Tuberculosis in Pregnancy

Author: Dr. Humairalatif

Last updated: August 2025

Introduction

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading infectious cause of maternal and perinatal morbidity and mortality globally. Pregnancy induces complex immunological shifts, affecting susceptibility to TB, its progression, diagnosis, treatment, and outcomes for both mother and child. This comprehensive article explores the epidemiology, pathophysiology, clinical presentation, diagnostic strategies, management protocols, safety of anti-tubercular therapy (ATT), effects on pregnancy outcomes, prevention, and public health implications of TB in pregnancy.

1. Epidemiology of Tuberculosis in Pregnancy

Globally, an estimated 10 million people developed TB in 2023; a significant proportion were women of reproductive age (15–49 years). Many of these women were pregnant at the time of infection or diagnosis. TB rates are higher in low- and middle-income countries: sub-Saharan Africa, Southeast Asia, parts of Eastern Europe, and South America bear the greatest burden.

Pregnant women living with HIV face additional risk. Coinfection accelerates disease progression and increases maternal and neonatal complications. High-resolution data remains limited, but mortality risk is notably elevated when TB is undiagnosed or untreated during pregnancy.

2. Pathophysiology and Immunology in Pregnancy

Pregnancy is a state of immunomodulation. To tolerate fetal antigens, maternal immunity shifts toward a T-helper 2 (Th2)– dominant response, with suppressed Th1-mediated cellular immunity. Since effective control of M. tuberculosis relies on Th1 responses (e.g., IFN-γ, IL-2), pregnant women experience relative immunosuppression, increasing the risk of latent TB reactivation or progression of new TB infection.

Placental pathology in maternal TB can include granulomatous inflammation, villitis, and placentitis, with risk of vertical transmission. Hematogenous spread to the fetus may occur, especially in miliary TB.

3. Clinical Presentation

Symptoms of TB in pregnancy overlap with common pregnancy complaints, delaying diagnosis. Key clinical features include:

• Persistent cough (≥2–3 weeks), sometimes with hemoptysis
• Fever, often low-grade and evening-predominant
• Night sweats
• Unintentional weight loss or failure to gain adequately
• Fatigue, malaise, anorexia
• Chest pain or dyspnea in advanced or pleural cases

Extrapulmonary TB (EPTB) may present with lymphadenopathy, tubercular meningitis (headache, altered mental state), skeletal TB (back pain), abdominal discomfort, or genitourinary involvement.

Because routine antenatal care often overlooks TB symptoms, a high index of suspicion is required in endemic areas or among high-risk groups (HIV-positive women, malnourished women, close contact with TB cases).

4. Diagnosis

4.1 Clinical Assessment

Start with a thorough history: TB symptoms, past TB exposure or treatment, HIV status, nutritional status, and socioeconomic determinants. Perform a comprehensive physical exam, including respiratory, lymphatic, and neurological evaluation if indicated.

4.2 Radiographic Evaluation

While chest X-ray (CXR) is safe in pregnancy when using abdominal shielding, clinicians often hesitate. However, CXR remains a cornerstone for diagnosing pulmonary TB. If the initial CXR is inconclusive, consider an ultrasound for pleural effusion or an obstetric ultrasound to assess fetal well-being.

4.3 Microbiologic Tests

• Sputum smear microscopy: Detects acid-fast bacilli (AFB); low sensitivity in pregnancy due to paucibacillary disease.
• Culture: Gold standard with high sensitivity, but slower turnaround (weeks).
• Nucleic acid amplification tests (NAATs)/Xpert MTB/RIF Ultra: Rapid detection of TB and rifampicin resistance; preferred as first-line diagnostic in high-burden settings when available.

4.4 Latent TB Infection (LTBI)

Screen with a tuberculin skin test (TST) or interferon-gamma release assay (IGRA). Both are safe in pregnancy. If LTBI is diagnosed, weighing the risk-benefit of preventive therapy is critical, especially in HIV-positive women or those recently exposed.

4.5 Extrapulmonary TB Diagnosis

Often requires imaging (e.g., ultrasound, MRI without contrast) and, when feasible, biopsy or culture of extrapulmonary tissue. Balancing diagnostic yield with maternal–fetal safety is essential.

5. Treatment and Management

5.1 General Principles

Treat all forms of active TB in pregnancy. The benefits of prompt, effective therapy outweigh concerns about fetal exposure. Unrecognized or untreated maternal TB poses a far greater risk to both mother and child than most anti-TB drugs.

