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TC:TOPIC_PAGE
Tuberculosis in pregnancy
Authors
Lloyd N Friedman, MD
Lynn T Tanoue, MD
Section Editors
C Fordham von Reyn, MD
Charles J Lockwood, MD
Deputy Editor
Elinor L Baron, MD, DTMH
Disclosures
All topics are updated as new evidence becomes available and our
peer review process is complete.
Literature review current through: Oct 2013. | This topic last
updated: Jan 8, 2013.
INTRODUCTION Prenatal care presents a unique opportunity
for evaluation and management of latent and active tuberculosis
(TB) in pregnant women [ 1 ]. Routine tuberculin skin test (TST)
screening is not indicated for all pregnant women. However,
individuals with an increased risk of tuberculosis may seek medical
care only during pregnancy (such as foreign born individuals within
five years of immigration from TB endemic countries or individuals
with HIV infection) [ 2 ]. (See "Epidemiology of tuberculosis" .)
The pathogenesis of tuberculosis infection and disease in pregnant
women is similar to that in nonpregnant women [ 3,4 ]. There is no
firm evidence that the risk of new infection or reactivation of
tuberculosis in pregnant women is significantly different from
matched controls. However, tuberculosis in pregnant women can
present insidiously, since symptoms of malaise and fatigue may be
attributed to pregnancy rather than disease [ 5 ]. In addition, during
pregnancy it can be difficult to recognize weight loss. (See
"Microbiology and pathogenesis of tuberculosis" .)
Since pregnancy has not been shown to increase the risk of TB, the
epidemiology of TB in pregnancy is a reflection of the general
incidence of disease [ 6 ]. This also is true in HIV-infected women,
as shown in a group of predominantly HIV-infected pregnant women
in New York City during 1991 to 1992, where the rate of TB was
94.8 per 100,000 deliveries [ 7 ].
Issues related to diagnosis and treatment of latent TB infection and
active TB disease in pregnant women will be reviewed here. Issues
related to the management of latent and active TB in nonpregnant
patients are discussed in detail separately. (See "Diagnosis of latent
tuberculosis infection in HIV-negative adults" and "Diagnosis of
pulmonary tuberculosis in HIV-negative patients" and "Treatment of
pulmonary tuberculosis in HIV-negative patients" .)
LATENT TB Pregnancy has not been shown to influence the
pathogenesis of TB or the likelihood of progression from latent to
active disease, nor has it been shown to affect the response to
treatment [ 8,9 ].
Diagnosis Routine testing for latent tuberculosis in pregnant
women is not indicated. Testing should be performed during
pregnancy only if there is an indication for prompt treatment of
latent tuberculosis infection (LTBI); a decision to test presupposes a
decision to treat promptly if the test is positive. However, contact
with the health system during pregnancy is an opportunity to
identify patients at risk for LTBI who should be evaluated further
following pregnancy. Appropriate groups for testing include those at
high risk for progression of LTBI to active disease, especially those
who are significantly immunocompromised (eg, HIV infection,
immunosuppressive therapy) or those who have been infected with
TB recently [ 10 ]. (See "Diagnosis of latent tuberculosis infection in
HIV-negative adults" .)
If indicated, testing for LTBI prior to pregnancy is preferred (if
feasible); this allows opportunity for counseling about the risk of
becoming pregnant while on therapy [ 11 ]. If treatment for LTBI is
initiated and the patient becomes pregnant subsequently, therapy
should be continued [ 12 ]. In the absence of major risk factors for
progression to active infection during pregnancy, testing and
treatment for LTBI in those for whom targeted testing is indicated
should be delayed until three months after delivery to minimize risk
of adverse drug effects. (See 'Toxicity and monitoring' below.)
Diagnostic tools for latent tuberculosis include tuberculin skin
testing (TST) and interferon gamma release assays (IGRAs).
Tuberculin skin testing can be performed safely in pregnant women,
and pregnancy does not alter the response to the TST [ 10,13 ].
