early
inadvertent and occasional exposure to cow’s milk pro-
teins may initiate sensitization in predisposed neonates;
subsequent exposure to minute amounts of bovine milk
proteins in human milk may then act as booster doses
eliciting allergic reactions.24
The current directives from position papers and con-
sensus documents from many countries now recognize that
restriction of the maternal diet during pregnancy and lacta-
tion is probably contraindicated in allergy prevention.
The AAP2 suggests that antigen avoidance dur-
ing lactation does not prevent atopic disease,
with the caveat that more data are needed to
substantiate this conclusion.
The European Academy of Allergology and
Clinical Immunology states that “no conclusive
evidence for protective effect of maternal exclu-
sion diet during pregnancy or lactation has been
The Australasian Society of Clinical Immunology
and Allergy states, “Dietary restrictions in preg-
nancy are not recommended,” and “Maternal
dietary restrictions during breast feeding are
not recommended.”25
In summary, professional groups do not recommend the
elimination of any specific foods from the maternal diet
during breastfeeding, except for the mother’s own aller-
gens, unless the baby has been diagnosed with allergy
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to 1 or more foods, in which case the baby’s allergenic
food should be avoided by its mother as long as she is
Formula Feeding
It is not always possible for a baby to be breastfed, and
when the infant is at risk for or has developed allergies,
making the best choice of formula is extremely important.
Most authorities suggest that if a baby has no signs or
symptoms of cow’s milk allergy, a conventional cow’s
milk–based formula is safe for infant feeding.
However, in high-risk-for-allergy babies, there is
emerging evidence that hydrolyzed infant formulas pro-
vide a measure of protection against the development of
atopic disease26 compared to conventional milk-based
formulas. Hydrolysis of cow’s milk breaks the protein into
smaller, potentially less allergenic proteins.
On the basis of evidence from a variety of studies,27-29
the AAP, in its position paper published in 2008,2 states
that “in studies of infants at high risk of developing atopic
disease who are not breast-fed exclusively for 4 to 6
months or are formula fed, there is modest evidence that
atopic dermatitis may be delayed or prevented by the use
of extensively hydrolyzed or partially hydrolyzed formulas,
compared with cow’s milk formula, in early childhood.”
The AAP further stated that “extensively hydrolyzed for-
mulas may be more effective than partially hydrolyzed in
the prevention of atopic disease.” However, the authors of
a more recent research study (2011) stated that, “Despite
current dietary guidelines, we found no evidence to sup-
port recommending the use of pHWF (partially hydro-
lysed whey formula) at weaning for the prevention of
allergic disease in high-risk infants.”30
There is good consensus among pediatric groups
worldwide that no evidence exists for the use of soy-based
infant formula for the purpose of allergy prevention.2,25,31
So in summary, it is fair to state that if a baby at high
risk for allergy cannot be exclusively breastfed to 4–6
months of age, the preferred method of feeding in the
prevention of atopic disease is an extensively hydrolyzed
Introducing Solid Foods
The first consensus document on the introduction of
solid foods for the food-allergic infant was published in
July 2006 by the Adverse Reactions to Foods Committee
of the American College of Allergy, Asthma and
Immunology.32 It recommended that introduction of the
multiple allergens in solid foods to the allergic infant is
preferably delayed until after 6 months of age. Until this
age, the authors suggest that the infant’s immature diges-
tive tract and immune system may increase the risk of
sensitization and development of allergy. Furthermore, it
was recommended that the most highly allergenic foods
should not be introduced until after 1 year of age or later.
Specific times of introduction were suggested as follows:
cow’s milk at 12 months; egg at 24 months; and peanut,
tree nut, and fish at 3 years.
However, more recent research has demonstrated
that these recommendations were neither supported by
evidence-based research nor were effective in practice.
Newer position papers reflect this change in approach.
The AAP paper, published in 2008,2 states, “The evidence
. . . does not allow one to conclude that there is a strong
relationship between the timing of the introduction of
complementary foods and development of atopic disease.”
According to the published guidelines of all pediatric
societies and consensus committees, solid foods should
be introduced individually and gradually, starting at about
4–6 months of age. Each food should be introduced, ide-
ally over a 4-day period, with careful monitoring of the
baby for the development of signs of allergy. No mixed
foods should be given until each food in the mixture has
been given to the baby and is tolerated.
Prognosis for Infant Food Allergy
Many children outgrow their early allergies to foods spon-
taneously. A few examples are as follows.
