Latent tb and pregnancy


TB and Pregnancy

While dealing with a TB diagnosis in pregnancy is not easy, there is a greater risk to the pregnant woman and her baby if TB disease is not treated. Babies born to women with untreated TB disease may have lower birth weight than those babies born to women without TB. Rarely, a baby may be born with TB.

Testing for TB

The tuberculin skin test is considered both valid and safe to use throughout pregnancy. The TB blood test is safe to use during pregnancy, but has not been evaluated for diagnosing TB infection in pregnant women. Other tests are needed to diagnose TB disease.


Pregnant women who are diagnosed with TB disease should start treatment as soon as TB is detected. Although the TB drugs used in treatment cross the placenta, these drugs do not appear to have harmful effects on the baby.

Pregnant women who are diagnosed with TB disease should start treatment as soon as TB is detected. Although the TB drugs used in treatment cross the placenta, these drugs do not appear to have harmful effects on the baby.

Diagnosis Treatment
Latent TB Infection
  • Isoniazid (INH) daily or twice weekly for 9 months, with pyridoxine (vitamin B6) supplementation
  • 3HP INH and Rifapentine is not recommended for pregnant women or women expecting to be pregnant in the next 3 months
TB Disease
  • The preferred initial treatment regimen is INH, rifampin (RIF), and ethambutol (EMB) daily for 2 months, followed by INH and RIF daily, or twice weekly for 7 months (for a total of 9 months of treatment).
  • Streptomycin should not be used because it has been shown to have harmful effects on the fetus.
  • Pyrazinamide (PZA) is not recommended to be used because its effect on the fetus is unknown.
HIV-Related TB Disease
  • Treatment of TB disease for pregnant women co-infected with HIV should be the same as for nonpregnant women, but with attention given to additional considerations. For more information please review the Guidelines for Prevention and Treatment of OpportunisticInfections in HIV-Infected Adults and Adolescents.
  • TB treatment regimens for HIV-infected pregnant women should include a rifamycin.
  • PZA during pregnancy is not recommended in the United States, the benefits of a TB treatment regimen that includes PZA for HIV-infected pregnant women may outweigh the undetermined potential risks to the fetus.


The following antituberculosis drugs are contraindicated in pregnant women

  • Streptomycin
  • Kanamycin
  • Amikacin
  • Capreomycin
  • Fluoroquinolones

Women who are being treated for drug-resistant TB should receive counseling concerning the risk to the fetus because of the known and unknown risks of second-line antituberculosis drugs.


Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis drugs because the concentrations of these drugs in breast milk are too small to produce toxicity in the nursing newborn. For the same reason, drugs in breast milk are not an effective treatment for TB disease or LTBI in a nursing infant. Breastfeeding women taking INH should also take pyridoxine (vitamin B6) supplementation.

Related Links

For Patients
For Health Care Providers
  • Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIVexternal icon
  • Testing and Diagnosis Fact Sheets
  • Testing and Diagnosis Guidelines
  • TB Treatment Guidelines

Treatment During Pregnancy

You may worry that taking medicine for tuberculosis may harm your unborn child. It’s much worse to leave it untreated. TB drugs you take do reach your baby. But they haven’t been shown to cause harm in unborn babies.

Some TB drugs can lead to birth defects or other problems in a growing baby. But your doctor won’t prescribe those drugs if you’re pregnant or thinking about getting pregnant.

The medicine you get will depend on what kind of TB you have.

Latent TB. If you have no symptoms but tests show that you have the disease, you’ll likely take a drug called isoniazid. You may need to take it every day for 9 months, or just twice a week during that time. You’ll have to take vitamin B6 supplements at the same time.

Active TB. Usually, you’ll get three drugs at first: isoniazid, rifampin, and ethambutol. You’ll probably need to take all three every day for 2 months. For the rest of your pregnancy, it’s likely that you’ll take only isoniazid and rifampin, either daily or twice a week.

HIV and TB. If you also have HIV, your doctor probably will give you the same drugs to treat both diseases that she would give someone who’s not pregnant. Talk to your doctor so you understand the safest options for you and your baby.

