Congenital Tuberculosis

Introduction

Congenital tuberculosis (TB) is a rare but severe form of tuberculosis acquired by the fetus during intrauterine life. While tuberculosis in pregnant women is not uncommon, true congenital transmission is relatively rare. However, with the resurgence of TB and the HIV pandemic, the incidence has potential to rise. The term "Perinatal Tuberculosis" is often preferred as it encompasses both true congenital cases (acquired in utero) and neonatal forms acquired during delivery or immediately postpartum. The distinction is primarily epidemiological, as the clinical presentation and management are largely similar. Congenital TB has a high mortality rate if untreated, often due to delayed diagnosis because its symptoms mimic common neonatal conditions like sepsis and TORCH infections.

Pathogenesis and Transmission

Unlike postnatal TB, which is almost exclusively airborne, congenital TB has unique routes of transmission. The fetus can be infected via two main mechanisms:

1. Hematogenous Transmission (Transplacental)

• Mechanism: This occurs when the mother has a primary infection or disseminated disease (miliary/meningeal) resulting in bacillemia. Tubercle bacilli infect the placenta (placentitis) and spread to the fetus through the umbilical vein.
• Primary Complex: Since the oxygenated blood from the umbilical vein first passes through the fetal liver, the primary focus (Ghon complex) is typically formed in the liver or the periportal lymph nodes.
• Dissemination: From the liver, bacilli enter the fetal circulation and disseminate to other organs, including the lungs, spleen, and bone marrow.

2. Aspiration or Ingestion (Infected Amniotic Fluid)

• Mechanism: This occurs if the mother has tuberculous endometritis or if a placental caseous lesion ruptures into the amniotic cavity. The fetus may aspirate infected amniotic fluid in utero or during the birth process.
• Primary Complex: In this scenario, the primary focus develops in the lungs (due to aspiration) or the gastrointestinal tract (due to ingestion).

3. Intrapartum/Postpartum Transmission (Neonatal TB)

• Intrapartum: Direct contact with infected genital secretions or abrasions during delivery.
• Postpartum: Inhalation of airborne droplet nuclei from an infectious mother or close contact (household relative) shortly after birth. This is technically "neonatal" rather than "congenital" TB, but clinically they overlap.

Clinical Manifestations

The clinical presentation of congenital TB is protean and nonspecific, often leading to a diagnosis of "sepsis syndrome" or "failure to thrive."

1. Maternal History

• A history of maternal TB is the most significant risk factor. However, the mother is often asymptomatic or has nonspecific symptoms like fever of unknown origin (FUO) or failure to gain weight during pregnancy.
• Maternal history of infertility (genital TB) or recent HIV infection increases risk.

2. Neonatal Presentation

Symptoms usually appear by the 2nd to 3rd week of life, although they can be present at birth.

• Systemic: Prematurity, intrauterine growth restriction (IUGR), low birth weight, and temperature instability are common.
• Respiratory: Respiratory distress, tachypnea, and cyanosis. Symptoms may mimic severe bacterial pneumonia or hyaline membrane disease.
• Abdominal: Hepatomegaly (often disproportionate to splenomegaly) is a hallmark sign, especially in transplacental transmission. Abdominal distension and ascites may occur.
• Lymphadenopathy: Generalized lymphadenopathy or regional node enlargement.
• Dermatological: Papular or pustular skin lesions, petechiae, or purpura (due to thrombocytopenia).
• Ear: Chronic ear discharge (otorrhea) in a neonate is a classical, though rare, sign of TB.
• CNS: Meningitis occurs in 20-50% of cases, presenting with lethargy, irritability, poor feeding, or seizures.

Diagnostic Criteria

The revised Cantwell’s Criteria are commonly used to define congenital tuberculosis. A diagnosis requires the presence of a proven tuberculous lesion in the infant plus at least one of the following:

1. Lesion occurring in the first week of life.
2. A primary hepatic complex or caseating hepatic granulomas.
3. Tuberculosis infection of the placenta or the maternal genital tract.
4. Exclusion of the possibility of postnatal transmission (thorough investigation of contacts).

Diagnostic Evaluation

Diagnosis requires a high index of suspicion.

1. Microbiological Confirmation (Gold Standard)

• Gastric Aspirate (GA): This is the preferred specimen. Samples should be collected on 2 consecutive mornings (fasting) and sent for Cartridge Based Nucleic Acid Amplification Test (CBNAAT/GeneXpert) and culture (MGIT).
• Other Specimens:
  • Endotracheal Aspirate: In ventilated neonates.
  • Ear Discharge/Skin Biopsy: High yield if lesions are present.
  • Bone Marrow/Liver Biopsy: May be required in disseminated cases.
  • Placenta: Pathological examination of the placenta is vital. Histology may show granulomas, and ZN stain may show AFB.

