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Tuberculosis in Pregnancy

(15 Marks — MD Examination Answer)

[Source: Sharma SK & Mohan A — Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases, 3rd Edition, Chapter 25; Creasy & Resnik's Maternal-Fetal Medicine; Fishman's Pulmonary Diseases]

1. INTRODUCTION

TB in pregnancy has been a subject of concern since the time of Hippocrates. TB in a pregnant woman can present in several ways: past history of TB, de novo diagnosis during symptoms, or incidental detection during screening. In 2011, more than 200,000 cases of active TB occurred among pregnant women globally, with the greatest burden in Africa and South-East Asia. Increasing HIV-TB co-infection adds an entirely new dimension to the natural history of disease. Atypical presentations pose diagnostic difficulties, and TB in pregnancy has important implications for both mother and child.

2. EPIDEMIOLOGY

CDC (1985): TB in pregnancy occurred at 49.6/100,000 among Asians/Pacific Islanders, 26.7/100,000 in African-Americans, 5.7/100,000 in American whites.
Margono et al: 12.4 cases/100,000 deliveries (1985–90), rising to 94.8/100,000 deliveries (1991–92) — reflecting the HIV epidemic.
London district general hospital study: 252/100,000 deliveries in high-prevalence area.
Prevalence of LTBI in pregnancy: 19–34% among HIV-negative women in India; up to 49% in HIV-seropositive women in South Africa.
Pulmonary TB is the most common form during pregnancy. EPTB (miliary, lymph node, bone, kidney TB, TB meningitis, TB mastitis, TB peritonitis, perineal TB) occurs less commonly.

3. CLINICAL PRESENTATION

About one-half to two-thirds of pregnant women with TB remain asymptomatic. Symptoms that do occur may mimic physiological changes of pregnancy, making diagnosis difficult.

Common symptoms (Good et al, Good et al series):

Cough — 74%
Fever — 30%
Malaise/fatigue — 30%
Weight loss — 14%
Haemoptysis — 19% (less common than in men)

WHO recommends screening in symptomatic women with cough of any duration, fever, or malaise. CDC additionally recommends screening in women with recent TB contact.

In high-burden countries like India, LTBI screening is not routinely done. In low-burden countries, screening is recommended only in high-risk groups: known TB contacts, injection drug users, HIV-positive persons, foreign-born individuals, or those in congregate settings.

4. EFFECT OF PREGNANCY ON TB

Historical view: Pregnancy was once believed to have a deleterious effect on TB, and therapeutic abortion was advocated.

Current view: Pregnancy neither predisposes to TB nor results in disease progression:

Hedvell's study (250 untreated pregnant women): TB improved in 9.1%, progressed in 7%, most remained stable.
de March: Pregnancy, labour, puerperium, and lactation did NOT predispose to relapse when disease was adequately treated.
Schaefer et al: 88–91% of women remained stable in both pre-chemotherapy and chemotherapy eras.

Important caveat: A small but definite risk of relapse in the post-partum period exists (Good et al — 11 of 27 relapses occurred postpartum). Prognosis is worst in women diagnosed with advanced disease in the puerperium or those with HIV co-infection.

5. EFFECT OF TB ON PREGNANCY (Obstetric Complications)

Following effective anti-TB chemotherapy, TB does not significantly adversely affect pregnancy if treated promptly. However, untreated or late-diagnosed TB carries significant risks:

Complication	Comment
Prematurity	Increased with EPTB at non-lymph node sites
Foetal growth restriction / Low birth weight	Common in EPTB (33% vs 11% controls)
Increased perinatal mortality	Especially if treatment started late in pregnancy
Spontaneous abortion	Selikoff: 7 early abortions in 616 women
Intrauterine foetal death	9-fold higher in TB study group (16–28 weeks)
Pregnancy-induced hypertension	7.4% vs 4.7% in controls
Vaginal bleeding	4.1% vs 2.2%
Low Apgar scores	19% vs 3% in EPTB at non-lymph node sites
Maternal mortality	Higher with drug-resistant TB and HIV co-infection

EPTB lymphadenitis (most common EPTB form) has no adverse effect on maternal and foetal outcomes. Other EPTB forms (intestinal, spinal, endometrial, meningeal) carry significant risks.