TABLE 4. 1990 Centers for Disease Control and Prevention Recommendations for the Use of Preventive Therapy for Tuberculosis in the United States


Age <35

Age >35

Risk factor present:

Treat for PPD >4 mm; treat 12 months for

Treat as in <35 y/o

immunocompromised (HIV), HIV risk

immunocompromised individuals; immunocompetent

factors, close contacts, recent

contacts or converters, treat for 6–9 months

converters (within 2 years), HIV-

seronegative IVDUs, chronic medical

conditions, radiographic evidence of

old tuberculosis

High-incidence groups with no risk

Treat for PPD >9 mm; treat for 6 months



factors: foreign born from a high-

prevalence country, medically

underserved minority populations,

residents of long term care facilities

No risk factor, low-incidence group

Treat for PPD >14 mm



Centers for Disease Control and Prevention: The use of preventive therapy for tuberculosis infection in the United States: Recommendations of the advisory committee for elimination of tuberculosis. MMWR Morb Mortal Wkly Rep 39 (RR-8):9—12, 1990

Delay may not be wise choice for a variety of reasons. First, the risk of active tuberculosis is much greater than the risk of isoniazid-related hepatitis or death. The risk of active tuberculosis within high-risk or high-prevalence populations, who do not receive preventive chemotherapy, is 2% in the subsequent year. Even with aggressive chemotherapy, 5% die (case death rate of 1000 per 100,000). With isoniazid therapy, the incidence of clinical hepatitis and death in pregnant and postpartum women are 260 and 54 per 100,000, respectively. Second, the efficacy of isoniazid is clear. Among household contacts of index cases of active tuberculosis the incidence of active tuberculosis fell 61% (1550 to 610 cases per 100,000).50 Of the tuberculin-positive women who enter nursing homes, 2.3% develop active tuberculosis without preventive chemotherapy; with isoniazid preventive chemotherapy, the incidence is less than 0.3%. Among women whose tuberculin test converted, 7.6% develop active tuberculosis without preventive chemotherapy and only 0.2% with isoniazid preventive chemotherapy.48,50,51 Third, isoniazid-related hepatotoxicity is usually not an acute process, taking weeks to develop. Often, there is a component of patient or physician delay in the identification of symptoms. Biochemical monitoring of liver function tests may reduce the mortality considerably. Fourth, the recommendation is based on one study49 with 28% of subjects lost to follow up, small numbers (two deaths among treated group and one death in nonpregnant group). These deaths occurred months postpartum, and the recommendation to delay prophylactic isoniazid therapy until 3 to 6 months postpartum may increase the risk of active tuberculosis and not change the risk of hepatitis or death. The study also had an inappropriate comparison group with very different demographics, and it failed to control for the concomitant other hepatotoxic agents such as alcohol or acetaminophen.

Pregnant or postpartum women should receive isoniazid preventive therapy (300 mg/day for 6 continuous months and 12 months for immunocompromised individuals), regardless of gestational age, in high-risk or high-prevalence populations when the tuberculin test result is positive. In low-risk populations, isoniazid should be started after the first trimester.

Liver function tests should be obtained at baseline and every month. The patient is educated about compliance, hepatotoxic drugs and medications, and the signs and symptoms of hepatitis. Isoniazid blocks the conversion of substrate to pyridoxal phosphate and increases the urinary excretion of vitamin B6. Deficiency of vitamin B6 is associated with developmental defects in laboratory animals and a pyridoxine responsive-peripheral neuropathy. Because pregnancy is associated with low pyridoxine levels, 50 mg/day of vitamin B6 is recommended during isoniazid therapy.52 Prenatal vitamins contain 2 to 10 mg of pyridoxine. Isoniazid has been linked to vitamin K deficiency in the newborn. Supplemental vitamin K (10 mg) is recommended in the last 2 weeks of pregnancy and in the newborn.

