TB in pregnancy and lactation research toolkit

TB in pregnancy and lactation research toolkit

WHO / Harrison Thane
Midwife Rahmi (Mimi) performs a prenatal ultrasound to check the health of Inawati’s baby at the Pala Island Village Health Post, Indonesia.
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Introduction

Tuberculosis (TB) during pregnancy is a significant concern, with an estimated 336 900 pregnant and postpartum women affected annually (1). Congenital TB is rare, but TB-related adverse outcomes – such as maternal and infant mortality, prematurity, and low birth weight – are common among pregnant women with TB (2). Early and effective TB treatment can improve these outcomes, yet specific evidence on dosing and safety of TB medicines during pregnancy remains limited. Recent studies raise concerns about inadequate dosing of isoniazid and ethambutol in pregnancy (3-5). For drug-resistant TB, no specific evidence-based guidance exists for pregnant or lactating women, often resulting in use of longer, more toxic treatments – and, in some settings, recommendations for pregnancy termination. Postpartum women with TB are often advised to stop breastfeeding due to limited data on drug transfer through breastmilk.

These data gaps stem from the historic exclusion of pregnant and lactating women from TB research. In 2025, the WHO Department for HIV, Tuberculosis, Hepatitis and Sexually Transmitted Infections initiated a process for building consensus to advance the earlier and optimal inclusion of pregnant and lactating women in TB therapeutic and vaccine trials. As part of the consensus process, five thematic working groups were established covering preclinical TB research, TB therapeutics research, TB vaccine research, maternal TB surveillance systems and advocacy. Subsequently, WHO published a consensus statement and call to action which promote the earlier and optimal inclusion of these populations in TB studies (6, 7). These documents outline several tangible actions that various groups of stakeholders (including researchers) can take to safely include pregnant and lactating women in TB research. One of the actions included the development of a TB research toolkit to facilitate inclusion of pregnant and lactating women in TB drug trials. The research toolkit is also informed by a scoping review and the prior work of the working groups. This toolkit supports TB researchers and trialists in implementing the approaches outlined in the 2025 WHO consensus statement. It offers guidance on the design, implementation, analysis, and monitoring of studies that include pregnant and lactating women, supplemented by case studies and practical resources. 

​​​Mafirakureva, et al. (1) describes new estimates of TB in pregnant and postpartum women.

​​​Jonsson, et al. (8) describes the increased risk of TB during pregnancy and the postpartum period.

​​​Sobhy et al. 2) is a comprehensive review and meta-analysis of maternal and perinatal outcomes associated with TB during pregnancy.

Key references

Optimal and early inclusion of pregnant and lactating women in tuberculosis research: consensus statement
19 August 2025

Optimal and early inclusion of pregnant and lactating women in tuberculosis research: consensus statement

In 2024, the World Health Organization Global Programme on Tuberculosis & Lung Health (WHO/GTB) led a consensus building process to advance the earlier...

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Accelerating research to end tuberculosis in pregnant and lactating women: a call to action
19 August 2025

Accelerating research to end tuberculosis in pregnant and lactating women: a call to action

This call to action accompanies the consensus statement on the optimal and early inclusion of pregnant and lactating women in tuberculosis research and...

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References

  1. Global estimates of tuberculosis incidence during pregnancy and postpartum: a rapid review and modelling analysis. Mafirakureva N, Cartledge A, Bradshaw I, Bekker A, Salazar-Austin N, Meehan S-A et al. Lancet Glob Health. 2026;14(3):e337–e346.

  2. Maternal and perinatal mortality and morbidity associated with tuberculosis during pregnancy and the postpartum period: a systematic review and meta-analysis. Sobhy S, Babiker ZOE, Zamora J, Khan KS, Kunst H. BJOG 2017;124(5):727–33.

  3. Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV. Abdelwahab MT, Leisegang R, Dooley KE, Mathad JS, Wiesner L, McIlleron H et al. Antimicrob Agents Chemother. 2020;64(3):10.1128/aac.01978-19.

  4. Pharmacokinetics and safety of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum: results from IMPAACT P1026s. Van Schalkwyk M, Bekker A, Decloedt E, Wang J, Theron GB, Cotton MF et al. Antimicrob Agents Chemother. 2023:e0073723. 

  5. Pharmacokinetics of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum with and without efavirenz-based antiretroviral treatment: IMPAACT P1026s study. Van Schalkwyk M, Bekker A, Decloedt E, Wang J, Theron GB, Cotton MF et al. Antimicrob Agents Chemother. 2025;69(9):e00052–25. 

