Asthma In Pregnancy
WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).
Acute asthma attacks render both the mother and fetus vulnerable to progressive hypoxia and potentially disastrous results. Patient education is the key in controlling asthma since self-monitoring is the cornerstone of ambulatory management. 5% to 9% of pregnancies are complicated by asthma, which is most common chronic medical problem in young women and of growing concern in the general population of the United States and other industrialized countries. According to the Centers for Disease Control and Prevention about 7 % of the general population currently has asthma. Status asthmaticus, the most severe form of asthma complicates about 0.2% of pregnancies. Every effort to prevent acute exacerbations of patient's asthma and to reduce her symptoms to a bare minimum should be the goal of every healthcare provider.
The purpose of this document is to explore the treatment options of the patients with asthma and to manage during pregnancy and childbirth. Early studies of pregnant women with asthma revealed high rates of perinatal complications, including perinatal loss, prematurity, preeclampsia, and low birth-weight. Prospective studies performed in the last decade demonstrate essentially normal perinatal outcomes with modern management of asthma. Poor outcomes with some evidence of increased perinatal mortality and morbidity are also seen if the intensity of asthma therapy is decreased.
Pathophysiology of Asthma:
Asthma is obstructive disease of the large or small airways. It combines reversible airway constriction, inflammation, airway edema and mucous plugging. Multiple aspects of the inflammatory pathway are triggered with release of leukotrienes and histamines, recruitment of eosinophils, neutrophils, TH-2 lymphocytes, antigen-presenting cells and mast cell degranulation. Asthma is a chronic inflammatory airway disorder with a major hereditary component. The hallmarks of asthma are reversible airway obstruction from bronchial smooth muscle contraction, mucus hypersecretion, and mucosal edema. There is airway inflammation and responsiveness to a number of stimuli, including irritants, viral infections, aspirin, cold air, and exercise. Mast cell activation by cytokines mediates broncho-constriction by release of histamines, prostaglandin D2, and leukotrienes. Because F-series prostaglandins and ergonovine exacerbate asthma, these commonly used obstetrical drugs should be avoided if possible. Chronic inflammation may lead to bronchial hyper-reactivity and smooth muscle hyperplasia.
Clinical Signs and Symptoms:
Asthma represents a broad spectrum of clinical illness ranging from mild wheezing to severe broncho-constriction. It may present with a cough, a sensation of chest tightness or discomfort, dyspnea, or audible wheezing. When asking the patient's history, remember to ask how frequently she uses asthma medication, whether she has limitations on activity or fatigues easily, what her exercise tolerance is, whether there are factors that exacerbate the asthma, and how complaint she is with medication. Acute exacerbation should also prompt you to ask about viral and respiratory infections. Physical examination of the pregnant asthmatic during an acute exacerbation should include assessment of respiratory effort and rate, perfusion status, a qualitative assessment of airflow, and signs of infection.
Reversible broncho-constriction manifests itself with restriction of airflow in the large to medium bronchi, resulting in a decrease in peak expiratory flow rate (PEFR), measured with a hand-held peak flow meter, or decreased forced expiratory volume (FEV1) as measured by spirometry. The risk of hypocapnia increases with PEFR values less than 25% of predicted or less than 120 L/min (1). Although these changes are generally reversible and well tolerated in the healthy non-pregnant individuals, even early stages of asthma may be dangerous for the pregnant women and her fetus. The smaller functional residual capacity and the increased effective shunt render her more susceptible to hypoxia and hypoxemia.
clinical stages of asthma are summarized as: Mild respiratory alkalosis; Respiratory alkalosis, Danger zone and Respiratory acidosis. With mild disease, hypoxia initially is well compensated by hyperventilation, as reflected by a normal arterial PO2, decreased PCO2, and resultant respiratory alkalosis. As airway narrowing worsens, ventilation-perfusion defects increase, and arterial hypoxemia ensues. With severe obstruction, ventilation becomes impaired because fatigue causes early CO2 retention. Because of hyperventilation, this may only be seen initially as an arterial PCO2 returning to the normal range. Finally, with critical obstruction, respiratory failure follows, characterized by hypercapnia and academia (2).
