Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 51. Tuberculosis, Sarcoidosis, and Cystic Fibrosis

TUBERCULOSIS

Tuberculosis in foreign-born persons accounts for over half of the active tuberculosis cases in the United States. In addition, 10 to 15 million persons in the United States have latent tuberculosis manifest by a positive tuberculin skin test. Though pregnancy was once thought to have an adverse effect on the course of tuberculosis, this is no longer true with modern antituberculosis therapy. However, tuberculosis may adversely affect pregnancy outcome. Preterm delivery, low birth weight, growth restriction, and perinatal mortality rates are all increased in the setting of incomplete treatment and advanced or extrapulmonary tuberculosis.

Neonatal Tuberculosis

Congenital tuberculosis is a rare and often fatal disease, usually acquired by hematogenous spread through the umbilical vein, or by aspiration of infected secretions at delivery. It is often associated with maternal HIV infection and untreated active tuberculosis and manifests with hepatosplenomegaly, respiratory distress, fever, and lymphadenopathy.

Screening for Tuberculosis

Current guidelines include skin testing of women in high-risk groups as shown in Table 51-1. The preferred antigen is purified protein derivative (PPD) in the intermediate strength of 5 tuberculin units. If the intracutaneously applied test is negative, no further evaluation is needed. A positive skin test is interpreted according to risk factors. For very high-risk patients—that is, those who are HIV-positive, those with abnormal chest radiography, or those who have a recent contact with an active case—5 mm or greater is considered positive. For those at high risk—foreign born, intravenous drug users who are HIV-negative, low-income populations, or those with medical conditions that increase the risk for tuberculosis—10 mm or greater is considered positive. For persons with none of these risk factors, 15 mm or greater is defined as positive. The in vitro QuantiFERON-TB Gold test is recommended by the Centers for Disease Control and Prevention for the same indications as skin testing to diagnosis latent infection. It also distinguishes between immune responses due to infection and responses resulting from bacilli Calmette-Guérin (BCG) vaccination.

TABLE 51-1. Groups at High Risk for Having Latent Tuberculosis Infection

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Clinical Course

Infection is via inhalation of Mycobacterium tuberculosis, which incites a granulomatous pulmonary reaction. In over 90 percent of patients, infection is contained and lies dormant for long periods. In some women, especially those who are immunocompromised or who have other diseases, tuberculosis becomes reactivated to cause clinical disease. Clinical manifestations usually include cough with minimal sputum production, low-grade fever, hemoptysis, and weight loss. A variety of infiltrative patterns are seen on chest x-ray, and there may be associated cavitation or mediastinal lymphadenopathy. Acid-fast bacilli are seen on stained smears of sputum in about two-thirds of culture-positive patients. Extrapulmonary tuberculosis may occur in any organ, and almost 40 percent of HIV-positive patients have disseminated disease.

Treatment

Whether to treat or not in pregnancy is determined by a number of factors. For the HIV-negative woman with a positive PPD and no evidence of active disease, treatment is usually held until postpartum. Known recent skin-test converters are treated because the incidence of active infection is 3 percent in the first year. Skin-test positive women exposed to active infection are treated because the incidence of infection is 0.5 percent per year. Finally HIV-positive women are treated because they have an 8 percent annual risk for active disease.

Because of emerging drug resistance, the Centers for Disease Control recommends a four-drug regimen for the initial treatment of nonpregnant patients with symptomatic or active tuberculosis. These are isoniazid, rifampin, and pyrazinamide with ethambutol or streptomycin given until susceptibility studies are done. Drug susceptibility testing is performed on all first isolates. Fortunately, most first-line tuberculostatic drugs do not appear to affect the fetus adversely. An exception is streptomycin, which may cause congenital deafness. Moreover, the safety of pyrazinamide given in early pregnancy has not been established.

