REVIEW ARTICLE

Asthma and Allergic Diseases in Pregnancy

A Review
Isabella Pali-Scholl, PhD,1 Cassim Motala, MD, FACAAI, FAAAAI,2 and Erika Jensen-Jarolim, MD1
Abstract: Asthma and allergic disorders can affect the course and
outcome of pregnancy. Pregnancy itself may also affect the course of
asthma and related diseases. Optimal management of these disorders during pregnancy is vital to ensure the welfare of the mother and
the baby.
Specic pharmacological agents for treatment of asthma or
allergic diseases must be cautiously selected and are discussed here
with respect to safety considerations in pregnancy. Although most
drugs do not harm the fetus, this knowledge is incomplete. Any drug
may carry a small risk that must be balanced against the benets of
keeping the mother and baby healthy. The goals and principles of
management for acute and chronic asthma, rhinitis, and dermatologic
disorders are the same during pregnancy as those for asthma in the
general population.
Diagnosis of allergy during pregnancy should mainly consist of
the patients history and in vitro testing.
The assured and well-evaluated risk factors revealed for sensitization in mother and child are very limited, to date, and include alcohol
consumption, exposure to tobacco smoke, maternal diet and diet of
the newborn, drug usage, and insufcient exposure to environmental
bacteria. Consequently, the recommendations for primary and
secondary preventive measures are also very limited in number and
verication.
Key Words: allergy, atopy, newborn, pregnancy, prevention
(WAO Journal 2009;2:26Y36)

llergy is a hypersensitivity reaction initiated by specic

immunologic responses1,2 against foreign, usually harmless, substances. The most common allergens worldwide
include pollen, dust mites, molds, animal dander, cockroach,
insect venom, and certain foods.

CLASSIFICATION AND MECHANISM

Hypersensitivity against allergens can be mediated by
either antibodies or T lymphocytes. Allergies or hyperreactivReceived for publication November 13, 2008; accepted December 29, 2008.
From the 1Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria; and
2
Division of Allergy, School of Child and Adolescent Health, Red Cross
War Memorial Childrens Hospital, Cape Town, South Africa.
Research for this article was supported by Hertha Firnberg stipend T283-B13
and SFB F1808-B13 from the Austrian Science Fund (FWF). A synopsis
from this review is also submitted for publication on the WAO homepage
(http://www.worldallergy.org/adrc/). We would like to acknowledge
Gefried Pali for the photograph arts.
Reprints: Isabella Pali-Scholl, PhD, Department of Pathophysiology, Center of
Physiology, Pathophysiology and Immunology, Medical University of
Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. E-mail: isabella.
[email protected].
Copyright * 2009 by World Allergy Organization

26

ities have been classied by Gells and Coombs into types I

through IV, with types I, II, and III being mediated by
antibodies or immune complexes and type IV reactions as well
as chronic stages of allergic diseases being mediated by T
cells.1 The focus of this review is set on asthma and type I
allergy associated with pregnancy. The sensitization process
involves the production of allergen-specic immunoglobulin
E (IgE) antibodies, which are xed to mast cells via their
high-afnity receptor, Fc epsilon receptor I (Fc?RI). On a
subsequent encounter with the allergen, bridging of 2 or more
IgE antibodies leads to degranulation of the mast cell with
release of preformed mediators such as histamine, serotonin,
tryptase, chymase, kininogenase, and heparin. Cross-linking is
more likely if the allergen occurs in dimerized or multimerized
form.3 The mediator release results in the well-recognized
acute allergic inammation characterized by itching, redness,
and tissue edema involving the skin, respiratory tract, circulation, and gastrointestinal tract. Immediate-phase type I
allergic symptoms usually occur within several minutes after
allergen contact. After degranulation, mast cells lose membrane area, become activated, and start a de novo synthesis of
prostaglandins and leukotrienes from membrane arachidonic
acid.4,5 The newly synthesized cytokines and chemokines lead
to the late-phase reaction associated with tissue edema by
recruitment and activation of additional inammatory cells,
including basophils, eosinophils, and T helper type 2 (Th2)
lymphocytes.6 Late-phase reactions are observed several hours
to days after allergen contact.

PART 1: SPECIFIC ALLERGIC DISEASES

IN PREGNANCY
Epidemiology: Prevalence of Asthma and Allergy
in Pregnant Women
Allergic sensitization to common allergens can be
detected in approximately 25% to 35% of the general
population in industrialized countries.7 In the United States,
about 18% to 30% of women in the childbearing age have
allergic diseases, especially rhinitis8 and asthma.9 Other
allergic diseases that may complicate pregnancy include
conjunctivitis, acute urticaria, anaphylaxis, food allergy, and
drug allergy. These disorders represent the most common
group of medical conditions that complicate pregnancy.
Asthma and allergic disorders can affect the course and
outcome of the pregnancy. Pregnancy itself may also affect the
course of asthma and other diseases.10 Optimal management
of these disorders during pregnancy is vital to ensure the
welfare of the mother and the baby.
Specic pharmacological agents for treatment of asthma
or allergic diseases must be cautiously selected. Although
WAO Journal

& March 2009

WAO Journal

& March 2009

most drugs do not harm the fetus, this knowledge is incomplete. Any drug may carry a small risk that must be
balanced against the benets of keeping the mother and baby
healthy.

Safety of Asthma and Allergy Medication

in Pregnancy
The ideal situation during pregnancy is Bno pharmacological therapy,[ especially during the rst trimester. However,
the reality is that medications must be considered for pregnant
patients with medical disorders, based on a thorough
appreciation of the potential deleterious effects of untreated
disease. For instance, women with asthma or allergic diseases
require drug therapy during pregnancy to prevent symptoms
severe enough to be life threatening to the mother or the fetus
(eg, severe acute asthma that can result in hypoxia).
Of the available medications for allergic rhinitis (AR),
chlorpheniramine is recommended as the rst-generation
antihistamine of choice for use during pregnancy.11 Based
on the information available (Table 1), loratadine or cetirizine
may be considered the second-generation antihistamines of
choice. The decision whether to use a rst-generation or
second-generation antihistamine for a particular patient must
be individualized.
Although most of the existing data regarding asthma and
allergy medications during pregnancy have not demonstrated
adverse effects, data regarding the use of oral corticosteroids
have not been totally reassuring. In a recently published metaanalysis,12 6 cohort studies evaluating the relationship
between rst trimester maternal use of oral corticosteroids
and congenital malformations did not show an increased risk
of congenital malformations (summary odds ratio, 1.45; 95%
condence interval, 0.08Y2.60). However, meta-analysis of
the 4 case-control studies revealed a signicantly increased
risk of oral clefts in infants of corticosteroid-treated mothers
(odds ratio, 3.35; condence interval 1.97Y5.69).12 Other
adverse outcomes have also been attributed to oral corticosteroids, including an increased risk of preeclampsia,13,14
preterm birth,12,15 and lower birth weight.16 However, the

Asthma and Allergic Diseases in Pregnancy

TABLE 2. Normal Physiological Respiratory Changes During

Pregnancy
Increased
Tidal volume
Minute ventilation
Alveolar-arterial O2 gradient
Oxygen partial pressure
pH, normal or slightly elevated
(respiratory alkalosis)
Respiratory rate unchanged

Decreased
Functional residual capacity
Residual volume
Diffusion capacity
PaCO2

Adapted from Weinberger et al.17

potential side effects of any drug must be balanced against the

risks of the mother or the infant having inadequately treated
disease. In the case of asthma, the risk of uncontrolled severe
asthma (which may include maternal or fetal mortality) would
usually be the greater risk, suggesting that oral corticosteroids
must still be used when indicated for the management of
severe gestational asthma.