Bacille Calmette-Guérin Vaccination

In 1921, Dr. Weil Halle administered a live-attenuated strain of M. bovis (i.e. bacille Calmette-Guérin) to a child at risk for acquired tuberculosis. The child experienced no untoward effects. By 1945, BCG vaccination was well established in Europe, although less so in the United States. Starting in 1935, controlled trials were initiated to determine the efficacy of BCG vaccination in reducing tuberculosis morbidity.35 The protective effect ranged from a risk of increased morbidity in the treated group of 56% to an 80% reduction in tuberculosis morbidity. Clemens and coworkers35 reviewed in detail the biases and methodologic errors in the trials. He measured allocation safeguards, equidistribution of tuberculosis risk, surveillance bias, diagnostic testing bias, diagnostic interpretation bias, and adequate statistical precision. The best designed studies had similar beneficial effects, BCG reduced tuberculosis by 75% to 80%. Currently, BCG is not given routinely to any population in the United States. It may be considered in neonates on a case-by-case basis in unavoidable tuberculosis exposure especially MDR-TB. In developing countries where active tuberculosis is common, prolonged chemotherapy is problematic, and the delivery of health care is limited, BCG vaccination remains a preventive modality with important public health benefits.

The issue for most American practitioners is among foreign-born immigrants who may or may not have had BCG vaccine. Many developing countries have public health policies that recommend routine vaccination of infants and sometimes of older children. However, the BCG vaccination coverage is only partial. Only 10% to 40% of eligible infants are vaccinated in Central and South America, with the exception of Cuba, Chile, and Costa Rica.37 If the patient describes a vaccination for tuberculosis, the interpretation of the tuberculin skin test depends on the age at vaccination and the interval to skin testing. In Quebec,36 BCG vaccination increased the incidence of positive tests (>10 mm) from 2.6% in unvaccinated individuals to 12.6% in vaccinated individuals. During tuberculin skin testing as an adult, 4.1% of unvaccinated individuals had a positive skin test, 10.3% if they were vaccinated as infants, and 25.5% if they were vaccinated when older. When the children were tuberculin skin tested in the sixth grade, the incidence of positive testing was 1.5% for unvaccinated, 4.9% for vaccinated as an infant, or 12.5% for vaccinated when older. Pregnancy does not seem to affect the reaction to tuberculin skin testing in BCG-vaccinated pregnant women.38

Therapeutic Management of Tuberculosis

All patients with microbiologically confirmed tuberculosis (i.e. positive acid-fast smear or positive culture), chest radiography suggesting active disease or cavitary lesions, or extrapulmonary lesions are considered to have active tuberculosis. All patients require multiagent therapy and intense follow-up for progression of disease and to confirm compliance.53Table 5 describes the antibiotics and toxicities used in the treatment of active tuberculosis.

TABLE 5. Standard Therapy and Toxicities For Active Tuberculosis

Drug Toxicity


Daily Dose

2× Weekly Dose

Isoniazid (INH)


5 mg/kg (300 mg)

15 mg/kg (900 mg)

Hepatitis, neuropathy,

central nervous system


Rifampin (RIF)


10 mg/kg (600 mg)

10 mg/kg (600 mg)

Orange color of secretions

and urine, hepatitis,

coagulopathy, flu-like

symptoms, rash

Ethambutol (EMB)


15–25 mg/kg

50 mg/kg

Optic neuritis evidenced by

decreased red-green

discrimination and visual


Pyrazinamide (PZA)


15–30 mg/kg (2 g)

50–70 mg/kg (4 g)

Gastrointestinal upset,

hepatitis, hyperuricemia,

arthralgias, rash

Streptomycin (SM)


15 mg/kg; max, 1 g

25–30 mg/kg;

Deafness (dose related),

max, 1.5 g


(dose related)

Atkins JN: Maternal plasma concentration of pyridoxal phosphate during pregnancy: Adequacy of vitamin B6 supplementation during isoniazid therapy. Am Rev Respir Dis 126:714–716, 1982

The initial treatment of active tuberculosis in the nonpregnant woman should include four drugs (i.e. isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) and continued for 6 months. Immunocompromised patients (e.g. HIV seropositive) require 12 months of four-agent therapy. Pregnant women should receive triple therapy (i.e. isoniazid, rifampin, and ethambutol) for 9 months. For populations in which the likelihood of resistance to any antibiotic is more than 4%, pyrazinamide should be added. Breast-feeding mothers should receive four-agent therapy. When a woman with active tuberculosis delivers without therapy for tuberculosis, both the mother and infant are treated. The issue of whether to separate the mother from her neonate is controversial. Many physicians advocate at least a 1 week of maternal therapy before returning the infant to its mother. This is very difficult for the breast-feeding mother. If the mother and the infant are receiving chemotherapy, there does not seem to be reasonable to separate them. Household contacts should be screened for tuberculosis before discharge. Table 6 describes the fetal and breast-feeding effects of chemotherapy for active tuberculosis.