National Asthma Education and Prevention Program defines mild intermittent asthma as symptoms that occur less than two times per month, and pulmonary function (either PEFR or FEV1) greater than 80% of predicted. Mild persistent asthma constitutes symptoms that occur twice a week or more but not daily, night symptoms three to four times per month, and pulmonary function greater than 80% of predicted value. Moderate asthma is classified as daily symptoms, night symptoms five or more times per month, and pulmonary function 60% to 80% of predicted value. A patient's asthma is considered severe if she experiences continuous symptoms of asthma, frequent night symptoms, and pulmonary function less than 60% of predicted value. These classifications should be of value in quantifying control of a patient's asthma as well as the severity of her illness. Consider some flexibility in clinical use of the definitions, however, since a patient who has been hospitalized for asthma or placed in intensive care should probably be considered to have more severe disease even if her symptoms are currently mild and intermittent.
Effects of pregnancy on asthma:
The severity of asthma worsens in 20% to 35% of pregnant women, remains stable in 40% to 50% and improves in 20% to 30%. There is no evidence that pregnancy has a predicable effect on underlying asthma. Disease exacerbation is more common at the end of the second trimester and the early third trimester. As pregnancy progresses, typical changes in respiratory physiology include an increased respiratory rate and a decrease in diaphragmatic excursion with a decrease in functional residual capacity. In the second half of pregnancy, normal PCO2 readings for pregnant women fall to 32 torr. Early blood gas changes with acute asthma exacerbation include worsening hypocapnia, while more severe and sustained asthma attacks are associated with normalization of PCO2. During the second and third trimester, a "normal" PCO2 during an attack indicates very serious CO2 retention as a result of inadequate ventilation (3).
Generally, unless there is severe disease, asthma has relatively minor effects on pregnancy outcome. Many individuals who have asthma are aware of what triggers their attacks and will already have implemented environmental controls. Tobacco smoke from both primary and secondary exposure should be absolutely avoided. A slightly increased incidence of prematurity and low birth weight has been suggested in severe cases of asthma, but the cause-and-effect relationship is not clear. Most studies describe a slightly increased incidence of preeclampsia, preterm labor, low-birth weight infants, and perinatal mortality. Life-threatening complications from status asthmaticus include muscle fatigue with respiratory arrest, pneumothorax, pneumo-mediastinum, acute cor pulmonale, and cardiac arrhythmias. Maternal and perinatal mortality is substantively increased when mechanical ventilation is required.
The incidence of fetal growth restriction increases with severity of asthma. The realization that the fetus may be seriously compromised as asthma severity increases under-scores the need for aggressive management of all pregnant women with acute asthma. Monitoring the fetal response is, in effect, an indicator of maternal status. In addition, possible teratogenic or adverse fetal effects of drugs given to control asthma are a concern. Considerable published data indicates there is no evidence that commonly used anti-asthmatic drugs are harmful (4).
According to the National Asthma Education Program (2005), effective management of asthma during pregnancy includes:
- Objective assessment of pulmonary function and fetal well-being.
- Avoidance or control of environmental precipitating factors.
- Pharmacological therapy.
- Patient education.
General Supportive Measures:
The general principles of management for pregnant asthmatic patients are similar to those for non-pregnant patients. The following steps should be taken: prevent exposure to known allergens; treat sinusitis; avoid anti-prostaglandin drugs (eg. aspirin) in aspirin-intolerant asthma; avoid strenuous exercise and exposure to cold; treat viral infections rigorously; treat reflux esophagitis to avoid induction of bronchospasm; stop cigarette smoking. In general, women with moderate to severe asthma are instructed to measure and record their PEFR twice daily. Predicted values range from 380 to 550 L/min. Each woman has her own baseline value, and therapeutic adjustments can be made using this. Patients with asthma should be vaccinated for influenza to lessen the risk that severity respiratory illness will complicate their disease. Many individuals who have asthma are aware of what triggers their attacks and will already have implemented environmental controls. Tobacco smoke, from both primary and secondary exposure also should be absolutely avoided.