Asthma
Certain physiological changes occur normally during
pregnancy (Table 2).17 These alterations are primarily the
result of hormonal effects. They could potentially affect the
course of asthma and predispose to hypoxia. The physiologically elevated position of the diaphragm and hyperventilation
in pregnancy further increase the risk of hypoxia. Preexisting
asthma symptoms may worsen, improve, or remain unchanged
during pregnancy. Each of these 3 possibilities are observed in
about one third of all cases.10

TABLE 1. Recommendations for Treatment of Asthma and

Allergies in Pregnancy
Drugs preferred for use during pregnancy
Anti-inflammatory: cromolyn beclomethasone, prednisone
Bronchodilator: inhaled A2-adrenergic agonist, theophylline
Antihistamine: chlorpheniramine, tripelennamine
Decongestant: pseudoephedrine, oxymetazoline
Cough: guaifenesin, dextromethorphan
Antibiotic: amoxicillin
Drugs that generally should be avoided during pregnancy
>-Adrenergic compounds (other than pseudoephedrine)
Epinephrine (other than for anaphylaxis)
Iodides
Sulfonamides (in late pregnancy)
Tetracyclines
Quinolones
Adapted from the NAEPP expert group report.21

* 2009 World Allergy Organization

FIGURE 1. Potential side effects of any drug taken during

pregnancy by the mother must be balanced againts the risk of
the mother of the infant suffering from inadequately treated
symptoms.

27

WAO Journal

Pali-Scholl et al

In general, patients with severe asthma are more likely to

experience worsening of their disease during pregnancy.
Alterations in maternal immunity, particularly a decrease in
cell-mediated immunity, may predispose the pregnant asthmatic to infections and thus to acute exacerbations of asthma.
Severe or poorly controlled asthma may be associated with an
increased risk of fetal death, low birth weight, congenital
malformations,18 and parental complications.14 Pregnant
patients with severe or uncontrolled asthma should be
considered high-risk and be treated promptly and optimally
to ensure a favorable outcome for mother and baby. Thus,
optimal asthma treatment is crucial, as the risk of preeclampsia, premature birth, low birth weight,19 and maternal and
neonatal hypoxia and morbidity10,20 posed by undertreated
asthma may be greater than that from the use of oral steroids
for the treatment of asthma.

Management of Chronic Asthma

The goals of management during pregnancy are the
same as those for asthma in general, including prevention of
severe exacerbations, improvement of quality of life (no
interference with sleep or daily activities), and maintenance of
normal lung function. Frequent regular follow-up visits to or
by health professionals skilled in managing asthma are
essential to ensure optimal success and safety of asthma
management during pregnancy. The importance of effective 3way communication among the patient, asthma specialist, and
obstetrician cannot be overemphasized. Patients should have
easy access to their physicians during times of increased
symptoms. Education about asthma and its interaction with
pregnancy reduces anxiety and improves compliance.
The recommendations for medical treatment have been
summarized by a Working Group of the National Asthma
Education and Prevention Program in a report on managing
asthma during pregnancy.21 A stepwise approach is suggested
for medical treatment, where inhaled salbutamol is the
preferred short-acting A agonist with an outstanding safety
prole, and inhaled corticosteroids (eg, budesonide) should be
used condently as long-term control medications. Salmeterol
is the preferred agent when long-acting A2 agonists are
indicated in pregnant women as add-on treatment of persistent
asthma. Leukotriene modiers may be used as alternative addon treatment; montelukast and zarlukast are the preferred
antileukotriene drugs (but zileuton is not).
Patients whose asthma is not controlled with maximal
doses of bronchodilators and anti-inammatory agents may
need systemic corticosteroids. The lowest possible effective
dose (alternate-day dose or single daily dose) should be used.
Patients must be monitored closely for potential adverse
effects of corticosteroids, especially gestational diabetes,
preeclampsia, and intrauterine growth retardation.

Management of Acute Asthma

Treatment of acute asthma is similar to that recommended for nonpregnant patients including inhaled A2
agonists, oxygen (essential), and corticosteroids (oral or
parenteral).22 It is also reasonable to add nebulized ipratropium bromide in patients who do not respond to A2 agonists.

28

& March 2009

Intravenous aminophylline is not generally recommended in

the emergency management of acute asthma (because of its
potentially harmful effects) but may be used in pregnant
patients hospitalized for acute asthma (theophylline levels
should be monitored). Criteria for admission and hospital
management of the pregnant woman with acute asthma should
be more lenient than for nonpregnant patients. Intravenous
magnesium sulfate may be benecial in acute severe asthma as
an adjunct to inhaled A2 agonists and corticosteroids.

Rhinitis
Signicant nasal symptoms occur in approximately 30%
of pregnant women.23 Pregnancy-associated hormones have
direct and indirect effects on nasal blood ow and mucous
glands. The most common causes of nasal symptoms
necessitating treatment during pregnancy are AR, rhinitis
medicamentosa, sinusitis, and (non-AR) vasomotor.24 Vasomotor rhinitis of pregnancy is a syndrome of nasal congestion
and vasomotor instability limited to the gestational period.
Allergic rhinitis is often preexisting but may occur or be
recognized for the rst time during pregnancy. Allergic rhinitis
commonly coexists with asthma; 80% of asthmatic adults also
have AR, and 20% to 50% of patients with AR also have
asthma.25 In a group of 1245 adult patients with documented
asthma, 24% had seasonal AR only, 6% had perennial AR
only, and 22% were considered to have both.26
As with asthma, preexisting AR can worsen, improve, or
remain unchanged during pregnancy.27 Furthermore, during
pregnancy, nasal congestion can worsen, although the exact
mechanism for this is not dened.
The general principles of treatment of pregnant women
with asthma21,22,28 and AR29 do not differ from the stepwise
approach recommended for treatment of nonpregnant women.
Intranasal cromolyn, intranasal steroids, and montelukast are
the preferred drugs for the treatment of rhinitis because of the
low risk of systemic effects. Second-generation antihistamines
such as loratadine or cetirizine21,29 can also be used (after the
rst trimesterVas a general precaution). Adjunctive treatment
of rhinitis, which is permitted in pregnancy, includes
oxymetazoline drops or spray for nasal congestion, pseudoephedrine (after the rst trimester) for persistent nasal
congestion, and buffered saline sprays for nasal dryness,
nasal bleeding, and vascular congestion associated with
pregnancy.

Anaphylaxis
The exact prevalence of anaphylaxis during pregnancy is
unknown, but it is extremely uncommon.30 The fetus seems to
be relatively protected from anaphylaxis perhaps because the
placenta does not transmit specic IgE antibodies to the
fetus.31 However, maternal hypoxia or hypotension associated
with anaphylaxis may be catastrophic not only to the mother
but also to her fetus. Maternal anaphylaxis has been associated
with fetal distress, brain injury, and fetal loss (presumably
because of diminished uteroplacental perfusion), as well as
neonatal death.32Y35 Any agent that can cause anaphylaxis in
the nonpregnant state could also cause anaphylaxis in the
susceptible or sensitized pregnant patient. Even breast-feeding
has been associated with anaphylaxis in 2 postpartum women.
WAO Journal

& March 2009

WAO Journal

& March 2009

The reactions occurred within 1 to 3 days postpartum and

resolved within 1 to 2 days. Changing levels of progesterone
and triggering by nonsteroidal anti-inammatory drugs were
suggested as potential causes.36
The management of anaphylaxis during pregnancy is the
same as for nonpregnant patients. Of the routine antianaphylaxis medications, epinephrine and diphenhydramine have
been implicated in causing fetal malformations. However, the
tentative nature of these data and the lack of equally effective
substitutes justify their use in pregnancy for this lifethreatening emergency. Adequate intravascular volume repletion and oxygenation are particularly important in the
management of anaphylaxis during pregnancy to prevent
both maternal and fetal complications. The pregnant hypotensive patient should be placed on her left side to prevent added
positional hypotension resulting from compression of the
inferior vena cava by the gravid uterus.37 Intravenous
epinephrine may be required despite its potential to cause
decreased uteroplacental blood ow. Glucocorticoids should
be administered early to patients with severe anaphylaxis. For
laryngeal spasm, intubation and, in rare cases, tracheotomy
may be necessary.

