Symposium Cont.
Management of Asthma during
Pregnancy
Michael S. Blaiss, M.D.
ABSTRACT
Asthma is estimated to affect up to 4% of pregnancies. Man-
agement of asthma during pregnancy follows the same approach
as in the general population. Aggressive treatment should be
entertained because asthma under poor control during pregnancy
can lead to poor outcomes for the mother and child. The founda-
tions of management are environmental avoidance procedures,
proper pharmacologic agents, and specific allergen immunother-
apy. For pregnant women with persistent asthma, the use of
inhaled cromolyn or inhaled budesonide should be considered as
first-line agents. Short-acting ␤-agonists can be used as needed in
all asthma categories. Other agents such as salmeterol, leukotri-
ene modifiers, newer inhaled corticosteroids, and omalizumab
may be considered in women who showed a good response to these
agents before pregnancy. (Allergy and Asthma Proc 25:375–379,
2004)
From the Department of Pediatrics and Medicine, University of
Tennessee Center for the Health Sciences, College of Medicine,
Memphis, Tennessee
Presented at the Postconference Symposium of the Southwest
Allergy Forum, Eastern Allergy Conference and Texas Allergy,
Asthma & Immunology Society Combined Meeting on Allergy,
Asthma and Immunology, Puerto Vallarta, Mexico, January 18,
2004
Supported by an unrestricted educational grant from Aventis
Pharmaceuticals
Address correspondence and reprint requests to Michael S. Blaiss,
M.D., 7205 Wolf River Boulevard, Germantown, TN 38138
Copyright © 2004, OceanSide Publications, Inc., U.S.A.
Allergy and Asthma Proc.
A sthma is the most frequent respiratory disease during
pregnancy. It is estimated to affect up to 4% of
pregnancies.1 Uncontrolled, severe asthma may result in
maternal hypertension, preeclampsia, placenta previa, uter-
ine hemorrhage, oligohydramnios, and caesarian delivery in
the mother.2– 4 Premature birth, low birth weight, and still-
birth may result when the mother’s asthma is poorly con-
trolled.5,6 Therefore, uncompromising management during
pregnancy is vital in achieving good outcomes for mother
and child.
There are several maxims, which have developed about
the effect of pregnancy on asthma. This condition can in fact
present for the first time during pregnancy. Asthma follows
a rule of thirds during pregnancy as one-third of pregnant
women get better, one-third stay the same, while one-third
worsen in symptoms.7 Schatz et al. recently reported from a
prospective study of asthma during pregnancy that 30% of
women displayed an increase in their asthma symptoms
during pregnancy and 23% experienced a decrease in their
symptoms.8 The degree of asthma severity during preg-
nancy parallels the severity of rhinitis.9
Most women during pregnancy will continue the same
severity of asthma during successive pregnancies as their
first pregnancy.10 The highest rate of exacerbations during
pregnancy is during the 24th and 36th week of gestation,
while flare-ups are rare during the last 4 weeks of pregnancy
and during labor and delivery. Nearly 75% of women go
back to their prepregnancy status within 3 months after
delivery.3
What are the physiological changes that occur during
pregnancy and how do they affect asthma control? The
resting minute ventilation increases during pregnancy with
the PaCO2 falling from 40 mmHg to 32–34 mmHg due to
progesterone’s stimulation of the central respiratory cen-
ter.11 The main change in lung volume during pregnancy is
a decrease in the functional residual capacity related to
375
enlargement of the uterus. Pregnancy does not change the
forced expiratory volume in 1 second, forced vital capacity,
and forced expiratory flow at 25–75% and therefore ob-
structive patterns during pregnancy should not be thought of
being caused by pregnancy, but abnormal, as in the non-
pregnant patient.12 Just like in the nonpregnant patient, an
asthma exacerbation can lead to a decrease in arterial PO2.
This can be devastating to the fetus because even small
decreases in maternal PO2 can lead to significant decreases
in fetal oxygenation. This can be harmful to the health of the
fetus, which is why aggressive control of asthma during
pregnancy is so essential.
