Asthma in Pregnancy Case File

Asthma in Pregnancy Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 36

A 23-year-old African American G3P2002 at 22 0/7 weeks by LMP consistent with a first-trimester ultrasound presents as a new patient because she has recently moved to the area. Her medical history is significant for asthma since the age of 7. Her asthma has always been well controlled rarely requiring the use of her albuterol inhaler. One month before conception, however, she had “several” mild exacerbation relieved easily with the use of her inhaler. Last month she had four asthma exacerbations which required a visit to the emergency room for nebulizer treatment. It was recommended that she start a “new inhaler” but she did not fill the prescription prior to relocating. 

She is currently using her albuterol inhaler daily for symptoms and has exacerbations 2 to 3 times per week. She also reports chest tightness, wheezing, and waking up 1 to 2 times per week at night. In addition, she has congestion with yellow nasal discharge and sinus tenderness for 1 month not relieved with over-the-counter decongestants. She denies allergies, fever, or sick contacts. She denies prior intubations, use of steroids, and has never measured a baseline peak flow. Her obstetrical history is significant for two prior vaginal deliveries without asthma complications. With her last delivery she had postpartum hemorrhage requiring blood transfusion due to a “floppy” immediately after delivery. She is otherwise healthy and denies other medical problems. Prenatal labs are unremarkable. 

Her BP is 100/78 mm Hg, weight 135 lb, height 5 ft 1 in, urine dips negative for protein, glucose, ketones. Her examination is significant for sinus tenderness bilaterally, erythematous nasal mucosa bilaterally, purulent nasal discharge, no nodes palpable, throat and tympanic membranes are clear bilaterally. Bilateral expiratory wheezing throughout all lung fields is noted. Fetal hear tones are detected.

➤ What is your next step?

➤ How would you classify this patient’s asthma?

➤ What are the potential maternal complications associated with asthma in pregnancy?

➤ What are the potential fetal complications?

ANSWERS TO CASE 36:

Asthma in Pregnancy

Summary: This is a 23-year-old woman G3P2002 at 22 0/7 weeks gestation with a history of asthma that has worsened during this pregnancy.

➤ Next step: Evaluate patient with peak expiratory flow rate (PEFR).

➤ Classify this patient’s asthma: This patient has moderate persistent asthma because she has daily symptoms with exacerbations > 2 times/wk and nocturnal symptoms > 1 time/wk. Patients with moderate persistent asthma also have pulmonary function test 60% to 80% of predicted and may experience some interference with normal activities.

➤ Potential maternal complications associated with asthma in pregnancy: Patients with moderate or severe asthma may have increased number of exacerbations, hospitalizations, and unscheduled visits. The risk of cesarean delivery may also be increased in these women. Women with severe asthma may have an increased risk of preeclampsia and gestational diabetes mellitus (GDM). Women with mild or well-controlled asthma tend do well in pregnancy with outcomes similar to nonasthmatics. Although rare, potential life-threatening complications of untreated severe asthma include pneumothorax, pneumomediastinum, acute cor pulmonale, and respiratory arrest.

➤ Potential fetal complications: Preterm birth (< 37 wk) and small-forgestational- age infants (SGA) may complicate pregnancies in those with severe asthma or those who require the use of oral corticosteroids.

ANALYSIS

Objectives

1. Review current asthma classification guidelines.
2. Understand implications of asthma on maternal/perinatal outcome.
3. Review management of asthmatics in outpatient and inpatient setting.

Considerations

This patient’s asthma has progressively worsened during this pregnancy. New environmental triggers and an upper respiratory infection have contributed to her recent asthma exacerbations. With suboptimal treatment, this patient is unlikely to improve and both maternal and perinatal morbidity may be increased.

