Introduction to Congenital (Neonatal) Tuberculosis

Congenital tuberculosis (TB) is a rare but severe form of tuberculosis that affects newborns. It occurs when Mycobacterium tuberculosis is transmitted from an infected mother to her fetus in utero or during delivery. This condition is distinct from postnatal TB acquired through airborne transmission after birth. Congenital TB presents significant diagnostic and therapeutic challenges due to its nonspecific clinical presentation and the difficulty in confirming the diagnosis in neonates.

Etiology of Congenital Tuberculosis

Congenital tuberculosis is caused by Mycobacterium tuberculosis, the same bacterium responsible for pulmonary and extrapulmonary TB in adults and children. The infection can be transmitted to the fetus or newborn through two main routes:

1. Hematogenous spread: M. tuberculosis crosses the placenta and infects the fetus via the umbilical vein.
2. Direct contact: The newborn inhales or ingests infected amniotic fluid or maternal blood during delivery.

Risk factors for congenital TB include:

• Maternal TB infection, especially if untreated or recently diagnosed
• HIV co-infection in the mother
• Extrapulmonary TB in the mother, particularly genital or disseminated TB
• Late or inadequate maternal TB treatment

Epidemiology of Congenital Tuberculosis

Congenital tuberculosis is a rare condition, with its true incidence difficult to determine due to diagnostic challenges and underreporting. However, some key epidemiological points include:

• Global incidence: Estimated at less than 300 cases reported in the literature worldwide
• Geographic distribution: More common in areas with high TB prevalence, such as parts of Africa and Asia
• Maternal TB: Occurs in approximately 1-2% of infants born to mothers with active TB
• HIV co-infection: Increased risk in areas with high HIV prevalence due to the synergistic relationship between HIV and TB

The rarity of congenital TB can be attributed to several factors:

• The placenta acts as a barrier to M. tuberculosis
• The lack of oxygen in the fetal environment may inhibit bacterial growth
• Improved TB control programs in many countries
• Difficulties in diagnosis leading to potential underreporting

Pathophysiology of Congenital Tuberculosis

The pathophysiology of congenital tuberculosis involves several stages:

1. Maternal infection: Active TB in the mother, often involving the lungs or genital tract
2. Placental involvement: M. tuberculosis infects the placenta, forming tubercles
3. Fetal transmission: Bacteria enter the fetal circulation through the umbilical vein
4. Primary complex formation: Development of a primary focus in the fetal liver, with spread to regional lymph nodes
5. Dissemination: Hematogenous spread to other fetal organs, including lungs, spleen, and brain

Key pathophysiological features:

• The liver is often the primary site of infection due to the flow of blood from the umbilical vein
• Unlike adult TB, congenital TB often presents as a disseminated disease
• The immature neonatal immune system may contribute to rapid disease progression
• Lack of granuloma formation in early stages due to immature cellular immunity

Clinical Presentation of Congenital Tuberculosis

The clinical presentation of congenital tuberculosis can be nonspecific and may mimic other neonatal infections. Symptoms typically appear within the first few weeks of life, often by 2-3 weeks of age.

Common clinical features include:

• Respiratory distress
• Fever
• Poor feeding and failure to thrive
• Hepatosplenomegaly
• Lymphadenopathy
• Abdominal distension
• Lethargy or irritability

Less common manifestations:

• Skin lesions (e.g., papules, pustules, or abscesses)
• Jaundice
• Ear discharge
• Meningitis
• Seizures

The clinical presentation can vary depending on the route of transmission and the organs involved. The nonspecific nature of symptoms often leads to delays in diagnosis, highlighting the importance of maintaining a high index of suspicion in at-risk neonates.