Cow’s Milk Allergy
Most children with early cow’s milk allergy outgrow their
allergy by 3 years of age. A 1990 study reported that 56%
of the infants with cow’s milk allergy outgrew their allergy
at 1 year, 77% at 2 years, and 87% at 3 years.33 However, a
2007 study34 reported that 19% of their patients with cow’s
milk allergy developed tolerance by age 4 years, 42% by age
8 years, 64% by age 12 years, and 79% by age 16 years.
Those children with the highest level of cow’s milk–spe-
cific IgE were least likely to outgrow their cow’s milk
allergy. Furthermore, children with asthma, atopic rhino-
conjunctivitis (hay fever), and atopic dermatitis (eczema)
are reported to be less likely to outgrow their early cow’s
milk allergy, suggesting that the most highly allergic indi-
viduals are most at risk for persistent food allergies.35
Egg Allergy
It has been reported that 80% of infants with egg allergy
are able to consume egg by 5 years of age.36 Other more
recent reports using predicted resolution of egg allergy
are more pessimistic: 4% of egg-allergic children were
predicted to outgrow their allergy by 4 years, 12% by 6
years, 37% by 10 years, and 68% by 16 years of age.37 The
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Infant Food Allergy / Joneja 53S
persistence of egg allergy was related to the presence of
asthma and allergic rhinitis and higher levels of egg-
specific IgE. Nevertheless, the consensus from published
studies concludes that most patients with egg allergy are
likely to develop tolerance to egg by late childhood, with
the exception of patients with an egg IgE >50 kUA/L, in
whom egg allergy is likely to persist into adulthood.
Peanut Allergy
Recent reports suggest that at least 21% of peanut-allergic
children will outgrow their peanut allergy over time38
(median age 6 years). Traditionally, allergy to peanut was
considered to be lifelong and unlikely to be outgrown. Those
children with lower peanut-specific IgE (<5 kUA/L at time of
challenge) and lower rates of asthma and allergic rhinitis
were reported to be more likely than those with high levels
to outgrow their peanut allergy. An earlier report from the
United Kingdom indicated that 9.8% of their peanut-allergic
patients outgrew their peanut allergy39 in childhood.
Tree Nut Allergy
Allergy to tree nuts is another condition that traditionally
has been considered to be rarely outgrown. However, a
study of 278 tree nut allergic patients reported that 9%
outgrew their tree nut allergy, including some who had
previous severe reactions.40 The authors suggested that
patients aged 4 years or older with tree nut–specific IgE
levels of 5 kUA/L or less should be considered for chal-
lenge of tree nuts under medical supervision to determine
whether they remain allergic to tree nuts.
It is important that children who have outgrown their
early allergy to foods should be identified so that the pre-
viously allergenic food can be included in their diet. This
is important for several reasons:
The diet becomes easier to formulate and
The vigilance previously exerted to avoid the
culprit food can be relaxed, which reduces the
stress associated with maintaining restricted
diets, especially those that contain foods that
may be considered “life-threatening.”
Including the now-tolerated food in the diet on
a regular basis reduces the likelihood of recur-
rence of the allergy because maintenance of
tolerance reduces this risk.41
Oral Tolerance in the Management of
Established Food Allergy
In some cases, desensitization or tolerance to a food
allergy can be achieved even if the child has not sponta-
neously outgrown the allergy. This is a relatively new
concept as previous directives for food allergy manage-
ment emphasized strict avoidance of the culprit allergen.
Now specific desensitization protocols are being devel-
oped that expose the allergic child to the offending aller-
gen by the oral route in a safe environment in order to
induce tolerance to it.
Several studies have reported achievement of toler-
ance to cow’s milk by starting with minute quantities of
milk and increasing the dosage over time, a process
termed specific oral tolerance induction (SOTI). Examples
include the following:
One study reported that starting with 1 drop of
milk and increasing to 120 mL over a period of
136 days, 13 of 16 children achieved tolerance
to 120 mL milk in 3–12 months.42
Starting with an initial dose of 0.05 mL cow’s
milk, reaching 1 mL on the first day, and
increasing the dosage weekly until a dose of
200–250 mL of milk taken once a day was toler-
ated, 16 of 18 patients 4 years and older
achieved tolerance after a median length of 14
weeks (range, 11–17 weeks). Thirteen children
continued to tolerate 200–250 mL per day of
milk after more than a year.43
Another study44 reported achievement of toler-
ance to cow’s milk in 7 of 10 children with
established milk allergy, starting with 1 drop of
milk and increasing weekly over a period of 4
months until a dose of 200 mL was tolerated.
A similar tolerance to foods other than milk have
been achieved, for example, to egg45,46 and peanut.47,48
Undoubtedly, successful SOTI to other allergenic foods
will be achieved over time.