Adverse Reactions to Food

No studies have focused explicitly on the prevalence of
food allergy in pregnant women primarily because often the
immune response in the offspring is the main focus of
research. A cohort study on the Isle of Wight, United
Kingdom, found adverse reactions to food in approximately
20% of 969 pregnant women.38 The results of this observational study were based on questionnaires lled out by the
mothers after childbirth. From murine studies, it may be
expected that the sensitization of a mother to a (food) allergen
will also bias the immune response of the offspring toward
Th2.39,40

Atopic Eczema (Dermatitis)

Gestational itchy dermatoses are relatively common,
with eczema being diagnosed in 30% to 50% of all cases.41
However, the exact prevalence of allergic forms of dermatitis
in the pregnant population is not known. The importance of an
exacerbation of eczema and dermatitis during pregnancy
should not be underestimated as readout of the atopic state,
being of interest for the genetic predisposition of the
newborn.42 Most women with atopic dermatitis have lived
with their condition long before becoming pregnant. The
course is variable.43
Treatment of atopic dermatitis during pregnancy should
emphasize avoidance of triggering factors and reliance on
topical treatment in an attempt to reduce dryness and pruritus,
modulate inammation, and treat secondary infections. Oral
antihistamines should be avoided during the rst trimester,
unless denitely clinically indicated, and then should be used
at the lowest effective dose, starting with chlorpheniramine,
loratadine, or cetirizine. Topical steroids should be selected
based on potency considerations, given the potential for
systemic absorption and increased skin surface area of
pregnancy. Severe intrauterine growth retardation occurred
in the infant of a mother who applied 40 mg/d of topical
* 2009 World Allergy Organization

Asthma and Allergic Diseases in Pregnancy

triamcinolone cream from week 12 to 29 of gestation to treat

her atopic dermatitis.44 Topical corticosteroid treatment
should be initiated when clinically indicated, with the least
potent preparations such as hydrocortisone (0.5% to 1%),
reserving more potent preparations for more recalcitrant areas
in selected patients. The recently introduced topical calcineurin inhibitors (pimecrolimus and tacrolimus), although
effective in the treatment of atopic eczema, are not
recommended for use in pregnant patients because of the
lack of safety data.

Urticaria and Angioedema

The pattern and causes of urticaria and angioedema in
pregnancy are similar to those in nonpregnant patients. A
unique form of urticaria associated with pregnancy, which
tends to recur in subsequent pregnancies (pregnancy urticaria), has been reported.45 The pathogenesis of this condition
is unknown, although there is speculation that it may be caused
by allergic sensitization to endogenous hormones.46,47 The
rst step in treatment of urticaria and angioedema in
pregnancy is identication and avoidance of causative factors.
Antihistamines should be avoided if possible, but if required,
chlorpheniramine, loratadine, or cetirizine may be used.
Rarely, systemic corticoids may be used for severe recalcitrant
urticaria and angioedema during pregnancy.

Drug Allergy
There is a lack of data on the prevalence of adverse drug
reactions during pregnancy. The diagnosis and treatment of
drug allergy are the same in pregnant as in nonpregnant
patients.

Diagnosis of Allergy During Pregnancy

The diagnosis of allergy in pregnant women should
focus on a detailed medical history and symptom analysis. For
diagnosis, a diary of allergy symptoms and avoidance of
specic allergens accompanied by monitoring of changes of
allergic symptoms may be helpful. However, it is important
not to put the mother on a rigid elimination diet because this
could negatively inuence the nutrition of both the mother and
the growing infant.48
In vitro diagnostic tools such as serological testing, for
example, radioallergosorbent test for type I allergy or the
lymphocyte transformation test for type IV allergy49 are
preferred to in vivo testing. Although not contraindicated, skin
prick testing should be postponed until after birth because of
possible, although rare, anaphylactic reactions to skin prick
testing. The same applies to in vivo tests such as food
challenge tests and patch tests. Only in situations where in
vitro diagnosis is not conclusive and the mother is at risk for
developing allergy symptoms should in vivo skin tests be used.
Examples include the occurrence of generalized eczema
requiring identication of the cause before treatment or a
suspected allergy to a drug needed for therapy of the mother
(eg, penicillin for treating syphilis).50 Importantly, when
performing in vivo testing such as skin tests or provocation
test, the exceptional immunologic status accompanying
pregnancy should be considered when interpreting test results.

29

Pali-Scholl et al

WAO Journal

& March 2009

Any unexpected test result and any symptoms that change over
time should be reevaluated after pregnancy. In addition, the
attending physician should bear in mind that some symptoms
may be a direct result of pregnancy and not allergy related, for
example, vasomotor rhinitis in the last trimester51 and
gestational urticaria (pruritic urticarial papules and plaques
in pregnancy).52

may not be restricted to the organ at which the mother experiences allergic symptoms because asthma or wheezing
in children was associated not only with asthma and AR,
but also with eczema or any allergic disease in their parents
and siblings.56,57

Nonpharmacological Management of Allergic

Diseases During Pregnancy

The allergic status of the mother can potentially affect

the immune response of the offspring through numerous
factors that are transferable via the placenta or breast milk. The
direct transfer of food or inhalant allergens via the placenta or
breast milk has long been recognized.58Y60 In addition,
antibodies can be transferred to the child via placenta (IgG,
IgA) or breast milk (IgA, IgG, IgM, IgE),61,62 and even a
transamniotic transfer of intact maternal IgE into the amniotic
uid can occur.63
Only a very limited number of human studies on the
maternofetal transfer of cytokines and chemokines are
available. For instance, interferon-F (IFN-F) and interleukin6 (IL-6) were detected in the colostrums of healthy women.64
The transfer of maternal cytokines was conrmed in a study of
suckling piglets.65 In vivo and in vitro models have shown that
such transfer may lead to reduced neonatal immunity. Also
chemokines, for example, IL-8, a cytokine that is regulated
on activation with normal T cell expressed and secreted
(RANTES), IFN-FYinducible protein 10, and monokine
induced by IFN-F have been detected in breast milk.66,67
However, cytokines and other soluble inammation markers
are found in breast milk from atopic as well as in nonatopic
women.
Another factor that should be considered is the composition of fatty acids present in breast milk, which may
inuence the immune response of the child.68
In addition to the previously mentioned soluble factors,
also cells are transferred in utero, for instance, leukocytes pass
from mother to fetus. This seems to be important because
allergen-specic T cells transferred from 1 mouse mother
to another can transmit asthma risk to the offspring of the
recipient mouse mother.69 Trafcking of cells could therefore
be responsible for the passing of allergy risk from mother
to fetus.

Mothers with diagnosed allergy should avoid exposure

to and contact with specic allergens (including food
allergens) and should especially avoid the inhalation of potent
triggers for asthma, such as animal dander, house dust,
tobacco smoke, and irritating pollutants.22
Hyposensitization (immunotherapy), which may be
selectively indicated in certain patients with AR, bee venom
sensitivity, and asthma should not be initiated during
pregnancy because of the risk of systemic reactions. For
patients who were already on immunotherapy before the
pregnancy, maintenance treatment may be continued safely
during pregnancy. However, the allergen dose should not be
increased during pregnancy but rather reduced if necessary.29

Summary
Many women experience type I allergies during
pregnancy. Allergy diagnosis during pregnancy should
preferentially consist of recording the patients history for
precise recommendation of allergen avoidance and in vitro
testing only. In vivo testing should generally be postponed
until after pregnancy, unless diagnosis for therapeutic intervention is urgently needed. In general, treatment of asthma
and allergic diseases does not differ from that in nonpregnant
women. Immunotherapy may be continued as maintenance
treatment but should not be initiated during pregnancy.

PART 2: PREVENTION OF ASTHMA

AND ALLERGIES IN EARLY LIFE
Infants With High-Risk of Allergy
The potential risk for the development of atopy among
newborns is high. Genetic components and complex environmental factors contribute to the etiology of asthma and atopic
diseases. To date, there are no biomarkers that can reliably
predict which newborn will develop atopy. However, an atopic
family history has been recognized to be a simple and
inexpensive risk indicator. The degree of risk seems to be
directly related to the family history of allergy and especially
to maternal atopy,53 particularly when the mother has
diagnosed atopic eczema and has elevated IgE levels. If
neither parent is allergic, the chance for allergies in the child is
about 15%. If 1 parent is allergic, the risk increases to 30%,
and if both are allergic, the risk is greater than 60%, especially
for developing the same organ-specic symptoms.54 The
inuence of maternal sensitization on the immune response
of newborns was recently shown in a human observational
study of AR, in which only the organ-specic symptoms of
the mother but not the father were demonstrated to be relevant for the imprinting of the child.55 However, sensitization

30

Transfer Mechanisms of Allergy

(Immunopathogenesis of Atopy)

Environmental Risk Factors for Atopy

The causes of allergy in general and of specic
sensitization in newborns in particular have not yet been
completely determined. Besides the role of genetic predisposition, some factors have been identied that may either
contribute to sensitization of the mother and to the subsequent
transfer of a predisposition for allergy to the offspring, or that
directly induce sensitization in offspring that manifests shortly
after birth or at a young age.