Definitions of positive skin tests are outlined in the Table ( table 1 ).
Interferon gamma release assays are also safe in pregnancy and
likely as effective for diagnosis of LTBI in pregnancy as in other
circumstances; data are limited [ 14-17 ]. (See "Interferon-gamma
release assays for diagnosis of latent tuberculosis infection" .)
Patients with positive LTBI screening results ( table 1 ) must
undergo clinical evaluation to rule out active tuberculosis. This
includes evaluation for symptoms (eg, fever, cough, weight loss)
and radiographic examination of the chest (with appropriate
shielding). (See "Interferon-gamma release assays for diagnosis of
latent tuberculosis infection" .)
Treatment Testing and treatment for latent tuberculosis
infection should be pursued during pregnancy only if there is an
indication for prompt management of LTBI (usually in recent
infection or immunocompromised hosts); a decision to test
presupposes a decision to treat promptly if the test is positive (even
during the first trimester). Therefore, patients appropriately
targeted for LTBI screening with positive TST results should initiate
treatment during pregnancy [ 10 ]. If treatment for LTBI is initiated
prior to pregnancy for the usual indications noted in the CDC
statement [ 10 ], and the patient becomes pregnant subsequently,
therapy should be continued [ 12 ]. (See 'Diagnosis' above and
"Diagnosis of latent tuberculosis infection in HIV-negative adults" .)
However, if a skin test has been performed in the absence of an
indication for prompt LTBI management and is positive, a chest
radiograph should be performed. Delaying therapy is appropriate for
patients with positive TST in the absence of a major risk factor for
progression to active disease, ie, recent infection or
immunosuppression. Therapy may be initiated three months after
delivery to minimize concern for hepatitis in the postpartum period.
If treatment for LTBI is deferred until after delivery, repeat
evaluation for active disease, including chest x-ray, should be
performed to confirm that active tuberculosis did not develop in the
intervening time between diagnosis and treatment. (See 'Toxicity
and monitoring' below.)
Adherence may suffer when patients identified with LTBI during
pregnancy delay treatment. In a study evaluating 393 women with
LTBI during pregnancy who delayed treatment until the postpartum
period, only 42 percent attended a follow up visit in the TB clinic,
and only 18 percent completed treatment [ 18 ]. Therefore, close
follow-up is required.
The regimen of choice for treatment of LTBI is isoniazid (5 mg/kg up
to 300 mg daily) for nine months ( table 2 ). This should be
combined with pyridoxine supplementation (25 mg daily) [ 10 ].
Minor interruptions in therapy are acceptable, so long as 270 doses
are completed within 12 months. A six month regimen of daily
isoniazid also provides protection but is less desirable, although in
the setting of difficulty with adherence, providers may prefer to
concentrate efforts in ensuring six months of therapy [ 10 ].
Another choice for treatment of LTBI is rifampin (daily for four
months) ( table 2 ) [ 10 ]. Rifampin should be used for patients who
are intolerant of INH or who are presumed to have infection with
INH-resistant, rifampin-sensitive strains of TB. It may also be useful
in the setting of difficulty with adherence. (See "Diagnosis of latent
tuberculosis infection in HIV-negative adults" .)
Toxicity and monitoring Pregnancy and the early postpartum
period may confer increased risk for isoniazid hepatotoxicity [ 19-22
]. Among 3681 pregnant and postpartum women with LTBI,
isoniazid was associated with a 2.5-fold increase in fulminant
hepatitis and a fourfold increase in mortality compared with
nonpregnant women, although these data did not reach statistical
significance [ 19 ].
Pregnant and postpartum women should have pre-treatment liver
transaminases and bilirubin function tests and, if normal, isoniazid
can be started with follow up symptom evaluations, and exams
every month. Initially LFTs should be obtained every month for at
least two months until shown to remain within normal limits. The
evaluation of pregnant and postpartum women receiving LTBI
treatment (either isoniazid or rifampin ) also should include testing
for HIV, hepatitis B and C, and a general evaluation for chronic liver
disease, alcohol use, and exposure to other hepatotoxins. If there is
a mild elevation of transaminases, more frequent monitoring may
be necessary until stability is established.