2. Radiological Investigations

• Chest X-ray (CXR): May show miliary mottling (snowstorm appearance), persistent pneumonia, or hilar adenopathy. However, CXR can be normal initially or show nonspecific infiltrates.
• USG Abdomen: Essential to look for hepatic focal lesions, hypoechoic splenic microabscesses, retroperitoneal lymphadenopathy, or ascites.
• Neuroimaging (USG/CT/MRI): To rule out congenital TBM or hydrocephalus.

3. Immunological Tests

• Tuberculin Skin Test (TST): Usually negative (anergic) in the newborn period due to immature cellular immunity and severe disease. It may become positive after 1–3 months of treatment.
• IGRA: Not routinely recommended in neonates due to low sensitivity.

Differential Diagnosis

Congenital TB mimics other intrauterine infections collectively known as TORCH:

1. Congenital Syphilis: Hepatomegaly, rash, snuffles, periostitis (differentiated by VDRL/TPHA).
2. Cytomegalovirus (CMV): Microcephaly, periventricular calcifications, chorioretinitis (differentiated by Urine/Saliva PCR).
3. Toxoplasmosis: Intracranial calcifications, hydrocephalus (differentiated by IgM/PCR).
4. Neonatal Sepsis: Bacterial sepsis (GBS, E. coli, Listeria) presents similarly with respiratory distress and shock.
5. Biliary Atresia/Neonatal Hepatitis: If jaundice and hepatomegaly are the predominant features.

Management

The treatment of congenital TB follows the principles of pediatric TB management but requires careful attention to dosing and toxicity in the neonate.

1. Antitubercular Therapy

According to NTEP 2022 Guidelines, the regimen for drug-sensitive TB in neonates is:

• Intensive Phase (2 months): Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E).
  • Note: Streptomycin is generally avoided due to ototoxicity unless essential.
• Continuation Phase (4 months): Isoniazid (H), Rifampicin (R), and Ethambutol (E).
• Total Duration: 6 months. (Extended to 9-12 months for TBM or miliary/bone TB).

Dosages (Daily):

• Isoniazid: 10 mg/kg (7–15)
• Rifampicin: 15 mg/kg (10–20)
• Pyrazinamide: 35 mg/kg (30–40)
• Ethambutol: 20 mg/kg (15–25).

2. Adjunct Therapy

• Pyridoxine: Recommended for all neonates on Isoniazid to prevent neuropathy and seizures.
• Corticosteroids: Prednisolone (1–2 mg/kg) is indicated for TB meningitis, severe miliary TB with alveolocapillary block, or pericardial effusion.

Management of Neonate Born to Mother with Active TB

This is a common clinical scenario. Management depends on assessing the infant for active disease.

Algorithm (NTEP 2022 / IAP)

Step 1: Evaluation

• Do not separate the baby from the mother. Encourage breastfeeding (mother should use a mask/cough etiquette).
• Assess the newborn for symptoms (fever, poor feeding, respiratory distress).
• Perform Chest X-ray and USG abdomen if symptomatic.

Step 2: Decision Making

• Scenario A: Active TB in Infant (Congenital TB):
  • If investigations (Gastric aspirate/CXR/USG) confirm TB: Start Full Treatment (2HRZE + 4HRE).
• Scenario B: No Active Disease in Infant (Exposure):
  • TB Preventive Therapy (TPT): Start Isoniazid (10 mg/kg) daily for 6 months.
  • BCG Vaccination: Give BCG at birth. It does not interfere with INH, and INH does not kill the BCG strain (as BCG is usually resistant to primary INH levels or simply effective regardless).
  • Follow-up: Monitor the infant monthly for symptoms. If the infant remains asymptomatic for 6 months, stop INH. If symptoms develop, re-evaluate for active TB.

Step 3: Maternal Management

• Treat the mother effectively.
• Separation is only required if the mother has MDR-TB, is non-adherent to therapy, or is too ill to care for the baby.
• If the mother has MDR-TB, the infant should not receive standard TPT (efficacy of fluoroquinolone prophylaxis in neonates is not established). Careful infection control and close monitoring are required.

Prognosis

• Mortality: Historically up to 50% without treatment. With early diagnosis and therapy, the prognosis is good.
• Morbidity: Neurological sequelae (developmental delay, hydrocephalus) are common if TBM is present. Liver damage from primary hepatic TB generally resolves with therapy.