( See also Tuberculosis (TB) Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more in adults and Overview of Neonatal Infections Overview of Neonatal Infections Neonatal infection can be acquired In utero transplacentally or through ruptured membranes In the birth canal during delivery (intrapartum) From external sources after birth (postpartum) Common... read more .)
Infants may acquire tuberculosis (TB) by the following means:
Transplacental spread through the umbilical vein to the fetal liver
Aspiration or ingestion of infected amniotic fluid
Airborne inoculation from close contacts (family members or nursery personnel)
About 50% of children born to mothers with active pulmonary tuberculosis develop the disease during the first year of life if chemoprophylaxis or bacille Calmette-Guérin (BCG) vaccine is not given.
Symptoms and Signs of Perinatal TB
The clinical presentation of neonatal tuberculosis is nonspecific but is usually marked by multiple organ involvement. The neonate may look acutely or chronically ill and may have fever, lethargy, respiratory distress or non-responsive pneumonia, hepatosplenomegaly, or failure to thrive.
Diagnosis of Perinatal TB
Culture of tracheal aspirate, gastric washings, urine, and cerebrospinal fluid (CSF)
Sometimes skin testing
All neonates with suspected congenital tuberculosis and infants born to mothers who have active TB should have a chest x-ray and culture of tracheal aspirates, gastric washings, and urine for acid-fast bacilli; a lumbar puncture should be done to measure cell counts, glucose, and protein as well as to obtain CSF for culture. The placenta should be examined and cultured as well. Skin testing is not extremely sensitive, particularly initially, but should be done. TB-specific interferon-gamma release assays, which are useful in adults, are not approved for use in infants because of low sensitivity. Biopsy of the liver, lymph nodes, lungs, or pleurae may be needed to confirm the diagnosis. HIV testing of the infant Diagnosis Human immunodeficiency virus (HIV) infection is caused by the retrovirus HIV-1 (and less commonly by the related retrovirus HIV-2). Infection leads to progressive immunologic deterioration and... read more should be done.
Well-appearing neonates whose mothers have a positive skin test but a negative chest x-ray and no evidence of active disease should have close follow-up, and all household members should be evaluated. If there is no exposure to a case of active TB, the neonate does not need treatment or testing. If significant exposure to a case of active TB is found in the neonate’s environment after birth, the neonate should be evaluated for suspected TB as described previously.
Pearls & Pitfalls
Treatment of Perinatal TB
Isoniazid (INH) for positive skin test or high-risk exposure
Addition of other drugs (eg, rifampin, ethambutol, ethionamide, pyrazinamide, an aminoglycoside) if TB is present
Management depends on the whether there is active TB disease or only a positive skin test (in mother, infant, or both) indicating infection without disease.
Pregnant women with a positive tuberculin test
Women are evaluated for active TB. If active disease is excluded, INH use may be deferred until after the postpartum period because the hepatotoxicity of 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. However, if the woman has had recent contact with a person with contagious TB (in which case the benefit outweighs the risk), treatment is given for 9 months, along with supplemental pyridoxine. Treatment for a pregnant woman exposed to contagious TB should be deferred until the 1st trimester is complete.
Neonates with a positive tuberculin test
If there is no clinical, laboratory, or x-ray evidence of disease, neonates should receive INH 10 to 15 mg/kg orally once a day for 9 months and should be closely monitored. Exclusively breastfed neonates should receive pyridoxine 1 to 2 mg/kg orally once a day.
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 oral treatment regimen in the US includes INH 300 mg, ethambutol 15 to 25 mg/kg (maximum 2.5 g), and rifampin 600 mg. All pregnant and breastfeeding women receiving INH should also receive pyridoxine 25 to 30 mg orally. All these drugs can be given once daily. The recommended duration of therapy is at least 9 months; if the organism is drug-resistant, an infectious disease consultation is recommended, and therapy may need to be extended to 18 months.
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.
Patients with active TB should be reported to the local health department. Mothers with active TB should be tested for HIV.
Asymptomatic neonates whose mother or close contacts have active TB
The neonate is evaluated for congenital TB as above and is usually separated from the mother only until effective treatment of both mother and neonate is under way. If congenital TB is excluded and once the neonate is receiving INH, separation is no longer necessary unless the mother (or a household contact) has possible multidrug-resistant organisms or poorly adheres to treatment (including not wearing a mask if TB is active) and directly observed therapy is not possible. Family contacts should be investigated for undiagnosed TB before the infant goes home.