Probiotics and Allergy
Studies in the past decade have indicated that the intes-
tinal microflora might be the major source of microbial
stimulation that promotes maturation of the immune
system in early childhood.49 The appropriate microbial
stimulus soon after birth may be extremely important in
balancing the Th1/Th2 response of the immune system,
which is skewed to the Th2 (allergy) type at birth.50
Lactic acid bacteria and bifidobacteria are found more
commonly in the intestinal flora of nonallergic children,
and atopic children appear to have a different microflora
composition than nonatopics, with higher levels of
clostridia and lower levels of bifidobacteria.51 These obser-
vations may pave the way for selecting probiotic strains
that might promote the intestinal environment most ben-
eficial in developing tolerance rather than sensitization to
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allergens in the immature infant. A number of studies sug-
gest that the appropriate selection of the bacterial strains
used in probiotics may help in certain allergic conditions,
but at the present time, we have insufficient evidence to
recommend probiotics as a therapy for allergy prevention
in regular clinical practice.52,53
The use of probiotic therapy to prevent allergic dis-
ease has been demonstrated in a few studies using the
probiotic strain Lactobacillus rhamnosus GG in neonates.
This seemed to be particularly effective in reducing the
incidence and severity of atopic eczema.54
In a Finnish study, infants with milk allergy and
atopic dermatitis had milder symptoms and fewer inci-
dences of intestinal infections if their milk formula was
fortified with lactobacilli.55 However, a similar study from
Singapore reported that administration of a cow’s milk
formula supplemented with probiotics (Bifidobacterium
longum and L rhamnosus) for the first 6 months showed
no effect on prevention of eczema or allergen sensitiza-
tion in the first year of life in Asian infants at risk of
allergic disease.56 Another study using the probiotics L
rhamnosus or Lactobacillus GG in infant formula for 3
months in children younger than 5 months as prevention
or management of atopic dermatitis (AD) concluded that
the results “indicate that oral supplementation with these
probiotic bacterial strains will not have a significant
impact on the symptoms of infantile AD.”57
A positive effect of probiotics on symptoms of allergy
was reported in a study from Sweden that evaluated the
effects of feeding Lactobacillus F19 in cereals during wean-
ing on the incidence of eczema in children aged between 4
and 13 months (89 in the study group; 90 in the control
group). At 13 months of age, the incidence of eczema was
reported as 11% in the study group and 22% in the placebo
group. The authors conclude that “feeding Lactobacillus
F19 during weaning could be an effective tool in the preven-
tion of early manifestations of allergy, e.g. eczema.”58
The problem with comparing such studies at the pre-
sent time is that there are so many variables to consider
before any conclusions can be made as to the effective-
ness of probiotics, prebiotics, and synbiotics on childhood
allergy—for example:
The specific species and strains of the micro-
The number of micro-organisms required to be
delivered orally (dosage) as colony-forming
units (CFU)
The number of micro-organisms surviving in
their movement through the digestive tract
The number colonizing (implantation and mul-
tiplication in) the bowel, usually measured as
live organisms in the feces
The age at which the probiotic is administered,
whether prenatally or postnatally
The duration of consumption of the probiotic
The means of administering the probiotic (in
milk, formula, cereal, or other)
The selection of an appropriate prebiotic (milk,
oligosaccharides [eg, fructo-oligosaccharide],
inulin) or other appropriate substrates
It is hoped that evidence-based studies will begin to answer
these questions, possibly offering an additional method for
managing pediatric food allergies in the future.
1. Host A, Koletzko B, Dreborg S, et al. Dietary products used in
infants for treatment and prevention of food allergy: joint state-
ment of the European Society of Paediatric Allergology and
Clinical Immunology (ESPACI) Committee of Hypoallergenic
Formulas and the European Society for Paediatric Gastroenetrology,
Hepatology and Nutrition (ESPGHAN) Committee on Nutrition.
Arch Dis Child. 1999;8:80-84.
2. Greer FR, Sicherer SH, Burks AW, and the Committee on
Nutrition and Section on Allergy and Immunology Effects of Early
Nutritional Interventions on the Development of Atopic Disease in
Infants and Children. The role of maternal dietary restriction,
breastfeeding, timing of introduction of complementary foods, and
hydrolyzed formulas. Pediatrics. 2008;121(1):183-191.
3. Moat MF, Cookson WOCM. Gene identification in asthma and
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... IgG, the antibody that offers protection throughout maternal and infant fluids, has 4 subtypes, IgG1, IgG2, IgG3, and IgG4. 17 In mothers without IgE-mediated food allergies or with previous food elimination, production of IgG1 and IgG3 are abundant. These antibodies cross the placenta and protect the fetus from food proteins in utero, building oral tolerance. ...