Exposure to Tobacco Smoke

One of the most frequently discussed risk factors for
induction of sensitization in all populations and age groups is
tobacco smoke (active smoking or the passive environmental
exposure). In a recent mouse study, exposure to smoke in utero
induced a higher risk of sensitization against allergens in adult
WAO Journal

& March 2009

WAO Journal

& March 2009

age in the offspring.70 Accordingly, in human blood samples,

Th2 cytokines responsible for a predisposition toward allergy
were elevated in the neonates only of mothers who had
smoked during pregnancy.71 In addition, total and specic IgE
levels,72,73 total eosinophil counts,74 incidence of airway
disease,74 and positive results on skin prick tests75 were also
increased in children who were exposed to smoke either during
pregnancy or in early childhood. Alarmingly, in the birth
cohort study from the Isle of Wight, about 43% of children had
been exposed to environmental tobacco smoke during their
rst year of life.38

Alcohol Consumption
Alcohol consumption by the mother during pregnancy is
associated with higher total IgE levels in cord blood.76
Alcohol consumption in adults is also a risk factor for elevated
specic IgE levels against food antigens.77,78

Maternal Diet
The maternal dietary component consumed during
gestation could inuence the immune status of the child. For
instance, different polyunsaturated fatty acids (PUFAs) have
been shown to differently inuence the outcome of eczema in
the child. A diet higher in n-6 PUFAsVas present, for
example, in margarine and vegetable oilsVseems to be more
likely to induce eczema than n-3 PUFAs, which are for
instance found in sh.79 Accordingly, another study showed
that sh consumption decreased eczema.80 However, it may
not be the absolute content but the ratio of n-6 to n-3 PUFAs
that may inuence the development of either tolerance or
sensitization to food, as a high ratio of 9 of n-6/n-3 in the diet
of the mother prevented the induction of oral tolerance to
ovalbumin in the offspring in a rat study.81 Celery and citrus
fruits seem to increase the risk of food sensitization, whereas
vegetable oils, raw sweet pepper, and again citrus fruit increase
sensitization to respiratory antigens.79 Interestingly, apples
consumed during pregnancy were able to decrease wheezing
in children.80
According to a directive of the Commission of European
Communities from 2005, the most allergenic foods have to be
labeled because of their potency of eliciting severe allergic
reactions: these are crustacean, sh, nuts, milk, egg, wheat/
gluten, peanuts, soy, sesame, mustard, and celery. It has long
been proposed that the mother should avoid such foods
containing potential allergens during pregnancy and lactation
to prevent food sensitization in the child. However, recent
studies suggest that allergen exposure may be necessary to
induce tolerance, and moreover, a balanced diet prevents
malnutrition of both mother and child.82 Furthermore,
alterations of the maternal diet, that is, avoidance of milk
and egg consumption during pregnancy did not seem to lower
the risk of sensitization in the child.83,84

Use of Antiacid Medications

The changing hormone levels during pregnancy lead to a
lower esophageal sphincter pressure in the mother, and
concomitantly with growing volume of the fetus, these factors
often result in heartburn, reux, and abdominal pain. Studies
* 2009 World Allergy Organization

Asthma and Allergic Diseases in Pregnancy

found that about 70% of pregnant women are affected by these

symptoms during their last trimenon,85 and 50% of them are
likely to take acid-suppressing medication. However, recent
animal and human studies indicate that acid suppression and
the resulting elevated pH in the stomach may lead to an
increased risk of sensitization to food.86,87 This sensitization
of the mother was shown to lead to an increased risk of food
allergy in the newborn in a BALB/c mouse model.39 As
previously discussed, an allergic status of the mother has the
potency to affect the immune response of the offspring by
numerous factors transferable via placenta or breast milk and
even via the transamniotic route, for instance, intact maternal
IgE in amniotic uid, maternal DNA in cord blood, leukocytes,
and chemokines such as IL-8, RANTES, interferonFYinducible protein 10, or monokine induced by IFN-F,
allergens, as well as antibodies. Furthermore, the offspring of
sensitized mothers are prone to experience suppression and a
later onset of normal levels of the Th1 cytokine IFN-F because
of a lower frequency of IFN-FYproducing cells, and therefore a
further bias toward a Th2 immune response.

Infants Diet
Regarding the nutrition of the baby, reduced breastfeeding and early introduction of solid food have been
discussed as confounders to allergy development. However,
a randomized trial revealed quite contrary that promoted and
prolonged (exclusive) breast-feeding is not able to prevent
development of allergy or asthma in children at the age of
about 6 years.88 In addition, a systematic review of several
studies found no clear negative association between early solid
food introduction and the development of asthma, food
allergy, AR, or animal dander allergy.89

Prematurity and Low Birth Weight

As shown within the Manitoba birth cohort study,
prematurity and low birth weight are not associated with an
increased risk for development of food allergy in childhood.90
The impact of these 2 factors for sensitization to other
allergens, such as aeroallergens, has not been investigated.
However, 1 study showed that adolescents who had been born
prematurely had a substantially decreased expiratory volume
and increased bronchial hyperresponsiveness, making them
potential candidates for developing asthma.91

Birth by Cesarean Delivery

The delivery of a baby by cesarean delivery has been
suggested to be associated with increased risk of allergies and
atopic diseases in the child, most probably because of a lower
bacterial exposure for the child. In a recent population-based
cohort study in Norway, it was shown that a positive
association exists for cesarean delivery and risk of asthma in
the child (especially when the cesarean delivery was
performed because of an emergency in contrast to a planned
section).92 Bager and colleagues93,94 also showed an increased
risk for asthma, allergic rhinitis, and possibly for food allergies
in their meta-analysis. However, because of the low numbers
of an allergic outcome associated to cesarean delivery (only
1%Y4%), the authors concluded that the epidemic increase of

31

Pali-Scholl et al

allergic diseases might not be attributable to the increased

numbers of cesarean delivery.

Insufcient Exposure to Environmental Bacteria

The hygiene hypothesis states that low exposure of the
mother during pregnancy and of the newborn in early life to
environmental bacteria contributes to a Th2-biased immune
response. This hypothesis has been conrmed by several
experimental animal and epidemiological human studies
(reviewed in Renz et al95).

Preventive Measures for Mother and Child

Strategies for prevention of atopic diseases may be categorized as primary, secondary, and tertiary. Primary prevention
addresses symptom-free children at risk (ie, without the
established disease). Secondary prevention addresses individuals with early indicators of atopic disease. Tertiary
prevention is directed at patients with a chronic disease to
prevent additional problems related to the disease.
Primary prevention has been suggested for those
newborns who have at least 1 parent or sibling with proven
atopy. However, it must be borne in mind that a proportion of
children who develop atopic manifestations in the rst years of
life come from families in which neither parents nor siblings
are atopic. In addition, a signicant percentage of infants from
families with an atopic background do not develop atopy
during childhood. This suggests the possibility that some
infants who would never have developed atopy would undergo
preventive regimens, whereas others who become symptomatic in early life would not have received adequate advice.
This review will deal only with dietary and environmental
control measures (see later) for the prevention (primary and
secondary) of atopic diseases. Preventive pharmacotherapy
and immunotherapy will not be discussed.

Smoking
Maternal smoking and passive exposure to smoke
should both be avoided. This is especially important for
pregnant asthmatic patients, in whom smoking-related morbidity is independent ofVand adds toVthe morbidity
resulting from asthma.96 Although there are contradicting
epidemiological and experimental results regarding the direct
inuence of smoking on total and specic IgE production,97,98
smoking should nevertheless be avoided for obvious reasons,
such as carcinogenic smoke constituents and the vasoconstrictive effect of nicotine.

