Over 470,000 people in Ireland have asthma and many of these are women of childbearing age.¹ International estimates of the prevalence of asthma in pregnancy range from 4-12%.² Poorly controlled asthma during pregnancy poses a significant risk to both the wellbeing of the mother and the baby. Many pregnant women experience a change in their level of asthma control, with one-third of women improving, one-third of women worsening and one-third of women remaining stable during pregnancy.³ Studies have shown that 36% of pregnant women with asthma have a severe exacerbation requiring medical intervention and approximately 5.8% are hospitalised for asthma exacerbations.^4,5 Therefore, the appropriate care of pregnant patients with asthma is an important public health concern. 

Breathlessness and pregnancy

Breathlessness in pregnancy is a common symptom and up to two-thirds of women report dyspnoea during pregnancy.⁶ It is proposed that the effect of elevated progesterone levels, causing increased minute ventilation, accounts for the normal physiological dyspnoea of pregnancy rather than the mechanical enlargement of the gravid uterus. The effects of pregnancy-related anaemia and the presence of worsening heart disease (in particular mitral stenosis) should be considered when a woman presents with breathlessness during pregnancy. 

The diagnosis of asthma is straightforward in most pregnant women as the majority will have a history of the disease which predates the pregnancy. In the right clinical context, demonstration of airflow obstruction with a 12% or greater improvement in FEV1 after inhaled bronchodilator, is strongly supportive of asthma. Patients with normal spirometry but a complete clinical history may demonstrate variability on serial peak expiratory flow testing. 

There is no data on the safety in pregnancy of bronchial provocation testing which is normally performed to investigate possible asthma in those with normal spirometry. Similarly skin prick testing for potential allergens is also contraindicated during pregnancy due to the risk of a systemic reaction to testing. 

Effect of asthma on outcomes of pregnancy

If asthma is well controlled throughout pregnancy, there is little or no increased risk of adverse maternal or foetal complications.⁷ Baseline asthma severity determines what happens to the course of asthma in pregnancy. Asthma exacerbations are a recognised risk factor for intra-uterine growth restriction and low birth weight. The effect is comparable to that of maternal smoking which doubles the risk of low birth weight and the use of inhaled corticosteroid is protective against this adverse outcome. Some studies have found an association between oral steroid use in asthma and pregnancy-induced hypertension or pre-eclampsia, pre-term labour and foetal growth but this association may be confounded by indication, ie. these effects likely reflect the severity of asthma itself rather than the treatment. There is no evidence that perinatal or neonatal mortality in women with asthma is higher than in women without asthma.² 

Management

Monitoring

Patients should be questioned regularly about frequency and severity of symptoms and requirement for rescue medication. FEV1 and peak flow measurements do not change considerably in pregnancy and therefore can be used in the assessment of asthma control as reliably in pregnant patients as those who are not pregnant. 

Education

Patients with asthma who are pregnant, or who are contemplating having a baby, should be counselled on the relationship between asthma and pregnancy and have their inhaler technique checked. 

Many pregnant women reduce the intensity of their asthma treatment, increasing the risk of having babies of lower birth weight. In view of this, the importance of medication compliance should be particularly emphasised and an action plan established for potential worsening of disease and exacerbations. Women who smoke should be advised regarding the effects of smoking on the foetus and should be strongly advised to quit smoking. 

Triggers 

Recognised asthma triggers such as allergens (dust mite, animal dander), rhinitis and gastro-oesophageal reflux should be identified and avoided where possible. Blood testing can be performed for specific IgE to a range of allergens if required.

Medications

Pregnant patients with well-controlled asthma should take their asthma medications as normal during pregnancy. Guidelines recommend consideration of a step-down in asthma therapy with controlled disease for three or more months in non-pregnant patients, but in pregnant patients continuing at the same level of therapy for the duration of pregnancy, if the disease is controlled, is reasonable and avoids the risk of a lack of control with therapy reduction.⁸

Patients with poorly controlled disease should be frequently reviewed during pregnancy and their treatment should be increased for optimal control. 

Drugs and safety during pregnancy

In general, the medications used to treat asthma are safe in pregnancy and the risk to the foetus of any of the medications is outweighed by the risk of under-treated asthma. No significant association has been demonstrated between major congenital malformations or adverse perinatal outcomes and the use of inhaled bronchodilators or steroids. In terms of inhaled corticosteroids, budesonide is the oral steroid of choice as it has the largest body of data supporting its use. Prednisolone is the preferred oral agent to treat maternal asthma in pregnancy as only 10% of it reaches the foetus due to placental metabolism. 