... These antibodies cross the placenta and protect the fetus from food proteins in utero, building oral tolerance. 17 IgG4 is commonly associated with IgE and does not easily cross the placenta. Therefore, in mothers with undetected IgE-mediated food allergies, IgG1 and IgG3 are transferred in insufficient quantities, contributing to poor establishment of oral tolerance toward potential antigens. ...
... Therefore, in mothers with undetected IgE-mediated food allergies, IgG1 and IgG3 are transferred in insufficient quantities, contributing to poor establishment of oral tolerance toward potential antigens. 17 Allergenspecific IgE found in maternal blood, cord blood, and newborn blood suggests IgE sensitization may occur in utero as the frequency of positive allergenspecific IgE in cord blood is found to be associated with sensitization to allergy in children. 10,17 This increases the susceptibility of becoming sensitized to allergens after birth, developing allergic symptoms early in life. ...
Breast milk contains a perfect blend of macronutrients, vitamins, minerals, and water. This supports a baby’s nutritional needs exclusively for the first 6 months and beyond when paired with solid foods. Human milk also provides a unique blend of hormones, growth factors, and protective nutrients that support healthy functioning of the body as it matures, especially the microbiome within the digestive system. As a direct carrier of beneficial microbes, breast milk contains growth factors, oligosaccharides, lactoferrin, and lysozymes, which support the microbiome and immune system. These components regulate host–microbe interactions and establish the innate and adaptive immune response within the body. When the infant’s gastrointestinal tract is adequately colonized with an intact mucosal barrier, oral tolerance to antigens and pathogens creates a strong immune defense, avoiding expression of disease and atypical immune responses. There are many perinatal factors that affect the bacterial composition of breast milk and the maternal/infant gastrointestinal tract such as maternal body mass index, mode of delivery, perinatal antibiotic use, formula supplementation, and inflammation. Dysbiosis contributes to an increased expression of immune-mediated and allergic disease states. The impact of perinatal factors cannot always be prevented. When alternatives are not available, medical nutrition therapy can be key in supporting a healthy microbiome as well as improving maternal and infant gut function to prevent or treat food sensitivities. This article aims to address the role of maternal diet in pregnancy and lactation through optimizing the microbiome and immune system and reducing the infant allergy risk.
... The evidence suggests that breastfeeding can offer protective measures against food allergies when the mother is non-atopic. However, breastfeeding infants of atopic mothers may put them at higher risk of developing allergies (35), which can be explained by the higher levels of cytokines and chemokines and lower levels of transforming growth factor (TGF)-b1 in the breast milk of atopic mothers. Since TGF-b1 promotes food tolerance in the intestinal immune response, a healthy level present in the mother's colostrum and breast milk would logically facilitate tolerance against various food allergens encountered by the infant from breastfeeding to ingestion of formula milk and solids. ...
... The American Academy of Pediatrics and several European committees and organizations recommend using atopic family history to identify high-risk infants and administer appropriate interventions for allergy prevention. A documented parental or relative food allergy would increase the likelihood of food allergy development in the offspring (35). For example, research has shown that a child can experience as high as a 7-fold increase in peanut allergy risk if he or she has a parent or sibling with the same condition (85). ...
Full-text available
Food allergies and other immune-mediated diseases have become serious health concerns amongst infants and children in developed and developing countries. The absence of available cures limits disease management to allergen avoidance and symptomatic treatments. Research has suggested that the presence of maternal food allergies may expose the offspring to genetic predisposition, making them more susceptible to allergen sensitization. The following review has focused on epidemiologic studies regarding maternal influences of proneness to develop food allergy in offspring. The search strategy was “food allergy OR maternal effects OR offspring OR prevention”. A systematically search from PubMed/MEDLINE, Science Direct and Google Scholar was conducted. Specifically, it discussed the effects of maternal immunity, microbiota, breastfeeding, genotype and allergy exposure on the development of food allergy in offspring. In addition, several commonly utilized prenatal and postpartum strategies to reduce food allergy proneness were presented, including early diagnosis of high-risk infants and various dietary interventions.
... [6], [7], [8], [9], [10] The analysis of literary information indicates that the assessment of illness forecasting based on individual or isolated indicators is not promising. [11], [12], [13] In this regard, the preparation of forecasting programs on a mathematical basis would be a rational and, most probably, the only true approach to the solution of forecasting. [14], [15], [16], [17], [18], [19] Any event in clinical medicine can be currently assessed as a probable process and studied by the theory of probability. ...