Asthma is one of the most common medical conditions complicating pregnancy, with an incidence of 4% to 9%1 (Level III). The clinical course of asthma in pregnancy is relatively unpredictable; however, there is evidence to suggest that worsening of asthma may be related to baseline asthma severity. Approximately one-third of pregnant asthmatics experience worsening of symptoms while one-third improve and one-third remain the same. Exacerbations are more common in the second and third trimester and are less frequent in the last 4 weeks of pregnancy. Asthma typically follows a similar clinical course with successive pregnancies. As such, this patient would be expected to do relatively well given that her symptoms were well controlled prior to this pregnancy and in previous pregnancies. This patient has not received appropriate treatment and her asthma severity has deteriorated. This case underscores the importance that all asthmatics, even those with mild or well-controlled disease, need to be monitored for symptoms and treated accordingly during pregnancy.

Asthma symptoms correlate poorly with objective measures of pulmonary function.2 Therefore, the next step in the evaluation of this patient is to perform an objective measure of airway obstruction. The single best measure is the forced expiratory volume (FEV1), which is the volume of gas exhaled in 1 second by a forced exhalation after a full inspiration. This value, however, can only be obtained by spirometry, thus limiting its clinical use. The peak expiratory flow rate (PEFR) correlates well with FEV1 and can be measured with inexpensive, disposable portable peak flow meters. Both the FEV1 and PEFR remain unchanged throughout pregnancy and may be used as measures of asthma control and severity. 

A patient who presents to the outpatient setting with worsening symptoms but is without evidence of a severe exacerbation may be treated and followed closely as an outpatient. This patient has moderate persistent asthma according to the current classification system by the 2004 National Asthma Education and Prevention Program Working Group on Asthma and Pregnancy (NAEPP)3 (Level III). In addition to the clinical history, a PEFR of 60% to 80% of personal best or predicted will support this diagnosis. One of the recommended treatments for moderate persistent asthma is a low-dose inhaled corticosteroid (ICS), such as budesonide plus a long-acting β2-agonist (salmeterol). This patient also has a chronic sinus infection which is evident by the purulent nasal discharge and sinus tenderness. A broad-spectrum antibiotic would be effective in treating her sinus infection. Sinusitis, rhinitis, and gastroesophageal reflux are all conditions that may exacerbate asthma and their treatment is an integral part of asthma management. 

This patient should be counseled to recognize the signs and symptoms of early asthma exacerbations such as coughing, chest tightness, dyspnea, wheezing, or a 20% decrease in PEFR so that therapy can be initiated promptly. She should also be educated on how to control her environmental triggers such as cold air, dust, strong fumes, exercise, inhaled irritants, emotional stress, food additives (sulfites), drugs (aspirin and beta-blockers) and smoke. Measures that can be taken include removing carpets, changing filters in the home heating and cooling systems, avoiding smokers, moving pets outside, avoiding the home for 1 hour after vacuuming or dusting, encasing mattresses and pillows in airtight covers, washing bed linens weekly in 130°F water, lowering home humidity to no more than 50%, closing windows, and using air conditioning4,5 (Level III).

Finally, it is also important to discuss the effect of asthma on pregnancy. Recent data from large prospective studies indicate that classification of asthma severity and appropriate treatment may result in favorable pregnancy outcome. These studies have shown that excellent maternal and fetal outcomes can be achieved in women with mild or well-controlled asthma. Those with severe and poorly controlled asthma may have an increased risk of preeclampsia, GDM, and preterm birth < 37 weeks. Cesarean delivery may also be increased in women with moderate or severe asthma. In a large prospective study in pregnant subjects, the exacerbation and hospitalization rates for mild asthmatics were 12.6% and 2.3%, respectively. In moderate asthma, the exacerbations and hospitalization rates were 25.7% and 6.8%, respectively while in those with severe, these rates were 51.9% and 26.9%, respectively6 (Level II-2). 

It is very reasonable to be cautiously optimistic about this patient’s pregnancy outcome. Nonetheless, she should be followed closely until her asthma is back to her baseline. She should be instructed to follow-up in several days but to notify her physician if symptoms are not improving or are worsening. If her asthma control is difficult to achieve with the previously recommended interventions, then a multidisciplinary team approach, including maternal fetal medicine and pulmonary specialists, is recommended.