5.2 Standard Regimen for Drug-Susceptible TB

The standard therapy involves a two-phase approach:

Phase	Duration	Drugs (Dosage)*
Intensive	2 months	Isoniazid (INH) + Rifampicin (RIF) + Ethambutol (EMB) ± Pyrazinamide (PZA)**
Continuation	4 months	Isoniazid + Rifampicin

• Many international guidelines include Pyrazinamide (PZA) as part of TB treatment during pregnancy. Current evidence supports its safety, and the World Health Organization (WHO) endorses its use. However, some countries choose to omit PZA due to limited safety data and national policy preferences.

  Isoniazid should be administered daily in conjunction with pyridoxine (vitamin B6, 25–50 mg daily) to minimize the risk of peripheral neuropathy.
• Ensure careful dosing based on maternal weight, especially in later trimesters when pharmacokinetics change.

5.3 Drug-Resistant TB

For rifampicin-resistant (RR) or multidrug-resistant (MDR) TB, expert consultation is essential. Some newer drugs (e.g., bedaquiline, delamanid, linezolid, fluoroquinolones) can be used, but data in pregnancy are limited. The risk of untreated MDR-TB generally outweighs potential drug teratogenicity. Close maternal-fetal surveillance is critical.

5.4 HIV-Coinfection Management

Initiate or continue antiretroviral therapy (ART) per HIV-pregnancy guidelines. Monitor for drug–drug interactions between rifampicin and certain ART agents. Adjust regimens accordingly.

5.5 Follow-Up and Adherence Support

• Monthly clinical evaluation: monitor symptoms, weight gain, side effects.
• Sputum smear or NAAT monitoring at 2 months and end of treatment (for pulmonary TB).
• Adherence support: counseling, DOT (directly observed therapy) when feasible.
• Nutrition: Ensure adequate maternal nutrition and micronutrients.

6. Safety of Anti-Tubercular Drugs in Pregnancy

Extensive observational data indicate that first-line TB drugs (INH, RIF, EMB, PZA) are generally safe:

• Isoniazid: Not teratogenic; risk of hepatotoxicity—monitor liver enzymes, particularly postpartum.
• Rifampicin: Not teratogenic; rare reports of neonatal hemorrhage, preventable with vitamin K at birth.
• Ethambutol: Not teratogenic; optic neuritis is rare and dose-dependent.
• Pyrazinamide: Data are reassuring; widely used per WHO pregnant TB treatment guidelines.

Second-line agents carry more unknowns. Use only under expert guidance, and when benefits justify risk.

7. Impact on Pregnancy Outcomes

Untreated maternal TB is associated with adverse pregnancy outcomes, including:

• Spontaneous abortion and miscarriage
• Preterm birth and low birth weight
• Intrauterine growth restriction (IUGR)
• Perinatal mortality and stillbirth
• Higher risk of maternal morbidity (e.g., obstetric complications)
• Congenital TB (rare but devastating) and neonatal TB

Timely diagnosis and treatment significantly mitigate these risks. Neonatal outcomes improve with maternal therapy and vigilant newborn care (INH prophylaxis, early screening).

8. Prevention Strategies

8.1 Screening and Prophylaxis

Assess all pregnant women in TB endemic areas or those with known exposure for symptoms and risk factors. Screen for LTBI and, when indicated (e.g., HIV-positive or recent contact), consider prophylactic isoniazid with pyridoxine—balance timing against potential hepatotoxicity and adherence feasibility.

8.2 Infection Control

Avoid exposure to active TB cases during pregnancy. In healthcare settings, implement airborne infection control, ventilation, open windows, N95 masks for all staff, and isolation of suspected TB cases.

8.3 Maternal Education

Educate pregnant women on TB symptoms, transmission risks, and the importance of early ANC. Encourage completion of TB treatment and adherence.

9. Neonatal Care

For newborns of mothers with active pulmonary TB:

• Mother and infant should only be separated if the mother is infectious. Separation should continue until she becomes smear-negative or has received adequate therapy, typically around two weeks. Breastfeeding is considered safe if the mother is undergoing treatment and is no longer infectious. Mask use is recommended until she is confirmed smear-negative.

  Administer isoniazid prophylaxis (5 mg/kg daily) to the neonate for at least 6 months; perform TST and CXR at the end of prophylaxis.
• If the newborn develops symptoms or TB is confirmed, initiate full ATT with pediatric dosing per guidelines.