Environmental control, proper pharmacologic treatment,
and specific allergen immunotherapy are the cornerstones
for the care of all patients with asthma. During pregnancy,
it is even more important to lessen exposures to triggers
because this may help decrease the need for medication and
prevent exacerbations that may be harmful to the mother
and fetus. Steps should be taken to decrease indoor allergens
such as dust mites and animal danders, which have been
reviewed in numerous articles.13,14 Irritants, such as active
or passive cigarette smoke, also can be a factor in worsening
asthma symptoms and avoidance is paramount for good
asthma control.15 Instructing the woman on proper allergen
avoidance procedures can lead to improved control during
pregnancy.
Unfortunately, even aggressive environmental control
measures will usually not prevent the need for pharmaco-
therapy for asthma during pregnancy. According to the U.S.
Food and Drug Administration (FDA), no asthma drugs can
be considered “safe” during pregnancy. Fear of adverse fetal
effects may thus lead to restrictive use of asthma drugs
during pregnancy. The problem is that there are no double-
blind placebo-controlled studies of medications during
pregnancy. Epidemiological data from population studies
and length of time the agent has been available for use have
been the criteria for recommendations for medications dur-
ing pregnancy. In general, agents recommended usually are
older prescription drugs with good safety records because
they have been around the longest. Because there are few
safety studies on medication use during pregnancy, the FDA
has developed categories for drugs (A, B, C, D, and X;
Table I). Category A is given to medications in which
controlled studies in women failed to show a danger to the
fetus in the first trimester. Few medications have category A
labeling. Category B is given to agents in which animal
studies have not shown fetal danger but there are no con-
trolled studies in humans. Category C is used for agents in
which adverse fetal effects have been described in animals
and no controlled studies in women or no studies in animals
are available. Category D is placed on medications for
which there is clear data showing risk to the fetus, but the
benefits from use in pregnancy may be acceptable despite
the risks. Category X is used for drugs that can cause fetal
abnormalities, as indicated in animal and human studies,
and should never be used in women who are or may become
376
TABLE I
FDA Pregnancy Risk Categories (1998)
A—Adequate studies in pregnant women have not shown
a risk to the fetus in the first trimester of pregnancy
and there is no evidence of risk in later trimesters.
B—Animal studies have not shown a risk to the fetus, but
there are no adequate studies in pregnant women; or
animal studies have shown an adverse effect, but
adequate studies in pregnant women have not shown a
risk to the fetus in the first trimester of pregnancy, and
there is no evidence of risk in later trimesters.
C—Animal studies have shown an adverse effect on the
fetus, but there are no adequate studies in humans; the
benefits from the use of the drug in pregnant women
may be acceptable despite its potential risks; or there
are no animal reproduction studies and no adequate
studies in humans.
D—There is evidence of human fetal risk, but the
potential benefits from the use of the drug in pregnant
women may be acceptable despite its potential risks.
X—Studies in animals or humans show fetal
abnormalities, or adverse reaction reports indicate
evidence of fetal risk. The risk of use in a pregnant
woman clearly outweighs any possible benefit.
pregnant. Presently, these guidelines are under review by
the FDA because there are many shortcomings. Health care
providers need better data in determining the risk/benefit
ratio in using a particular agent during pregnancy.
Most asthma medications fall under categories B and C
(Table II). To address the need for guidelines to help phy-
sicians manage asthma during pregnancy, the National In-
stitute of Health (NIH) developed a Working Group on
Asthma and Pregnancy.16 Their report was revised in 1997
to make recommendations on medical treatment in relation-
ship to the NIH classifications of asthma severity.17 The
most recent position paper on medical management of
asthma during pregnancy was published in 2000. A com-
mittee of the American College of Obstetrics and Gynecol-
ogy and American College of Allergy, Asthma, and Immu-
nology published updated guidelines taking in consideration
medications approved for asthma use since the 1997 re-
port.18 Additional revisions to asthma management in preg-
nancy should be forthcoming with our increased knowledge
of the disease and safety of available treatments.