APPROACH TO

Asthma in Pregnancy

Optimal management of asthma during pregnancy includes severity classification, subjective and objective monitoring of asthma control, avoiding or controlling asthma triggers, educating patients, and individualizing pharmacologic therapy to maintain normal pulmonary function. The ultimate goal of the management of asthma is to prevent hypoxic episodes in the mother which in turn ensures adequate oxygenation of the fetus. 

The 2004 NAEPP established a classification scheme of asthma according to clinical symptoms and objective tests of pulmonary function3 (Level III). Asthma is graded according to the patient’s most severe symptoms while on or off controller medication and therapy is tailored accordingly (Table 36–1). It is important to remember that approximately 30% of those initially thought to be mild asthmatics may be reclassified as moderate or severe during pregnancy. Each prenatal visit should therefore include an evaluation of asthma

severity and symptom frequency, nocturnal symptoms, medications, emergency visits, and hospital admissions for exacerbations. The 2004 NAEPP guidelines recommend spirometry at initial assessment and PEFR for routine monitoring at subsequent follow-up visit. Patients should be instructed to record PEFR immediately upon rising in the morning and again 12 hours later. They should establish their personal best PEFR during a period when their asthma is under good control. This value can then be used to recognize worsening of symptoms and subsequent response to treatment. 

It is important to also ascertain a detailed asthma history. Patients with potentially fatal asthma include those with a history of prior intubation for asthma; two or more hospitalizations for asthma in the past year; three or more emergency care visits for asthma in the past year; hospitalization or an emergency care visit for asthma within the past month; current use of systemic corticosteroids or recent withdrawal from systemic corticosteroids; past history of syncope or hypoxic seizure due to asthma; prior admission for asthma to a hospital-based intensive care unit; and serious psychiatric disease or psychosocial problems. Patients with one or more of these risk factors are particularly concerning and any changes in their symptoms should prompt immediate medical attention in the outpatient or inpatient setting as appropriate. 

It is also imperative to establish accurate determination of gestational age with a first-trimester ultrasound so that comparison may be made later for fetal growth. Routine obstetric monitoring for the pregnant asthmatic should include Doppler assessment of fetal heart tones and daily kick counts. Once fetal viability is achieved, the need for fetal surveillance may be based on asthma severity. Ultrasound for fetal growth and antenatal surveillance with either nonstress test (NST) or biophysical profile (BPP) testing may be considered in those with moderate or severe asthma, fetal growth restriction,

asthma exacerbation, or decreased fetal movement.

Treatment

Since asthma is a disease of chronic airway inflammation and acute episodes of bronchospasm, treatment is directed at reducing this inflammation and reversing bronchospasm. The aim of therapy is to use the minimum medication needed to maintain control with the least risk of adverse effects. The 2004 NAEPP guidelines recommend a “step” therapy approach to pharmacologic treatment of asthma during pregnancy. With this approach, the number and frequency of medications are increased as necessary to establish control (step up) and reduced when possible to maintain control (step down). It is safer for women to be treated with asthma medications than to have asthma symptoms and exacerbations during pregnancy. 

Asthma medications may be divided into two arms: rescue therapy and long-term control therapy. All pregnant asthmatics should have an inhaled short-acting β2-agonist for rescue treatment of acute symptoms. β2-Agonists relax the smooth muscle of the bronchioles and are used for relieving acute symptoms as well as preventing exacerbations from exposure to a trigger. Their onset of action is less than 5 minutes with duration of only 4 to 6 hours, and repetitive administration produces incremental bronchodilation. Albuterol is preferred over other short-acting β2-agonists due to extensive safety-related information during pregnancy (category C). However, there is no evidence of fetal adverse effects with the use of other short-acting inhaled β2-agonists. Inhaled albuterol can be delivered via a metered dose inhaler (MDI) or by nebulizer (2.5 mg or 0.5 mL of a 0.5% solution diluted in 2.5 mL normal saline). 

