INTRODUCTION — Worldwide, the burden of tuberculosis (TB) disease in pregnant patients is substantial [1]. It was estimated that more than 200,000 cases of active TB occurred among pregnant patients globally in 2011; the burden was greatest in Africa and Southeast Asia [2]. In the United States between 2003 and 2011, the incidence of TB in pregnancy was 26.6 per 100,000 births [3]. (See "Epidemiology of tuberculosis".)

Prenatal care presents a unique opportunity for evaluation and management of latent and active TB among individuals with risk of TB who may not otherwise present for medical care [4,5].

Issues related to diagnosis and treatment of latent TB infection and active TB disease in pregnant patients will be reviewed here. Issues related to the management of latent and active TB in nonpregnant patients are discussed in detail separately, as are issues related to perinatal TB infection. (See "Tuberculosis disease in children", section on 'Perinatal infection' and "Diagnosis of pulmonary tuberculosis in adults" and "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults".)

NATURAL HISTORY OF TB IN PREGNANCY — Tuberculosis (TB) infection is caused by inhalation of viable bacilli, which may persist in an inactive state (known as latent TB infection [LTBI]) or progress to active TB disease.

Individuals with LTBI are asymptomatic and not contagious. Latent TB bacilli remain viable and may reactivate, causing active symptomatic TB disease, which can be transmitted via airborne spread.

Pregnancy has not been shown definitively 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 [6-13]. However, a cohort study including pregnant patients in the United Kingdom between 1996 and 2008 noted that the incidence of postpartum TB diagnosis was significantly increased (incidence rate ratio [IRR] 1.95, 95% CI 1.24-3.07), whereas there was no significant increase in the incidence of TB during pregnancy (IRR 1.29, 95% CI 0.82-2.03) [14].

Postpartum patients with active pulmonary TB can transmit infection to their infants; this is discussed further below. (See 'Controlling transmission' below.)

Maternal active TB may be associated with congenital infection by hematogenous dissemination via the placenta; this is very rare. (See "Tuberculosis disease in children", section on 'Perinatal infection'.)

LATENT TUBERCULOSIS INFECTION IN PREGNANCY

Screening for LTBI

Whom to test — Testing asymptomatic patients for latent TB infection (LTBI) during pregnancy is warranted only for patients with significant risk factors for progression to active TB disease during pregnancy [15]; these include (see 'Timing of treatment' below and "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults", section on 'Indications for LTBI testing'):

●Patients with recent contact with a patient with untreated active respiratory TB

●HIV-infected patients not on antiretroviral therapy (ART) and those with CD4 count ≤350 cells/mm³ (some experts favor a lower CD4 threshold of ≤200 cells/mm³)

●Patients with other significant immunocompromise

A positive test should prompt an evaluation for active TB (see 'Diagnostic evaluation after positive test' below); patients with active TB should be treated immediately. (See 'Active tuberculosis disease in pregnancy' below.)

If active TB is excluded, decisions regarding timing of treatment are based on individual circumstances. (See 'Timing of treatment' below.)

For patients with TB risk factors not included above, LTBI testing and treatment should be delayed until three months after delivery to minimize risk of adverse drug effects related to treatment. (See "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults".)

If indicated, LTBI testing prior to pregnancy is preferred (if feasible); this allows opportunity for counseling about the risk of becoming pregnant while infected with LTBI [16].

How to test — There is no test that definitively establishes a diagnosis of LTBI. LTBI is a clinical diagnosis established by demonstrating an immune response to Mycobacterium tuberculosis antigens and excluding active TB disease.

Available tests to detect the immune response to TB antigens include the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs). These measure immune sensitization (type IV or delayed-type hypersensitivity) to mycobacterial protein antigens that occurs following exposure to (and infection by) mycobacteria. (See "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults".)

TST can be performed safely in pregnant patients, and test results are not altered by pregnancy [15,17]; definitions of positive TST are summarized in the table (table 1). Additional issues related to TST interpretation, including causes of false-negative and false-positive tests, are discussed separately. (See "Use of interferon-gamma release assays for diagnosis of latent tuberculosis infection (tuberculosis screening) in adults".)

