Asthma is a chronic condition that is thought to affect approximately 2.5 million Australians. Present in up to 8% of pregnant women, asthma is one of the most common chronic conditions managed during pregnancy.

Some women may overestimate the risks associated with continuing their asthma treatment regimens during pregnancy. In the quest for a medication-free pregnancy, the risks of poorly controlled asthma are often overlooked. However, poorly controlled asthma is associated with a range of adverse perinatal outcomes, including the following:

  • Low birth weight
  • Pre-term labour and delivery
  • Pre-eclampsia
  • Uterine haemorrhage
  • Congenital anomalies
  • Foetal growth restriction
  • Neonatal hypoglycaemia, seizures, tachypnoea, and admission to neonatal intensive care units

Therefore, it is important that women maintain optimal asthma control during pregnancy.

Asthma control often changes during pregnancy. Although some women may experience an improvement in their symptoms, asthma control will deteriorate for at least one-third of women. A multitude of physiological changes occurs during pregnancy that can worsen asthma control. Pregnancy increases maternal metabolic rate which, in turn, increases oxygen requirements. Also, the increasing size of the uterus places upward pressure on the diaphragm which may reduce the functional residual capacity of the lungs. In addition, the complex immunologic changes that occur during pregnancy can also reduce asthma control.

Studies have demonstrated that up to 6% of women with asthma are hospitalised for an acute exacerbation during pregnancy. The risk appears to be highest for women with severe asthma, although medication non-compliance and viral infections may also be significant causes of exacerbations.This highlights the importance of educating and supporting patients with this chronic condition.

Pregnant women with asthma should receive a review of their asthma management plan. Patients should be encouraged to continue their treatment after a discussion of the risks posed by medication and the risks of poorly controlled asthma.

β2-agonists:

Short-acting β2-agonists such as salbutamol and terbutaline are category A medications. These inhaled medications are considered safe to use during pregnancy.

There is limited data available for the use of long-acting β2-agonists during pregnancy. Therefore, salmeterol and formoterol are categorised as B3 medications. Animal studies looking at long-acting β2-agonists used doses that resulted in significantly higher systemic exposures than would occur in clinical use. While the Asthma Management Handbook does not encourage initiating a long-acting β2-agonist in the first trimester, it does recommend continuing treatment if they are necessary to control symptoms. A retrospective study cited in the handbook demonstrated no increased risk of adverse perinatal outcomes.

During lactation, short-acting β2-agonists are considered safe at the usual doses. If large oral doses of salbutamol are used, the infant should be monitored for signs of tremor and agitation. Long-acting β2-agonists have been detected in milk during animal studies. However, the amount excreted into milk following inhalation is expected to be negligible.

Corticosteroids:

Inhaled corticosteroids are not associated with a significant increase in the incidence of adverse perinatal outcomes. A randomised controlled study of women with asthma exacerbations found a 55% reduction in subsequent exacerbations and hospitalisations in those treated with beclomethasone. It is recommended that women continue to use their preventer medications during pregnancy.

Budesonide is classified as a category A medication; ciclesonide, fluticasone, and beclomethasone are category B3. For women who are planning to become pregnant, it may be prudent to consider switching their current inhaled corticosteroid to budesonide as there is more evidence of safety during pregnancy with this agent. However, for women who are already pregnant and are well-controlled with an alternative inhaled corticosteroid, it is advisable to continue current therapy.

Oral corticosteroids may be underutilised in the treatment of acute exacerbations of asthma during pregnancy. Use of systemic corticosteroids during pregnancy have been associated with preeclampsia, premature labour, and low birth weight. However, these adverse outcomes may also be related to poor asthma control.

Prednisolone is the oral corticosteroid most commonly used in the treatment of asthma exacerbations. Prednisolone is a category A medication and is considered safe to use as the risks of non-treatment may be greater. The use of oral corticosteroids in the first trimester has been associated with an increased risk of orofacial clefts. However, studies demonstrating this association used small sample sizes and higher doses than what is normally used in the treatment of asthma. Additional larger studies suggest that if there is an association with orofacial clefts, the increased risk is very small. If oral corticosteroids are required, the lowest effective dose should be used for the shortest time possible. Prolonged duration may increase the risk of low birth weight and adrenal suppression in the newborn. Corticosteroids increase insulin resistance, so blood glucose should be monitored, especially if gestational diabetes is present.

During lactation, budesonide is reported to result in minimal to no excretion into breastmilk following inhalation. Excretion of fluticasone into breast milk is unknown. However, systemic absorption following inhalation is negligible. Therefore, levels in breast milk are unlikely to be an issue. Prednisolone is excreted into the breast milk in small amounts. At doses of less than 80mg per day, exposure to the infant is minimal. For larger doses, it is recommended to withhold feeds for three to four hours after each dose.

Cromones:

Inhaled cromones are classified as category B1. Animal reproductive studies have not demonstrated a link between the use of inhaled cromones and adverse perinatal outcomes.
Systemic absorption of inhaled cromones is low. Therefore, the amount excreted into breastmilk is expected to be low. In addition, sodium cromoglycate is safely used in paediatric patients.

Montelukast:

Montelukast, a leukotriene receptor antagonist, is also classified as category B1. There is a lack of quality studies assessing montelukast as the sole therapeutic agent. Rare cases of congenital limb defects have been reported during post-marketing surveillance. However, in the majority of these cases, the women were also taking other asthma medications during their pregnancy. Therefore, montelukast is not recommended during pregnancy unless it is clearly indicated and other safer treatments have been trialled.

Animal studies show that montelukast is excreted into milk and it is also expected to be excreted into human breast milk. The effect on the infant is not known. Therefore, caution is recommended when used during lactation.

Conclusion:

Australian guidelines align with international recommendations that recommend continuation of the therapy during pregnancy that provided adequate asthma control before conception. Patients should also receive monitoring of their asthma as part of their overall care plan. While there is limited data concerning the safety of asthma medications during lactation, these recommendations remain valid through the post-natal period. Systemic absorption of inhaled medications is usually minimal and poses little threat to the breastfed infant.

References:

  1. Bain E, Pierides KL, Clifton VL, Hodyl NA, Stark MJ, Crowther CA, et al. Interventions for managing asthma in pregnancy. Cochrane DB Syst Rev. 2014; (10): CD010660.
  2. Cosette B, Forget A, Beauchesne MF, Rey E, Lemiere C, Larivee P, et al. Impact of maternal use of asthma-controller therapy on perinatal outcomes. Thorax 2013; 68(8): 724-30.
  3. Lim A, Hussainy SY, Abramson MJ. Asthma drugs in pregnancy and lactation. Aust Prescr. 2013; 36: 5-6.
  4. Lim A, Stewart K, Konig K, George J. Systematic review of the safety of regular preventive asthma medications during pregnancy. Ann Pharmacother. 2011; 45(7-8): 931-45.
  5. Lokeln YC, editor. Pregnancy and breastfeeding medicines guide. Melbourne: Pharmacy Department, Royal Women’s Hospital; 2010.

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