TB Manual

Population studies demonstrate an elevated risk of TB in pregnant and postpartum women, with incidence rates nearly twice that of women who are not pregnant.^2,158

Pregnancy suppresses T-helper cell-mediated immune function, increasing susceptibility to TB infection and progressive disease.^159,160 However, immune suppression seen during pregnancy can also mask the symptoms of progressive disease, making recognition more difficult.¹⁶¹ Furthermore, insidious symptoms of active TB may be attributed to pregnancy itself. Hesitancy to perform chest radiography may further delay diagnosis.¹⁶² After delivery, T-helper cell suppression is immediately reversed and, in some cases, the symptoms of TB disease are exacerbated as a result.¹⁵⁹

TB in pregnancy is associated with significant morbidity for both woman and their infants.^163,164 Pregnant women with TB have higher rates of miscarriage, cesarean sections, anemia, pre-term labor and mortality.^165,166 Infants born to mothers with active TB are more likely to be premature or low birthweight.¹⁶⁵ Thus, referral to an obstetrician for expert prenatal care is recommended for all pregnant women with TB.

Initiation of treatment for active TB in pregnancy should never be deferred, as the benefits of TB treatment greatly outweigh risks to mother and fetus. TB is not by itself an indication for termination of pregnancy. Treatment of TB in pregnant women is largely the same as in nonpregnant women.^162,167 Treatment failure and relapse are not more common in pregnancy and treatment extension is not necessary.^168,169 Dose adjustments are not required with advancing gestation as clinically significant changes to pharmacokinetics of the TB drugs have not been demonstrated.¹⁷⁰ Adverse effects from TB drugs, including drug-induced hepatitis, may be more common in pregnant women and careful monitoring is required.¹⁷¹

The first-line anti-TB drugs are all categorized as “Category C” by the US Food and Drug Administration. This classification reflects the lack of controlled studies in pregnant women and possible harm to fetus in animal reproductive studies. However, INH, rifampin and EMB have long track records of safety in pregnancy and are considered acceptable for first-line treatment.^167,172,173

Because PZA is not absolutely necessary to cure TB, and because there is a lack of formal studies on the fetal safety of this drug, its inclusion in treatment regimens for pregnant woman is usually decided on a case-by-case basis. To date, no reports of PZA teratogenicity in humans have emerged despite a long history of use²¹ and the WHO continues to recommend its use in pregnant women.¹⁷⁴ If PZA is not used, TB treatment is extended to nine months.

Fluroquinolone use in pregnancy has not been associated with adverse pregnancy outcomes.¹⁷⁵ However, larger studies that include pregnant women exposed to longer treatment durations are needed to better establish safety; at the present time. these drugs should be used only if there are no safer alternatives.

There is considerably less experience with second-line TB agents in pregnancy¹⁶⁷ (see Chapter 8: Drug-resistant Tuberculosis). Consultation with an expert in multidrug-resistant TB is recommended.

Recommendations

• We strongly recommend using isoniazid, rifampin and ethambutol as initial treatment in pregnant women, as all 3 are considered safe in pregnancy (good evidence).

• We conditionally recommend adding pyrazinamide to the regimen in pregnant women with extensive disease, smear-positive pulmonary disease, disseminated TB or intolerance of any of the other first-line drugs (poor evidence).

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