Asthma in pregnancy and lactation

• Physiological changes which occur during pregnancy may affect asthma control.
• Regular monitoring (monthly or every six weeks) of asthmatic women should occur throughout pregnancy.
• Regular therapy, including the use of inhaled steroids, is recommended.
• Well-controlled asthma should have no adverse effects on pregnancy, labour or breastfeeding.
• Medicines used to control asthma carry less risk to the mother and baby than a severe attack of asthma.
• Good asthma management will result in a birth outcome similar to that experienced by women without asthma.

Factors responsible for the variation in asthma severity during pregnancy include an increase in circulating free cortisol,^7,8 a decrease in bronchomotor tone and an increase in serum concentrations of cyclic adenosine monophosphate.⁸ These changes would normally improve the asthma, but in pregnancy other competing factors, including exposure to fetal antigens and alterations in cell-mediated immunity, may worsen asthma symptoms.⁸ Asthma may be further complicated by sinusitis and rhinitis, which occur in about 35% of pregnant women, but vascular dilatation and congestion of the mucosa of the upper respiratory tract (vasomotor rhinitis of pregnancy) does not involve the lower airways.⁹

The physiological respiratory changes which occur during pregnancy may affect asthma control (Box). Changes in blood gases secondary to acute asthma will be superimposed on the physiological respiratory alkalosis of pregnancy. Therefore, a normal or elevated PCO₂ associated with acute asthma will indicate respiratory compromise of greater severity in pregnancy than in the non-pregnant state. The dyspnoea of pregnancy must be differentiated from dyspnoea caused by asthma. Indeed, patients who develop asthma during pregnancy may wrongly attribute dyspnoea to the pregnancy, which can lead to undermedication and severe maternal and fetal hypoxaemia.

It is difficult to predict which women will experience worsening of their asthma during pregnancy, but the severity of the condition before pregnancy,^2,8 and an absence of the expected decrease in IgE concentration during pregnancy,^8,13 should alert the clinician to this possibility. If asthma is going to worsen, it will usually do so between 24 and 36 weeks' gestation. Symptoms are likely to be less troublesome in the peripartum period. In most women, asthma severity returns to the prepregnant state within three months of delivery,^1,5 but in rare cases it may be worse than before the pregnancy.

Poorly controlled asthma or severe asthma attacks further threaten the fetus because of increased maternal hypoxaemia and diminution of uterine artery bloodflow secondary to hypocapnic vasoconstriction. These women have an increased incidence of low birthweight and premature babies, neonatal hypoxia, complications during labour, and perinatal and maternal mortality.^14-17 Hyperemesis gravidarum, maternal haemorrhage and pre-eclampsia are more common in this group.¹⁴

For these reasons, it has been argued that a pregnancy complicated by asthma should be regarded as a high risk pregnancy.¹⁶ However, the babies of most asthmatic women (i.e., those with well controlled asthma) show no difference in birthweight, Apgar scores or rates of congenital malformation when compared with those of non-asthmatic mothers.^5,15,16

Bronchospasm relaxants
β₂-Agonists (category A): There is no evidence of a teratogenic risk with the commonly used inhaled β₂-agonists salbutamol, terbutaline and fenoterol. Intravenous salbutamol may be used to delay the onset of labour in some circumstances and there is a theoretical risk that oral β₂-agonists could also have this effect. Delayed labour does not occur with bronchodilators administered by metered-dose inhaler or wet nebulisation.

Ipratropium bromide (category B1): Although there is less experience with this drug, it appears to be safe for use during pregnancy, as it is poorly absorbed when administered by the inhaled route and has not been identified as imparting an increased risk of fetal malformations.

Salmeterol (category B3): These newer long-acting agents have not been tested extensively in pregnant women.

Theopyllines (category A): The use of theophyllines remains controversial. They may aggravate the nausea and reflux suffered by some pregnant women and can cause transient neonatal tachycardia and irritability.^20,21 Teratogenicity has been shown in animals,^22,23 and there are occasional case reports of cardiovascular abnormalities in humans.²⁴ However, larger human studies have not shown any significant increase in fetal abnormalities.^25,26

It has been suggested that theophyllines be withheld during the first trimester.²⁶ If they are used, serum theophylline levels should be measured as drug metabolism may alter during pregnancy.

Preventive inhalations and aerosols
Sodium cromoglycate (category A): This drug appears to have no adverse fetal effects.

Nedocromil sodium (category B1): Animal studies have not shown any teratogenic effects, but, as with all new drugs, care should be exercised, especially in the first trimester.

Inhaled corticosteroids
Beclomethasone and budesonide (category B3): These are the mainstay of treatment in moderate to severe asthma and both appear to have a good safety profile in pregnancy. Although beclomethasone is a known animal teratogen, its use in pregnant women has not been associated with teratogenicity. The largest human experience of inhaled corticosteroids is with beclomethasone and it is therefore the inhaled steroid of choice in pregnancy.⁹

Less information is available on the use of budesonide in pregnancy as it is a newer drug. If moderate to severe asthma is well controlled with budesonide, the risks of destabilising the condition by changing from budesonide to beclomethasone must be weighed against the potential benefits of using a medicine which has been more extensively studied.

Fluticasone (category B3): Experience with this drug in pregnancy is more limited.

Oral corticosteroids
(Category A) These are sometimes necessary for severe asthma in pregnancy but usually only for short periods. An increased risk of cleft palate and placental abnormalities has been reported in animals given huge doses of oral steroids.^27,28 These abnormalities have not been reported in humans, and the results of animal studies should not deter the practising clinician from using oral corticosteroids if required.

Methotrexate and other steroid-sparing agents have an occasional role in the treatment of some individuals with severe resistant asthma. However, these drugs are contraindicated in women of childbearing age who are trying to conceive or who are pregnant.

Symptoms of asthma during labour are generally easily controlled with standard asthma therapy. Acute asthma attacks in labour are rare, but prostaglandin F_2alpha (Dinoprost, UpJohn) and ergometrine cause bronchoconstriction. Their use in the induction of labour, the initiation of the third stage of labour and for placental separation should be avoided.²⁹ There is no evidence that oxytocin causes bronchoconstriction.

Breast milk may contain very small amounts of the drugs used to treat asthma, but, in general, these are not known to be harmful to the infant. Corticosteroids are about 90% protein bound in the blood and are not secreted into breast milk in any significant quantity. However, the manufacturers of budesonide have recommended discontinuation of this drug during lactation because of an absence of information regarding its transmission into breast milk. The decision to alter a successful medication regimen that is controlling the mother's asthma must be weighed against any potential detrimental effects to the infant from continuation of the drug.

Although less than 1% of maternal theophylline is transferred to the infant,³⁰ it has been suggested that women breastfeed their baby before taking this drug to minimise its side effects.³¹

It is recommended that tetracycline antibiotics and iodine-containing mixtures be avoided in pregnant and lactating women as they may cause dental discoloration and goitre in the baby.

If a woman with asthma is closely monitored, pregnancy outcomes approaching those of the general population can be expected.³⁴ Well-controlled asthma should have no adverse effect on pregnancy, labour or breastfeeding.

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Department of Respiratory Medicine, St Vincent's Hospital, Melbourne, VIC.
Jonathan G W Burdon, MD, FRACP, Consultant Respiratory Physician.

Reprints: Dr J G W Burdon, Director, Department of Respiratory Medicine, St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065.

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