Tuberculosis during pregnancy

Antonio Addis, Pharmd; Doug Blowey, MD; Gideon Koren, MD, FRCPC

August, 1996

Tuberculosis (TB) in pregnant women has been a concern since the days of Hippocrates. Because of improved living conditions and the discovery of effective chemotherapy, the incidence of TB has rapidly declined. However, recently there has been a resurgence.¹ The increase in TB cases is due most likely to many factors, including the human immunodeficiency virus (HIV) epidemic, drug abuse, poverty, homelessness, a deterioration in the health care infrastructure, and an increasing number of cases among immigrants.²

Tuberculin skin testing with purified protein derivative (PPD) during pregnancy has not been associated with teratogenic effects. In fact, screening for active or latent TB using PPD is indicated for certain pregnant women (including women who have symptoms of TB, have recently been exposed to TB, or have medical conditions, such as HIV infection, that predispose them to TB) and women in other high-risk categories (eg, HIV-positive, drug abusers). Pregnancy does not appear to affect the validity of PPD, and it is now accepted that tuberculin skin testing is valid throughout pregnancy.³ The most helpful activity in containing TB is prompt initiation of chemotherapy.

Central to understanding the therapeutic options for pregnant women or women of childbearing age infected with TB is knowledge of the effect of pregnancy on the clinical course of TB, the effect of TB on pregnancy, the safety of treatment during pregnancy, and recommendations for newborn babies of infected mothers.

Historically, pregnancy was thought to have a deleterious influence on the clinical course of TB, but data evaluating 1565 pregnancies during active TB infection suggested that pregnancy had no adverse effects on the clinical course of TB.⁴ This notion is supported by other studies, which in addition emphasize the success of chemotherapy in treating TB during pregnancy.⁴ A 10-year follow-up study of 215 patients who had received adequate chemotherapy for pulmonary TB concluded that pregnancy does not predispose patients to relapse, even patients with a persistent pulmonary cavity. ⁵ Finally, the clinical presentation of TB is not altered during pregnancy, although the symptoms of pregnancy might delay diagnosis of TB. The conclusion from available information is that pregnancy has little, if any, effect on the clinical course of TB.⁶

No evidence suggests that TB affects or complicates either the course of pregnancy or delivery ; women with and without TB had similar rates of normal, spontaneous deliveries.⁴ The prognosis of TB changed dramatically after specific chemotherapeutic agents were developed. Because drug resistance develops rapidly when a single drug is used, chemotherapy regimens for TB use at least three drugs, which vary depending upon the organism's susceptibility.

Most experts consider rifampin, combined with isoniazid and ethambutol, to be safe and effective for treating TB during pregnancy. ^7,8 Despite the fact that all these drugs cross the placenta and reach low concentrations in human fetal fluids and tissues, no reports linking the use of these drugs with congenital anomalies have been located. Both rifampin and isoniazid have been implicated as potential causes of hemorrhagic disease in newborns. ⁹ Although the risk for these complications is supported only by case reports, women should take oral prophylactic vitamin K₁, during the last month of pregnancy.

All pregnant women receiving isoniazid should take pyridoxine. Streptomycin is the only licensed anti-TB drug documented as having harmful effects on fetuses ; several cases describing congenital ototoxicity in newborns exposed in utero to streptomycin have been reported. ⁴ With the exception of eighth cranial nerve damage, no other congenital defects due to streptomycin have been reported. Routine use of pyrazinamide also is not recommended during pregnancy, not because teratogenicity has been documented, but because there is insufficient data to assess risk. Pyrazinamide should be considered only when the organism is found to be resistant to the drugs known to be safe in pregnancy. Pregnant women with inactive TB are generally administered prophylactic isoniazid therapy to prevent latent TB from progressing to clinical disease. ⁸

Infection with TB in utero is rare. Infants suspected of having congenital TB (eg, TB present in the placenta or history of miliary TB) should be referred to an infectious disease specialist. Almost all newborns who get TB acquire it from postpartum exposure to an untreated source (eg, mother or family member). Management of newborns whose mothers or household contacts have or are suspected of having TB is based on whether contacts have evidence of current disease and whether they are considered contagious. Management emphasizes proper evaluation of all individuals to whom the infant will be exposed. If this evaluation is not immediately possible, newborns should be given isoniazid therapy until the evaluation is completed. Because therapy is based on individual case considerations, and infectious disease specialist should be consulted for specific guidelines. ⁸

Because the low concentrations of anti-TB drugs in breast milk do not produce toxicity in nursing newborns, breastfeeding should be encouraged. However, because drug levels are so low in breast milk, they cannot be relied upon for either prophylaxis or therapy for nursing infants.

References

1. Centers for Disease Control and Prevention. Tuberculosis among pregnant women - New York City, 1985-1992. JAMA 1993; 270(11): 1293-6.
2. Centers for Disease Control and Prevention. Initial therapy for tuberculosis in the era of multidrug resistance; recommendations of the Advisory Council for the Elimination of Tuberculosis. JAMA 1993;270(6):694-8.
3. Huebner RE, Schein MP, Bass JB. The tuberculin skin test. Clin Infect Dis 1993;17:968-75.
4. Hamadeh MA, Glassroth J. Tuberculosis and pregnancy. Chest 1992;101(1):1114-20.
5. Summers L. Understanding tuberculosis: implications for pregnancy. J Perinat Neonatal Nurs 1992;6(2):12-24.
6. Davidson PT. Managing tuberculosis during pregnancy. Lancet 1995;346:199-200.
7. Ad Hoc Committee of the Scientific Assembly on Microbiology. Tuberculosis and pulmonary infections. Treatment of tuberculosis and tuberculosis infection in adults and children. Clin Infect Dis 1995;21:9-27.
8. Pregnant women with active tuberculosis should be treated. Drug Ther Perspect 1996;7:9-11.
9. Briggs GG, Freeman RK, Yaffee SJ, editors. Drugs in pregnancy and lactation. Baltimore, Md: Williams & Wilkins, 1994.