TABLE 6. Chemotherapy for Tuberculosis During Pregnancy and Breast-feeding



Percent of

Neonatal Effects


Plasma Ratio

Therapeutic Dose

With Breast-


Serum Ratio

Fetal Effects

(Daily Dose)

for Infants





1.0 (24 mg)






0.2 (6 mg)





1.0 (1.5 mg)






0.12–0.47 (21 mg)


None, no oral

ototoxicity (rare)




None recorded

0.4 (3 mg)


None known, slow


Data from references 53, 54, and 55.

Isoniazid, ethambutol, and rifampin are considered safe to use in pregnancy because the risk of defects in human birth appears to be no greater than baseline incidences. Although the risk of congenital ototoxicity is small, streptomycin should not be used in pregnant women unless required by drug sensitivities. In breast-feeding women, the optimal drug combinations should not be changed. The infant should be managed as if he or she were not breast-feeding; the recommended doses for neonates should not be altered.

Patients under therapy need close follow-up. Liver function tests should be obtained monthly and the patient should be educated concerning hepatitis. At 2-week intervals after the initiation of therapy, three early morning sputum samples are obtained for AFB smears. This is repeated at 1, 2, 3, and 6 months after the start of therapy. The AFB smear should be negative by 2 months; if not negative by 4 months, drug resistance must be suspected. Two drugs for which the isolate is sensitive are substituted in the regimen. A chest radiograph is obtained every 2 months until cure is recognized.

A major cause of drug-resistant tuberculosis and subsequent treatment failure is the patients noncompliance with the antibiotics. Treatment failure and multidrug resistance are life-threatening events. Noncompliance leads to death and more new infections in the community. Directly observed therapy (DOT) is an effective method of increasing compliance. One study in New York City reported a compliance rate of only 11% with standard follow-up, but the rate of compliance rose to 98% after the initiation of DOT.53 The State of North Carolina recommends that all patients under therapy for tuberculosis have DOT.

Environmental Control of Tuberculosis

The environmental control of tuberculosis refers to building-associated interventions to prevent institutional airborne transmission from unsuspected cases or diagnosed cases before they are treated. The airborne infectious nuclei of tuberculosis (1 to 5 μm) allow wide dispersion through airflow patterns in the hospital. In the late 1950s, a classic experiment in hospital infection control was conducted at the Baltimore Veterans Administration Hospital by R.L. Riley.57,58 All the air from a chronic tuberculosis ward was pumped through a guinea pig colony in another room. The guinea pigs were skin tested monthly, and bacilli recovered from infected guinea pigs were matched by drug sensitivity patterns of the bacilli recovered from the patients. An intervention was conducted in the second 2 years of the study; the airflow was split, and one half was disinfected with ultraviolet light before exposure of a colony of guinea pigs. These experiments established that tuberculosis is an airborne disease; the infectiousness of a patient varies widely (1 to 250 infectious nuclei per hour) and is not well correlated with symptoms; an average concentration of one infectious nuclei per 11,000 cf in the well-ventilated room was sufficient to causes an tuberculosis rate similar to human epidemics. Ultraviolet light is an effective intervention.

The most frequent interventions in clinics or wards include increased ventilation, air filtration, and ultraviolet irradiation.59 Ventilation is the centerpiece of environmental control of tuberculosis. Engineering designs control dispersion of the organism (negative pressure gradient), dilute the concentration of tuberculosis per unit area (air exchanges), direct the contaminated air to the outside, or in-line ultraviolet irradiation.

Directional airflow is the creation of a room pressure that is less than the air pressure of adjacent rooms or hallways. Negative pressure is achieved by exhausting isolation room air faster than it can enter. This limits the dispersion of tuberculosis outside of the isolation room. The challenges to the maintenance of negative pressure include unrecognized air leaks and opening and closing doors and windows. The isolation room needs to be sealed except for a portal entry. A small anteroom with intermediate pressures can buffer the entry exchange of outside air. Entry and exit to the isolation room is strictly limited.

