Data regarding the use of most LTBI treatment regimens during pregnancy are limited, with the majority of data available for INH monotherapy. Observational data have suggested a possible increased risk of INH-induced hepatotoxicity during pregnancy and the first three months postpartum.64 Furthermore, a recent RCT of 28 weeks of INH preventive therapy in pregnant and postpartum patients with HIV who were on antiretroviral therapy showed an increased risk of adverse pregnancy outcomes in those receiving INH.65 No data have been published regarding rifampin for TPT during pregnancy. However, rifampin is considered safe during pregnancy for treatment of active TB disease, suggesting safety for TPT as well. Only limited data are available for 3HP. Notably, an analysis of the subgroup of 126 pregnant patients in two large trials showed rates of adverse pregnancy outcomes similar to background rates and no increased risk in 3HP vs 9H.66
The potential risk of TPT must be weighed against the risk of progression to active TB. Some observational data suggest an increase in the risk of active TB disease in the postpartum period, and possibly during pregnancy,67 although this finding is not consistent across studies.68 The potential risk of TPT must be weighed against the risk of progression to active TB.
INH and rifampin are excreted in breast milk in small quantities, well below the usual therapeutic neonatal dose, and are unlikely to pose a substantive risk to infants.69 The US Red Book recommends against pyridoxine for breastfed infants who are not on INH, but whose mother is taking INH.70 The extent of rifapentine excretion in breastmilk and the safety of exposure in breastfed infants has not been determined.
We conditionally recommend that, if tuberculosis preventive treatment is given during pregnancy, 4 months of daily rifampin (4R) is the preferred option. Isoniazid-based regimens should be avoided until 3 months postpartum in all but exceptional circumstances (eg, a contact of a rifampin-resistant TB case who has a very high reactivation risk) (poor evidence).
Good practice statements
In pregnant patients, we suggest that tuberculosis preventive treatment should generally be deferred until after delivery unless the risk of reactivation is very high (eg, for recent close contacts of a person with active TB, people on immunosuppressants and/or people living with HIV).
Once weekly rifapentine and isoniazid for 3 months should generally be avoided during pregnancy and in breastfeeding mothers until more data are available.
Supplemental vitamin B6 is not required for breastfed infants whose mother is taking isoniazid but who are not taking isoniazid themselves.
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