- Overview of Neonatal Infections
- Neonatal Sepsis
- Neonatal Hospital-Acquired Infection
- Neonatal Pneumonia
- Neonatal Bacterial Meningitis
- Neonatal Listeriosis
- Neonatal Conjunctivitis
- Neonatal Herpes Simplex Virus (HSV) Infection
- Neonatal Hepatitis B Virus (HBV) Infection
- Congenital and Perinatal Cytomegalovirus Infection (CMV)
- Congenital Rubella
- Congenital Syphilis
- Congenital Toxoplasmosis
- Perinatal Tuberculosis (TB)
Tuberculosis can be acquired during the perinatal period. Symptoms and signs are nonspecific. Diagnosis is by culture and sometimes radiograph and biopsy. Treatment is with isoniazid and other antituberculous medications.Tuberculosis can be acquired during the perinatal period. Symptoms and signs are nonspecific. Diagnosis is by culture and sometimes radiograph and biopsy. Treatment is with isoniazid and other antituberculous medications.
(See also Tuberculosis in adults and Overview of Neonatal Infections.)
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)
Children younger than 5 years of age are at increased risk of developing active TB after exposure, particularly if chemotherapy is not given.
If TB infection is confirmed in mothers or neonates, local public health experts should be notified to assist with contact tracing and isolation recommendations.
Symptoms and Signs of Perinatal TB
The clinical presentation of neonatal tuberculosis is nonspecific but is usually marked by multiple organ involvement and can manifest as neonatal sepsis.
The neonate may look acutely or chronically ill and may have fever, lethargy, respiratory distress or non-responsive pneumonia, hepatosplenomegaly, or growth and weight faltering (formerly failure to thrive).
Diagnosis of Perinatal TB
Culture and nucleic acid amplification testing (NAAT) testing of tracheal aspirate, gastric washings, urine, and cerebrospinal fluid (CSF)
Chest radiograph
Sometimes skin testing or biopsy
All neonates with suspected congenital tuberculosis and infants born to mothers who have active TB should have a chest radiograph and culture and nucleic acid amplification testing (NAAT), when available, of tracheal aspirates, gastric washings, and urine for acid-fast bacilli; a lumbar puncture should be performed to measure cell counts, glucose, and protein as well as to obtain CSF for culture and NAAT. The placenta should be examined and cultured as well.
Skin testing is not extremely sensitive, particularly initially, but should be performed.
Biopsy of the liver, lymph nodes, lungs, or pleurae may be needed to confirm the diagnosis in infants suspected of having active TB.
Stool can also be tested with NAAT if processed according to World Health Organization (WHO) guidelines (1).
HIV testing of the infant should be performed.
TB-specific interferon-gamma release assays, which are useful in adults, are not approved for use in infants because of low sensitivity.
Well-appearing neonates whose mothers have a positive skin test but a negative chest radiograph 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
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Diagnosis reference
1. World Health Organization (WHO): Practical manual of processing stool samples for diagnosis of childhood TB. 2022. Accessed January 13, 2025.
Treatment of Perinatal TB
Isoniazid (INH) for positive skin test or high-risk exposureIsoniazid (INH) for positive skin test or high-risk exposure
Addition of other medications (eg, rifampin, ethambutol, ethionamide, pyrazinamide, an aminoglycoside) if TB is presentAddition of other medications (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 patients with a positive tuberculin test
For pregnant patients, if active disease is excluded, treatment may be deferred until 2 to 3 months postpartum because the hepatotoxicity of INH is increased in pregnancy (1). However, if the pregnant patient is at high risk of progression to active infection or has had recent contact with a person with contagious TB (in which case the benefit outweighs the risk), treatment is given without delay. Treatment duration varies from 3 to 9 months depending on the regimen used. Pregnant and breastfeeding people receiving INH should also receive pyridoxine.). However, if the pregnant patient is at high risk of progression to active infection or has had recent contact with a person with contagious TB (in which case the benefit outweighs the risk), treatment is given without delay. Treatment duration varies from 3 to 9 months depending on the regimen used. Pregnant and breastfeeding people receiving INH should also receive pyridoxine.
Pregnant patients with active TB
The recommended oral treatment regimen in the United States includes INH, ethambutol, and rifampin for 9 months (The recommended oral treatment regimen in the United States includes INH, ethambutol, and rifampin for 9 months (1). All pregnant and breastfeeding patients receiving INH should also receive pyridoxine. If the organism is drug-resistant, an infectious disease consultation should be obtained, and therapy may need to be extended to 18 months. ). All pregnant and breastfeeding patients receiving INH should also receive pyridoxine. If the organism is drug-resistant, an infectious disease consultation should be obtained, and therapy may need to be extended to 18 months.
