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. 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

中文翻译：

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孕产妇异烟肼预防性治疗的安全性：系统评价和荟萃分析

背景 世界卫生组织 (WHO) 建议对高危人群进行结核病 (TB) 预防性治疗。多年来，异烟肼预防性治疗 (IPT) 已在全球范围内用于此目的，包括在怀孕期间。本综述评估了目前有关妊娠期 IPT 安全性的知识。方法 我们检索了 PubMed、Embase、CENTRAL、全球健康图书馆以及 HIV 和 TB 相关会议摘要，直至 2019 年 5 月 15 日，以查找对孕妇进行 IPT 的随机对照试验 (RCT) 和非随机研究 (NRS)。感兴趣的结果是：1) 母体结果，包括由于药物不良反应永久停药、任何 3 或 4 级药物相关毒性作用、任何原因死亡和肝毒性；2) 妊娠结局，包括宫内胎儿死亡、新生儿死亡或死产，早产/早产、宫内生长受限、低出生体重和先天性异常。使用随机效应模型进行荟萃分析。结果 在筛选了 1342 次引文后，9 项研究（34 至 51 942 名参与者）符合纳入标准。在一项 RCT 中，我们发现与未接触 IPT 的孕妇相比，接受 IPT 的孕妇发生肝毒性的可能性增加（风险比 1.64，95% CI 0.78-3.44）。四项研究报告了对感染 HIV 的孕妇的 IPT 暴露与未暴露进行比较的妊娠结局。在一项 RCT 中，不良妊娠结局与妊娠期间 IPT 暴露有关（优势比 (OR) 1.51，95% CI 1.09-2.10），但三项 NRS 显示出保护作用。结论 我们发现 IPT 与不良妊娠结局之间存在不一致的关联。考虑到妊娠期活动性结核病的严重后果，目前的证据不支持将 IPT 系统性推迟到产后。需要进行安全性研究。研究报告异烟肼预防性治疗 (IPT) 与不良妊娠结局之间存在相互矛盾的联系。鉴于妊娠期活动性结核病的已知危害，研究结果不支持将 IPT 系统性推迟到产后。我们需要更多的安全研究。http://bit.ly/2R0Wc3G