IGRAs are also safe in pregnancy and are likely as effective for diagnosis of LTBI in pregnancy as in other circumstances [18-21]. (See "Use of interferon-gamma release assays for diagnosis of latent tuberculosis infection (tuberculosis screening) in adults".)

Diagnostic evaluation after positive test — Patients with a positive TST or IGRA must undergo clinical evaluation to rule out active TB. This includes evaluation for symptoms (eg, fever, cough, weight loss) and radiographic examination of the chest (with appropriate shielding), regardless of gestational age. (See 'Active tuberculosis disease in pregnancy' below and "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults".)

Patients with a positive TST or IGRA with no evidence of active TB may be presumed to have latent TB and should be managed as discussed below.

Clinical manifestations — Patients with LTBI are asymptomatic and not contagious. There is no risk for vertical transmission of LTBI.

Diagnosis — Issues related to diagnosis of LTBI are discussed above. (See 'Screening for LTBI' above.)

Treatment

Timing of treatment — The potential risks of adverse pregnancy outcomes associated with LTBI treatment during pregnancy must be weighed against the potential risks of progression to active TB during pregnancy.

All patients diagnosed with LTBI prior to pregnancy and started on treatment for an appropriate indication should continue LTBI treatment during pregnancy; the regimen should be modified (if necessary) to a regimen suitable for pregnancy, described below [15,22]. (See 'Selecting a regimen' below.)

For patients with significant immunocompromise (apart from HIV infection, which is discussed below), the decision to treat during pregnancy or defer until after delivery should be based on individual clinical circumstances including the degree of immunocompromise.

HIV-uninfected patients — Our approach to management of LTBI in HIV-uninfected patients depends on whether the patient had recent exposure to a patient with untreated active TB or recent infection (see "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults", section on 'Individuals with recent exposure (close and casual contacts)'):

●Recent exposure to a patient with untreated active respiratory TB or recent (within two years) conversion of a test for TB infection to positive – We initiate LTBI treatment during pregnancy, given the increased risk of progression to active TB in such cases. (See 'Selecting a regimen' below.)

●No recent exposure to a patient with untreated active respiratory TB – We defer LTBI treatment until three months after delivery, to minimize the risk of isoniazid hepatitis and adverse pregnancy outcomes and associated with LTBI treatment during pregnancy [23-25]. In such cases, close follow-up is required [26]. After delivery, such patients should have follow-up evaluation for active disease (including chest radiograph) to confirm that active TB did not develop in the interval since diagnosis of LTBI and the time that treatment for LTBI begins. (See "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults", section on 'Excluding active TB' and "Treatment of latent tuberculosis infection in HIV-uninfected nonpregnant adults".)

HIV-infected patients — Our approach to management of LTBI in HIV-infected patients depends on whether there was recent exposure to a patient with untreated active TB, as well as the HIV infection management status.

●Recent exposure to a patient with untreated active respiratory TB – We initiate LTBI treatment during pregnancy, given the increased risk of progression to active TB in such cases. (See 'Selecting a regimen' below and "Approach to diagnosis of latent tuberculosis infection (tuberculosis screening) in adults", section on 'Individuals with recent exposure (close and casual contacts)'.)

●No recent exposure to a patient with untreated active respiratory TB

•Patients on ART – Among patients on ART with CD4 count >350 cells/mm³ in the absence of a recent TB exposure, we defer LTBI treatment until three months after delivery. For patients with CD4 count ≤350 cells/mm³, we initiate LTBI treatment during pregnancy, given increased risk of progression to active TB. The CD4 cutoff is a matter of clinical judgement; some experts favor a lower threshold (CD4 count ≤200 cells/mm³) [27].