6. TRANSPLACENTAL TRANSMISSION AND CONGENITAL TB

Routes of transmission:

Haematogenous — Mtb reaches foetus via placenta → umbilical vein → primary complex forms in liver + portal lymph nodes; may bypass liver via ductus venosus → lungs
Aspiration of infected amniotic fluid in the perinatal period (from TB endometrium/genital tract)
Contiguous spread from endometrial TB

Key findings:

Mtb has been demonstrated in placental specimens and tissues from stillborn infants.
Subclinical endometrial infections can be an important source of transplacental transmission.
Nemir & O'Hare: Congenital TB with positive sub-umbilical lymph nodes indicating umbilical vein as route.
Over 300 cases of congenital TB reported in literature.

7. DIAGNOSIS

7a. Chest Radiograph

Routine chest X-ray during pregnancy is not recommended (Bonebrake et al).
If indicated (symptomatic or recent TB contact), should be done with abdominal shielding, preferably after first trimester.
Radiation: ~50 mrad to chest, 2.5–5 mrad to gonads — does not carry measurable risk to foetus.
Risk estimated at 0–1 case per 1,000 patients per rad in first 4 months.

7b. Tuberculin Skin Test (TST)

TST is safe in pregnancy — no risk to mother or foetus.
Pregnancy does not affect TST reactivity (Present & Comstock: 25,000 patients).
Identifies infection but not extent/activity of disease.
Becomes positive 2–10 weeks after initial exposure.

7c. IGRAs (Interferon-Gamma Release Assays)

Offer advantages over TST, but should not replace TST in low/middle-income countries.
Recent studies suggest pregnancy may impact both TST and QuantiFERON detection rates.

7d. Microbiological/Molecular Methods

ZN staining + Lowenstein-Jensen culture of sputum/body fluids = confirmatory.
Liquid culture and CBNAAT (Cartridge-Based Nucleic Amplification Test / GeneXpert) — promising for early diagnosis and drug susceptibility testing in pregnancy, but need further study.

8. TREATMENT OF ACTIVE TB IN PREGNANCY

Key principle: Untreated TB is far more hazardous to the pregnant woman and foetus than treatment side effects. Active disease in pregnancy should be immediately treated.

8a. First-Line Regimen

Standard HRZE regimen:

2 months Intensive Phase: Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E) — daily
4 months Continuation Phase: Isoniazid + Rifampicin + Ethambutol — daily
Total duration: 6 months (same as non-pregnant, no modification needed)
If PZA not included in initial regimen → minimum 9 months of treatment

8b. Individual Drug Safety Profile

Drug	Placental Crossing	Safety	Notes
Isoniazid (H)	Yes	Safe	No significant teratogenicity. Risk of hepatitis (↑ in pregnancy/postpartum). Add pyridoxine 50 mg/day to prevent neonatal seizures and maternal neurotoxicity
Rifampicin (R)	Yes	Safe	No teratogenicity (Snider et al). Essential component of regimen. Reduces OCP efficacy — alternative contraception needed
Pyrazinamide (Z)	Yes	Safe (WHO)	WHO approves use in pregnancy. Benefits outweigh risks in HIV+ve pregnant women. CDC previously did not recommend but current WHO guidelines support its use
Ethambutol (E)	Yes	Safe	Teratogenic in animals, but no ocular/developmental harm in human foetuses
Streptomycin	Yes	CONTRAINDICATED	Vestibular and auditory ototoxicity in newborn reported at all gestational ages — must not be used

8c. Second-Line Drugs

Little known about teratogenicity.
Ethionamide — teratogenic effects reported; avoid if possible.
Kanamycin & Capreomycin — theoretical ototoxicity (same class as streptomycin); avoid.
Injectable aminoglycosides and capreomycin should be avoided in pregnancy.
Most teratogenic effects occur in first trimester → if possible, delay second-line drugs until second trimester.

8d. Drug-Resistant TB (MDR-TB) in Pregnancy

Women receiving treatment for drug-resistant TB should receive counselling about risks to foetus.
Case series suggest treatment of MDR-TB in pregnancy is beneficial to both mother and child.
One study: second-line drugs associated with delivery of healthy term infants.
Treatment: combination of 3–4 drugs with demonstrated efficacy against infecting strain.
Standard second-line treatment guidelines should be followed (WHO/ATS).