Alcohol
Alcohol intake should be avoided by the pregnant
mother because of well-known toxic effects on both mother
and fetus. Moreover, alcohol consumption has been shown to
induce higher IgE levels against aeroallergens in atopic
patients.76

Maternal Diet During Pregnancy

A Cochrane database meta-analysis of 4 clinical studies
concluded that antigen avoidance during pregnancy is unlikely
to reduce the childs risk of developing atopic disease, and

32

WAO Journal

& March 2009

dietary restrictions could adversely affect maternal or fetal

nutrition.99 Although previously suggested that pregnant
women with risks avoid peanuts, a subsequent study found
no evidence of prenatal sensitization from maternal consumption of peanuts.100 In addition, recent publications revealed
that an effect (positive or negative) of peanut avoidance on
sensitization was not detectable (although too few valuable
subjects and the observational nature of the reports reduce the
ability to make rm conclusions).101,102 Generally, there is a
lack of evidence for maternal pregnancy restriction diets.
Additional recent studies about pregnancy diets reveal that
components other than specic allergens, such as fat, may
inuence atopy outcomes.103,104 Therefore, no special diet for
the mother is required during pregnancy. On the contrary, the
diet should be well balanced and consist of as many different
nutrients as possible, as the current literature suggests that
antigens obtained via the oral route during pregnancy and
lactation are needed to develop allergen tolerance in the
child.105 In line with this, there was no association between
maternal intake of foods during pregnancy and the occurrence
of asthma, respiratory disease, or allergy in 5-year-old
children.80 Furthermore, many studies found no benet of a
restricted diet avoiding the consumption of allergy-inducing
food during pregnancy.82
However, if the mother is already allergic or if there is a
family history of atopy or allergy, food comprising potential
allergens should be avoided. In such instances, the avoidance
of peanuts, nuts, sh, eggs, and sesame during the last 3
months of pregnancy may have a protective effect.106 In this
respect, government recommendations must be carefully
worded, as 1 study found that avoidance of peanuts was
overdone among pregnant women: although such avoidance
was recommended only for women with atopy risk, 65% of
all pregnant women had avoided peanuts during pregnancy
(42% of all women who responded had heard about the
advice, eg, from their midwives, and 50% subsequently
changed their diet).101
Numerous individual nutrients consumed by the mother
during pregnancy have been suggested as being preventive
for development of atopic diseases in the child; these include
apples or sh,80 vitamin D,107 vitamin E,108 and various probiotics, the latter having been shown to be effective in mouse
models109 and human studies.110

Antiacids During Pregnancy

Recent studies have indicated that acid-suppressing
medications can promote sensitization in adults.86,87 Therefore, it is suggested that antiacids should be taken only when
prescribed by an attending physician to the childbearing
mother. Treatment of reux during pregnancy should focus on
nonpharmacological measures, such as avoiding large meals
shortly before bedtime, sleeping with the upper body elevated,
and avoiding extensive consumption of coffee, sweets, and
fatty foods. In addition, smoking is a cause of reux and
should be avoided. If these measures are unsuccessful, then
prescription of antiacid drugs should be considered, for
example, in the form of a step-up program beginning with
antacids, and in case of failure with histamine-2 receptor
antagonists, whereas proton pump inhibitors should only be
WAO Journal

& March 2009

WAO Journal

& March 2009

used in women with intractable symptoms or complicated

reux disease.111,112

Avoidance of Other Allergens During Pregnancy

Avoidance of other allergens is necessary only if the
pregnant patients are already sensitized (eg, to cats, dogs,
horses, or house dust). However, allergen avoidance may not
be preventive or practical in all cohorts.113

Maternal Diet During Lactation

Regarding maternal lactation diets, a Cochrane database
meta-analysis99 found some evidence of reduced atopic
dermatitis, but suggested that more studies are needed. A
previous expert review that was not a structured meta-analysis
and did not exclude as many studies as the Cochrane review
concluded that special maternal lactation avoidance diets were
unnecessary.114 During lactation, a special diet for the mother
(or, if not breast-feeding, hypoallergenic formula nutrition for
the infant) should be considered only in individuals with an
established atopy risk or existing allergy.82,115

Diet of the Infants

As mentioned previously, for breast-feeding, there is
insufcient evidence to determine whether it is more
protective against allergies and asthma than bottle feeding
because in a recent study, prolonged and exclusive breastfeeding could not decrease the rate of allergies or asthma
in children.88 Furthermore, there are data supporting that
breast-feeding should not be continued beyond 9 months
of age because doing so seems to increase the childs risk
for atopic diseases, such as atopic dermatitis and food
hypersensitivity.116
Some studies investigated the effect of reduced exposure
of infants to allergen-provoking food. In cases where a
reduced sensitization to food was found, this protective effect
was short-lived and was primarily observed during the rst
year of life.
As a further preventive measure, the early introduction
of solid food (ie, baby food from jars and table food) into the
infants diet has to be revisited. It has been suggested that
foods containing allergy-provoking proteins such as milk, egg,
peanuts, tree nuts, sh, and seafood should not be introduced
into the diet of the child before the age of 6 months to 3
years.117 However, contact with and exposure to antigens may
be necessary in early life to develop tolerance in the immune
system.118 This process is active and specic, much like the
process of sensitization.119 Thus far, studies on delayed
introduction of solids led to conicting results.

Summary
Based on currently available evidence, guidelines for
primary and secondary prevention of allergic disease can be
summarized as follows (Table 3).

Smoking and Alcohol

Smoking and passive exposure to cigarette smoke as
well as alcohol consumption should be strictly avoided.
* 2009 World Allergy Organization

Asthma and Allergic Diseases in Pregnancy

TABLE 3. Primary Prevention of Asthma and Allergies in Early

Life
Preventive Measures
Smoking and exposure to environmental tobacco smoke should be avoided,
especially during pregnancy and early childhood
Alcohol consumption should be avoided by the mother during pregnancy
and lactation
Damp housing conditions should be avoided and indoor air pollutants
reduced, especially for high-risk children (history of atopy or allergy in a
first-degree relative)
Breast-feeding should be performed exclusively until 6 months with no
special diet for the lactating mother (except when the mother is already
diagnosed with food allergy)
Nonprescription drugs should be avoided during pregnancy and lactation
unless recommended by a physician

Diet
There should be no special diet for the mother during
pregnancy and lactation, unless the mother or child has a
diagnosed food sensitization. In infants with risk of allergy,
introduction of solid foods in general should be postponed
until 6 months of age, milk products until 12 months, hens egg
until 24 months, and peanut, tree nuts, sh, and seafood until
at least 36 months.

Other Allergens
Avoidance of allergens (pets, house dust, contact
allergens, drugs) is not recommended except when sensitization has already been diagnosed.

Reux Treatment
Pregnancy-associated reux should be treated by
nonpharmacological measures rst.

Atopy
For newborns at suspected risk for atopy, that is, with a
history of atopy/allergy in a rst-degree relative (parents,
siblings), exposure to irritating air pollutants and airborne
allergens such as molds should be minimized.

Breast-feeding
Infants should be breast-fed for at least 4 months but no
longer than 9 months. Special hypoallergenic formula
(extensively hydrolyzed, not soy-based) should be used only
if the child is diagnosed with atopy.

Drugs
All nonprescription drugs (eg, antiacids) should be
avoided during pregnancy and lactation unless recommended
by a physician; patients should avoid intake of any medication
including over-the-counter substances without consulting their
physicians.
For more information on primary, secondary, and
tertiary prevention of allergy, readers are referred to the
document, BPrevention of Allergy and Allergic Asthma,[ an
article based on ndings presented at the World Health
Organization/World Allergy Organization meeting in January

