Abstract
Background The World Health Organization (WHO) recommends tuberculosis (TB) preventive treatment for high-risk groups. Isoniazid preventive therapy (IPT) has been used globally for this purpose for many years, including in pregnancy. This review assessed current knowledge about the safety of IPT in pregnancy.
Methods We searched PubMed, Embase, CENTRAL, Global Health Library and HIV and TB-related conference abstracts, until May 15, 2019, for randomised controlled trials (RCTs) and non-randomised studies (NRS) where IPT was administered to pregnant women. Outcomes of interest were: 1) maternal outcomes, including permanent drug discontinuation due to adverse drug reactions, any grade 3 or 4 drug-related toxic effects, death from any cause and hepatotoxicity; and 2) pregnancy outcomes, including in utero fetal death, neonatal death or stillbirth, preterm delivery/prematurity, intrauterine growth restriction, low birth weight and congenital anomalies. Meta-analyses were conducted using a random-effects model.
Results After screening 1342 citations, nine studies (of 34 to 51 942 participants) met inclusion criteria. We found an increased likelihood of hepatotoxicity among pregnant women given IPT (risk ratio 1.64, 95% CI 0.78–3.44) compared with no IPT exposure in one RCT. Four studies reported on pregnancy outcomes comparing IPT exposure to no exposure among pregnant women with HIV. In one RCT, adverse pregnancy outcomes were associated with IPT exposure during pregnancy (odds ratio (OR) 1.51, 95% CI 1.09–2.10), but three NRS showed a protective effect.
Conclusions We found inconsistent associations between IPT and adverse pregnancy outcomes. Considering the grave consequences of active TB in pregnancy, current evidence does not support systematic deferral of IPT until postpartum. Research on safety is needed.
Abstract
Studies report conflicting links between isoniazid preventive therapy (IPT) and adverse pregnancy outcomes. Given known harms of active TB in pregnancy, the findings do not support systematic deferral of IPT until postpartum. We need more safety research. http://bit.ly/2R0Wc3G
Footnotes
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: Y. Hamada has nothing to disclose.
Conflict of interest: C. Figueroa has nothing to disclose.
Conflict of interest: M. Martín-Sánchez has nothing to disclose.
Conflict of interest: D. Falzon has nothing to disclose.
Conflict of interest: A. Kanchar has nothing to disclose.
- Received October 9, 2019.
- Accepted November 23, 2019.
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