Tuberculosis and pregnancy

Tuberculosis and
Pregnancy :
Changes & Challenges in
Management
Dr. Md. Khairul Hassan Jessy
Associate Professor
Respiratory Medicine,NIDCH

Outline of Presentation
 Facts in relation to tuberculosis and the changes
made over time
• The impact of pregnancy on TB and TB on pregnancy
• Screening and diagnosis
• Treatment
• Congenital / neonatal TB
 Key messages

Introduction
 TB is an ancient disease and pathological
evidence was found in Egyptian mummies
 It is the 2nd leading cause of death from an
infectious disease

Introduction
Charles Dickens
( 1812 – 1870 )
labeled TB as
“ the disease
which medicine
never cured ”

Introduction
• Still today physicians are constantly being
challenged by the same disease in different
forms
• Many changes have been made & many changes
are likely to come

Introduction
• It is one of the leading non-obstetric causes
of maternal mortality
• The number of pregnant women with TB is
increasing along with resurgence of TB
 In March 1993 WHO declared TB a global
public health emergency

Historical Perspective
Hippocratic view :
Pregnancy had a
beneficial effect on TB.
This view persisted up to the early
part of the 19th century.

As late as the 1835 :
Ramadge, a German physician, believed –
the enlarging uterus helps to collapse
the open cavities and improve the clinical
condition.
&
he recommended marriage and
pregnancy in unmarried women with TB.

In about the mid 19th century :
Grissole concluded that –
TB was harmful during pregnancy and
termination was recommended.
The view persisted up to the 1st half of the 20th
century.

In 1953, the view changed showing
no apparent relationship except higher risk of
activation during puerperium and 1st
postpartum year.

Impact of Pregnancy on TB
The pendulum swung from one extreme to the other
and now has taken an intermediate position

CURRENT OPINION IS
Pregnancy does not predispose to the
progression of TB

Untreated TB is associated with higher risk of
- abortion
- IUGR
- LBW babies
- prematurity
- congenital TB
- neonatal TB

WHO Report 2014 – Global Picture
In 2014, an estimated 3.2 million women fell ill with TB
TB is one of the top five killers of women among adult women
aged 20–59 years. 480 000 women died from TB in 2014, including
140 000 deaths among women who were HIV-positive.
Of the 330,000 HIV-related TB deaths among adults (age ≥15)
globally in 2014, just over 40% were among women, accounting for
about a third of all AIDS-related deaths among female adults.
Almost 90% of these HIV-associated TB deaths among
women were in Africa.

Millennium Development Goal (MDG)
 In September 2000, at the United Nations millennium summit,
Heads of States of 189 countries adopted a declaration
 The declaration was translated into 8 Goals (MDG) to be
achieved by 2015
 There were 8 goals, 18 targets and 48 indicators
 MDG 6 is linked to TB
 Bangladesh Govt. is committed to reduce the prevalence and
mortality from TB along with others

Millennium Development Goal (MDG)
 Combat HIV/AIDS, malaria and other diseases
 Target 6.c Halt and begin to reverse the incidence of TB by 2015
 Indicator 6.9 Incidence, prevalence and death rates
associated with TB
 Indicator 6.10 Proportion of TB cases detected and cured
under DOTS

Presentation
The presentation of TB in pregnancy is similar to
that in non pregnant women
Diagnosis is often delayed in pregnancy due to
non specific nature of early symptoms
A high index of clinical suspicion is often needed

Presentation…
Common symptoms are
Cough
Weight loss
Fever
Malaise
Fatigue

Screening
Routine screening – important in HIV
prevalent setting
Screening is indicated in women who are
HIV positive
immuno-compromised
having symptoms of TB
recently exposed to active TB
immigrants from high prevalent countries

Screening…
Recommended tests:
 Sputum microscopy
 TST/MT
 Chest radiograph if MT positive
 Interferon gamma release assays ( IGRAs )
~ quantiferon gold TB Gold In Tube
test/ T- spot. TB test

Screening…
Mantoux Test/Tuberculin Test

Screening…
CHEST RADIOGRAPH
 Routine screening with X-ray chest
is not indicated
 If possible, X – ray chest should be
avoided in
first trimester
• If indicated strongly it should be
done with proper abdominal shielding
Last test to be done in pregnancy

Screening…
Sputum Microscopy ( AFB )

Evidence Based Medicine
EBM can be defined as systematic, scientific and explicit
use of current best evidence in making decisions about
the care of individual patients.
 EBM is graded as –
Grade A : Based on RCT, meta-analysis or systematic
review
Grade B : Based on well designed cohort/case control
studies
Grade C : Based on uncontrolled studies/expert opinion

Pregnancy Category of Drugs
Category A : Controlled studies show no risk ( large sample size )
Category B : No evidence of risk in humans ( limited sample size )
B1 : No evidence of risk in animals
B2 : Inadequate information regarding risk in animals
B3 : Evidence of fetal damage in animal studies ( uncertain in humans)
Category C : May cause reversible harmful effects on foetus /
neonate no risk of malformations
Category D : Risk of malformation or reversible damage
Category X : Contraindicated, as there is high risk of Damage

Treatment
TB in pregnancy should be treated as for non
pregnant patients regardless of gestational
age. If possible Fetotoxic drugs should be
avoided in pregnancy
The safety of the first line drugs has been
established except streptomycin. Experience
with 2nd line drugs in pregnancy is limited.