This approach is based on a clinical trial published in 2019 demonstrating more frequent adverse pregnancy outcomes among patients in high TB incidence settings treated with isoniazid during pregnancy than among patients treated three months after delivery [24]. The study included more than 900 HIV-infected pregnant patients (CD4 count 351 to 670 cells/mm³ on ART) randomly assigned to initiate LTBI treatment with isoniazid immediately or defer treatment until 12 weeks after delivery. Excluded patients included patients in the first trimester and those with recent TB exposure; mothers and infants were followed for 48 weeks after delivery. The incidence of TB was comparable between the groups (0.60 versus 0.59 per 100 person-years). However, the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight, preterm delivery, or congenital anomalies) was observed more frequently among patients in the immediate group than the deferred group (23.6 versus 17.0 percent; difference 6.7 percentage points; 95% CI 0.8-11.9). The rate of hepatotoxicity was similar between the groups (6.2 versus 7.2 percent; relative difference -1.0; 95% CI -4.3 to 2.3).

Our approach to management of HIV-infected pregnant patients differs from the World Health Organization 2018 LTBI statement [28], which favors LTBI treatment during pregnancy in all cases but was published before the 2019 study described above. The United States Department of Health and Human Services (DHHS) guidelines recommend delaying LTBI treatment until three months after delivery in the absence of a recent TB exposure, but do not specify a CD4 threshold [29].

•Patients not on ART – Among HIV-infected pregnant patients not on ART, ART should be initiated promptly; the risk of progression from LTBI to active TB disease in individuals on ART is significantly decreased [30,31]. Issues related to management of ART in pregnancy are discussed separately. (See "Antiretroviral selection and management in pregnant women with HIV in resource-rich settings".)

Data to guide LTBI management for HIV-infected pregnant patients not on ART are limited, and there is no consensus on the optimal approach. Pending further study, we favor initiation of LTBI treatment during pregnancy for all HIV-infected patients not on ART; other experts favor initiation of LTBI treatment during pregnancy only for those with CD4 count ≤200 cells/mm³ (with deferral of treatment until three months after delivery for those with CD4 count >200 cells/mm³).

Selecting a regimen

General approach — We are in agreement with the United States Centers for Disease Control (CDC) which favors the following regimens for treatment of LTBI in pregnancy (table 2) [32]:

●Rifampin (daily for 4 months; 4R)

●Isoniazid and rifampin (daily for 3 months; 3HR)

●Isoniazid daily for 9 or 6 months

Support for use of 4R and 3HR in pregnancy is based on extrapolation of by data from studies in nonpregnant patients. Among nonpregnant adults, 4R has been shown to be noninferior to isoniazid (daily for nine months) and associated with a higher rate of treatment completion [33]; 3HR has similar efficacy and hepatotoxicity to that of INH administered for six months [34]. (See "Treatment of latent tuberculosis infection in HIV-uninfected nonpregnant adults", section on 'Rifampin (4R)' and "Treatment of latent tuberculosis infection in nonpregnant adults with HIV infection", section on 'Isoniazid and rifampin (3HR)'.)

In August 2020, the US Food and Drug Administration (FDA) announced detection of nitrosamine impurities in samples of rifampin. Some such compounds have been implicated as possible carcinogens in long-term animal studies, with toxicity largely related to cumulative exposure. Because the risks from TB appear to be greater than those from cancer, and the risks for serious toxicity such as isoniazid-induced hepatitis may be substantial with alternative regimens, the CDC and FDA recommend that these rifampin and rifapentine continue to be used for treatment of LTBI and TB disease. This should be done following individual patient discussion of benefits, risks, and alternatives. (See 'Selecting a treatment regimen' below and "Treatment of latent tuberculosis infection in HIV-uninfected nonpregnant adults".)

If isoniazid is used, we favor daily administration for 9 months given its established efficacy. Patients on regimens including isoniazid should also receive pyridoxine supplementation (25 to 50 mg daily).

Isoniazid daily for 6 months provides some protection; in the setting of difficulty with adherence, providers may prefer to concentrate efforts in ensuring 6 months of therapy. This approach is favored by the World Health Organization. However, regimens shorter than 9 months should not be used for patients with fibrotic lesions on chest radiograph.

The approach to selecting a regimen for treating LTBI is similar in patients with HIV infection during pregnancy, with special consideration given to potential drug-drug interactions for patients receiving antiretroviral medications, especially with rifamycins.

The 3-month weekly isoniazid and rifapentine (3HP) regimen is not recommended for individuals who are pregnant or expecting to become pregnant during the treatment period; its safety during pregnancy has not been studied [35].