33

WAO Journal

Pali-Scholl et al

2002.120 This document also includes a summary of evidencebased guidelines and strength of recommendations.
REFERENCES
1. Gell PGH, Coombs RRA. The classification of allergic reactions
underlying disease. Oxford: Blackwell Science; 1963.
2. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF,
et al. Revised nomenclature for allergy for global use: report of the
Nomenclature Review Committee of the World Allergy Organization,
October 2003. J Allergy Clin Immunol. 2004;113:832Y836.
3. Scholl I, Kalkura N, Shedziankova Y, Bergmann A, Verdino P,
Knittelfelder R, et al. Dimerization of the major birch pollen allergen
Bet v 1 is important for its in vivo IgE cross-linking potential in mice.
J Immunol. 2005;175:6645Y6650.
4. Dvorak AM, Schleimer RP, Lichtenstein LM. Morphologic mast cell
cycles. Cell Immunol. 1987;105:199Y204.
5. Xiang Z, Block M, Lofman C, Nilsson G. IgE-mediated mast cell
degranulation and recovery monitored by time-lapse photography.
J Allergy Clin Immunol. 2001;108:116Y121.
6. Ogawa Y, Grant JA. Mediators of anaphylaxis. Immunol Allergy Clin
North Am. 2007;27:249Y260.
7. Braun-Fahrlander C, Gassner M, Grize L, Takken-Sahli K, Neu U,
Stricker T, et al. No further increase in asthma, hay fever and atopic
sensitisation in adolescents living in Switzerland. Eur Respir J.
2004;23:407Y413.
8. Incaudo GA. Diagnosis and treatment of allergic rhinitis and sinusitis
during pregnancy and lactation. Clin Rev Allergy Immunol.
2004;27:159Y177.
9. Kwon HL, Belanger K, Bracken MB. Asthma prevalence among
pregnant and childbearing-aged women in the United States: estimates
from national health surveys. Ann Epidemiol. 2003;13:317Y324.
10. Schatz M, Dombrowski MP, Wise R, Thom EA, Landon M, Mabie W,
et al. Asthma morbidity during pregnancy can be predicted by severity
classification. J Allergy Clin Immunol. 2003;112:283Y288.
11. Schatz M. H1-antihistamines in pregnancy and lactation. Clin Allergy
Immunol. 2002;17:421Y436.
12. Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L,
Hunnisett L, et al. Birth defects after maternal exposure to
corticosteroids: prospective cohort study and meta-analysis of
epidemiological studies. Teratology. 2000;62:385Y392.
13. Schatz M. The efficacy and safety of asthma medications during
pregnancy. Semin Perinatol. 2001;25:145Y152.
14. Stenius-Aarniala B, Piirila P, Teramo K. Asthma and pregnancy: a
prospective study of 198 pregnancies. Thorax. 1988;43:12Y18.
15. Perlow JH, Montgomery D, Morgan MA, Towers CV, Porto M. Severity
of asthma and perinatal outcome. Am J Obstet Gynecol.
1992;167:963Y967.
16. Reinisch JM, Simon NG, Karow WG, Gandelman R. Prenatal exposure
to prednisone in humans and animals retards intrauterine growth.
Science. 1978;202:436Y438.
17. Weinberger SE, Weiss ST, Cohen WR, Weiss JW, Johnson TS.
Pregnancy and the lung. Am Rev Respir Dis. 1980;121:559Y581.
18. Blais L, Forget A. Asthma exacerbations during the first trimester of
pregnancy and the risk of congenital malformations among asthmatic
women. J Allergy Clin Immunol. 2008;121:1379Y1384 [1384 e1371].
19. Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett WS, Leaderer
BP. Asthma symptoms, severity, and drug therapy: a prospective study of
effects on 2205 pregnancies. Obstet Gynecol. 2003;102:739Y752.
20. Dombrowski MP, Schatz M, Wise R, Momirova V, Landon M, Mabie W
et al. Asthma during pregnancy. Obstet Gynecol. 2004;103:5Y12.
21. NAEPP expert panel report. Managing asthma during pregnancy:
recommendations for pharmacologic treatmentV2004 update. J Allergy
Clin Immunol. 2005;115:34Y46.
22. Namazy JA, Schatz M. Current guidelines for the management of asthma
during pregnancy. Immunol Allergy Clin North Am. 2006;26:93Y102.
23. Mabry RL. Rhinitis of pregnancy. South Med J. 1986;79:965Y971.
24. Schatz M, Zeiger RS. Diagnosis and management of rhinitis during
pregnancy. Allergy Proc. 1988;9:545Y554.
25. Bousquet J, Vignola AM, Demoly P. Links between rhinitis and asthma.
Allergy. 2003;58:691Y706.
26. Leynaert B, Bousquet J, Neukirch C, Liard R, Neukirch F. Perennial

34

27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.

39.
40.

41.

42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.

& March 2009

rhinitis: an independent risk factor for asthma in nonatopic subjects:

results from the European Community Respiratory Health Survey.
J Allergy Clin Immunol. 1999;104:301Y304.
Mazzotta P, Loebstein R, Koren G. Treating allergic rhinitis in
pregnancy. Safety considerations. Drug Saf. 1999;20:361Y375.
Dombrowski MP. Asthma and pregnancy. Obstet Gynecol.
2006;108:667Y681.
Yawn B, Knudtson M. Treating asthma and comorbid allergic rhinitis in
pregnancy. J Am Board Fam Med. 2007;20:289Y298.
Hayashi RH. Emergency care in pregnancy. In: Queenan JT, editor.
Management of high-risk pregnancy. Oxford: Blackwell Science;
1999:377.
Baraka A, Sfeir S. Anaphylactic cardiac arrest in a parturient. Response
of the newborn. JAMA. 1980;243:1745Y1746.
Klein VR, Harris AP, Abraham RA, Niebyl JR. Fetal distress during a
maternal systemic allergic reaction. Obstet Gynecol. 1984;64:15SY17S.
Erasmus C, Blackwood W, Wilson J. Infantile multicystic
encephalomalacia after maternal bee sting anaphylaxis during
pregnancy. Arch Dis Child. 1982;57:785Y787.
Luciano R, Zuppa AA, Maragliano G, Gallini F, Tortorolo G. Fetal
encephalopathy after maternal anaphylaxis. Case report. Biol Neonate.
1997;71:190Y193.
Entman SS, Moise KJ. Anaphylaxis in pregnancy. South Med J.
1984;77:402.
MacDonell JW, Ito S. Breastfeeding anaphylaxis case study. J Hum Lact.
1998;14:243Y244.
Witter FR, Niebyl JR. Drug intoxication and anaphylactic shock in the
obstetric patient. In: Berkowitz RL, editor. Critical care of the obstetric
patient. New York: Churchill Livingstone; 1983.
Venter C, Pereira B, Grundy J, Clayton CB, Roberts G, Higgins B, et al.
Incidence of parentally reported and clinically diagnosed food
hypersensitivity in the first year of life. J Allergy Clin Immunol.
2006;117:1118Y1124.
Scholl I, Ackermann U, Ozdemir C, Blumer N, Dicke T, Sel S, et al.
Anti-ulcer treatment during pregnancy induces food allergy in mouse
mothers and a Th2-bias in their offspring. FASEB J. 2007;21:1264Y1270.
Uthoff H, Spenner A, Reckelkamm W, Ahrens B, Wolk G, Hackler R,
et al. Critical role of preconceptional immunization for protective and
nonpathological specific immunity in murine neonates. J Immunol.
2003;171:3485Y3492.
Ambros-Rudolph CM, Mullegger RR, Vaughan-Jones SA, Kerl H,
Black MM. The specific dermatoses of pregnancy revisited and
reclassified: results of a retrospective two-center study on 505 pregnant
patients. J Am Acad Dermatol. 2006;54:395Y404.
Sugiyama M, Arakawa H, Ozawa K, Mizuno T, Mochizuki H,
Tokuyama K, et al. Early-life risk factors for occurrence of atopic
dermatitis during the first year. Pediatrics. 2007;119:e716Ye723.
Kemmett D, Tidman MJ. The influence of the menstrual cycle and
pregnancy on atopic dermatitis. Br J Dermatol. 1991;125:59Y61.
Katz VL, Thorp JM Jr, Bowes WA Jr. Severe symmetric intrauterine
growth retardation associated with the topical use of triamcinolone.
Am J Obstet Gynecol. 1990;162:396Y397.
Champion RH, Roberts SO, Carpenter RG, Roger JH. Urticaria and
angio-oedema. A review of 554 patients. Br J Dermatol.
1969;81:588Y597.
Bierman SM. Autoimmune progesterone dermatitis of pregnancy.
Arch Dermatol. 1973;107:896Y901.
Farah FS, Shbaklu Z. Autoimmune progesterone urticaria. J Allergy Clin
Immunol. 1971;48:257Y261.
Gortz J, Goos M. Diagnosis of allergy in pregnancy [In German].
Hautarzt. 1989;40:545Y547.
Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis
of drug hypersensitivity. Allergy. 2004;59:809Y820.
Macy E. Penicillin skin testing in pregnant women with a history of
penicillin allergy and group B Streptococcus colonization. Ann Allergy
Asthma Immunol. 2006;97:164Y168.
Incaudo GA, Takach P. The diagnosis and treatment of allergic rhinitis
during pregnancy and lactation. Immunol Allergy Clin North Am.
2006;26:137Y154.
Brzoza Z, Kasperska-Zajac A, Oles E, Rogala B. Pruritic urticarial
papules and plaques of pregnancy. J Midwifery Womens Health.
2007;52:44Y48.