From review of the data, it appears prudent that pharma-
cologic management of asthma during pregnancy should be
no different than the latest 2002 NIH asthma treatment
guidelines (Table III).19 Short-acting ␤-agonists are the
preferred rescue medication by the inhalation route. Their
use in pregnancy for acute exacerbations follows the same
recommendations as the nonpregnant patient. These agents
have not been shown to have any adverse effects on preg-
nancy outcomes or teratogenic effects on the fetus.20 In-
November-December 2004, Vol. 25, No. 6
 Alternative therapies for mild persistent asthma are cro-
TABLE II
molyn sodium, nedocromil, leukotriene receptor antago-
Pharmaceutical Agents in Asthma and FDA nists, and theophylline. There are long-term safety data with
Pregnancy Risk Categories inhaled cromolyn and it is a viable option for care for
Agents Risk Category women during pregnancy.24 The leukotriene receptor antag-
onists zafirlukast and montelukast have been labeled with
Bronchodilators FDA category B for pregnancy. So far, there have been no
Albuterol C
human or animal teratogenic effects seen with these
Pirbuterol C
Levalbuterol C agents.25 Therefore, it would not be unreasonable to con-
Salmeterol C tinue this group of agents during pregnancy if the mother
Formoterol C had been previously under good control with these medica-
Ipratropium B tions, although one needs to keep in mind that they have
Cromolyn sodium B only been approved for use in the United States since 1996.
Nedocromil B Theophylline, which has been used for over 50 years, also
Leukotriene agents has been shown to lack teratogenic effects during preg-
Zarfilukast B nancy, although its use has radically decreased because of
Montelukast B possible toxicity with elevated serum levels and the devel-
Inhaled corticosteroids opment of newer, safer agents.20
Budesonide B
Long-acting ␤-agonists are the preferred add-on therapy
Beclomethasone C
Fluticasone C to inhaled corticosteroids in the management of moderate to
Triamcinolone C severe persistent asthma, while leukotriene antagonists, the-
Flunisolide C ophylline, cromolyn, and nedocromil are alternative
Fluticasone/Salmeterol C choices.19 There are no human data on salmeterol or for-
Oral corticosteroids C moterol during pregnancy, although there are no reports of
Theophylline C congenital defects.1 It appears to be prudent to use an
Omalizumab B inhaled long-acting ␤-agonist with an inhaled corticosteroid
during pregnancy especially if the patient has used one of
these agents without problems before pregnancy.
haled corticosteroids are the gold standard for control of Oral corticosteroids are administered for acute asthma
mild persistent asthma. Published data are supportive for episodes in short bursts when a patient fails to respond to
beclomethasone and budesonide during pregnancy and, in short-acting ␤-agonists and chronically in severe persistent
fact, budesonide has a pregnancy category B by the FDA. In asthma. There is concern for the use of oral corticosteroids
a surveillance study of over 229,000 Michigan Medicaid during pregnancy. There is a question of increased risk of
receipts from 1985 to 1992, 395 mothers were exposed to cleft palates (three- to sixfold increased risk), decreased
beclomethasone during the first trimester with no evidence fetal weight gain, and preeclampsia.24,26 These complica-
of association between this inhaled corticosteroid and con- tions appear to be related to dosage and duration of treat-
genital defects.21 Norjavaara and de Verdier published data ment with oral corticosteroid, especially in doses of ⬎10
derived from the Swedish Medical Birth Register, which mg/day of prednisone.27 Long-term use of oral corticoste-
includes 99% of births in Sweden. During 1995–1998, roids carries the risk of significant hyperglycemia and wors-
293,948 newborn infants were identified. Pregnancy out- ening gestational diabetes or preexisting diabetes. As with
comes were compared for mothers in Sweden reporting all medication during pregnancy, it is important to weigh the
asthma medication usage with those reporting no asthma risk versus benefit.
medication usage. They found that 2968 mothers who re- Omalizumab, an immunoglobulin G monoclonal anti-
ported use of inhaled budesonide during early pregnancy body directed against immunoglobulin E has been approved
gave birth to infants of normal gestational age, birth weight, in the United States for the treatment of moderate to severe
and length, with no increased rate of stillbirths or multiple allergic asthma, which has failed the use of inhaled corti-
births.22 Another prospective study suggested no terato- costeroids.28 It received the FDA pregnancy category B,
genic effect with triamcinolone acetonide during preg- because of no teratogenic effect seen in animal studies.
nancy.23 Newer inhaled corticosteroids, such as fluticasone, Also, several women who participated in clinical studies
are more potent per microgram than older agents, but appear with omalizumab before FDA approval became pregnant
to have less bioavailability. Data are lacking on safety and delivered normal infants. Because of the newness of this
during pregnancy though the April 2000 position paper agent, it is important to weigh the benefit to risk before use
states “it would not be unreasonable to continue a different during pregnancy.