9. HIV-TB CO-INFECTION IN PREGNANCY

Increasing HIV-TB co-infection presents newer management challenges.
Standard treatment guidelines should be followed.
Efavirenz-based ART with rifampicin-containing TB treatment requires dose adjustments (TSHEPISO study).
Nevirapine-based ART carries increased risk of maternal hepatotoxicity in pregnancy.
Immediate LTBI treatment is recommended for HIV-seropositive pregnant women (CDC, WHO).
Conversion to active TB in HIV-coinfected patients is significant — treat immediately to protect neonate, mother, and community.

10. TREATMENT OF LATENT TB INFECTION (LTBI) IN PREGNANCY

For HIV-seronegative pregnant women at low risk: delay LTBI treatment until 2–3 months postpartum (CDC recommendation) — due to higher risk of INH-induced hepatitis in pregnant/postpartum women.
Exception: recent known TB contact → treat immediately even in pregnancy.
For HIV-seropositive pregnant women: early treatment recommended (both CDC and WHO) despite increased hepatotoxicity risk.
A systematic review confirmed pregnant women benefit from LTBI screening; IGRAs and TST are comparable in screening during pregnancy.
High TB endemic areas (e.g., India): efficacy/safety of INH chemoprophylaxis in pregnancy remain unclear.

11. MANAGEMENT OF THE NEONATE BORN TO A MOTHER WITH TB

Assess for congenital TB — symptoms, signs
TST at birth (may be negative in early disease)
Chest radiograph
Smear and culture of gastric aspirate
Examine placenta for Mtb infection
If active TB excluded: give isoniazid preventive therapy for 2–3 months OR until mother is smear/culture negative and compliant with treatment
If active TB confirmed in neonate: full course of rifampicin + isoniazid + pyrazinamide (ethambutol preferably avoided in neonates — difficult to monitor ocular toxicity)
BCG vaccination should be given at birth; delay if congenital TB confirmed

12. BREASTFEEDING

Breastfeeding is not contraindicated in mothers receiving anti-TB treatment.
Anti-TB drugs are secreted in breast milk in small, non-toxic concentrations.
Drugs in breast milk do not constitute effective treatment or chemoprophylaxis for the infant.
Pyridoxine supplementation should be given to breastfeeding women taking isoniazid.
If mother is infectious (smear-positive), consider separating until sputum negativity achieved.
Transmission via breast milk is very unlikely, except in rare cases of TB mastitis.

13. ATT AND CONTRACEPTION

Rifampicin induces the hepatic P-450 mixed function oxidase system, which metabolises oral contraceptive pills (OCPs), reducing their reliability.
Alternative contraceptive measures (barrier methods, IUD) should be recommended to all post-partum women requiring anti-TB treatment.

SUMMARY TABLE: Key Points for Exam

Topic	Key Fact
Most common form	Pulmonary TB (85% of cases)
Effect of pregnancy on TB	No worsening; pregnancy does not predispose or cause progression
Effect of TB on pregnancy	Prematurity, FGR, ↑ perinatal mortality (untreated/late-treated)
Contraindicated drug	Streptomycin (ototoxicity)
Safest first-line drugs	INH + Rifampicin + Ethambutol (all safe; add pyridoxine with INH)
Pyrazinamide	WHO: safe; use recommended; CDC historically cautious
Regimen duration	6 months (same as standard; 9 months if no PZA)
LTBI in HIV-negative	Defer to postpartum (2–3 months)
LTBI in HIV-positive	Treat immediately
Breastfeeding	Allowed; not effective treatment for infant
OCP failure	Due to rifampicin — use alternative contraception
Pyridoxine dose	50 mg/day (prevents maternal neurotoxicity + neonatal seizures)

Sources: Sharma SK & Mohan A, Textbook of Tuberculosis and NTM Diseases (3rd ed.), Chapter 25 (pp. 346–353); Creasy & Resnik's Maternal-Fetal Medicine (p. 1403); Fishman's Pulmonary Diseases (p. 1704); WHO TB Treatment Guidelines 2010/2022.

