1. Evidence Based Approach for the Management of Asthma in Pregnancy
By: Muhamad Na’im B. Ab Razak (MD USM)
Image of a pregnant lady using the inhaler taken from Science Photo Library at this link
http://www.sciencephoto.com/media/289804/enlarge
Asthma is an increasingly common chronic illness in pregnancy with the prevalence may
reach up to 8%. [Holland & Thomson, 2006]. Pregnancy is characterized by a physiological
immunosuppression, an immunological tolerance that protects the fetus from maternal
immune response against paternal antigens expressed by the fetus. [Lilla Tamasi et al, 2011]
Physiological pregnancy has been described as a Th2-dominated state, and current studies
show that a trimester dependent, pregnancy-induced increase in regulatory T cell (Tregs)
number has a key role in the maintenance of maternal tolerance to paternal antigens during
pregnancy, exerting an inhibition on the activation of effector T lymphocytes and NK cells.
[Lilla Tamasi et al, 2011] Absence of trimester dependent regulatory T cell elevation in
asthmatic pregnancy leads to impaired inhibition of T lymphocyte and NK cell activation and
proliferation. Elevated numbers of activated effector T lymphocytes and NK cells may cause
immune mediated alteration of fetal growth and enhancement of allergic/asthmatic response.
[Lilla Tamasi et al, 2011]

2. Pregnancy may alter the natural course of asthma. Asthma improves during pregnancy in
about one-third, remains the same in another one-third, and worsens in one-third of pregnant
women. More severe asthma before pregnancy increases the risk of worsening during
pregnancy, and there is a concordance between the courses of asthma during subsequent
pregnancies [Lilla Tamasi et al, 2011]. Lung inflammation, smoking, obesity , altered
placental function [Ross E. Rocklin, 2011] and female fetuses are also recognized risk factor
for asthma exacerbation. [Lilla Tamasi et al, 2011] and poor pregnancy outcomes.
Patient may also suffers from co- morbid condition such as obesity, pregnancy-induced
hypertension and gastro-oesophageal reflux. [Holland & Thomson, 2006] Asthma represents
a risk factor for several maternal and fetal complications, such as asthma exacerbations, use of
oral corticosteroids, hospitalizations due to asthma attacks, preeclampsia, gestational
hypertension, preterm delivery, cesarean delivery, low birth weight, intrauterine growth
restriction, and fetal death [Lilla Tamasi et al, 2011].
Most of the asthma exacerbation are usually mild and self limiting and rarely causing severe
attack. However, if severe exacerbation occur, it will cause significant morbidity and
mortality to the patient as well as the fetus. Major risk of asthma to the mother and fetus are
due to under treatment or poorly controlled disease and may be compounded by poor maternal
compliance with treatment due to fears of side-effects on the unborn child [Holland &
Thomson, 2006] Apart from that, Jennifer W. Mc Callister et al, has found out that there is a
disparities of treatment for acute exacerbation of asthma in emergency department especially
in term of systemic steroid administration. This should not happen and pregnancy should be
considered an indication for maximizing therapy during an exacerbation, rather than
withholding it.
Congenital malformation may complicate maternal asthmatic exacerbation in early trimester
as maternal hypoxia together with respiratory alkalosis may decrease the placental blood flow.
Decreased fetal blood oxygen could result in abnormal growth and development of the fetus.
Furthermore, maternal hypoxia has been found to be associated with an increased risk of cleft
lip and palate in mice.[ Lucie Blais & Amelie Forget, 2008]

3. Short acting beta 2 agonist (SABA) is safe eventhough it is previously being said that the
usage of this agent will increase the risk of developing pregnancy induced hypertension. The
explaination laid behind this hypothesis was that the inhaled SABA will enter the systemic
circulation and cause vasodilation of the blood vessel. This will then cause reduction in
diastolic blood pressure and cause reflex tachycardia. Study by Marie-Jose´e Martel et al
however shows that inhaled SABA actually reduced the risk of PIH and the use of this
medication is safe throughout pregnancy. The reasons for the previous hypothesis of relation
between SABA-PIH could be due to some reason including smoking and masking effect of
SABA that reduce the diastolic blood pressure, hence lead to under diagnosed of PIH. The
usage of SABA alone is safe, however, it should be pointed out that all patients with
persistent asthma require a controller medication such as an inhaled steroid [R.E. Rocklin et
al, 2011]
Long-acting Beta 2 agonists are now recommended to be used in conjunction with inhaled
steroids. The use of these long-acting bronchodilators as monotherapy was reported in one
study that did not find any evidence of an effect on fetal growth in humans [R.E. Rocklin et al,
2011]
The usage of high dose ICS may increase the risk of congenital malformation if use in the first
trimester. Lucie Blais et al in her study observed that women who took high doses of ICSs
during the first trimester of pregnancy were 63% more likely to have a baby with a congenital
malformation than women taking low to moderate doses of ICSs. However, low to moderate
dose of ICS is safe. Furthermore, current asthma guidelines recommend ICSs for the
management of all levels of persistent asthma during pregnancy and recommend that pregnant
women be treated as aggressively as nonpregnant women to achieve and maintain control of
asthma. [Marie-Claude Breton et al, 2010] The risk of perinatal mortality was not found to
be significantly associated with ICS use during pregnancy. The result associated with higher
doses of ICSs is limited due to a lack of statistical power and a possibility of residual
confounding by asthma severity and control. [Marie-Claude Breton et al, 2010] Furthermore,
a trend towards higher Treg cell prevalence was observed compared to those with inadequate
adherence to ICS treatment. [Lilla Tamasi et al, 2011] Therefore, asthmatic pregnant women
should be managed with the minimum effective ICS dose. But if higher doses of ICSs are
needed to control asthma, their benefits outweigh their risks. [Marie-Claude Breton et al,
2010]

