Impact of Tuberculosis Preventive Treatment on Adverse Pregnancy Outcomes in women living with HIV in Uganda: A Quasi-experimental study using routine care data

Background: The World Health Organization recommends tuberculosis preventive treatment (TPT) for people living with HIV, including pregnant women. However, data on the safety of TPT during pregnancy particularly from routine care settings in high tuberculosis (TB) burden countries remain limited. We evaluated the association between TPT exposure and adverse pregnancy outcomes among pregnant women living with HIV (WLHIV) in Uganda. Methods: We conducted a quasi-experimental study using routinely collected data from five public urban primary health care facilities in Kampala, Uganda. We included pregnant WLHIV on antiretroviral therapy (ART) between 2016 and 2023. The primary outcome was a composite of adverse pregnancy outcomes: miscarriage, stillbirth, low birth weight, congenital anomalies, or maternal/neonatal death. The primary exposure was 6-months isoniazid TPT (IPT) during pregnancy. Analyses used inverse probability of treatment weighting (IPTW) using logistic regression model to adjust for confounding and multiple imputation for handling missing data. Results: Analysis included 521 pregnant WLHIV, 44% were exposed to IPT during pregnancy. Overall, 10.0% experienced an adverse pregnancy outcome, with no significant difference between IPT-exposed and unexposed groups (10.3% vs. 9.6%; p = 0.81). Adjusted IPTW analysis showed no significant association between IPT exposure and adverse outcomes (pooled weighted odds ratio 1.04; 95% CI: 0.69–1.58). Sensitivity and subgroup analyses yielded consistent results. Conclusion: We found no evidence that 6-month isoniazid TPT increases the risk of adverse pregnancy outcomes. However, limitations in outcome and adverse event documentation from routine care may affect these findings. Strengthening pharmacovigilance and clinical reporting is essential to safeguard maternal and neonatal health as TPT coverage expands in high TB/HIV burden settings.