Full-text available
Background: Early forecasting of any pathological process is of great significance from both medical and economic point of view. An illness requires much more attention in the light of exhaustion of resources of the body, and a doctor should be maximally aware of the near and far future of a patient. In this regard, the preparation of forecasting programs on a mathematical basis would be a rational and, most probably, the only true approach to the solution of forecasting. Aims and objectives: The aim of the article is to study the forecasting of atopic dermatitis (AD) in newborns. Methodology: The authors studied 109 clinical and laboratory indicators in children without and with AD. Discriminant analysis was used as an algorithm for the resolution of diagnostic issues. Results: The main indicators acceptable as a forecasting criterion in the formation of AD in children were defined. The sensitivity, specificity, and general diagnostic value of statistically valid differing factors in the formation of AD were studied. Key rules of the forecast were formed after processing all indicators through the KU-Kruskal-Wallis discriminant criterion, a universal computer method. Conclusion: It was concluded that the power of influence of rhinitis, cluster of differentiation 31, mucin 2, and intestinal trefoil factor 3 are higher in the AD model.
... Crying babies have elevated serum proinfl ammatory markers 6 9,10 But this important data is now being interpreted, yet again, through the medicalised lens of linear causality, to conclude that babies cry a lot from gut pain due to colonic infl ammation and gas produced by dysbiosis (in the absence of colonic lesions or objective increase in gas). 11 The hypothesis that altered pain thresholds due to nocioceptive sensitisation, previously used to justify the diagnosis of gastroesophageal refl ux disease and treatment in the absence of oesophageal lesions, is now used to explain colonic infl ammation and gas pain in the absence of lesions or quantifi ably increased gas. ...
Full-text available
Parents trying to cope with problem crying in babies are faced with a barrage of conflicting and confusing advice, much of which lacks a sound evidence base. Part 2 The Medical Republic Crying Baby Series
... In the whey fraction, β-lactoglobulin (BLG) is one of the main allergens. In an increasing number of patients, CMA fails to resolve spontaneously and persists for life which is often associated with a more severe phenotype or increased risk for other allergic disorders (3). Although allergenspecific immunotherapy is being developed and can lead to desensitization of patients while on therapy, CMA management in the clinic mainly involves the avoidance of the symptomeliciting food (4). ...
Full-text available
Cow’s milk allergy (CMA) prevails in infants and brings increased risk of developing other allergic diseases. Oral administration of specific β-lactoglobulin (BLG)-derived peptides (PepMix) and a specific blend of short- and long-chain fructo-oligosaccharides and Bifidobacterium breve M-16V (FF/Bb) was found to partially prevent CMA development in mice. In this study, we aimed to expand the knowledge on the preventive potential and the underlying mechanisms of this approach. Three-week-old female C3H/HeOuJ mice were orally exposed to PepMix±FF/Bb prior to a 5-week oral sensitization with whole whey and cholera toxin as an adjuvant. The acute allergic skin response was determined after an intradermal challenge with whole whey protein. Following an oral challenge with whey, regulatory T cells (Tregs) in the small intestine lamina propria (SI-LP) and mRNA expression of immune markers in the Peyer’s patches (PP) were investigated. The early impact of PepMix and FF/Bb interventions on the immune system during the oral tolerance (OT) induction phase was investigated after the last OT administration. Pre-exposing mice to PepMix+FF/Bb partially prevented the acute allergic skin response compared to PBS and increased Tregs and activated T cells in the SI-LP compared to sham-sensitized mice. It also increased the mRNA expression of Tbet over GATA3 in the PP of whey-sensitized mice. Directly upon the 6-day OT phase, FF/Bb intervention enhanced cecal content levels of propionic and butyric acid in PepMix-fed mice and the former was positively correlated with Foxp3+ cell numbers in the colon. In the PP of PepMix+FF/Bb-exposed mice, IL-22 mRNA expression increased and IL-10 followed the same tendency, while the Foxp3 expression was increased over GATA3 and RorγT. In the colon, the Tbet mRNA expression increased over GATA3, while IL-22 decreased. In addition, the Foxp3+/GATA3+ and regulatory/effector T cell ratios in the mesenteric lymph nodes and the CD11b+/CD11b− conventional dendritic cells ratio in the SI-LP were increased. In conclusion, the FF/Bb diet facilitates the capacity of the specific BLG-peptides to partially prevent the allergic response after sensitization to whole whey protein, possibly by creating a tolerance-prone environment during the OT phase. Such a dietary intervention might contribute to tailoring successful strategies for CMA prevention.
... Research has suggested that the early introduction of solids can increase islet autoimmunity, obesity, adult-onset celiac disease, eczema, anemia and diarrheal disease. 6 The contribution of EBF to maternal and child health has been the subject of 3 Lancet series (Lancet breast-feeding series 2016:; Lancet maternal and child nutrition series: ...
