Tuberculosis, Neonatal

Tuberculosis can be acquired in the perinatal period. Symptoms and signs are nonspecific. Diagnosis is by culture and perhaps x-ray and biopsy. Treatment is with antituberculous drugs.

Infants may acquire tuberculosis (TB) by transplacental spread through the umbilical vein to the fetal liver, by aspiration or ingestion of infected amniotic fluid, or via airborne inoculation from close contacts (family members or nursery personnel). About 50% of children born to mothers with active pulmonary TB develop the disease during the 1st year of life if chemoprophylaxis or BCG vaccine is not given.

Symptoms, Signs, and Diagnosis

The clinical presentation of neonatal TB is nonspecific but is usually marked by multiple organ involvement. The neonate may look acutely or chronically ill. Fever, lethargy, respiratory distress, hepatosplenomegaly, or failure to thrive may indicate TB in a neonate with a history of exposure.

All neonates with suspected congenital TB should have chest x-ray and culture of tracheal aspirates, gastric washings, urine, and CSF for acid-fast bacilli. Skin testing is not extremely sensitive but should be performed; biopsy of the liver, lymph nodes, lung, or pleura may be needed to confirm diagnosis. Well-appearing neonates whose mothers had a positive skin test but a negative chest x-ray and no evidence of active disease should have a skin test q 3 mo for 1 yr. If the test is positive, chest x-ray and cultures for acid-fast bacilli are obtained as above.

Treatment

Pregnant women with a positive tuberculin test: Because the hepatotoxicity of isoniazid
(INH) is increased in pregnancy, and because the risk of contracting TB from a mother with a positive tuberculin test is greater for the neonate than for the fetus, INH use is deferred until the 3rd trimester unless the woman has active TB. Treatment is given for 9 mo, along with supplemental pyridoxine.

Infants with a positive tuberculin test: If there is no clinical or radiologic evidence of disease, the infant should receive INH 10 mg/kg po once/day for 9 mo and should be closely followed.

Pregnant women with active TB: INH, ethambutol, and rifampin use in recommended doses during pregnancy has not been shown to be teratogenic to the human fetus. The recommended initial treatment regimen in the US includes INH (300 mg po), ethambutol (15 to 25 mg/kg), and rifampin (600 mg po). All pregnant and breastfeeding women receiving INH should also take pyridoxine (25 mg po). All these drugs can be given once/day. The recommended duration of therapy is at least 9 mo unless the organism is drug-resistant, in which case an infectious disease consultation is recommended, and therapy may need to be extended to 18 mo. Streptomycin is potentially ototoxic to the developing fetus and should not be used early in pregnancy unless rifampin is contraindicated. If possible, other antituberculous drugs should be avoided because of teratogenicity (eg, ethionamide) or lack of clinical experience during pregnancy. Breastfeeding is not contraindicated for mothers receiving therapy who are not infective.

Asymptomatic infants of women with active TB: The infant usually is separated from the mother until effective treatment is under way or acid-fast stains of her sputum become negative (usually 2 to 12 wk). Family contacts should be investigated for undiagnosed TB before the infant goes home.

If compliance can be reasonably assured and the family is nontuberculous, the infant is started on a regimen of INH as above and sent home at the usual time. Skin testing should be performed at ages 3 and 6 mo. If the infant remains tuberculin-negative, INH is stopped and the infant is monitored with monthly to bimonthly clinical evaluations, and skin tests at 12 mo.

If compliance in a nontuberculous environment cannot be ensured, BCG vaccine may be considered for the infant, and INH therapy should be started as soon as possible. (Although INH inhibits the multiplication of BCG organisms, the combination of BCG vaccine and INH is supported by clinical trials and anecdotal reports.) BCG vaccination does not ensure against exposure to and development of tuberculous disease, but offers significant protection against serious and widespread invasion (eg, tuberculous meningitis). Infants should be monitored for development of tuberculous illness, particularly in the 1st year. (Caution: BCG vaccine is contraindicated in immunosuppressed patients and those suspected of being infected with HIV. However, in high-risk populations, the WHO recommends that asymptomatic HIV-infected infants receive BCG vaccine at birth or shortly thereafter.)

Neonates with active TB: The American Academy of Pediatrics recommends treatment once/day with INH (10 to 15 mg/kg po), rifampin (10 to 20 mg/kg po), pyrazinamide (20 to 40 mg/kg po), and streptomycin (20 to 40 mg/kg IM) for 2 mo, with INH and rifampin continued for another 10 mo. Alternatively, a 10-mo regimen of INH and rifampin twice/wk can be given after the 2-mo initial therapy. Depending on results of testing for resistance, capreomycin or kanamycin may be used instead of streptomycin. Breastfed infants should also receive pyridoxine supplementation.

When the CNS is involved, initial therapy also includes corticosteroids (1 mg/kg po once/day for 6 to 8 wk, then gradually tapered). Therapy continues until all signs of meningitis have disappeared and cultures are negative on 2 successive lumbar punctures at least 1 wk apart. Therapy can then be continued with INH and rifampin once/day or twice/wk for another 10 mo.

TB in infants and children that is not congenitally acquired or disseminated; does not involve the CNS, bones, or joints; and results from drug-susceptible organisms can be treated effectively with a 6- to 9-mo (total) course of therapy. Organisms recovered from the infant or mother should be tested for drug sensitivity. Hematologic, hepatic, and otologic symptoms should be monitored frequently to determine response to therapy and drug toxicity. Frequent laboratory analysis is not usually necessary.

Directly observed therapy (DOT) is used to improve compliance and the success of therapy. Many anti-TB drugs are not available in pediatric dosages. Administering these drugs to children may be improved in settings with experienced personnel.

Prevention

Routine neonatal BCG vaccination is not indicated in developed countries but may curb the incidence of childhood TB or decrease its severity in populations at increased risk for infection.

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