INH, ethambutol, and rifampin use in recommended doses during pregnancy has not been shown to be teratogenic to the human fetus (2). Streptomycin is potentially ototoxic to the developing fetus and should not be used early in pregnancy. If possible, other antituberculous medications should be avoided because of teratogenicity (eg, ethionamide) or lack of clinical experience (eg, pyrazinamide) during pregnancy.
Breastfeeding is not contraindicated for patients receiving treatment for TB who are not infective.
Patients with active TB should be reported to the local health department. Pregnant patients with active TB should be tested for HIV.
Neonates with a positive tuberculin test
If there is no clinical, laboratory, or radiographic evidence of active disease, neonates should receive INH for preferably 9 months and should be closely monitored. Exclusively breastfed neonates should receive pyridoxine. Therapy should be modified if resistant TB is suspected. If there is no clinical, laboratory, or radiographic evidence of active disease, neonates should receive INH for preferably 9 months and should be closely monitored. Exclusively breastfed neonates should receive pyridoxine. Therapy should be modified if resistant TB is suspected.
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 not infectious (ie, the mother is being treated and no other transmission risks are present), the neonate is started on a regimen of INH or rifampin and sent home at the usual time. Exclusively breastfed infants should receive pyridoxine if given INH. If adherence can be reasonably assured and the family is not infectious (ie, the mother is being treated and no other transmission risks are present), the neonate is started on a regimen of INH or rifampin and sent home at the usual time. Exclusively breastfed infants should receive pyridoxine if given INH.
Skin testing should be performed at age 3 or 4 months. If the skin test is negative and the initial infectious contact has adhered to treatment and has a positive response, INH or rifampin is stopped. If the skin test is positive, chest radiograph and cultures for acid-fast bacilli are performed as described previously. If active disease is excluded, treatment with INH is continued for a total of 9 months or with rifampin for a total of 4 months. If cultures become positive for TB at any time, the neonate should be treated for active TB disease. is stopped. If the skin test is positive, chest radiograph and cultures for acid-fast bacilli are performed as described previously. If active disease is excluded, treatment with INH is continued for a total of 9 months or with rifampin for a total of 4 months. If cultures become positive for TB at any time, the neonate should be treated for active TB disease.
Neonates with active TB
The prognosis for infants with congenital TB is poor. Treatment includes INH, rifampin, pyrazinamide, and ethambutol. This regimen should be modified as indicated based on results of testing for resistance.The prognosis for infants with congenital TB is poor. Treatment includes INH, rifampin, pyrazinamide, and ethambutol. This regimen should be modified as indicated based on results of testing for resistance.
For TB acquired after birth, the suggested oral regimen is treatment once a day with INH, rifampin, pyrazinamide, and ethambutol. If meningitis or drug resistance is suspected, treatment should include alternative agents. When the central nervous system (CNS) is involved, initial therapy also includes corticosteroids. Corticosteroids may also be considered for infants and children with severe miliary disease, pleural or pericardial effusions, endobronchial disease, or abdominal TB.For TB acquired after birth, the suggested oral regimen is treatment once a day with INH, rifampin, pyrazinamide, and ethambutol. If meningitis or drug resistance is suspected, treatment should include alternative agents. When the central nervous system (CNS) is involved, initial therapy also includes corticosteroids. Corticosteroids may also be considered for infants and children with severe miliary disease, pleural or pericardial effusions, endobronchial disease, or 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 medications are not available in pediatric dosages. When possible, experienced personnel should give these medications to children.
Treatment references
1. Centers for Disease Control and Prevention (CDC): Treatment for TB During Pregnancy. Accessed January 13, 2025.
Prevention of Perinatal TB
BCG vaccination is recommended by the World Health Organization for neonates in areas with high rates of tuberculosis and leprosy and in others at high risk of exposure (1).
Prevention reference
1. World Health Organization. BCG vaccine: WHO position paper, February 2018 - Recommendations. Vaccine. 2018;36(24):3408-3410. doi:10.1016/j.vaccine.2018.03.009
Key Points
Tuberculosis (TB) may be acquired transplacentally, through aspiration of infected amniotic fluid, or by respiratory transmission after birth.
Clinical manifestations of neonatal TB are nonspecific, but multiple organs (including lungs, liver, and/or central nervous system) are usually involved.
Do chest radiograph and TB culture of tracheal aspirate, gastric washings, urine, and cerebrospinal fluid.
Give isoniazid (INH) for positive skin test or high-risk exposure.Give isoniazid (INH) for positive skin test or high-risk exposure.
Add other medications (eg, rifampin, ethambutol, pyrazinamide, ethionamide, an aminoglycoside) for active TB.Add other medications (eg, rifampin, ethambutol, pyrazinamide, ethionamide, an aminoglycoside) for active TB.