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Oral tolerance is a promising approach for allergy prevention in early life, but it strongly depends on allergen exposure and proper immune environment. Small tolerance-inducing peptides and dietary immunomodulatory components may comprise an attractive method for allergy prevention in at-risk infants. This study aimed to investigate whether early oral exposure to β-lactoglobulin-derived peptides (BLG-peptides) and a specific synbiotic mixture of short- and long- chain fructo-oligosaccharides (scFOS/lcFOS, FF) and Bifidobacterium breve (Bb) M-16V (FF/Bb) can prevent cow’s milk allergy (CMA). Three-week-old female C3H/HeOuJ mice were orally exposed to phosphate buffered saline (PBS), whey protein, or a mixture of four synthetic BLG-peptides combined with a FF/Bb-enriched diet prior to intragastric sensitization with whey protein and cholera toxin. To assess the acute allergic skin response and clinical signs of allergy, mice were challenged intradermally with whole whey protein. Serum immunoglobulins were analyzed after a whey protein oral challenge. Cytokine production by allergen-reactivated splenocytes was measured and changes in T cells subsets in the spleen, mesenteric lymph nodes, and intestinal lamina propria were investigated. Pre-exposing mice to a low dosage of BLG-peptides and a FF/Bb-enriched diet prior to whey protein sensitization resulted in a significant reduction of the acute allergic skin response to whey compared to PBS-pretreated mice fed a control diet. Serum immunoglobulins were not affected, but anaphylactic symptom scores remained low and splenocytes were non-responsive in whey-induced cytokine production. In addition, preservation of the Th1/Th2 balance in the small intestine lamina propria was a hallmark of the mechanism underlying the protective effect of the BLG-peptides–FF/Bb intervention. Prior exposure to BLG-peptides and a FF/Bb-enriched diet is a promising approach for protecting the intestinal Th1/Th2 balance and reducing the allergic response to whole whey protein. Therefore, it might have implications for developing successful nutritional strategies for CMA prevention.
The prevalence of food allergies in infants has increased, indicating that maturation of the infant's immune system and the development of oral tolerance to food antigens are hampered. Exposure to an altered Western diet and hygienic living conditions appear to skew the infant’s immune response toward an atopic phenotype. Allergen avoidance strategies are challenged nowadays and active tolerance induction via immunomodulatory food components and/or modified allergens is of key interest. Dietary interventions with probiotics, prebiotics, synbiotics, n-3 polyunsaturated fatty acids, or antioxidants show potential in supporting tolerance induction. Clinical trials have provided promising results. However, variation in the timing, dose, duration, and type of dietary intervention used delay its implementation in early-life strategies for allergy prevention. Modulation of the infant's immune response might benefit from applying dietary interventions prenatally as well as postnatally.
Optimal nutrition supports growth, development and good health by providing adequate energy and nutrients. Breast milk is the ideal milk for infants because it is both nutritionally adequate and contains a range of immunological substances that cannot be manufactured. In addition to providing a more concentrated source of nutrition, complementary feeding alongside milk feeds provides the opportunity for infants to develop feeding skills and learn to like a variety of new tastes and textures at an age when they are happy to do so. Continuing breastfeeding throughout complementary feeding affords maximum benefits for infants. A combination of nutritious foods provides nutritional sufficiency except for vitamin D unless commonly consumed foods are fortified with vitamin D. How easily parents manage to feed their young children depends to some extent on parental knowledge and parenting skills. At the same time, developmental changes in toddlers affect how they respond to food and meals.
The use of human milk (mother's own milk and/or donor milk) in ill or medically compromised infants frequently requires some adaptation to address medical diagnoses and/or altered nutrition requirements. This tutorial describes the nutrition and immunological benefits of breast milk as well as provides evidence for the use of donor milk when mother's own milk is unavailable. Several strategies used to modify human milk to meet the medical and nutrition needs of an ill or medically compromised infant are reviewed. These strategies include (1) the standard fortification of human milk to support adequate growth, (2) the novel concept of target fortification in preterm infants, (3) instructions on how to alter maternal diet to address cow's milk protein intolerance and/or allergy in breast milk-fed infants, and (4) the removal and modification of the fat in breast milk used in infants diagnosed with chylothorax.