Status Asthmaticus or Severe Attacks of Asthma:
Severe asthma of any type not responding after 30 to 60 minutes of intensive therapy is termed status asthmaticus. The patient must be hospitalized. Oxygen may be administered by mask or nasal catheter. Correction of dehydration and electrolyte imbalance is achieved by adequate intravenous fluids. Blood gas determinations are mandatory. Aminophylline, 0.25 -- 0.5 g in 30 mL of saline, is given slowly intravenously and followed with continuous intravenous infusion of 0.9 mg/kg/h. Hydrocortisone sodium succinate or equivalent, 100-200 mg, is given intravenously every 2-4 hours as necessary. If the patient fails to improve clinically with the previous measures and there is evidence of progressive hypoxemia and hypercapnia, intubation and controlled ventilatory assistance may be required. Consideration should be given to early intubation when maternal respiratory status worsens despite aggressive treatment. Fatigue, carbon dioxide retention, and hypoxemia are indications for mechanical ventilation. Criteria for intubating pregnant asthmatic patients are: maternal PO2 <60 mm Hg; maternal PCO2 >45 mmHg; evidence of maternal exhaustion; worsening acidosis (pH <7.35); and altered maternal consciousness.
Mild to Moderate attacks of Asthma:
Epinephrine injection (1:1000), 0.2-0.5 mL given subcutaneously, will often stop the attack. For moderately severe attacks, it may be repeated every 1-2 hours. Inhalation of epinephrine or isoproterenol (1/200 in aqueous solution) or use of a nebulizer, 1 or 2 inhalations every 30-60 minutes as necessary, may suffice for mild attacks. If the attack is not controlled by epinephrine or isoproterenol, give aminophylline, 0.25-0.5 g in 10-20 mL of saline slowly intravenously. Aminophylline may also be given rectally in solution or as a suppository. Epinephrine (sulfate or hydrochloride) 25-50 mg orally 2-3 times daily, may relieve mild attacks. Oral theophylline is also useful. Phenobarbital, 30 mg orally 3-4 times a day, may be used to counteract over-stimulation by bronchodilator drugs. Heavy sedation must be avoided.
The main drugs used in long-term management of asthma include methylxanthines, beta-adrenergic agonists, glucocorticoids, and cromolyn sodium. Beta-adrenergic agonists such as terbutaline can be used for asthma uncontrolled with theophylline. Medication should generally be added one by one until adequate control is achieved. It is important to maintain a high index of suspicion for bacterial respiratory infections during pregnancy, particularly for bacterial sinusitis, which has been estimated to be six times more common during pregnancy. Cough preparations with iodides and dexatromethorphan should be avoided because of the risks of fetal goiter and malformation, respectively. Antihistamines should be avoided during the first trimester.
Cromolyn and nedocromil inhibit mast cell degranulation. They are ineffective for acute asthma and are taken chronically for prevention. They likely are not superior to inhaled corticosteroids. Theophylline is a methylxanthine, and its various salts are bronchodilators and possibly anti-inflammatory agents. These drugs have been used less frequently since inhaled steroids became available. Women taking theophylline have a significantly higher discontinuation rate because of side effects. Leukotrienes modifiers inhibit their synthesis and include zileuton, zafirinkast, and montelukast. These drugs are given either orally or by inhalation for prevention, but they are not effective for acute disease. For maintenance, they are used in conjunction with inhaled steroids to allow minimal dosing.
Management of Labor and Delivery:
Vaginal delivery is the best for asthmatic patients unless obstetric indications demand cesarean section. During normal labor, minute ventilation can approach or exceed 20 L/min; therefore, the therapeutic goal should be stable pulmonary function without bronchospasm. For patients who have received systemic or inhaled corticosteroids during pregnancy, hydrocortisone 100 mg intravenously, is given immediately and every 8 hours until delivery has occurred. Paracervical, pudendal, or epidural block is preferable to general anesthesia. A non-histamine releasing narcotic, such as fentanyl, may be preferable to meperidine for labor. Maintenance medications are continued through delivery. The PEFR or FEV1 should be determined on admission and serial measurements made if symptoms develop.