WAO Journal

& March 2009

WAO Journal

& March 2009

53. Liu CA, Wang CL, Chuang H, Ou CY, Hsu TY, Yang KD. Prenatal
prediction of infant atopy by maternal but not paternal total IgE levels.
J Allergy Clin Immunol. 2003;112:899Y904.
54. Litonjua AA, Carey VJ, Burge HA, Weiss ST, Gold DR. Parental
history and the risk for childhood asthma. Does mother confer more
risk than father? Am J Respir Crit Care Med. 1998;158:176Y181.
55. Shinohara M, Wakiguchi H, Saito H, Matsumoto K. Symptoms of
allergic rhinitis in women during early pregnancy are associated with
higher prevalence of allergic rhinitis in their offspring. Allergol Int.
2007;56:411Y417.
56. Bener A, Janahi I. Association between childhood atopic disease and
parental atopic disease in a population with high consanguinity. Coll
Antropol. 2005;29:677Y682.
57. Alper Z, Sapan N, Ercan I, Canitez Y, Bilgel N. Risk factors for
wheezing in primary school children in Bursa, Turkey. Am J Rhinol.
2006;20:53Y63.
58. Szepfalusi Z, Loibichler C, Pichler J, Reisenberger K, Ebner C, Urbanek
R. Direct evidence for transplacental allergen transfer. Pediatr Res.
2000;48:404Y407.
59. Thornton CA, Vance GH. The placenta: a portal of fetal allergen
exposure. Clin Exp Allergy. 2002;32:1537Y1539.
60. Vance GH, Lewis SA, Grimshaw KE, Wood PJ, Briggs RA, Thornton
CA, et al. Exposure of the fetus and infant to hens egg ovalbumin via the
placenta and breast milk in relation to maternal intake of dietary egg.
Clin Exp Allergy. 2005;35:1318Y1326.
61. Victor JR Jr, Fusaro AE, Duarte AJ, Sato MN. Preconception
maternal immunization to dust mite inhibits the type I hypersensitivity
response of offspring. J Allergy Clin Immunol. 2003;111:
269Y277.
62. Jarrett EE, Hall E. IgE suppression by maternal IgG. Immunology.
1983;48:49Y58.
63. Thornton CA, Holloway JA, Popplewell EJ, Shute JK, Boughton J,
Warner JO. Fetal exposure to intact immunoglobulin E occurs via the
gastrointestinal tract. Clin Exp Allergy. 2003;33:306Y311.
64. Bocci V, von Bremen K, Corradeschi F, Franchi F, Luzzi E, Paulesu L.
Presence of interferon-gamma and interleukin-6 in colostrum of normal
women. Lymphokine Cytokine Res. 1993;12:21Y24.
65. Nguyen TV, Yuan L, Azevedo MS, Jeong KI, Gonzalez AM, Saif LJ.
Transfer of maternal cytokines to suckling piglets: in vivo and in vitro
models with implications for immunomodulation of neonatal immunity.
Vet Immunol Immunopathol. 2007;117:236Y248.
66. Michie CA, Tantscher E, Schall T, Rot A. Physiological secretion of
chemokines in human breast milk. Eur Cytokine Netw. 1998;9:
123Y129.
67. Takahata Y, Takada H, Nomura A, Nakayama H, Ohshima K, Hara T.
Detection of interferon-gammaYinducible chemokines in human milk.
Acta Paediatr. 2003;92:659Y665.
68. Reichardt P, Muller D, Posselt U, Vorberg B, Diez U, Schlink U, et al.
Fatty acids in colostrum from mothers of children at high risk of atopy in
relation to clinical and laboratory signs of allergy in the first year of life.
Allergy. 2004;59:394Y400.
69. Hubeau C, Apostolou I, Kobzik L. Adoptively transferred
allergen-specific T cells cause maternal transmission of asthma risk.
Am J Pathol. 2006;168:1931Y1939.
70. Penn AL, Rouse RL, Horohov DW, Kearney MT, Paulsen DB, Lomax L.
In utero exposure to environmental tobacco smoke potentiates adult
responses to allergen in BALB/c mice. Environ Health Perspect.
2007;115:548Y555.
71. Noakes PS, Holt PG, Prescott SL. Maternal smoking in pregnancy alters
neonatal cytokine responses. Allergy. 2003;58:1053Y1058.
72. Kulig M, Luck W, Wahn U. The association between pre- and postnatal
tobacco smoke exposure and allergic sensitization during early
childhood. Multicentre Allergy Study Group, Germany. Hum Exp
Toxicol. 1999;18:241Y244.
73. el-Nawawy A, Soliman AT, el-Azzouni O, Amer el S, Demian S,
el-Sayed M. Effect of passive smoking on frequency of respiratory
illnesses and serum immunoglobulin-E (IgE) and interleukin-4 (IL-4)
concentrations in exposed children. J Trop Pediatr. 1996;42:166Y169.
74. Ronchetti R, Macri F, Ciofetta G, Indinnimeo L, Cutrera R, Bonci E,
et al. Increased serum IgE and increased prevalence of eosinophilia in
9-year-old children of smoking parents. J Allergy Clin Immunol.
1990;86:400Y407.

* 2009 World Allergy Organization

Asthma and Allergic Diseases in Pregnancy

75. Lindfors A, van Hage-Hamsten M, Rietz H, Wickman M, Nordvall SL.

Influence of interaction of environmental risk factors and sensitization
in young asthmatic children. J Allergy Clin Immunol. 1999;104:
755Y762.
76. Gonzalez-Quintela A, Vidal C, Gude F. Alcohol-induced alterations in
serum immunoglobulin e (IgE) levels in human subjects. Front Biosci.
2002;7:e234Ye244.
77. Bakos N, Scholl I, Szalai K, Kundi M, Untersmayr E, Jensen-Jarolim E.
Risk assessment in elderly for sensitization to food and respiratory
allergens. Immunol Lett. 2006;107:15Y21.
78. Linneberg A, Hertzum I, Husemoen LL, Johansen N, Jorgensen T.
Association between alcohol consumption and aeroallergen sensitization
in Danish adults. Clin Exp Allergy. 2006;36:714Y721.
79. Sausenthaler S, Koletzko S, Schaaf B, Lehmann I, Borte M, Herbarth O,
et al. Maternal diet during pregnancy in relation to eczema and allergic
sensitization in the offspring at 2 y of age. Am J Clin Nutr. 2007;85:
530Y537.
80. Willers SM, Devereux G, Craig LC, McNeill G, Wijga AH,
Abou El-Magd W, et al. Maternal food consumption during pregnancy
and asthma, respiratory and atopic symptoms in 5-year-old children.
Thorax. 2007;62:772Y778.
81. Korotkova M, Telemo E, Yamashiro Y, Hanson LA, Strandvik B. The
ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of
neonatal immunological tolerance to ovalbumin. Clin Exp Immunol.
2004;137:237Y244.
82. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during
pregnancy or lactation, or both, for preventing or treating atopic disease
in the child. Cochrane Database Syst Rev. 2006;3:CD000133.
83. Lilja G, Dannaeus A, Foucard T, Graff-Lonnevig V, Johansson SG,
Oman H. Effects of maternal diet during late pregnancy and lactation on
the development of IgE and egg- and milk-specific IgE and IgG
antibodies in infants. Clin Exp Allergy. 1991;21:195Y202.
84. Falth-Magnusson K, Kjellman NI. Allergy prevention by maternal
elimination diet during late pregnancyVa 5-year follow-up of a
randomized study. J Allergy Clin Immunol. 1992;89:709Y713.
85. Marrero JM, Goggin PM, de Caestecker JS, Pearce JM, Maxwell JD.
Determinants of pregnancy heartburn. Br J Obstet Gynaecol.
1992;99:731Y734.
86. Scholl I, Untersmayr E, Bakos N, Roth-Walter F, Gleiss A,
Boltz-Nitulescu G, et al. Antiulcer drugs promote oral sensitization
and hypersensitivity to hazelnut allergens in BALB/c mice and humans.
Am J Clin Nutr. 2005;81:154Y160.
87. Untersmayr E, Bakos N, Scholl I, Kundi M, Roth-Walter F, Szalai K,
et al. Anti-ulcer drugs promote IgE formation toward dietary antigens in
adult patients. FASEB J. 2005;19:656Y658.
88. 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.
89. Tarini BA, Carroll AE, Sox CM, Christakis DA. Systematic review of
the relationship between early introduction of solid foods to infants
and the development of allergic disease. Arch Pediatr Adolesc Med.
2006;160:502Y507.
90. Liem JJ, Kozyrskyj AL, Huq SI, Becker AB. The risk of developing food
allergy in premature or low-birth-weight children. J Allergy Clin
Immunol. 2007;119:1203Y1209.
91. Halvorsen T, Skadberg BT, Eide GE, Roksund OD, Carlsen KH, Bakke
P. Pulmonary outcome in adolescents of extreme preterm birth: a
regional cohort study. Acta Paediatr. 2004;93:1294Y1300.
92. Tollanes MC, Moster D, Daltveit AK, Irgens LM. Cesarean section and
risk of severe childhood asthma: a population-based cohort study.
J Pediatr. 2008;153:112Y116.
93. Bager P, Melbye M, Rostgaard K, Benn CS, Westergaard T. Mode of
delivery and risk of allergic rhinitis and asthma. J Allergy Clin Immunol.
2003;111:51Y56.
94. Bager P, Wohlfahrt J, Westergaard T. Caesarean delivery and risk of
atopy and allergic disease: meta-analyses. Clin Exp Allergy.
2008;38:634Y642.
95. Renz H, Blumer N, Virna S, Sel S, Garn H. The immunological basis of
the hygiene hypothesis. Chem Immunol Allergy. 2006;91:30Y48.
96. Schatz M, Zeiger RS, Hoffman CP. Intrauterine growth is related to
gestational pulmonary function in pregnant asthmatic women.