Treatment
WHO recommends
Treatment of Active TB (new cases)2HRZE/4HR
Ethambutal (E), Isoniazid (H), Rifampicin (R) and
Pyrazinamide (Z)
for 2 months (intensive phase)
followed by
INH & RMP for 4 months
(continuation phase)

Treatment
Initial Phase 2m Continuation Phase 7 m
INH INH
Rifampicin Rifampicin
Ethambutal
If pyrazinamide is not used the regimen will be
2HRE / 7HR

Treatment
SPECIAL CONSIDERATIONS
Streptomycin (S)
Streptomycin is hazardous throughout pregnancy
( independent of critical period of organogenesis)
1 in 6 foetuses can develop ototoxicity

Treatment
PZA
WHO recommends the use of PZA in
pregnancy
Extensive clinical trials have proved that it is
safe in pregnancy

Treatment
Rifampicin
As there is risk of hypo- prothrombinaemia,
Vit K should be given to both mother and
infant postpartum

Treatment
INH
Increased risk of hepatotoxicity in pregnancy
. So, periodic evaluation of LFT is
recommended.
Pyridoxine supplementation is recommended
for all pregnant women taking INH.

Pregnancy and MDR-TB
Treatment of gestational MDR-TB is controversial
Routine termination of pregnancy is not
recommended by many
An approved treatment regimen does not exist
Insignificant studies regarding the safety of 2nd
line drugs - an important contributory factor

Pregnancy and MDR-TB..
There are some case studies / cohort studies
showing successful outcomes with aggressive
treatment of gestational MDR-TB patient
( Studies with larger sample size are needed )

MODERN OPINION:
Aggressive treatment should be initiated without
delay to prevent
~ congenital / neonatal TB
~ adverse pregnancy outcome
~ maternal progression of disease

Severity of the disease
&
maturity of the foetus
Important determining factors in managing a pregnant
women with MDR-TB

There are some case studies / cohort
studies showing successful outcomes with
aggressive treatment of gestational MDR-
TB patient
( Studies with larger sample size are needed
)

In Clinically Stable Patients
Therapy may be delayed until the second
trimester
Aminoglycosides and ethionamide should be
avoided in pregnancy
Capreomycin may be used if an injectable is
unavoidable

In Advanced Disease
 Despite teratogenic potential
aggressive treatment should be continued
with effective drugs
 Risks should be fully discussed
 Option should be given whether to
continue/terminate the pregnancy

Potential Risk of Anti MDR-TB Drugs
Intra uterine exposure to
• Aminoglycosides - ototoxicity
• Ethionamide - CNS defect
• Fluoroquinolones - cartilage defects

Review of Literature
3 Studies in Lima Peru
&
1 case report in Iran
show/reveal
immediate and no long term or late presentation
toxicities associated
with
in – utero exposure to second line drugs

Reference Number 1:Shin S, Guerra D, Rich M, Seung KJ, Mukherjee
J, Joseph K, et al. Treatment of multidrug-resistant tuberculosis
during pregnancy: a report of 7 cases. Clin Infect Dis 2003;36:996–
1003..
• 7 pregnant women with advanced MDR-TB
disease were treated with 2nd line agents
(Ethionamide, Prothionamide, Co-Amoxiclav
Capreomycin, Kanamycin) .
• All of them carried their pregnancies
successfully to term & delivered healthy babies. 6
out of 7 babies were evaluated postnataly.

Reference Number 2: Drobac PC, del Castillo H, Sweetland A, Anca G, Joseph JK,
Furin J, et al. Treatment of multidrug-resistant tuberculosis during pregnancy:
long-term follow-up of 6 children with intrauterine exposure to second-line
agents. Clin Infect Dis 2005;40:1689–92.
Long term ( 15m-6.5 yrs ) follow up of 6 children
having intrauterine exposure to 2nd line agents
revealed no congenital / neonatal TB and no
neurological / developmental defect except mild
ototoxicity in one ( exposed to Capreomycin in 1st
trimester)

Contd..
•In the 1st trimester
2 babies were exposed to Capreomycin
4 “ “ “ “ Cycloserine
4 “ “ “ “ Amoxi – CA
2 “ “ “ “ Ethionamide
1 “ baby “ “ Prothionamide
1 “ “ “ “ KM
1 baby was exposed to Streptomycin in 2nd trimester

