Maternal and Infant Outcomes Among Pregnant Women Treated for Multidrug/Rifampicin-Resistant Tuberculosis in South Africa

Abstract

Background: Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programs.

Methods: Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, South Africa, from 1 January 2013 to 31 December 2017, were included. We conducted a record review to describe maternal treatment and pregnancy outcomes, and a clinical assessment to describe infant outcomes.

Results: Of 108 pregnant women treated for MDR/RR-tuberculosis, 88 (81%) were living with human immunodeficiency virus.. Favorable MDR/RR-tuberculosis treatment outcomes were reported in 72 (67%) women. Ninety-nine (91%) of the 109 babies were born alive, but overall, 52 (48%) women had unfavorable pregnancy outcomes. Fifty-eight (54%) women received bedaquiline, and 49 (45%) babies were exposed to bedaquiline in utero. Low birth weight was reported in more babies exposed to bedaquiline compared to babies not exposed (45% vs 26%; P = .034). In multivariate analyses, bedaquiline and levofloxacin, drugs often used in combination, were both independently associated with increased risk of low birth weight. Of the 86 children evaluated at 12 months, 72 (84%) had favorable outcomes; 88% of babies exposed to bedaquiline were thriving and developing normally compared to 82% of the babies not exposed.

Conclusions: MDR/RR-tuberculosis treatment outcomes among pregnant women were comparable to nonpregnant women. Although more babies exposed to bedaquiline were of low birth weight, over 80% had gained weight and were developing normally at 1 year.

Keywords: drug-resistant; outcome; pregnancy; treatment; tuberculosis.

Figure 1.

Schema of enrollment and attrition (1 January 2013–31 December 2018). Abbreviations: KDH, King Dinuzulu Hospital; MDR/RR-TB, multidrug/rifampicin-resistant tuberculosis.

Figure 2.

Mycobacterial drug susceptibility test pattern for pregnant women treated for multidrug/rifampicin-resistant tuberculosis. Fluoroquinolones: Resistance to any fluoroquinolone. (Some isolates were tested for resistance to levofloxacin, some to moxifloxacin, and in some, a genotypic result was provided that stated fluoroquinolone resistance without specifying individual drug). Injectables: Resistance to any second-line injectable drug. (Some isolates were tested for resistance to amikacin, some to kanamycin, some to capreomycin, and in some, a genotypic result was provided that stated injectable resistance without specifying individual drug). During the study period, no drug susceptibility testing was done for ethambutol, ethionamide, pyrazinamide, para-aminosalicylic acid, or terizidone.

Figure 3.

Individual drugs to which fetuses were exposed in utero. Abbreviations: AMK, amikacin; AUG, augmentin; BDQ, bedaquiline; CAP, capreomycin; CFZ, clofazimine; CLM, clarithromycin; EMB, ethambutol; ETH, ethionamide; INH, isoniazid; KAN, kanamycin; LVX, levofloxacin; LZD, linezolid; MXF, moxifloxacin; OFX, ofloxacin; PAS, para-aminosalicylic acid; PTH, prothionamide; PZA, pyrazinamide; RIF, rifampin; TRD, terizidone.

Figure 4.

Primary outcomes.