35

WAO Journal

Pali-Scholl et al

97.

98.

99.

100.
101.

102.

103.
104.

105.
106.

107.

36

Kaiser-Permanente Asthma and Pregnancy Study Group. Chest.

1990;98:389Y392.
Raherison C, Nejjari C, Marty ML, Filleul L, Barberger-Gateau P,
Dartigues JF, et al. IgE level and Phadiatop in an elderly population from
the PAQUID cohort: relationship to respiratory symptoms and smoking.
Allergy. 2004;59:940Y945.
Noakes P, Taylor A, Hale J, Breckler L, Richmond P, Devadason SG,
et al. The effects of maternal smoking on early mucosal immunity and
sensitization at 12 months of age. Pediatr Allergy Immunol.
2007;18:118Y127.
Host A, Koletzko B, Dreborg S, Muraro A, Wahn U, Aggett P, et al.
Dietary products used in infants for treatment and prevention of food
allergy. Joint Statement of the European Society for Paediatric
Allergology and Clinical Immunology (ESPACI) Committee on
Hypoallergenic Formulas and the European Society for Paediatric
Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on
Nutrition. Arch Dis Child. 1999;81:80Y84.
Lack G, Fox D, Northstone K, Golding J. Factors associated with the
development of peanut allergy in childhood. N Engl J Med.
2003;348:977Y985.
Dean T, Venter C, Pereira B, Grundy J, Clayton CB, Higgins B.
Government advice on peanut avoidance during pregnancyVis it
followed correctly and what is the impact on sensitization? J Hum Nutr
Diet. 2007;20:95Y99.
Hourihane JO, Aiken R, Briggs R, Gudgeon LA, Grimshaw KE,
DunnGalvin A, et al. The impact of government advice to pregnant
mothers regarding peanut avoidance on the prevalence of peanut allergy
in United Kingdom children at school entry. J Allergy Clin Immunol.
2007;119:1197Y1202.
Chatzi L, Torrent M, Romieu I, Garcia-Esteban R, Ferrer C, Vioque J,
et al. Mediterranean diet in pregnancy is protective for wheeze and atopy
in childhood. Thorax. 2008;63:507Y513.
Calvani M, Alessandri C, Sopo SM, Panetta V, Pingitore G, Tripodi S,
et al. Consumption of fish, butter and margarine during pregnancy
and development of allergic sensitizations in the offspring: role of
maternal atopy. Pediatr Allergy Immunol. 2006;17:94Y102.
Salvatore S, Keymolen K, Hauser B, Vandenplas Y. Intervention during
pregnancy and allergic disease in the offspring. Pediatr Allergy Immunol.
2005;16:558Y566.
Zeiger RS, Heller S, Mellon MH, Forsythe AB, OConnor RD,
Hamburger RN, et al. Effect of combined maternal and infant
food-allergen avoidance on development of atopy in early infancy: a
randomized study. J Allergy Clin Immunol. 1989;84:72Y89.
Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW,
Weiss ST, Gold DR, et al. Maternal intake of vitamin D during

108.
109.

110.

111.
112.
113.
114.

115.
116.

117.

118.
119.
120.

& March 2009

pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J

Clin Nutr. 2007;85:788Y795.
Devereux G, Barker RN, Seaton A. Antenatal determinants of neonatal
immune responses to allergens. Clin Exp Allergy. 2002;32:43Y50.
Blumer N, Sel S, Virna S, Patrascan CC, Zimmermann S, Herz U, et al.
Perinatal maternal application of Lactobacillus rhamnosus GG
suppresses allergic airway inflammation in mouse offspring. Clin Exp
Allergy. 2007;37:348Y357.
Abrahamsson TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm
MC, Bjorksten B, et al. Probiotics in prevention of IgE-associated
eczema: a double-blind, randomized, placebo-controlled trial. J Allergy
Clin Immunol. 2007;119:1174Y1180.
Richter JE. Gastroesophageal reflux disease during pregnancy.
Gastroenterol Clin North Am. 2003;32:235Y261.
Ali RA, Egan LJ. Gastroesophageal reflux disease in pregnancy.
Best Pract Res Clin Gastroenterol. 2007;21:793Y806.
Torrent M, Sunyer J, Munoz L, Cullinan P, Iturriaga MV, Figueroa C,
et al. Early-life domestic aeroallergen exposure and IgE sensitization
at age 4 years. J Allergy Clin Immunol. 2006;118:742Y748.
Muraro A, Dreborg S, Halken S, Host A, Niggemann B, Aalberse R,
et al. Dietary prevention of allergic diseases in infants and small children.
Part III: critical review of published peer-reviewed observational and
interventional studies and final recommendations. Pediatr Allergy
Immunol. 2004;15:291Y307.
Zeiger RS. Food allergen avoidance in the prevention of food allergy in
infants and children. Pediatrics. 2003;111:1662Y1671.
Pesonen M, Kallio MJ, Ranki A, Siimes MA. Prolonged exclusive
breastfeeding is associated with increased atopic dermatitis: a
prospective follow-up study of unselected healthy newborns from
birth to age 20 years. Clin Exp Allergy. 2006;36:1011Y1018.
Fiocchi A, Assaad A, Bahna S. Food allergy and the introduction of
solid foods to infants: a consensus document. Adverse Reactions to
Foods Committee, American College of Allergy, Asthma and
Immunology. Ann Allergy Asthma Immunol. 2006;97:10Y20
[quiz 21, 77].
Lack G. The concept of oral tolerance induction to foods. Nestle Nutr
Workshop Ser Pediatr Program. 2007;59:63Y68.[discussion 68Y72].
Calder PC, Krauss-Etschmann S, de Jong EC, Dupont C, Frick JS,
Frokiaer H, et al. Early nutrition and immunityVprogress and
perspectives. Br J Nutr. 2006;96:774Y790.
World Health Organization. Prevention of allergy and allergic asthma.
Document based on the WHO/WAO Meeting on the Prevention of
Allergy and Allergic Asthma; Geneva, Switzerland; January 8Y9, 2002.
Available at http://www.worldallergy.org/professional/who_paa2003.pdf
Accessed on 31 October 2007.

WAO Journal

& March 2009