Background: Allergy is common and may be associated with foods, including cow's milk formula (CMF). Formulas containing hydrolysed proteins have been used to treat infants with allergy. However, it is unclear whether hydrolysed formulas can be advocated for prevention of allergy in infants. Objectives: To compare effects on allergy and food allergy when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine which infants at low or high risk of allergy and which infants receiving early, short-term or prolonged formula feeding may benefit from hydrolysed formulas. Search methods: We used the standard search strategy of the Cochrane Neonatal Review Group supplemented by cross referencing of previous reviews and publications (updated August 2016). Selection criteria: We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Trials with ≥ 80% follow-up of participants were eligible for inclusion. Data collection and analysis: We independently assessed eligibility of studies for inclusion, methodological quality and data extraction. Primary outcomes included clinical allergy, specific allergy and food allergy. We conducted meta-analysis using a fixed-effect (FE) model. Main results: Two studies assessed the effect of three to four days' infant supplementation with an EHF whilst in hospital after birth versus pasteurised human milk feed. Results showed no difference in infant allergy or childhood cow's milk allergy (CMA). No eligible trials compared prolonged hydrolysed formula versus human milk feeding.Two studies assessed the effect of three to four days infant supplementation with an EHF versus a CMF. One large quasi-random study reported a reduction in infant CMA of borderline significance among low-risk infants (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.38 to 1.00).Prolonged infant feeding with a hydrolysed formula compared with a CMF was associated with a reduction in infant allergy (eight studies, 2852 infants; FE RR 0.82, 95% CI 0.72 to 0.95; risk difference (RD) -0.04, 95% CI -0.08 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 25, 95% CI 12.5 to 100) and infant CMA (two studies, 405 infants; FE RR 0.38, 95% CI 0.16 to 0.86). We had substantial methodological concerns regarding studies and concerns regarding publication bias, as substantial numbers of studies including those in high-risk infants have not comprehensively reported allergy outcomes (GRADE quality of evidence 'very low').Prolonged infant feeding with a hydrolysed formula compared with a CMF was not associated with a difference in childhood allergy and led to no differences in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy. Many of the analyses assessing specific allergy are underpowered.Subroup analyses showed that infant allergy was reduced in studies that enrolled infants at high risk of allergy who used a hydrolysed formula compared with a CMF; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF. Studies that enrolled infants at high risk of allergy; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF found a reduction in infant CMA. Authors' conclusions: We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergy. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA.In infants at high risk of allergy not exclusively breast fed, very low-quality evidence suggests that prolonged hydrolysed formula feeding compared with CMF feeding reduces infant allergy and infant CMA. Studies have found no difference in childhood allergy and no difference in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy.Very low-quality evidence shows that prolonged use of a partially hydrolysed formula compared with a CMF for partial or exclusive feeding was associated with a reduction in infant allergy incidence and CMA incidence, and that prolonged use of an EHF versus a PHF reduces infant food allergy.
The American Academy of Pediatrics is committed to breastfeeding as the ideal source of nutrition for infants. For those infants who are formula-fed, either as a supplement to breastfeeding or exclusively during their infancy, it is common practice for pediatricians to change the formula when symptoms of intolerance occur. Decisions about when the formula should be changed and which formula should be used vary significantly, however, among pediatric practitioners. This statement clarifies some of these issues as they relate to protein hypersensitivity (protein allergy), one of the causes of adverse reactions to feeding during infancy.
• A family history of allergy and asthma identifies children at high risk of allergic disease. • Dietary restrictions in pregnancy are not recommended. • Avoiding inhalant allergens during pregnancy has not been shown to reduce allergic disease, and is not recommended. • Breastfeeding should be recommended because of other beneficial effects, but if breast feeding is not possible, a hydrolysed formula is recommended (rather than conventional cow's milk formulas) in high-risk infants only. • Maternal dietary restrictions during breastfeeding are not recommended. • Soy formulas and other formulas (eg, goat's milk) are not recommended for reducing food allergy risk. • Complementary foods (including normal cow's milk formulas) should be delayed until a child is aged at least 4-6 months, but a preventive effect from this measure has only been demonstrated in high-risk infants. • There is no evidence that an elimination diet after age 4-6 months has a protective effect, although this needs additional investigation. • Further research is needed to determine the relationship between house dust mite exposure at an early age and the development of sensitisation and disease; no recommendation can yet be made about avoidance measures for preventing allergic disease. • No recommendations can be made about exposure to pets in early life and the development of allergic disease. If a family already has pets it is not necessary to remove them, unless the child develops evidence of pet allergy (as assessed by an allergy specialist). • Women should be advised not to smoke while pregnant, and parents should be advised not to smoke. • No recommendations can be made on the use of probiotic supplements (or other microbial agents) for preventing allergic disease at this time. • Immunotherapy may be considered as a treatment option for children with allergic rhinitis, and may prevent the subsequent development of asthma.