Data concerning long-acting beta agonists also indicate they are safe in pregnancy though these data are more limited than those on inhaled corticosteroids and short-acting beta agonists. To date there are no data available on the use of omalizumab in pregnancy.⁷ 

Acute exacerbations

Women with asthma should receive standard optimal treatment for an exacerbation as a severe asthma attack presents more of a risk to the foetus through the potential for foetal hypoxia than the asthma medications used. Treatment should be the same as that for a non-pregnant woman and should involve the use of systemic corticosteroids. 

Despite this, one study has shown that pregnant women are less likely to be prescribed oral corticosteroids than non-pregnant women and are more likely to report ongoing asthma symptoms subsequently as a result.⁹ Hospitalisation is required if the oxygen saturation on pulse oximetry is below 95%, if the FEV1 or peak expiratory flow is below 70% of the predicted value or if there is foetal compromise. Supplemental oxygen should be given to maintain saturations of 94-98%.⁶

Care of a pregnant patient with an asthma exacerbation should be co-ordinated between respiratory and obstetric specialist services and continuous foetal monitoring is recommended for severe acute asthma. 

Labour and delivery

A number of studies have demonstrated that asthma is a risk factor for delivery by Caesarean section (C-section), but it appears that this represents an increase in elective C-section rather than an increase in emergency C-section for foetal distress.² Use of asthma medications should be continued during labour and delivery. 

Asthma exacerbations are rare in labour. Because of the theoretical risk of maternal hypothalamic-pituitary adrenal axis suppression, women receiving steroid therapy at a dose exceeding prednisolone 7.5mg per day for more than two weeks prior to delivery should receive parenteral hydrocortisone 100mg six to eight-hourly during labour.⁷

Magnesium sulphate and terbutaline are the preferred tocolytic agents as they are bronchodilators in contrast to indometacin which can trigger bronchospasm. 

With monitoring for development of bronchospasm, prostaglandins E1 and E2 can be used in pregnant patients with asthma for cervical ripening and labour induction. Prostaglandin F_2a used to treat post-partum haemorrhage due to uterine atony, is a potent bronchoconstrictor and should only be used with extreme caution.¹⁰

Breastfeeding

Asthma medications are excreted in small amounts in breast milk. For example, the proportion of an oral or intravenous dose of prednisolone recovered in breast milk is less than 0.1%.⁷ None of the common asthma medications are a contraindication to breast feeding and women with asthma should be encouraged to breastfeed, using asthma medications as normal. 

Summary

Asthma is a very common medical problem during pregnancy. Poorly controlled asthma and disease exacerbations have the potential to adversely affect perinatal outcomes. In contrast, well controlled asthma does not pose any significant risk to the baby and pregnant women can be reassured regarding the safety of asthma medications in pregnancy.  

References 

1. Brennan N, McCormack S, O’Connor TM. Ireland needs healthier airways and lungs – the evidence. Supplement to the Irish Medical Journal 2008. Eur Respir J 2004; 24(1): 189
2. Murphy VE, Gibson PG. Asthma in pregnancy. Clin Chest Med 2011; 32: 93-110
3. Global Strategy for Asthma Management and Prevention (Revised 2012): Global Initiative for Asthma (GINA). www.ginasthma.org
4. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: incidence and association with adverse outcomes. Thorax 2006; 61: 169
5. Murphy VE, Gibson P, Talbot PI et al. Severe asthma exacerbations during pregnancy. Obstet Gynecol 2005; 106: 1046
6. Tenholder MF, South-Paul JE. Dyspnea in pregnancy. Chest 1989; 96(2): 381-388
7. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma. A national clinical guideline (2008; revised 2012). http://www.brit-thoracic.org.uk/Portals/0/Guidelines/AsthmaGuidelines/sign101%20Jan%202012.pdf
8. Schatz M, Dombrowski MP. Asthma in Pregnancy. N Engl J Med 2009; 360: 1862-1869
9. Cydulka RK, Emerman CL, Schreiber D et al. Acute asthma among pregnant women presenting to the emergency department. Am J Respir Crit Care Med 1999; 160: 887-892
10. Schatz M. Asthma during pregnancy: interrelationships and management. Ann Allergy 1992; 68(2): 123-133