If adherence can be reasonably assured and the family is nontuberculous (ie, the mother is being treated and no other transmission risks are present), the neonate is started on a regimen of INH 10 to 15 mg/kg orally once a day and sent home at the usual time. Exclusively breastfed infants should receive pyridoxine 1 to 2 mg/kg orally once a day.
Skin testing should be done at age 3 or 4 months. If the neonate is tuberculin-negative and the initial infectious contact has adhered to treatment and has a positive response, INH is stopped. If the skin test is positive, chest x-ray and cultures for acid-fast bacilli are done as described previously and, if active disease is excluded, treatment with INH is continued for a total of 9 months. If cultures become positive for TB at any time, the neonate should be treated for active TB disease.
If adherence in a nontuberculous environment cannot be ensured, BCG vaccine may be considered for the neonate, 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 TB but offers significant protection against serious and widespread invasion (eg, tuberculous meningitis). BCG should only be given if skin and HIV test results of the neonate are negative. Neonates should be monitored for development of TB, particularly during the first year.
(CAUTION: BCG vaccine is contraindicated in immunosuppressed patients and those suspected of being infected with HIV. However, in high-risk populations, the World Health Organization [unlike the American Academy of Pediatrics] recommends that asymptomatic HIV-infected neonates receive BCG vaccine at birth or shortly thereafter.)
Neonates with active TB
For congenital TB, the American Academy of Pediatrics recommends treatment once/day with INH 10 to 15 mg/kg orally, rifampin 10 to 20 mg/kg orally, pyrazinamide 30 to 40 mg/kg orally, and an aminoglycoside (eg, amikacin—see table Recommended Dosages of Select Aminoglycosides for Neonates Recommended Dosages of Select Aminoglycosides for Neonates ). This regimen should be modified as indicated based on results of testing for resistance. Pyridoxine is given if the neonate is exclusively breastfed. Ethambutol is usually avoided because it causes ocular toxicity, which is impossible to assess in neonates.
For TB acquired after birth, the suggested oral regimen is treatment once a day with INH 10 to 15 mg/kg, rifampin 10 to 20 mg/kg, and pyrazinamide 30 to 40 mg/kg. A fourth drug such as ethambutol 20 to 25 mg/kg orally once a day, ethionamide 7.5 to 10 mg/kg orally 2 times a day (or 5 to 6.67 mg/kg orally 3 times a day), or an aminoglycoside should be added if drug resistance or tuberculous meningitis is suspected or the child lives in an area where HIV prevalence among TB patients is ≥ 5%. After the first 2 months of treatment, INH and rifampin are continued to complete a 6- to 12-month course (depending on disease category) and other drugs are stopped. Breastfed infants should also receive pyridoxine.
When the central nervous system (CNS) is involved, initial therapy also includes corticosteroids (prednisone 2 mg/kg orally once/day [maximum 60 mg/day] for 4 to 6 weeks, then gradually tapered). Other therapy continues until all signs of meningitis have disappeared and cultures are negative on 2 successive lumbar punctures at least 1 week apart. Therapy can then be continued with INH and rifampin once a day or twice a week for another 10 months. Corticosteroids may also be considered for infants and children with severe miliary disease, pleural or pericardial effusions, or endobronchial disease or those with abdominal TB.
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-month (total) course of therapy. Organisms recovered from the child 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 is used whenever possible to improve adherence and the success of therapy. Many anti-TB drugs are not available in pediatric dosages. When possible, experienced personnel should give these drugs to children.
Prevention of Perinatal TB
Universal neonatal BCG vaccination is not routinely indicated in developed countries but may curb the incidence of childhood TB or decrease its severity in populations at increased risk of infection.
Tuberculosis (TB) may be acquired transplacentally, through aspiration of infected amniotic fluid, or by respiratory transmission after birth.
Manifestations of neonatal TB are nonspecific, but multiple organs (including lungs, liver, and/or central nervous system) are usually involved.
Do chest x-ray and TB culture of tracheal aspirate, gastric washings, urine, and cerebrospinal fluid.
Give isoniazid (INH) for positive skin test or high-risk exposure.
Add other drugs (eg, rifampin, ethambutol, pyrazinamide, ethionamide, an aminoglycoside) for active TB.