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TB IN PREGNANCY — 15 Marks (Exam Format)

INTRODUCTION

TB complicates pregnancy significantly — both affect each other. Pulmonary TB is the most common form (85%). Global burden: >200,000 cases/year in pregnant women, highest in Africa & South-East Asia. (Sharma & Mohan, Ch. 25)

EFFECT OF PREGNANCY ON TB

Pregnancy does NOT worsen TB or cause progression (de March; Hedvell)
Small but definite risk of relapse in post-partum period
Worst prognosis: advanced disease diagnosed in puerperium + HIV co-infection
~~Therapeutic abortion is no longer indicated~~

EFFECT OF TB ON PREGNANCY

Complication	Detail
Prematurity	↑ especially with EPTB
Low birth weight / FGR	EPTB non-lymph node: 33% vs 11% controls
Intrauterine foetal death	9× higher at 16–28 wks (Bjerkedal)
Spontaneous abortion	↑ in untreated disease
Perinatal mortality	↑ if treatment started late
PIH / vaginal bleeding	Slightly increased

EPTB lymphadenitis = most common EPTB; NO adverse effect on pregnancy outcome

CLINICAL FEATURES

50–66% of pregnant women with TB are asymptomatic
Symptoms: Cough (74%), Fever (30%), Malaise (30%), Weight loss (14%), Haemoptysis (19%)
Symptoms often masked by normal pregnancy changes → high index of suspicion needed

DIAGNOSIS

1. Chest X-ray

Not routine; done when indicated
Abdominal shielding + preferably after 1st trimester
Radiation dose: ~2.5–5 mrad to gonads — safe

2. TST (Tuberculin Skin Test)

Safe in pregnancy; pregnancy does not affect TST reactivity
Becomes positive 2–10 weeks post-exposure

3. IGRAs (QuantiFERON-TB)

Comparable to TST for LTBI screening in pregnancy
Should not replace TST in low/middle income countries

4. Microbiological

ZN stain + LJ culture of sputum/body fluids = confirmatory
CBNAAT (GeneXpert) — useful for early diagnosis + drug susceptibility

TREATMENT OF ACTIVE TB

Golden rule: Untreated TB is MORE dangerous to mother and foetus than treatment side effects → treat immediately

Regimen (same as non-pregnant):

2 HRZE / 4 HRE (6 months total)

If PZA excluded → minimum 9 months

Drug Safety:

Drug	Safety	Notes
Isoniazid (H)	✅ Safe	Add pyridoxine 50 mg/day (prevents neonatal seizures + maternal neurotoxicity)
Rifampicin (R)	✅ Safe	Essential; reduces OCP efficacy → use barrier contraception
Pyrazinamide (Z)	✅ Safe (WHO)	Benefits outweigh risks; if excluded → 9-month regimen
Ethambutol (E)	✅ Safe	No human foetal ocular toxicity
Streptomycin	❌ CONTRAINDICATED	Foetal ototoxicity at any gestational age

Second-line drugs:

Avoid: Aminoglycosides (kanamycin, amikacin), Capreomycin, Ethionamide (teratogenic)
Delay to 2nd trimester if unavoidable
MDR-TB in pregnancy: treat with 3–4 effective drugs; counsel about foetal risks

LATENT TB INFECTION (LTBI)

Patient	Recommendation
HIV-negative, low risk	Defer to 2–3 months postpartum
Recent TB contact (HIV-ve)	Treat immediately
HIV-positive	Treat immediately (CDC + WHO)

CONGENITAL TB

Routes of transmission:

Haematogenous via placenta → umbilical vein → liver (primary complex)
Aspiration of infected amniotic fluid
Contiguous spread from TB endometrium

MANAGEMENT OF NEONATE (Born to TB Mother)

TST + CXR + gastric aspirate smear/culture at birth
Examine placenta for Mtb
If no active TB → INH prophylaxis for 2–3 months
If active TB confirmed → HRZ (avoid Ethambutol — cannot monitor ocular toxicity in neonate)
BCG at birth (delay if congenital TB confirmed)

BREASTFEEDING

Allowed — anti-TB drugs in breast milk are at non-toxic levels
NOT effective treatment/prophylaxis for infant
Give pyridoxine to breastfeeding mothers on INH

ATT AND CONTRACEPTION

Rifampicin induces P-450 → reduces OCP efficacy
Advise barrier methods / IUD in all post-partum women on ATT

HIV-TB CO-INFECTION

Standard ATT + ART; follow standard guidelines
Nevirapine-based ART → ↑ maternal hepatotoxicity risk
Efavirenz + rifampicin → dose adjustment needed

~1.5 handwritten pages | Sharma & Mohan 3rd Ed., Ch. 25, pp. 346–353

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