Patients should receive explicit instructions to stop therapy
immediately and contact their healthcare provider upon the
development of any symptoms that are consistent with hepatitis.
Isoniazid should be discontinued if the patient is symptomatic and
the ALT is more than three times the upper limit of normal [ 23 ]. It
should be discontinued in asymptomatic patients when the ALT is
more than five times the upper limit of normal [ 23 ].
Other side effects of isoniazid include rashes, neuropsychiatric
disturbances including depression, mania, and memory loss,
pellagra, peripheral neuritis, and seizures [ 24 ].
Adverse effects due to rifampin include hepatitis, thrombocytopenia,
hemolytic anemia, and fever and rash. (See "Rifampin and other
rifamycins" and 'First line drugs' below.)
ACTIVE TB Pregnancy has not been shown to influence the
pathogenesis of TB or the likelihood of progression from latent
infection to active disease, nor has it been shown to affect the
response to treatment [ 8,9 ]. Active maternal infection can lead to
congenital infection by hematogenous dissemination via the
placenta, although congenital infection is very rare. (See 'Congenital
and neonatal TB' below.)
Clinical manifestations Pregnant patients with pulmonary
tuberculosis typically have the same clinical manifestations as
nonpregnant patients. However, tuberculosis in pregnant women can
present insidiously, since malaise and fatigue may be attributed to
pregnancy rather than disease [ 22 ]. In addition, during pregnancy
it can be difficult to recognize weight loss. In the setting of
extrapulmonary disease symptoms may be especially vague and the
diagnosis can be significantly delayed [ 25-27 ]. (See "Clinical
manifestations and evaluation of pulmonary tuberculosis" .)
Diagnosis The evaluation for active tuberculosis in pregnant
women should proceed as in nonpregnant individuals, including
chest X-ray, with appropriate protection of the fetus [ 28 ].
Evaluation for extrapulmonary disease should be guided by clinical
symptoms and/or radiographic findings. Diagnosis of TB also should
prompt evaluation for HIV infection. (See "Diagnosis of pulmonary
tuberculosis in HIV-negative patients" and "Acute and early HIV
infection: Treatment" .)
TREATMENT OF ACTIVE TB Treatment of tuberculosis in the
setting of pregnancy should be initiated if the suspicion of active
disease is moderate to high (such as a persistent upper lobe
infiltrate and cough in a high-risk individual and/or a positive AFB
smear or nucleic acid amplification test), since untreated disease
represents a greater hazard to the mother and fetus than
antituberculous therapy. The principles of treatment of active
tuberculosis in HIV-seronegative pregnant patients are the same as
for nonpregnant patients, except for the exclusion of certain
medications [ 29 ]. HIV-positive patients are discussed in detail
separately, and decisions about therapy in these individuals should
be made in consultation with an expert. (See "Treatment of
pulmonary tuberculosis in HIV-negative patients" and "Treatment of
pulmonary tuberculosis in the HIV-infected patient" .)
The approach to treatment also includes consideration of issues
related to transmission, including separation of mother from
newborn in certain circumstances. (See 'Controlling transmission'
below.)
First line drugs The initial treatment regimen (for presumed
drug sensitive disease) for active TB during pregnancy in the United
States typically consists of isoniazid , rifampin and ethambutol
administered for two months followed by isoniazid and rifampin for
seven months, for a total of nine months [ 4,8,15,29,30 ]. If the
results of drug sensitivity studies are available and the organism is
known to be susceptible to isoniazid and rifampin, then ethambutol
may be discontinued after one month.
Pyrazinamide is not absolutely necessary as part of a first line
regimen, and because of limited safety data, it is not used routinely
for pregnant women in the United States. However, pyrazinamide is
recommended by the World Health Organizations as part of a
standard regimen for treatment of TB in pregnant women [ 31,32 ].