Epidural analgesia for labor is ideal. For surgical delivery, conduction analgesia is preferred because tracheal intubation can trigger severe bronchospasm. Refractory postpartum hemorrhage is treated with prostaglandin E2 or other uterotonics instead of prostaglandin F2 alpha, which may cause significant bronchospasm in asthmatic patients. Oxygen desaturation following 15-methyl PGF2 alpha has been reported in women without reactive airway disease.
Women who continue to smoke during pregnancy must achieve very low levels of tobacco use to see improvements in infant birth weight, and they must quit entirely if their infants are to have birth weights similar to those of women who do not smoke. Children born to mothers who smoke during pregnancy are at increased risk for asthma (5).
Is your patient's asthma life threatening?
Several factors increase a pregnant asthmatic patient's risk of dying from the disease: a history of prior intubation for asthma; two or more hospitalizations for asthma within the past year; three of more emergency-room visits for asthma within the past year; hospitalization from an emergency-room visit for asthma within the past month; current use or recent withdrawal from systemic corticosteroids; history of syncope or hypoxic seizure due to asthma; previous admission for asthma to a hospital-based intensive care unit (ICU) and serious psychiatric disease or psychosocial problems. To protect mother and fetus alike, manage these patients just as aggressively as managing non-pregnant asthmatics.
Can allergy shots be started or continued during pregnancy?
The use of allergen immunotherapy, or "allergy shots", has been shown to be effective in improving asthma in patients with allergies. In two studies, no adverse effects of immunotherapy during pregnancy have been found (6). However, anaphylaxis is a risk of allergen injections, especially early in the course of immunotherapy when the dose is being escalated, and anaphylaxis during pregnancy has been associated with maternal death, fetal death, or both. In a patient who is receiving a maintenance or near-maintenance dose, not experiencing adverse reactions to the injections and apparently deriving clinical benefit, continuation of immunotherapy is recommended. In such patients, a dose reduction may be considered to further decrease the chance of anaphylaxis. Risk-benefit considerations do not usually favor beginning allergen immunotherapy during pregnancy.
How should women with asthma be counseled about breastfeeding?
In general, only small amounts of asthma medications enter breast milk. The National Asthma Education and Prevention Program found that the use of prednisone, theophylline, antihistamines, inhaled corticosteroids, beta-agonists, and cromolyn is not contraindicated for breast feeding (7).
Pregnant patients with asthma should be managed proactively to achieve a good perinatal outcome. Initial and ongoing assessment of the severity of an asthmatic woman's condition facilitates the stepwise addition of medication to optimize control of symptoms and prevent acute attacks. Educating patients is the key to their ability to use medication appropriately and initiate treatment before an acute disease process becomes critical. Most asthma medications are as safe to use in pregnancy as in the non-pregnant state. The benefits of good control clearly outweigh the risks of treatment with any commonly used asthma medication. Provide education, resources and feed-back to promote provider involvement in smoking cessation.
- Liu S, Wen SW, Demissie K, et al. Maternal asthma and pregnancy outcomes: a retrospective cohort study. Am J Obstet Gynecol. 2001;184:90-96
- Olsen C, Thrane N, Nielsen GL, et al. A population-based prescription study of asthma drugs during pregnancy: changing the intensity of asthma therapy and perinatal outcomes. Respiration. 2001;68:256-261
- Henderson CE, Ownby DR, Trumble A et al. Predicting asthma severity from allergic sensitivity to cockroaches in pregnant inner city women. J Repod Med. 2000;45:341-344
- Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol. 1999;93:392-395
- ACOG Committee Opinion. Smoking cessation during pregnancy. Number 316; October 2005
- ACOG Practice Bulletin. Asthma in Pregnancy. Number 90, February 2008
- American Academy of Pediatrics. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-789. (Level III)
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