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• TB disease occurs in a small but definite percentage of pregnant woman.
• Relative immuno-compromise may allow latent infection to progress to active TB disease.
• Pregnant women with active TB have a higher risk of complications (pre-eclampsia, vaginal hemorrhage and fetal loss).
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• Need to consider risks and benefits for the mother and fetus.
– Option 1: Stop or delay MDR-TB treatment
• Can be considered if TB disease is not an immediate threat to the health of the patient or if TB is diagnosed in the late stages of pregnancy.
– Option 2: Terminate the pregnancy
• May be considered in cases that require injectable agents for cure.
– Option 3: Continue treatment while pregnant
• Treatment is challenging but not contraindicated.
• There is minimal data about the safety of second-line antituberculous agents during pregnancy.
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Retrospective review of 3089 patients started on MDR-TB treatment from July 1996 to December 2005 in Peru:
– 1033 (33.4%) of these patients were women of child ‐ bearing age
(age, 15 –45 years);
– 38 (3.6%) were reported to be pregnant while receiving treatment for MDR ‐ TB;
– 14 women experienced no changes in their treatment regimen during pregnancy;
– MDR ‐ TB treatment was suspended after determination of pregnancy for 14 (36.8%) women; and
– 13 women (34.2%) subsequently resumed treatment after discussion with a physician a median of 1.9 weeks (IQR, 1.0
–4.6 weeks) after suspension of treatment.
Palacios E, Dallman R, Muñoz M, et al. Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin Infect Dis 2009;48(10):1413-9.
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Treatment outcome
Cure
Death
Default
Failure
In treatment
Not known
Total (%)
Healthy
21
3
24 (63.2)
Dead
2
5
1
8 (21.1)
In treatment Unknown
1
2
3 (7.9)
2
1
3 (7.9)
Total
(%)
23 (60.5)
5 (13.2)
5 (13.2)
2 (5.3)
2 (5.3)
1 (2.6)
38 (100.0)
Palacios E, Dallman R, Muñoz M, et al. Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin Infect Dis 2009;48(10):1413-9.
USAID TB CARE II PROJECT

• Follow ‐ up data were available for 26/38 children.
– 2 children were treated for latent TB (IPT per NTP protocol);
– 1 child was treated successfully for active MDR-TB at 19 months of age based on the DST of the mother;
– 1 child died of pneumonia shortly after birth (no TB involvement was reported);
– 25 children are currently healthy, including those who were treated for latent or active TB; and
– 2 children have minor health problems:
• 1 child was born with testicular malformation (unlikely to be related to exposure to second-line TB drugs in utero;
• 1 child has idiopathic growth retardation but has otherwise remained healthy.
Palacios E, Dallman R, Muñoz M, et al. Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin Infect Dis 2009;48(10):1413-9.
USAID TB CARE II PROJECT

• Ideally avoid treatment during the first trimester.
– If the clinical state is severe enough to pose a threat to the life of the patient, consider treatment during the first trimester.
• Start treatment during the second or third trimester so that the patient will be smear and culture negative at the time of giving birth.
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• A = safety established in human studies.
• B = safety presumed based on animal studies.
• C = safety uncertain; no human or animal studies reveal an adverse effect.
• D = safety uncertain; evidence of risk but use is justified in certain circumstances.
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• Safety class C
• Experience with patients suggests safety
• Pyridoxine (vitamin B6) should be used during pregnancy
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• Safety class C
• Experience with patients suggests safety
USAID TB CARE II PROJECT

• Safety class B
• Experience with pregnant patients suggests safety
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• Safety class C
• Formal studies are limited but there is much clinical experience
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• Safety class D
– Documented toxicity to the developing fetal ear (8-11%). Toxicity is higher in the first trimester.
• Risks and benefits should be carefully considered.
• Use should be limited to severe cases when clinical status and drug resistance warrants use.
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• Safety class D
– Documented fetal ototoxicity
– With use of KM, 2.3%
• Risks and benefits should be carefully considered.
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• Safety class C
– Less ototoxicity in adults compared with the aminoglycosides.
• If the risk of morbidity or mortality from TB during pregnancy is high, it is preferable to use CM in place of an aminoglycoside.
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• Safety class C
– No documented teratogenic effects in human studies. Mean duration given 2-4 weeks.
– In 240 pregnant patients, no congenital effects observed.
• Data regarding the prolonged use in pregnant patients is limited, but benefits likely outweigh risks.
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• Safety class C
– Animal studies (high doses);
– 2 studies of 47 cases and 1 of 70 cases without adverse effects;
– In another study, 7 of 23 children had congenital malformations.
• The use is controversial given the mixed data; if an adequate regimen cannot be constructed without it, the use of ethionamide is justified.
• Given its gastrointestinal side effects, nausea and vomiting during pregnancy may be aggravated.
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• Safety class C
– Few studies in pregnant patients
– Animal studies do not document toxicity
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• Safety class C
• No data to show teratogenicity
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• First-line medications have a variable concentration in breast milk.
• Injectables not absorbed by infant (minimal possibility of toxicity for breastfeeding infant).
• Effects of other medications during breastfeeding unknown.
• Advise mother that breastfeeding is not prohibited but she should consider the risks and benefits of the decision.
USAID TB CARE II PROJECT

• Of 38 Peruvian women who received MDR-TB therapy while pregnant:
– 3 patients (7.9%) were pregnant at the initiation of MDR ‐ TB therapy and had been pregnant for a median of 8.2 months (IQR,
7.3
–8.2 months).
– 35 patients (92.1%) became pregnant while receiving treatment; these patients became pregnant a median of 9.7 months (IQR,
4.4
–17.0 months) after treatment initiation.
Palacios E, Dallman R, Muñoz M, et al. Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin Infect Dis 2009;48(10):1413-9.
USAID TB CARE II PROJECT

• The best way to deal with MDR-TB and pregnancy is to prevent it.
• All women of child-bearing age should be offered a reliable method of family planning by the health care worker providing
MDR-TB treatment (integrated family planning).
– A “ reliable method
” excludes abstinence and condoms.
– Depo-Provera can be provided at 3 month intervals during the clinic visit.
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• Provide individualized care based on risks and benefits to the patient and fetus.
• The patient should be involved in therapeutic decisions.
• If pregnancy occurs during treatment and the patient is stable, treatment can be deferred until the second trimester unless there is clinical deterioration.
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• During the first 20 weeks of pregnancy, avoid the injectable if possible.
– Exception: if the risk of morbidity or mortality is high, an injectable agent should be used (preferably CM).
• There is limited evidence, but clinical experience has shown that cycloserine, fluoroquinolones, and PAS may be used in pregnant patients.
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• Ethionamide and prothionamide
– Some cases of congenital fetal defects;
– Not enough data to confirm the safety or risks of these medications.
• Use pyridoxine (vitamin B6) in all pregnant patients.
• Breastfeeding is permissible, however the risks and benefit should be discussed with the patient.
USAID TB CARE II PROJECT