Issues related to clinical and laboratory monitoring after initiation of therapy are discussed below. (See 'Monitoring during treatment' below.)

HIV-infected patients in high TB transmission settings — The WHO recommends that HIV-infected patients with and a positive or unknown LTBI test in settings with "high TB transmission" be treated with INH for at least 36 months [36]; however, the regional TB transmission level is not always known. In general, we support the use of extended INH (≥36 months) for settings with TB incidence >500 per 100,000 population (table 3). This is discussed further separately. (See "Treatment of latent tuberculosis infection in nonpregnant adults with HIV infection".)

ACTIVE TUBERCULOSIS DISEASE IN PREGNANCY

Clinical manifestations — Pregnant patients with pulmonary TB have the same clinical manifestations as nonpregnant patients; these may include fever, cough, weight loss, night sweats, and malaise. Active pulmonary TB may be transmitted via airborne spread.

TB in pregnant patients can present insidiously since malaise and fatigue may be attributed to pregnancy rather than disease [4,37-41]. In addition, during pregnancy it can be difficult to recognize weight loss. (See "Clinical manifestations and complications of pulmonary tuberculosis".)

Diagnosis — Diagnostic evaluation for active TB is warranted in the setting of clinical suspicion for active TB, based on clinical manifestations and epidemiologic factors (such as exposure to a known or suspected case, residence in or travel to an endemic area).

The approach to diagnosis for active TB in pregnant patients is the same as in nonpregnant individuals; it consists of clinical history (including epidemiologic assessment) and physical examination followed by chest radiography (with appropriate shielding to protect the fetus) [42].

Chest imaging suggestive of pulmonary TB should prompt submission of three sputum specimens (coughed or induced) for acid-fast bacilli smear and culture as well as at least one sputum specimen for M. tuberculosis nucleic acid amplification testing. (See "Diagnosis of pulmonary tuberculosis in adults".)

A positive TST or IGRA supports a diagnosis of TB infection but, in the absence of other evidence, is not sufficient for diagnosis of active TB. In addition, a negative TST or IGRA result does not rule out active TB.

Diagnosis of active TB should prompt evaluation for HIV infection. (See "Screening and diagnostic testing for HIV infection".)

Treatment

Whom to treat — Treatment of TB in the setting of pregnancy should be initiated if the suspicion of active disease is moderate to high (such as a positive sputum acid-fast bacilli smear, positive sputum nucleic acid amplification test, or cough and upper lobe infiltrate in an individual with relevant risk factors). (See "Epidemiology of tuberculosis", section on 'Risk factors'.)

Active TB in pregnancy is associated with adverse maternal and fetal outcomes; untreated active TB represents a greater hazard to the mother and fetus than antituberculous therapy [43].

Other principles for treatment of active TB in pregnant patients are the same as for nonpregnant patients. (See "Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults".)

Selecting a treatment regimen — The regimen of choice for empiric treatment of presumed drug-susceptible active TB during pregnancy in the United States consists of isoniazid, rifampin, and ethambutol administered for two months followed by isoniazid and rifampin for seven months, for a total of nine months of therapy [7,10,44,45]. If the results of drug susceptibility studies are available and the isolate is known to be susceptible to isoniazid and rifampin, ethambutol may be discontinued after one month.

In August 2020, the US Food and Drug Administration (FDA) announced detection of nitrosamine impurities in samples of rifampin [46]. Some such compounds have been implicated as possible carcinogens in long-term animal studies, with toxicity largely related to cumulative exposure. For treatment of TB disease, until more information is available from the FDA, we favor continued use of rifampin if acceptable to the patient, as the risk of not taking rifampin likely outweighs any potential risk from nitrosamine impurities. These recommendations are concordant with recommendations of the FDA and CDC. (See "Treatment of latent tuberculosis infection in HIV-uninfected nonpregnant adults".)