Reference Number 3:Palacios E, Dallman R, Munoz M, Hurtado R,
Chalco K, Guerra D, et al. Drug-resistant tuberculosis and
pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin
Infect Dis 2009;48:1413–9.
• 38 patients were treated during pregnancy with 2nd line TB
drugs
• 61% of patients were cured, 13 % had died, 5% remained
in treatment and 5% experienced treatment failure
• 5 of the pregnancies terminated in abortion, 1 baby was
stillborn, 3 babies were born with LBW, 1 was premature and
1 had foetal distress

Reference Number 4:Tabarsi P, Baghaei P, Mirsaedi M et al. Multidrug
Resistant TB in Pregnancy: Need for more intensive treatment. Infection
2007 ; 35: 477-478
• An 18 year old Afgan lady (Cat I and II failure) was on Ofloxacin,
Amikacin, Clofazimin, Pyrazinamide, INH & B6 became pregnant
• Co-Amoxiclave, Prothionamide was given in the 2nd trimester.
• She was given the option to terminate the pregnancy, but she
desired to continue
• She delivered a term healthy baby vaginally & the baby was
followed up for 18m having no complications

Pregnancy with TB/HIV Co-Infection
WHO recommends
TB treatment should be initiated
first, followed by ART as soon as
possible in the first 8 weeks of
starting treatment
(irrespective of CD4 count)

Pregnancy with TB/HIV Co-Infection..
Treatment
Early initiation may result in adverse side effects like
Immune reconstitution inflammatory syndrome ( IRIS )
Efavirenz (EFV) containing regimens should be
avoided in first trimester of pregnancy
Rifabutin is preferred to Rifampicin when ART is
used ( to avoid drug interaction )

Contraception
• A non hormonal method of contraception is
recommended for patients taking Rifampicin
containing regimen
• OCP with higher dose oestrogen (50 micrograms) may
be given e.g. LYNES, MAYA
Low dose pill

Latent Tuberculosis Infection (LTBI)
Diagnosed by - MT or Interferon gamma release assays
( IGRAs )
Indications of treatment
recent convertors
recent exposure to infected TB
immunocompromised women(e.g. HIV +ve)
Managed by -
6 - 9 months of INH therapy with pyridoxine

Congenital TB
Very rare
Occurs when the foetus is infected via
Umbilical vein or by aspiration / ingestion of
infected amniotic fluid
For diagnosis – Cantwell’s criteria is followed

Congenital TB..
Clinical Presentation
Symptoms and signs begin within 2nd and
3rd week
Symptoms are often non specific
Hepato-splenomegaly, respiratory distress,
fever & lymphadenopathy – common
Abdominal distension, irritability & lethargy –
may be present

Congenital TB..
Diagnosis
 From clinical suspicion
 Demonstration of AFB in tissue / fluids
 Chest radiograph
 Histopathology of placenta if possible

Congenital TB..
Once diagnosed baby should be treated by 6 m
course ( 2 HRZE/4 HR ) as in adult
But the dose should be strictly weight based
INH (10-15 mg/kg/day)
Rifampicin (10-20mg/kg/day)
Pyrazinamide (15-30 kg/day)
Ethambutal (15-25 mg/kg/day)
for the first 2 months followed by
INH and Rifampicin for 4 months
6m. Course have shown good results

Baby Management…
Mother with open TB can continue breast
feeding
But INH prophylaxis (5mg/kg) with Pyridoxine
should be given to the baby

Baby Management…
After 6 weeks –
TST should be performed
If negative
- BCG vaccine given
- Chemoprophylaxis stopped
If positive
- Active TB in the baby should be excluded
- INH prophylaxis continued for 6 months

Breast Feeding
Breast feeding is encouraged
in most cases
Contraindications are
- Mother with tuberculous
mastitis
- Maternal non-compliance with
treatment
- MDR-TB with prolonged
infectivity

Summary of Changes
The name changes from consumption, through
pthisis, the white plague, wasting disease to
TB over time. New diagnosis tests are
developing e.g. PCR, IGRAs

Summary of Changes..
Regarding treatment
-Rifampicin - recommended throughout
therapy
-Use of DST/DOTs – intensified
-Category I to IV – no longer used
-PZA – more extensively used.
-ART - recommended within 8 weeks of Anti-TB
treatment irrespective of CD4 count.

Key Messages
• Breast feeding is encouraged in most cases
• BCG vaccination is contraindicated in
pregnancy & HIV positive children

Key Messages..
First line Anti-TB drugs are safe except streptomycin
More research is needed with Second line drugs
Routine therapeutic termination –
not recommended
(even in MDR-TB cases)

Conclusion
With proper medical management a happy
conclusion is expected in most cases.

Tuberculosis and pregnancy

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