Direct exhaust airflow directs the contaminated air to outside dilution, filtration, or germicidal irradiation. Many jurisdictions require that contaminated air be exhausted at least 25 feet from the nearest entrance to the building (e.g. door, window) to prevent reentry of tuberculosis. As this requirement is hard to accomplish with reconstruction but easier in new construction; the airflow is often directed to filters or germicidal ultraviolet irradiation.

Negative pressure and direct ventilation are critical for limiting the spread of tuberculosis to the facility. In-room health care providers and visitors are not protected by the latter precautions. Dilution ventilation is a major technique used to reduce the risk to the individual who enters the room. Dilution ventilation is measured by air exchanges per hour. One air exchange per hour (ACH) can reduce the concentration of infectious particles by 63%, 3 ACHs by 95%, 6 ACHs by 99.75%, and 10 ACHs by more than 99.99%. The current standard for tuberculosis isolation rooms is 6 ACHs, with at least 2 ACHs being fresh outdoor air.

The two primary supplemental environmental control methods for tuberculosis are air filtration and ultraviolet germicidal irradiation. Mechanical filtration has been employed to control particulate dust, aerosols, and microorganisms for many years. Particles with an aerodynamic diameter of less than 0.3 μm are most difficult to remove by filtration. Because of its small size (0.5 to 5 μm), control of tuberculosis requires a highly efficient filter (i.e. HEPA filter). These filters have a removal efficiency of 99.97% at 0.3-μm particle size. HEPA filters are used in exhaust ventilation ducts, in modular air filtration units, for enhancing existing room ventilation, or in portable booths or canopy units where the need is temporary. Because of their efficiency and predilection to become clogged and block air flow, HEPA filters require intense and regular maintenance.

Ultraviolet germicidal irradiation has a lethal effect on a variety of microorganisms, including tuberculosis. The germicidal range for ultraviolet radiation is in the range of 220–300 nm with a maximum at 265 nm. Health care workers, visitors, and patients are at risk with direct exposure. Prolonged exposure to ultraviolet radiation among health care workers can result in erythema (sunburn), prokeratitis, and conjunctivitis.

There are three different applications of germicidal radiation to control tuberculosis within facilities: upper room irradiation, in-duct lamps, and recirculating room air cleaners. Normal in-room air movement carries the infectious particles to the ultraviolet light installed to irradiate the upper room near the 9-foot ceilings. The cleaning capacity of upper room ultraviolet is approximately 1.5 to 2.0 air exchange hour equivalents. With in-line duct ultraviolet, the cleaning capacity is equivalent to the air exchange rate. The efficiency of the cleaning is proportional to the flow rate; the greater the ACH, the less efficient is the cleaning power of ultraviolet radiation. Regardless of the lessened efficiency at high rates of ACH, there is significant increase in cleaning power when both methods are used. Ultraviolet irradiation is often combined with HEPA filters in modular units. Essentially, 100% of the tuberculosis particles are sterilized during each pass. The cleaning efficiency of ultraviolet irradiation is proportional to the ACH of the unit.

Effective environmental control of tuberculosis requires much more that placing equipment.60 An entire program with administrative support, technical support, monitoring systems, quality assurance, and staff and patient education is necessary for successful environmental control of tuberculosis. The advent of MDR-TB with its attendant 50% morbidity or mortality rate demands an appropriate system response to protect patients, visitors, and health care workers.

Table I.

An induration of 5 or more millimeters is considered positive in:

HIV-infected persons

A recent contact of a person with TB

Persons with fibrotic changes on chest radiograph, consistent with prior TB

Patients with organ transplants

Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-a antagonists)

An induration of 10 or more millimeters is considered positive in

Recent immigrants (< 5 years) from high-prevalence countries

Injection drug users

Residents and employees of high-risk congregate settings

Mycobacteriology laboratory personnel

Persons with clinical conditions that place them at high risk

Children < 4 years of age

Infants, children, and adolescents exposed to adults in high-risk categories

An induration of 15 or more millimeters is considered positive in any person, including persons with no known risk factors for TB. However, targeted skin testing programs should only be conducted among high-risk groups.

False positive reactions may occur in persons with infection with nontuberculosis mycobacteria, previous BCG vaccination, and incorrect TST method.