Background: Egg allergy is very common, affecting 1% to 2% of children. It is generally thought that the majority of children with egg allergy develop tolerance in early childhood; however, this has not been examined in a large cohort with egg allergy. Objective: The purpose of the study was to estimate the proportion of children with egg allergy who develop egg tolerance and to identify predictors of tolerance development. Methods: Retrospective chart review of patients with egg allergy seen in a tertiary referral clinic. Patients were considered to have developed egg tolerance if they tolerated concentrated egg. Results: Kaplan-Meier analysis predicted resolution in 4% of patients with egg allergy by age 4 years, 12% by age 6 years, 37% by age 10 years, and 68% by age 16 years. Patients with persistent egg allergy had higher egg IgE levels at all ages to age 18 years. A patient's highest recorded egg IgE, presence of other atopic disease, and presence of other food allergy were significantly related to egg allergy persistence. Conclusion: A majority of patients with egg allergy will develop egg tolerance, although the rate of tolerance development is slower than described previously. Egg IgE is predictive of allergy outcome and should be used in counseling patients on prognosis. Clinical implications: Most patients with egg allergy are likely to develop egg tolerance by late childhood, with the exception of patients with an egg IgE greater than 50 kU/L, who are unlikely to develop egg tolerance.
A cohort of 1749 newborns from the municipality of Odense born during 1985 at the University Hospital were followed prospectively for the development of IgE-mediated and non-igE-mediated cow milk allergy (CMA) during their first year. The diagnosis of CMA was based on the results of strict elimination/milk challenge procedures in a hospital setting, and continued clinical sensitivity to cow milk (CM) was assessed by rechallenging every 6–12 months until the age of3 years. Further, in infants with CMA, the Clinical course of adverse reactions to other foods and the development of allergy to inhalant allergens In 3 years were investigated. Of 117 (6.7 %) with symptoms suggestive of CMA, the diagnosis of CMA was proven m 39 infants (2.2%), 64% showed cutaneous symptoms. 59% gastrointestinal symptoms, and 33% had respiratory symptoms. 92% had two or more symptoms and 72 % symptoms from 2 organ systems. Based on a positive skin prick test ( 2 +) and/or AL-RAST class 2 to CM 16 infants at the time of diagnosis, and at reinvestigation at 1 year, a further five infants giving a total of 21, were classified as having IgE-mediated CMA, 19 infants showed “immediate reactions to CM (within 1 h after intake of 2.3 g milk protein) and 20 infants were “late reactors”, No significant correlation between IgE-mediated CMA and “immediate reactions” to CM was demonstrated, The overall prognosis of CMA was good with a total recovery of 22/39 (56%) at 1 year. 30/39 (77%) at 2 years, and 34/39 (87%) at 3 years. Adverse reactions to other foods, particularly egg, citrus, tomato, developed in a total of 21/39 (54%) with the maximum point prevalence of 15/39 (38%) at 18 months, and 9/39 (23%) were still intolerant to other foods at 36 months. Inhalant allergy before 3 years developed in 11/39 (28%), particularly against dog and cat to which the infants had been exposed. Infants with CMA and early IgE, sensitization to CM had an increased risk of persisting CMA (24%) development of persistent adverse reactions to other foods (38%), particularly egg white (29%), and finally, inhalant allergy (48%) before 3 years of age.
Objective: To make recommendations based on a critical review of the evidence for the timing of the introduction of solid foods and its possible role in the development of food allergy. Data Sources: MEDLINE searches using the following search algorithm: [weaning AND infant AND allergy]/[food allergy AND sensitization]/[dietary prevention AND food allergy OR allergens]/[Jan 1980-Feb 2006]. Study Selection: Using the authors' clinical experience and research expertise, 52 studies were retrieved that satisfied the following conditions: English language, journal impact factor above 1 or scientific society, expert, or institutional publication, and appraisable using the World Health Organization categories of evidence. Results: Available information suggests that early introduction can increase the risk of food allergy, that avoidance of solids can prevent the development of specific food allergies, that some foods are more allergenic than others, and that some food allergies are more persistent than others. Conclusions: Pediatricians and allergists should cautiously individualize the introduction of solids into the infants' diet. With assessed risk of allergy, the optimal age for the introduction of selected supplemental foods should be 6 months, dairy products 12 months, hen's egg 24 months, and peanut, tree nuts, fish, and seafood at least 36 months. For all infants, complementary feeding can be introduced from the sixth month, and egg, peanut, tree nuts, fish, and seafood introduction require caution. Foods should be introduced one at a time in small amounts. Mixed foods containing various food allergens should not be given unless tolerance to every ingredient has been assessed.