The Centers for Disease Control recommend that the orally prescribed regimen for pregnant women should include

1. Isoniazid, 5 mg/kg, not to exceed 300 mg daily, along with pyridoxine, 25 to 50 mg daily

2. Rifampin, 10 mg/kg daily, not to exceed 600 mg daily

3. Ethambutol, 5 to 25 mg/kg daily, not to exceed 2.5 g daily

These drugs are given for a minimum of 9 months and pyrazinamide is added if isoniazid resistant mycobacteria are prevalent in the patient’s area of resident (e.g., Texas, New Mexico, California, and many other states contact the local health department). For HIV-infected women, the use of rifampin or rifabutin may be contraindicated if certain nucleoside reverse transcriptase inhibitors are being administered. Breast feeding is not prohibited during antituberculous therapy.

Liver function testing should be performed as isoniazid is associated with an often transient elevation of liver enzymes, though therapy should only be discontinued if the elevation is increased fivefold over normal levels.

SARCOIDOSIS

Sarcoidosis uncommonly complicates pregnancy and seldom affects it adversely unless there is severe preexisting disease. It is a chronic, multisystem disease of unknown etiology characterized by an accumulation of T-lymphocytes and phagocytes within noncaseating granulomas. Pulmonary involvement is most common, followed by the skin, eyes, and lymph nodes. Its prevalence in the United States is 10 to 40 per 100,000 with equal sex distribution and a predilection for African Americans (10-fold). The clinical presentation varies, but most commonly dyspnea and a dry cough without constitutional symptoms develop insidiously over months.

Interstitial pneumonitis is the hallmark of pulmonary involvement. More than 90 percent of patients have an abnormal chest radiography at some point. Lymphadenopathy, especially of the mediastinum, is present in 75 to 90 percent of cases; 25 percent have uveitis; and 25 percent have skin involvement, usually manifest as erythema nodosum. Any other organ system can be involved. Confirmation of diagnosis is not possible without biopsy.

The decision to treat is based on symptoms, physical findings, chest x-ray, and pulmonary function tests. Unless respiratory symptoms are prominent, therapy is usually withheld for a several-month observation period, and if inflammation does not subside, then prednisone, 1 mg/kg, is given daily for 4 to 6 weeks. Treatment is the same in the pregnant and nonpregnant women.

CYSTIC FIBROSIS

Cystic fibrosis is one of the most common serious genetic disorders in Caucasians. It is caused by one of more than 1000 point mutations on the long arm of chromosome 7. Because of improvements in diagnosis and treatment, nearly 80 percent of females with cystic fibrosis now survive to adulthood. Although many are infertile because of delayed sexual development and perhaps abnormal cervical mucus production, pregnancy is not uncommon. Outcomes frequently reported include a preterm delivery rate of 10 to 50 percent and a maternal mortality rate of 1 to 5 percent during the pregnancy and up to 18 percent within 2 years of delivery. Pregnancy outcome is inversely related to severity of lung dysfunction. Bronchial gland hypertrophy with mucous plugging and small-airway obstruction leads to subsequent infection that ultimately causes chronic bronchitis and bronchiectasis. Bacteria that colonize the respiratory tract include Pseudomonas aeruginosa in over 90 percent; Staphylococcus aureus, Hemophilus influenzae, Stenotrophomonas maltophilia, and Burkholderia cepacia are recovered in a minority of instances. Acute and chronic parenchymal inflammation ultimately causes extensive fibrosis, and along with airway obstruction, there is a ventilation–perfusion mismatch. Pulmonary insufficiency is the end result.

MANAGEMENT IN PREGNANCY

Prepregnancy counseling is imperative, and genetic counseling is discussed in Chapter 6. Women who choose to become pregnant should be followed closely with serial pulmonary function testing and surveillance for superimposed infection, development of diabetes, and heart failure. An FEV1 of at least 70 percent is a good predictor of a successful pregnancy outcome. Careful attention is given to postural drainage and bronchodilator therapy. Inhaled recombinant human deoxyribonuclease 1 and inhaled 7 percent saline both improve lung function by reducing sputum viscosity. Immediate hospitalization is recommended if complications develop, especially pulmonary infection. For labor and delivery, epidural analgesia is recommended, especially for operative delivery.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 46, “Pulmonary Disorders.”