10. Public Health and Policy Considerations

To reduce the burden of TB in pregnancy, integrated approaches are essential:

• Embed TB screening into routine antenatal services, especially in high-burden regions.
• Ensure availability and affordability of rapid diagnostics (e.g., Xpert MTB/RIF), radiography, and ATT.
• Train healthcare workers in TB-pregnancy management and safe imaging use.
• Strengthen surveillance systems to capture TB in pregnant women and associated outcomes.
• Support research on optimal use of second-line TB drugs in pregnancy and long-term outcomes.

11. Special Situations

11.1 TB Meningitis in Pregnancy

A medical emergency—urgently evaluate with neuroimaging (MRI preferred) and cerebrospinal fluid analysis. Begin intensive-phase ATT plus adjunctive corticosteroids (e.g., dexamethasone) per standard protocols. Manage seizures and intracranial pressure; collaborate with neurology and obstetrics.

11.2 Miliary TB

This disseminated form often presents with fever, respiratory distress, hepatosplenomegaly, and failure to thrive. Hospitalize for intensive-phase ATT, supportive care (oxygen, fluids), and close fetal monitoring.

12. Case Study (Illustrative)

This section presents a fictional but realistic scenario for learning purposes.

Case: A 28-year-old G2P1 at 24 weeks’ gestation, from a high TB-prevalence area, presents with a 3-week history of productive cough, low-grade fever, night sweats, and 3 kg weight loss despite ANC attendance.

Assessment: HIV-negative, TST positive; chest X-ray (with shielding) reveals right upper lobe infiltrates; sputum NAAT detects M. tuberculosis sensitive to rifampicin.

Management Plan:

• Start standard ATT: INH, RIF, EMB, PZA plus pyridoxine.
• Monthly maternal monitoring (symptoms, liver enzymes, fundal growth); obstetric scans for fetal growth.
• At delivery, ensure neonatal INH prophylaxis and TST/CXR follow-up.

Outcome: The patient delivers at term a healthy 2.8 kg infant. The neonate completes 6 months of prophylaxis and remains TB-free during follow-up.

13. Summary Table

Aspect	Key Point
Epidemiology	High burden in reproductive-age women—sub-Saharan Africa, South Asia.
Immunology	Pregnancy skewed toward Th2 response; increases TB susceptibility.
Diagnosis	Symptom overlap with pregnancy; use CXR, NAAT, sputum culture, and LTBI screening.
Treatment	First-line ATT safe; MDR-TB needs specialist care; HIV coinfection requires ART adjustment.
Drug Safety	INH, RIF, EMB, and PZA is generally safe; monitor maternal hepatotoxicity and vitamin K/RIF interactions.
Pregnancy Outcomes	Untreated TB: miscarriage, PTB, LBW, perinatal death; treatment improves outcomes.
Neonatal Care	INH prophylaxis, safe breastfeeding, separation only if highly infectious.

14. Future Directions and Research Needs

Key areas for future focus include:

• High-quality data on pharmacokinetics and safety of second-line and novel TB drugs in pregnancy.
• Long-term developmental follow-up of children with in utero exposure to ATT.
• Operational research on implementing integrated TB–maternal health models.
• Vaccination development—effective, safe TB vaccines for women of reproductive age and pregnant persons.

Conclusion

Tuberculosis during pregnancy presents serious risks to both mother and child—but with timely and appropriate interventions, it is highly treatable. The safe use of first-line anti-tuberculosis therapy (ATT), combined with vigilant antenatal care, accurate diagnosis, and neonatal protection strategies, can significantly improve maternal and neonatal outcomes.

Addressing this persistent global health challenge requires a multi sectoral approach—from grassroots public health initiatives to cutting-edge research. Collaboration across healthcare systems, policy frameworks, and community engagement is essential to reduce TB-related morbidity and mortality in pregnancy.

FOR MORE ARTICLES ABOUT COMPLICATIONS DURING PREGNANCY, click the links given below.

https://dryasirhumaira342.blogspot.com/2025/08/intrauterine-growth-retardation-iugr.html

https://dryasirhumaira342.blogspot.com/2025/07/httpsdryasirhumaira342.blogspot.com202507pregnancy-induced-hypertension-complete-guide.html

https://dryasirhumaira342.blogspot.com/2025/07/polycystic-ovary-syndrome-pcos-causes.html