4. The usage of oral corticosteroid previously being said to be associated with increase risk of
congenital malformation particularly cleft lip, cleft palate or both. However, observation by
Lucie Blais & Amelie Forget in their study shows that women who had an asthma
exacerbation but who did not fill a prescription for oral corticosteroids were 2 times more
likely to have a baby with a major congenital malformation than women who did not have an
exacerbation. It is found that the hypothesis that link between the usage of oral corticosteroid
and congenital malformation are weak. Study by Ludmila N. Bakhireva et al, demonstrate that
the usage of systemic corticosteroid may resulting in deficit of about 200 g in birthweight
compared with controls and exclusive B2-agonist users. However, the result is not significant
to suggest that the usage of this agent impair fetal growth and it use should be weighed
against the necessity to control severe asthma.
Chromones such as cromolyn and nedocromil have an anti inflammatory activity but due to
their relatively limited efficacy, it should only be used in mild persistent asthma and
recommended as alternative medication only.
Leukotriane modifiers such as leukotriene receptor antagonists (montelukast and zirfirlukast)
and 5-lipoxygenase pathway inhibitors (zileuton) are not preferred as treatment option in mild
persistent asthma in pregnancy.
Theophylline that has bronchodilating activity and mild anti inflammatory properties are safe
to be used in pregnancy but it is considered as alternative treatment and not the preferred
therapy
In managing severe acute asthma, Oral corticosteroid should not be witheld. The British
Thoracic society guidelines has clearly stated that the medical management of asthma in
pregnant and non pregnant mother are same. Volume resuscitation should be considered as
there would be a volume deplition due to combination of hyperventilation and intercurrent
sepsis despite of difficulty in accessing the fluid balance. Central venous access is impractical
and potentially dangerous in severe asthmatic. Regional anesthesia especially epidural is more
preferred than general anesthesia if patient required operative delivery or as pain
management as it reduce hyperventilation and stress response to the pain. However,
judgement should be made clearly as regional anesthesia would be impractical in patient who

5. are severely breathless and precipitate deterioration of lung function due to loss of intercostal
muscle function
Apart from that, education about asthma, life style modification and smoking cessation should
be encourage to the patient. Main education topic should includes information about the
disease, use of inhaler devices, adherence to treatment and importance of regular visit,
environmental control measure to reduce exposure to allergens and irritants and self treatment
action plan. [Lilla Tamasi et al, 2011].
Reference:
1) Faranak Firoozi, Catherine Lemiere, Francine M. Ducharme et al, "Effect of
maternal moderate to severe asthma on perinatal outcomes", Respiratory
Medicine (2010) 104, 1278- 1287
2) Jennifer W. McCallister, Cathy G. Benninger, Heather A. Frey, et al, "Pregnancy
related treatment disparities of acute asthma exacerbations in the emergency
department", Respiratory Medicine (2011) 105, 1434-1440
3) Lilla Tamasi, Ildiko´ Horvath, Aniko Bohacs et al, " Asthma in pregnancy e
Immunological changes and clinical management", Respiratory Medicine (2011)
105, 159-164, Elsevier
4) Lucie Blais & Amelie Forget, "Asthma exacerbations during the first trimester of
pregnancy and the risk of congenital malformations among asthmatic women", J
Allergy Clin Immunol 2008;121:1379-84
5) Lucie Blais, Marie-France Beauchesne, Catherine Lemie` & Naoual Elftouh,
"High doses of inhaled corticosteroids during the first trimester of pregnancy and
congenital malformations", J Allergy Clin Immunol 2009;124:1229-34.

6. 6) Ludmila N. Bakhireva, Kenneth Lyons Jones, Michael Schatz et al, "Asthma
medication use in pregnancy and fetal growth", J Allergy Clin Immunol
2005;116:503-9.)
7) Marie-Claude Breton,, Marie-France Beauchesne, Catherine Lemie, et al, "Risk of
perinatal mortality associated with inhaled corticosteroid use for the treatment of
asthma during pregnancy", J Allergy Clin Immunol 2010;126:772-7.
8) Marie-Jose´e Martel, E´ velyne Rey, Marie-France Beauchesne, et al "Use of
short-acting b2-agonists during pregnancy and the risk of pregnancy-induced
hypertension", J Allergy Clin Immunol 2007;119:576-82
9) Ross E. Rocklin, "Asthma, asthma medications and their effects on maternal/fetal
outcomes during pregnancy", Reproductive Toxicology 32 (2011) 189–197
10) S. M. Holland, K. D. Thomson, "Acute severe asthma presenting in late
pregnancy", International Journal of Obstetric Anesthesia (2006) 15, 75–78