Diagnosis of Congenital Tuberculosis

Diagnosing congenital tuberculosis can be challenging due to nonspecific symptoms and limitations of diagnostic tests in neonates. A comprehensive approach is necessary:

Diagnostic criteria (Cantwell criteria, revised):

• Proven tuberculous lesions in the infant
• At least one of the following:
  • Symptoms occurring in the first week of life
  • Primary hepatic complex or caseating hepatic granulomas
  • Tuberculous infection of the placenta or maternal genital tract
  • Exclusion of postnatal transmission by thorough investigation of contacts

Diagnostic tests:

• Chest X-ray: May show miliary pattern or pneumonic infiltrates
• Abdominal ultrasound: To assess hepatosplenomegaly and abdominal lymphadenopathy
• Tuberculin skin test (TST): Often negative in neonates due to immature immune response
• Interferon-gamma release assays (IGRAs): Limited utility in infants <3 months
• Microbiological studies:
  • Gastric aspirates, tracheal aspirates, or bronchial lavage for acid-fast bacilli (AFB) smear and culture
  • Cerebrospinal fluid analysis if meningitis is suspected
• Nucleic acid amplification tests (e.g., Xpert MTB/RIF) on various specimens
• Histopathological examination of placenta or other tissues

A high index of suspicion and thorough maternal evaluation are crucial for timely diagnosis.

Treatment of Congenital Tuberculosis

Treatment of congenital tuberculosis follows principles similar to those for other forms of TB in children, with some considerations specific to neonates:

General principles:

• Early initiation of anti-tuberculous therapy is crucial
• Treatment should be supervised and directly observed when possible
• Multidrug regimens are used to prevent drug resistance

Standard treatment regimen:

• Intensive phase (2 months):
  • Isoniazid (INH): 10-15 mg/kg/day
  • Rifampicin (RIF): 15-20 mg/kg/day
  • Pyrazinamide (PZA): 30-40 mg/kg/day
  • Ethambutol (EMB) or Streptomycin: 15-25 mg/kg/day (EMB) or 20-30 mg/kg/day (Streptomycin)
• Continuation phase (4-10 months):
  • INH and RIF

Additional considerations:

• Total treatment duration may be extended in severe cases or CNS involvement
• Corticosteroids may be considered in cases of meningitis or severe disease
• Pyridoxine (Vitamin B6) supplementation is recommended for breastfed infants of mothers taking INH
• Close monitoring for drug toxicity and treatment response is essential

Supportive care:

• Nutritional support
• Management of complications (e.g., respiratory support, treatment of co-infections)
• Developmental follow-up

Prevention of Congenital Tuberculosis

Prevention of congenital tuberculosis primarily focuses on identifying and treating TB in pregnant women:

Strategies for prevention:

• Antenatal screening: Routine screening for TB in pregnant women, especially in high-risk populations
• Early diagnosis and treatment of maternal TB:
  • Prompt initiation of anti-tuberculous therapy in pregnant women with active TB
  • Use of TB drugs considered safe in pregnancy (e.g., INH, RIF, EMB)
• BCG vaccination: Not recommended for prevention of congenital TB, but may be given to exposed infants after excluding active disease
• Infection control measures: To prevent postnatal transmission in healthcare settings
• Chemoprophylaxis for exposed newborns:
  • INH prophylaxis for 3-6 months, followed by TST
  • If TST negative, discontinue INH; if positive, complete full treatment course

Challenges in prevention:

• Difficulty in diagnosing TB in pregnancy due to nonspecific symptoms
• Limited sensitivity of diagnostic tests in pregnancy
• Concerns about drug safety in pregnancy and during breastfeeding
• Lack of awareness about congenital TB among healthcare providers

Effective prevention requires a coordinated approach involving antenatal care, TB control programs, and neonatal services.

Prognosis of Congenital Tuberculosis

The prognosis of congenital tuberculosis has improved with advances in diagnosis and treatment, but it remains a serious condition with significant mortality and morbidity:

Factors affecting prognosis:

• Timing of diagnosis and treatment initiation
• Extent of disease at diagnosis
• Presence of complications (e.g., meningitis, respiratory failure)
• Maternal HIV status and treatment
• Drug susceptibility of the infecting M. tuberculosis strain

Outcomes:

• Mortality: Historically high (up to 50%), but has decreased with improved care
• Long-term sequelae may include:
  • Developmental delays
  • Neurological deficits (if CNS involvement)
  • Chronic lung disease
  • Growth impairment

Follow-up and monitoring:

• Regular clinical assessments during and after treatment
• Monitoring of growth and development
• Long-term follow-up for potential late complications
• Neurodevelopmental assessments

With early diagnosis and appropriate treatment, many infants with congenital TB can have favorable outcomes. However, the potential for severe disease and long-term complications underscores the importance of prevention and timely intervention.