Pyrazinamide is not absolutely necessary as part of a first-line regimen for active TB. Detailed teratogenicity data are not available for this agent, so it is often excluded from TB treatment for pregnant patients in the United States [11,44]. Nonetheless, pyrazinamide is recommended by the World Health Organization as part of a standard regimen for treatment of TB in pregnant patients [47,48], and this practice is gaining acceptance in the United States; the 2016 American Thoracic Society/CDC/Infectious Diseases Society of America treatment guidelines state that, for pregnant patients with TB and HIV, extrapulmonary TB, or severe TB, it is more beneficial to include pyrazinamide in the treatment regimen than to not include it [44]. If a decision is made to include pyrazinamide, the treatment duration can be shortened from nine months to six months in most patients [44].

Isoniazid, rifampin, and ethambutol are generally considered by experts to be acceptable for use in pregnancy [44,49,50].

●Use of isoniazid may be associated with increased risk of hepatitis and peripheral neurotoxicity in the peripartum period, especially in Hispanic or African-American individuals [23,44,45,49,50]. In general, the benefit of isoniazid (given its importance for treatment of active TB) justifies the potential risk. Pyridoxine should be administered to pregnant patients receiving isoniazid and to their breastfeeding infants (even if the infant is not receiving isoniazid therapy) [15,44].

●Use of rifampin has been associated with rare cases of fetal abnormalities and hemorrhagic disease [15,22,44,49]. Rifabutin often is used as an alternative to rifampin in patients with HIV infection on antiretroviral medications and may be used in pregnancy in consultation with an expert. Rifapentine should not be used in pregnancy as there is insufficient safety information. (See "Treatment of pulmonary tuberculosis in adults with HIV infection: Initiation of therapy".)

Dosing regimens for treatment of TB are summarized separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults".)

Treatment should be administered by directly observed therapy wherever possible. Patients should be seen and examined at least monthly to optimize adherence and to evaluate for drug toxicity. (See 'Monitoring during treatment' below.)

Patients diagnosed with TB and started on treatment prior to pregnancy should continue TB treatment while pregnant; the regimen should be modified to one of the regimens suitable for pregnancy described above.

Pregnant patients with HIV infection and TB should be treated with one of the regimens suitable for pregnancy described above. This should be done in consultation with an expert, and the TB treatment regimen should be compatible with the patient’s antiretroviral therapy. Outcomes in such patients may be poor; in one study including 80 HIV-infected pregnant patients with TB and 155 HIV-infected pregnant patients without TB, the patients with TB had higher rates of preeclampsia, their infants had higher rates of mortality and low birth weight, and 12 percent of these infants were born with TB [51]. Other issues related to TB and HIV are discussed further separately. (See "Treatment of pulmonary tuberculosis in adults with HIV infection: Initiation of therapy".)

Drug susceptibility data should be reviewed when available, and treatment should be adjusted if needed. Issues related to treatment of drug-resistant TB in pregnancy are discussed separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Pregnant women'.)

Treatment interruptions longer than two weeks, suspected or confirmed drug resistance, or sporadic adherence should prompt consultation with an expert in tuberculosis. Nonadherence within the first two months of treatment generally warrants restarting treatment from the beginning [44]. (See "Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults".)

Controlling transmission — Mothers with active pulmonary TB can transmit infection to their infants. Therefore, patients with known or suspected active TB at the time of delivery should be separated from the infant until both have been evaluated [50] (see "Tuberculosis disease in children", section on 'Diagnosis' and "Diagnosis of pulmonary tuberculosis in adults"):

●If both the mother and infant have active pulmonary TB (implying congenital TB, which is very rare), both should be started on treatment. The infant and mother need not be separated as long as both are adherent; the mother should wear a mask until no longer contagious.

●If the mother has active drug-susceptible pulmonary TB and the infant has a positive skin test (in the absence of evidence for active disease), the mother should be treated for active TB and the infant should be treated for latent TB. The infant and mother need not be separated as long as both are adherent; the mother should wear a mask until no longer contagious.

