Treatment outcomes among pregnant patients with multidrug-resistant tuberculosis. A systematic review and meta-analysis

Importance: The management of multidrug-resistant tuberculosis (MDR-TB) during pregnancy is challenging, yet no systematic synthesis of evidence has accurately measured treatment outcomes. Objective: To systematically synthesize treatment outcomes and adverse events among pregnant patients with MDR-TB. Data Sources: PubMed, Scopus, Web of Science, and ProQuest were searched from the inception of each database through August 31, 2021. Study Selection: Studies containing cohorts of pregnant patients with a defined treatment outcome were eligible. Data Extraction and Synthesis: Independent reviewers screened studies and assessed the risk of bias. The study followed the Preferring Reporting Items for Systematic Review and Meta-analyses reporting guideline. Meta-analysis was performed using random-effects models. The sources of heterogeneity were explored through metaregression. Main Outcomes and Measures: The primary outcome was the proportion of patients with each treatment outcome (including treatment success, death, loss to follow-up, and treatment failure), and the secondary outcomes included the proportion of patients experiencing adverse events during pregnancy. Results: In this systematic review and meta-analysis, 10 studies containing 275 pregnant patients with available data on treatment outcomes were included. The pooled estimate was 72.5% (95% CI, 63.3%-81.0%) for treatment success, 6.8% (95% CI, 2.6%-12.4%) for death, 18.4% (95% CI, 13.1%-24.2%) for loss to follow-up, and 0.6% (95% CI, 0.0%-2.9%) for treatment failure. Treatment success was significantly higher in studies in which the proportion of patients taking linezolid was greater than the median (20.1%) compared with studies in which this proportion was lower than the median (odds ratio, 1.22; 95% CI, 1.05-1.42). More than half of the pregnant patients (54.7%; 95% CI, 43.5%-65.4%) experienced at least 1 type of adverse event, most commonly liver function impairment (30.4%; 95% CI, 17.7%-45.7%), kidney function impairment (14.9%; 95% CI, 6.2%-28.3%), hypokalemia (11.9%; 95% CI, 3.9%-25.6%), hearing loss (11.8%; 95% CI, 5.5%-21.3%), gastrointestinal disorders (11.8%; 95% CI, 5.2%-21.8%), psychiatric disorders (9.1%; 95% CI, 2.5%-21.6%), or anemia (8.9%; 95% CI, 3.6%-17.4%). The pooled proportion of favorable pregnancy outcomes was 73.2% (95% CI, 49.4%-92.1%). The most common types of adverse pregnancy outcomes were preterm birth (9.5%; 95% CI, 0.0%-29.0%), pregnancy loss (6.0%; 95% CI, 1.3%-12.9%), low birth weight (3.9%; 95% CI, 0.0%-18.7%), and stillbirth (1.9%; 95% CI, 0.1%-5.1%). Most of the studies had low-quality (3 studies) or medium-quality (4 studies) scores. Conclusions and Relevance: In this systematic review and meta-analysis, high treatment success and favorable pregnancy outcomes were reported among pregnant patients with MDR-TB. Further research is needed to design shorter, more effective, and safer treatment regimens for pregnant patients with MDR-TB.