Long-term control medications are used for prevention of asthma exacerbations. Long-acting inhaled β2-agonists are used for moderate or severe persistent asthma. Salmeterol and formoterol have limited data in pregnancy, however, their pharmacologic and toxicologic profiles are considered to be similar to albuterol with the expected safety profile. Inhaled corticosteroids (ICS) are the first-line controller therapy for persistent asthma in pregnancy. Budesonide has been well studied in pregnancy (category B) and has not been shown to be teratogenic or associated with adverse perinatal outcome. Although budesonide is the ICS of choice, there are no data to indicate safety concerns with other ICS and maintaining a previously established treatment regimen may be more beneficial. Low, medium, and high doses of ICS can be used according to asthma severity (Table 36–2). Oral corticosteroids can be used as both maintenance and rescue therapy. Oral corticosteroids may increase the risk of cleft lip/palate if used in the first trimester. Whether they increases the risk of preeclampsia, preterm birth, and low-birth-weight infants remains uncertain as the available data make it difficult to separate the effects of oral corticosteroids from the effects of severe or uncontrolled asthma on pregnancy.

DPI = dry powder inhaler

MDI = metered-dose inhaler

Alternative drugs may be used as add-on controller therapy when using the step-therapy approach (Table 36–1). For example, cromolyn sodium (category B) is a mast cell stabilizer that can be used for the management of mild persistent asthma as an alternative to low-dose ICS. Leukotriene modifiers such as montelukast and zafirlukast (both category B) may be used as alternative addon therapy; however, there is limited data of use in pregnancy. Theophylline (category C) is another alternative add-on controller therapy for persistent asthma. The disadvantage of this drug is that it has a very narrow therapeutic index and requires serum monitoring. Although animal data have raised concerns of fetal growth abnormalities with theophylline use, human data have not confirmed this or any additional maternal or fetal risks.

Acute Asthma Exacerbation

Treatment of an acute exacerbation during pregnancy is similar to that of nonpregnant asthmatics. Patients should be taught how to recognize the signs and symptoms of early exacerbations so that they may begin treatment at home promptly. Initial treatment consists of a short-acting inhaled β2-agonist (albuterol) of 2 to 4 puffs by MDI at 20 minute intervals for up to three treatments, or single nebulizer treatment for up to 1 hour. A good response is characterized by PEFR greater than 80% of personal best and resolution of symptoms sustained for 4 hours. Patients may be continued on β2-agonists every 3 to 4 hours for 24 to 48 hours. Inhaled corticosteroids should be initiated or if already taking ICS, the dose should be doubled. Follow-up appointment with their physician should be made as soon as possible. Inadequate response to initial therapy (PEFR < 80%) or decreased fetal activity warrants immediate medical attention.

Table 36–3 CRITERIA FOR INTUBATION OF A PREGNANT ASTHMATIC

• Maternal PaO2 ≤ 60 mm Hg • Maternal PaCO2 ≤ 45 mm Hg • Evidence of maternal exhaustion • Worsening acidosis (pH < 7.35) • Altered maternal consciousness

 

Prevention of hypoxia is the ultimate goal for the pregnant woman who presents to the hospital during an acute asthma attack. Initial assessment should include a brief history and physical examination to assess the severity of asthma and possible trigger factors such as a respiratory infection. Patients with imminent respiratory arrest include those who are drowsy or confused, have paradoxical thoracoabdominal movement, absence of wheeze, bradycardia, and absence of pulsus paradoxus. Intubation and mechanical ventilation with 100% oxygen should be performed in these circumstances and the patient should be admitted to the intensive care unit. A PaCO2 greater than 35 mm Hg, with a pH less than 7.35 in the presence of a falling PaO2 is a sign of impending respiratory failure in a pregnant asthmatic. Intubation is warranted when the Paco2 is 45 mm Hg or more and rising (Table 36–3).