●If the mother has active drug-susceptible pulmonary TB and the infant has no evidence of active or latent TB, the mother should be treated for active TB and the infant should be treated for latent TB for three to four months. The infant and mother need not be separated as long as both are adherent; the mother should wear a mask until no longer contagious. After three to four months of treatment, the infant should have a repeat skin test. If the mother has drug-susceptible TB and has been adherent to treatment, at this point she should have been noncontagious (and the infant should have had no TB exposure) for at least 10 weeks:

•If the infant's repeat skin test is positive, the infant should be reevaluated for active TB (see "Latent tuberculosis infection in children" and "Tuberculosis disease in children"). The infant should receive a full course of treatment for either latent or active TB, based on the result of the reevaluation. The infant and mother need not be separated as long as both are adherent.

•If the infant's repeat skin test is negative, the infant need not continue LTBI treatment. The infant and mother need not be separated as long as the mother is adherent.

●If the mother is still contagious, both mother and infant warrant further investigation in conjunction with expert consultation. (See "Treatment of drug-resistant pulmonary tuberculosis in adults" and "Latent tuberculosis infection in children" and "Tuberculosis disease in children".)

There is no role for use of Bacille Calmette-Guérin (BCG) vaccination during pregnancy for prevention of TB since it is a live vaccine; issues related to BCG vaccination are discussed further separately. (See "Vaccines for prevention of tuberculosis".)

Issues related to controlling transmission in the setting of drug-resistant TB warrant expert consultation. General issues related to TB transmission and control are discussed further separately. (See "Tuberculosis transmission and control in health care settings".)

MONITORING DURING TREATMENT — Pregnancy and the early postpartum period may confer increased risk for isoniazid-induced hepatotoxicity, especially in Hispanic and African-American individuals. [23,38,52,53].

Therefore, pregnant patients and postpartum patients within three months of delivery should have baseline liver function testing (serum transaminases and bilirubin) prior to initiation of treatment for latent or active TB. Additional evaluation should include testing for HIV and hepatitis B and C as well as general evaluation for chronic liver disease, alcohol use, and exposure to other hepatotoxins.

In the absence of evidence for underlying liver disease, initiation of antituberculous drugs should be followed by monthly evaluation for symptoms of hepatitis, clinical examination, and liver function testing. In the setting of liver disease or abnormal liver function tests, more frequent monitoring may be warranted.

In addition, patients on antituberculous drugs should be educated about the symptoms of hepatitis and instructed to stop the medication should such symptoms occur and to seek prompt evaluation of symptoms to reduce risk for progression to severe disease [54]. Symptoms include anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever lasting three or more days, abdominal pain (particularly right upper quadrant discomfort), easy bruising or bleeding, or arthralgias.

Issues related to regimen adjustments and hepatotoxicity should be addressed as discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults", section on 'Regimen adjustments for drug intolerance'.)

Other side effects of isoniazid include rashes, neuropsychiatric disturbances including depression, mania, memory loss and/or psychosis, pellagra, peripheral neuritis, and seizures.

Adverse effects due to rifampin include hepatitis, thrombocytopenia, hemolytic anemia, fever, and rash. (See "Rifamycins (rifampin, rifabutin, rifapentine)".)

BREASTFEEDING — Breastfeeding should be encouraged among patients on treatment for latent TB and after at least two weeks of treatment for active TB [50]. The small concentrations of first-line antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) in breast milk do not produce toxic effects in the nursing infant [15,44,49,55]. Exclusively breastfed infants receiving isoniazid (either via breast milk or as directed therapy) should receive supplemental pyridoxine.

Decisions about breastfeeding with second-line agents should be made in consultation with an expert. (See "Treatment of drug-resistant pulmonary tuberculosis in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of tuberculosis".)

SUMMARY AND RECOMMENDATIONS

General principles

●Worldwide, the burden of tuberculosis (TB) disease in pregnant patients is substantial. Prenatal care presents a unique opportunity for evaluation and management of latent and active TB among individuals with risk of TB who may not otherwise present for medical care. (See 'Introduction' above.)

●TB infection is caused by inhalation of viable bacilli, which may persist in an inactive state (known as latent TB infection [LTBI]) or progress to active TB disease. Individuals with latent TB infection (LTBI) are asymptomatic and not contagious. Latent TB bacilli remain viable and may reactivate, causing active symptomatic TB disease, which can be transmitted via airborne spread. (See 'Natural history of TB in pregnancy' above.)