In circumstances such as HIV coinfection, tuberculous meningitis,
very extensive disease, and any form of drug resistance, it would be
prudent to consider the use of pyrazinamide [ 15,33 ]. The absence
of pyrazinamide from the treatment regimen results in a treatment
duration of nine months instead of six months.
Steroids for manifestations such as meningitis and pericarditis
should be used as discussed separately [ 29 ]. (See "Central
nervous system tuberculosis" and "Tuberculous pericarditis" .)
Pregnancy is not a risk factor for TB and has not been shown to
influence the pathogenesis of TB or the likelihood of progression
from latent infection to active disease. However, maternal infection
can lead to congenital infection or neonatal infection. In addition, TB
in pregnant women can present insidiously since symptoms of
malaise and fatigue may be attributed to pregnancy rather than
infection. (See 'Introduction' above.)
Screening for latent TB infection (LTBI) should be performed during
pregnancy only for those women at high risk for progression from
latent to active disease (eg, women who have been infected recently
and those who have HIV or are otherwise significantly
immunocompromised) ( table 1 ). (See 'Latent TB' above and
"Diagnosis of latent tuberculosis infection in HIV-negative adults" .)
Treatment of LTBI is reserved for pregnant women at high risk for
progression of LTBI to active disease, such as recent infection, HIV
infection, or immunosuppression. In these circumstances, we
recommend isoniazid for treatment of LTBI ( table 2 ) ( Grade 1B ).
We use daily therapy for nine months; for patients with difficulties
related to adherence, six months duration and/or twice weekly
directly observed therapy are alternatives. (See 'Latent TB' above.)
We recommend that the initial treatment regimen for active TB in
pregnancy (for presumed drug susceptible disease) consist of
isoniazid , rifampin and ethambutol administered for two months,
followed by isoniazid and rifampin for seven months for a total of
nine months ( table 2 ) ( Grade 1B ). Pyrazinamide is not absolutely
necessary as part of a first line regimen, and because of limited
safety data, it is not used routinely for pregnant women in the
United States. However, pyrazinamide is recommended by the World
Health Organizations as part of a standard regimen for treatment of
TB in pregnant women. It may be important to consider in the
setting of HIV coinfection, tuberculous meningitis, extensive
disease, and drug resistance. (See 'Treatment of active TB' above.)
We recommend NOT using streptomycin , kanamycin , amikacin or
capreomycin for treatment of TB in pregnancy ( Grade 1A ).
Streptomycin is a known teratogen that interferes with eighth nerve
development and may cause congenital deafness. Kanamycin and
amikacin presumably share this potential for toxicity, and although
they are also aminoglycosides, there is little specific information on
the fetal effects of these drugs. Capreomycin is assumed to have
eighth nerve and renal toxicity. (See 'Agents to avoid' above.)
The following agents may be useful when there are no suitable
alternatives, but should be considered in consultation with an expert
in treating TB: rifabutin , cycloserine , PAS ( para-aminosalicylic acid
), ethionamide and fluoroquinolones. (See 'Agents to consider'
above.)
Breast feeding is not contraindicated in mothers being treated for
active TB or LTBI with standard first line agents, since the small
concentrations of these drugs in breast milk do not produce toxic
effects in the nursing infant. Supplemental pyridoxine should be
administered to breastfeeding mothers receiving isoniazid as well as
to their infants, even if the infant is not taking isoniazid therapy.
Patients receiving treatment for drug resistant TB with second line
agents should not breast feed. (See 'Breast feeding' above.)
Congenital TB is very rare and most often associated with maternal
HIV infection or maternal miliary or uterine TB. Neonatal TB is more
common than congenital tuberculosis, and diagnosis can lead to
identification of a previously unrecognized diagnosis of TB in the
mother. The mortality of untreated congenital and neonatal TB is
about 50 percent. (See 'Congenital and neonatal TB' above.)
Issues related to separation of mother and infant for controlling
transmission are as outlined above. (See 'Controlling transmission'
above.)
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