If intubation is not immediately warranted, measurement of PEFR or FEV1 and arterial blood gas is important to determine the severity of asthma. Initial treatment should include supplemental oxygen to maintain a PaO2 greater than 60 mm Hg or an oxygen saturation of at least 95% with the patient on continuous pulse oximetry. Because the fetus operates on the steep portion of the oxygen dissociation curve, decreases in maternal PaO2, especially below 60 mm Hg, can result in profoundly decreased fetal PaO2 and fetal hypoxia. Maternal oxygen saturation must remain greater than 95% to ensure adequate fetal oxygenation.

Intravenous access is essential for both administration of medicines and adequate hydration. Albuterol should be delivered by nebulizer every 20 minutes for a total of three doses. If the patient is moving air poorly, rendering the nebulizer ineffective, terbutaline 0.25 mg can be administered subcutaneously

every 15 minutes for three doses. If the PEFR is < 40% of personal best, highdose inhaled albuterol plus ipratropium by nebulizer or MDI should be used every 20 minutes or continuously for 1 hour.

Systemic steroids should be administered to those not responding immediately to bronchodilators and for those already taking regular oral corticosteroids. Intravenous methylprednisolone, 40 to 80 mg, is usually given every 6 to 8 hours. This may be substituted with prednisone orally (60 mg initially, then 60-120 mg daily tapered over several days). If the patient is too breathless to maintain oral intake, parenteral administration is preferred. Regardless of the route of administration, their onset of action is several hours so a β2-agonist must be given as well. Response to treatment is considered good if PEFR or FEV1 is 70% or more of baseline, patient is asymptomatic, and fetal status is reassuring. Patients who fail to respond to treatment within 4 hours warrant admission to the hospital for further monitoring and management.

Preterm labor may complicate an acute asthma exacerbation; however uterine contractions will usually abate with successful treatment of the exacerbation. If tocolytics are necessary, magnesium sulfate or calcium channel blockers can be administered. Indomethacin may induce bronchospasm in aspirin-sensitive asthmatics and should therefore be avoided.

Antepartum and Intrapartum Management

There are no standard guidelines for timing of delivery but it is generally accepted that delivery be undertaken at term, or when maternal health can be improved by delivery; however, it is important to avoid delivery of a patient during an acute exacerbation.

When the pregnant asthmatic presents for delivery, continuous monitoring of both mother and fetus is important. PEFR should be measured upon admission and again every 12 hours. Regularly scheduled medications should be continued throughout labor. Stress-dose steroids should be administered to women who have taken systemic steroids in the preceding 4 weeks to avoid adrenal suppression. This can be accomplished with 100 mg hydrocortisone intravenously every 8 hours until 24 hours postpartum. Labor induction can be safely accomplished with oxytocin or cervical ripening methods such as prostaglandin E1 or E2. The analgesic chosen during labor should be a nonhistamine- releasing narcotic, such as fentanyl, as opposed to meperidine or morphine. Lumbar epidural or combined spinal epidural are appropriate options for pain management during labor. If uterine atony results in postpartum hemorrhage, oxytocin and prostaglandin E1 or E2 are the uterotonics of choice. Prostaglandin F2α and methylergonovine should be avoided as they both can cause bronchospasm. The use of oral or ICS, β2-agonists, antihistamines, and cromolyn is not contraindicated for breast-feeding women.

Comprehension Questions

36.1 A 19-year-old G1P0 at 9 weeks’ gestation presents for prenatal care. She has mild persistent asthma well controlled on a low-dose inhaled corticosteroid, beclomethasone. What controller treatment plan would you recommend?

A. Start low-dose budesonide and discontinue current ICS.

B. Continue the same ICS.

C. Discontinue the ICS.

36.2 A 28-year-old woman at 20 weeks’ gestation with asthma for 10 years comes into the OB triage area for exacerbation of her asthma. After two nebulized treatments, she is still dyspneic. Her arterial blood gas is as follows: pH 7.37, PO2 85 mm Hg, PCO2 35 mg Hg, and HCO3 18 mEq/L. Which of the following is the best description of her blood gas findings?