Latent tuberculosis

●Screening for LTBI during pregnancy should be pursued only for patients with significant risk factors for progression to active disease during pregnancy; these include patients with recent contact with a patient with untreated active respiratory TB, HIV-infected patients with CD4 count ≤350 cells/mm³ (some experts favor a lower CD4 threshold of ≤200 cells/mm³), HIV-infected patients not on antiretroviral therapy (ART), and patients with other significant immunocompromise. (See 'Whom to test' above.)

●Diagnostic tools for latent TB include tuberculin skin testing (TST) and interferon-gamma release assays (IGRAs). Definitions of positive TST are summarized in the table (table 1). Patients with a positive TST or IGRA must undergo clinical evaluation to rule out active TB; this includes evaluation for symptoms (eg, fever, cough, weight loss) and radiographic examination of the chest (with appropriate shielding), regardless of gestational age. (See 'How to test' above and 'Diagnostic evaluation after positive test' above.)

●The potential risks of adverse pregnancy outcomes associated with LTBI treatment during pregnancy must be weighed against the potential risks of progression to active TB during pregnancy. For most pregnant patients with LTBI, we suggest deferral of treatment until three months after delivery (Grade 2C). We initiate LTBI treatment during pregnancy for all patients with recent contact with a patient with untreated active respiratory TB and for HIV-infected patients with CD4 count ≤350 cells/mm³ (some experts favor a lower CD4 threshold of ≤200 cells/mm³). We also initiate LTBI treatment for HIV-infected patients not on ART; however, some experts would defer LTBI treatment for patients not on ART with CD4 >200 cells/mm³. (See 'Timing of treatment' above.)

●In general, for treatment of LTBI in pregnancy, we suggest a rifamycin-based regimen over isoniazid monotherapy, given the efficacy, favorable treatment completion rates, and relatively low hepatotoxicity rates of rifamycin-based regimens (table 2) (Grade 2C). Nitrosamine contamination of rifampin must be considered in the risk benefit analysis for any rifampin-based regimen. For treatment of LTBI in HIV-infected pregnant patients in settings with high TB transmission rates, we suggest daily isoniazid for 36 months (Grade 2C). (See 'Selecting a regimen' above.)

Active tuberculosis

●Pregnant patients with pulmonary TB have the same clinical manifestations as nonpregnant patients; these may include fever, cough, weight loss, night sweats, and malaise. TB in pregnant patients can present insidiously, since malaise and fatigue may be attributed to pregnancy rather than disease. In addition, it can be difficult to recognize weight loss during pregnancy. (See 'Clinical manifestations' above.)

●The approach to diagnosis of active TB in pregnant patients is the same as in nonpregnant individuals; it consists of clinical history (with epidemiologic assessment) and physical examination, followed by chest radiography (with appropriate shielding to protect the fetus). Chest imaging suggestive of pulmonary TB should prompt submission of three sputum specimens (coughed or induced) for acid-fast bacilli smear and culture as well as at least one sputum specimen for Mycobacterium tuberculosis nucleic acid amplification testing. (See 'Diagnosis' 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 (Grade 1B). Pyrazinamide is not absolutely necessary as part of a first-line regimen and is not used routinely for treatment of pregnant patients in the United States because of limited safety data; however, its use is gaining acceptance and it is beneficial in the setting of HIV coinfection, extrapulmonary TB, or severe TB. Pyrazinamide is recommended by the World Health Organization as part of a standard regimen for treatment of TB in pregnant patients. (See 'Treatment' above.)

Other principles

●Pregnant patients and postpartum patients within three months of delivery should have baseline liver function testing (serum transaminases and bilirubin) prior to initiation of treatment for latent or active TB. In the absence of evidence for underlying liver disease, initiation of antituberculous drugs should be followed by monthly evaluation for symptoms of hepatitis, clinical examination, and liver function testing. In the setting of liver disease or abnormal liver function tests, more frequent monitoring may be warranted. (See 'Monitoring during treatment' above.)

●Issues related to breastfeeding and controlling transmission are as summarized above. (See 'Breastfeeding' above and 'Controlling transmission' above.)