False negative reactions may occur in persons with cutaneous anergy, recent TB infection (within 8-10 weeks of exposure), very old TB infection (many years), recent live virus vaccination, overwhelming TB, and incorrect TST method.

A TB blood test (interferon-gamma release assays ) is a measure of how the immune system reacts to M. tuberculosis. This test does not differentiate active from latent TB. The test is based on the observation that white blood cells from most people infected with TB will release interferon-gamma (IFN-g) when mixed with antigens derived from M. tuberculosis. A prior BCG (bacille Calmette-Guerin) vaccination does not cause a false-positive IGRA test result.

3. Management

Untreated TB represents a greater hazard to a pregnant woman and her fetus than does its treatment. Treatment of pregnant women should be started when the chance of TB is moderate to high. Infants born to women with untreated TB may be of lower birth weight than those born to women without TB and, rarely, the infant may be born with TB. Although the drugs used in the initial treatment regimen cross the placenta, they do not appear to have harmful effects on the fetus.

The treatment of TB in pregnant women should be the same as that in nonpregnant women. The only exception is that aminoglycosides should be avoided in pregnancy, as they are ototoxic to the fetus.

Latent TB Infection (LTBI)

Isoniazid (INH) administered either daily or twice weekly for 9 months is the preferred regimen for treating LTBI in pregnant women. Women taking INH should also take pyridoxine (vitamin B6) supplementation.

Active TB Disease

Pregnant women should start treatment as soon as TB is suspected. The preferred initial treatment regimen is INH, rifampin (RIF), and ethambutol daily for 2 months, followed by INH & RIF daily or twice weekly for 7 months, for a total of 9 months of treatment. Streptomycin should not be used because it has been shown to have harmful effects on the fetus. In most cases, pyrazinamide (PZA) is not recommended because its effect on the fetus is unknown.

HIV Infection

HIV-infected pregnant women who are suspected of having TB should be treated without delay. TB treatment regimens for HIV-infected pregnant women should include a rifamycin. Although the routine use of PZA during pregnancy is not recommended in the United States, the benefits outweigh the undetermined potential risks to the fetus.

Optimal treatment of HIV-associated TB requires treatment with 2 multidrug regimens, typically 6 months of a 4-drug then a 2-drug regimen, to treat TB and a lifelong 3-drug antiretroviral regimen to reverse the functional immunosuppression that resulted in the development of active TB and to halt the further acceleration of HIV disease induced by active TB. Three recent trials have demonstrated the safety and superiority of initiating ART as soon as 2 weeks after the initiation of treatment for active TB, rather than at intervals of >2 to 6 months later.

Aminoglycosides and the fluoroquinolone antituberculosis drugs are contraindicated in pregnant women. However, the management of multidrug resistant TB (MDR-TB) in pregnancy is complex, and there is limited data on the safety of second-line drugs in pregnancy. In a large retrospective analysis on the treatment of MDR-TB in pregnancy, fluroquinolones were commonly continued while injectable aminoglycosides were generally stopped. Women who are being treated for drug-resistant TB should receive counseling about the risk to the fetus from second-line antituberculosis drug therapy.

Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis drugs because the concentrations of these drugs in breast milk are too small to produce toxicity in the nursing newborn. For the same reason, drugs in breast milk are not an effective treatment for TB disease or LTBI in a nursing infant. Breastfeeding women taking INH should also take pyridoxine (vitamin B6) supplementation.

4. Complications

Mother-to-child transmission of TB may occur in utero through hematogenous spread through the umbilical vein and aspiration or swallowing of infected amniotic fluid, and during the intrapartum period through contact with infected amniotic fluid or genital secretions.

Postpartum infection may occur through aerosol spread or infected breast milk from an active TB lesion in the breast. Although transmission through breast-feeding is negligible, an infant of a mother with active TB may still be infected through aerosol spread, even if formula fed.

5. Prognosis and outcome

There appears to be no statistically significant differences in pregnancy complications and pregnancy outcomes in pregnant women diagnosed and promptly treated for TB relative to matched controls who were pregnant and had no TB. Timely and appropriate treatment avoids the higher neonatal mortality rates associated with extreme prematurity in pregnancies with either untreated TB or when treatment is started late in the pregnancy.

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