A. Mild hypoxemia and normal ventilation

B. Severe hypoxemia and normal ventilation

C. Mild hypoxemia and significant hypercarbia

D. Severe hypoxemia and metabolic acidosis

E. Mild hypoxemia and metabolic acidosis

ANSWERS

36.1 B. Although budesonide is the preferred ICS for the treatment of mild persistent asthma due to favorable safety information of use in pregnancy, there are no concerns with other ICS. That being said, if a patient is well controlled on a previously established treatment regimen, it is reasonable to continue the same controller medication during pregnancy as well.

36.2 C. The PO2 is slightly low, but more alarming is the PCO2 which is elevated. The normal PCO2 in pregnancy is 28 mm Hg. In an asthmatic exacerbation, typically the PCO2 is decreased due to increased respiratory rate; when the PCO2 is elevated, it illustrates CO2 retention and forbodes impending respiratory failure and possible need for intubation if the trend continues.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ It is safer for pregnant women with asthma to be treated with asthma medications than it is for them to have asthma symptoms and exacerbations (Level III).

➤ The ultimate goal of asthma therapy in pregnancy is maintaining adequate oxygenation of the fetus by preventing hypoxic episodes in the mother (Level III).

➤ Inhaled corticosteroids are first-line controller therapy for persistent asthma during pregnancy (Level II-3).

➤ Inhaled albuterol is recommended rescue therapy for pregnant women with asthma (Level III).

➤ Ultrasound assessment of fetal growth and antenatal fetal testing should be considered for women who have moderate or severe asthma during pregnancy (Level III).

➤ Mild and well-controlled asthma can be associated with excellent maternal and perinatal pregnancy outcomes (Level II-3).

➤ Severe and poorly controlled asthma may be associated with perinatal complications and maternal morbidity and mortality (Level II-2).

REFERENCES

1. Kwon HL, Belanger K, Bracken MB. Asthma prevalence among pregnant and childbearing-aged women in the United States: estimates from national health surveys. Ann Epidemiol. 2003;13:317-324 (Level III). 

2. Stahl E. Correlation between objective measures of airway calibre and clinical symptoms in asthma: a systematic review of clinical studies. Respir Med. 2000 Aug;94(8):735-741. 

3. National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program. Working group report on managing asthma during pregnancy: recommendations for pharmacologic treatment-update 2004. NIH Publication No. 05-5236, March 2005. Since the 1993 recommendations, modification to the general asthma treatment guidelines, release of new asthma medications, revisions to the severity classification of asthma, and publication of new gestational safety data were sufficient to warrant an evidence- based update of these recommendations (Level III). 

4. National Asthma Education Program: Report of the Working Group on Asthma and Pregnancy: Executive Summary: management of asthma during pregnancy. National Heart, Lung and Blood Institute. NIH publication 93-3279, March 1993. In 1993, the National Asthma Education and Prevention Program (NAEPP) published the Report of the Working Group on Asthma and Pregnancy, which comprehensively reviewed the data to date and presented recommendations for the management of asthma during pregnancy (Level III). 

5. Gardner MO, Doyle NM. Asthma in pregnancy. Obstet Gynecol Clin North Am. 2004;31(2):385-413. 

6. Dombrowski MP, Schatz M, Wise R, et al. Asthma during pregnancy. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network and the National Heart, Lung, and Blood Institute. Obstet Gynecol. 2004;103:5-12. Multicenter, prospective, observational cohort study conducted over 4 years at 16 university hospital centers that looked at neonatal and maternal outcomes based on asthma severity during pregnancy. The study showed that when asthma is classified and therapy is tailored according to its severity, excellent maternal and infant outcomes can be achieved (Level II-2).

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