(from beclomethasone or budesonide) inhaled corticosteroid ␣-Adrenergic agents, except for pseudoephedrine, tetra-
in a patient well-controlled by that drug (fluticasone or other cycline, iodides preparations, and sulfonamides(in last tri-
newer agents) prior to pregnancy.”18 mester), should be avoided in the pregnant patient. There is

Allergy and Asthma Proc. 377

 TABLE III
2002 NHLBI Asthma Guidelines: Adults
Severity Class Symptoms/Day PEF or FEV1 Daily Medications
Symptoms/Night PEF Variability
Step 4—severe Continual ⱕ60%Preferred treatment:
persistent Frequent ⬎30% High-dose ICS ⫹ LABA and, if needed, corticosteroid
tablets or syrup long term
Step 3—moderate Daily ⬎60% to ⬍80% Preferred treatment:
persistent ⬎1 night/week ⬎30% Low- to medium-dose ICS ⫹ LABA
Alternative treatment: Increase ICS dose within medium-
dose range or low- to medium-dose ICS ⫹ LTM or
theophylline
If needed:
Preferred treatment: Increased medium-dose ICS ⫹ LABA
Alternative treatment: Increased medium-dose ICS ⫹ LTM
or theophylline
Step 2—mild ⬎2/week but ⬍1⫻/day ⱖ80% Preferred treatment: low-dose inhaled corticosteroid
persistent ⬎2 nights/month 20%–30% Alternative treatment: Intal, LTM, Tilade or theophylline
SR (serum concentration of 5–15 mcg/mL)
Step 1—mild ⱕ2 days/week ⱖ80% No daily medication needed
intermittent ⱕ2 nights/month ⬍20%
Source: Ref. 19.
PEF ⫽ peak expiratory flow; FEV1 ⫽ forced expiratory volume in 1 second; ICS ⫽ inhaled corticosteroid; NHLBI ⫽ National
Heart, Lung, and Blood Institute; LABA ⫽ long-acting ␤-agonist; LTM ⫽ leukotriene modifier.

some concern with epinephrine because it is linked to con-
genital defects in animals. It remains the definitive treat-
ment of choice for anaphylaxis, but caution should be used
in administering epinephrine for other causes during preg-
nancy.
Allergen immunotherapy is an important disease-mod-
ifying treatment that has been shown to decrease symp-
tomatology and need for medications in asthma. It is safe
and effective for the pregnant woman and can be contin-
ued during pregnancy.2,29 In general, allergen immuno-
therapy should not be started during pregnancy.1 Because
of the possible risk of an anaphylactic reaction, the
strength of the allergen extract should not be increased
during pregnancy.
What should be done for pregnant patients with asthma
who fail to respond to proper asthma therapy? Important
considerations are noncompliance with management, si-
nusitis, rhinitis, and gastroesophageal reflux disease.
Women may be very apprehensive about using any med-
ication during pregnancy. The health care provider must
clearly present the risk/benefit ratio for each agent used.
Importantly, the case for failure to control asthma during
pregnancy and its possible complications for mother and
child should be discussed thoroughly. Sinusitis and rhi-
nitis can lead to worsening asthma and should be evalu-
ated and managed aggressively. It is well known that
gastroesophageal reflux disease is commonly seen during
pregnancy and is a recognized malady that can worsen
asthma control.30 Antireflux procedures including medi-
cal management may be required to improve asthma
symptoms.
In conclusion, health care providers should aggressively
manage asthma during pregnancy. The literature points out
that the most commonly used controller therapies have a
high benefit/risk ratio. It is important for the mother to
understand that failure to control asthma during pregnancy
could lead to a poor outcome. During this special time,
frequent monitoring of the mother should ensure a healthy
outcome for both mother and child.
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