  6. Optimal and early inclusion of pregnant and lactating women in tuberculosis research: consensus statement. Geneva: World Health Organization; 2025.

  7. Accelerating research to end tuberculosis in pregnant and lactating women: a call to action. Geneva: World Health Organization; 2025.

  8. Increased risk of active tuberculosis during pregnancy and postpartum: a register-based cohort study in Sweden. Jonsson, J, Kuhlmann-Berenzon, S, Berggren, I, Bruchfeld, J. Eur Respir J. 2020;55(3).

Abbreviations

CAB Community Advisory Board

CDC Centers for Disease Control (United States of America)

EPTB extrapulmonary tuberculosis

FDA U.S. Food and Drug Administration

DART developmental and reproductive toxicity

NIH National Institutes of Health (United States of America)

NTP national tuberculosis programme

PBPK physiologically based pharmacokinetic modelling

PK pharmacokinetic

PopPK population pharmacokinetic

PTB pulmonary tuberculosis

RID relative infant dose

SOE schedule of evaluations

TB tuberculosis

TPT TB preventive treatment

TBTC TB Trials Consortium

WHO World Health Organization

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Acknowledgements

The development of the technical content was coordinated by Sabine Verkuijl, Kerri Viney and Fuad Mirzayev under the supervision of Matteo Zignol, World Health Organization (WHO), and under the leadership of Tereza Kasaeva, Director of the WHO Department for HIV, Tuberculosis, Hepatitis and Sexually Transmitted Infections. Substantial technical contributions were provided by Nicole Salazar-Austin and Madlen Nash (Johns Hopkins University, United States of America); as well as the following experts: Mallika Alexander (Center for Infectious Diseases in India, India); Rebecca Barry (RTI International, United States of America); Lee Fairlie (Wits RHI, South Africa); Yael Hirsch - Moverman (Columbia University, United States of America); Sharon Jepkorir Sawe (University of Cape Town, South Africa); Emma Kalk (University of Cape Town, South Africa); Soyeon Kim (Frontier Science Foundation, United States of America); Christina Lancioni (Oregon Health & Science University, United States of America); Sue Ann Meehan (Stellenbosch University, South Africa); Grace Montepiedra (Harvard University, United States of America, now retired); Louvina van der Laan (Stellenbosch University, South Africa); Catriona Waitt (University of Liverpool, United Kingdom of Great Britain and Northern Ireland) and Ethel Weld (Johns Hopkins University, United States of America).

WHO sincerely thanks the following external collaborators for providing input to or reviewing the content of the toolkit (in alphabetical order, by topic):

Community engagement: Dimple Chudgar (Advanced Laparoscopy and Infertility Centre, India); Evaline Kibuchi (Stop TB Partnership, Kenya); Erin McConnell (Treatment Action Group, United States of America); Bianca Tasca (KNCV Tuberculosis Foundation, Kingdom of the Netherlands).

Ethical considerations: Anne Drapkin Lyerly (University of North Carolina, United States of America).

Preclinical studies: Angela Colbers (Radboud University Medical Center, Kingdom of the Netherlands); Stephanie Gaw (University of California, San Francisco, United States of America).

Therapeutics: Lelia Chaisson (University of California San Francisco, United States of America); Paolo Denti (University of Cape Town, South Africa); Ahizechukwu Eke (Johns Hopkins University, United States of America); Jennifer Hughes (Stellenbosch University, South Africa); Sylvia LaCourse (University of Washington, United States of America); Jyoti Mathad (Weill Cornell Medical, United States of America); Lynne Mofenson (Elizabeth Glaser Pediatric AIDS Foundation, United States of America).

TB vaccines: Benjamin Kagina (University of Cape Town, South Africa); Flor Munoz-Rivas (Baylor College of Medicine, United States of America); Edna Tembo (Coalition of Women Living with HIV/AIDS, Malawi).

Surveillance studies and registries Alison Abboud (The University of Melbourne, Australia); Leslie Enane (Indiana University, United States of America); Shahin Lockman (Harvard University, United States of America); Marian Loveday (South African Medical Research Council, South Africa); Lynne Mofenson (Elizabeth Glaser Pediatric AIDS Foundation, United States of America); Daniele Maria Pelissari (National TB Programme, Brazil); Moorine Sekadde (National TB and Leprosy Programme, Uganda); Claire Townsend (WHO consultant).

Case Studies: Francesca Conradie (University of the Witwatersrand, South Africa); Kelly Dooley (Vanderbilt University Medical Center, United States of America); Anneke Hesseling (Stellenbosch University, South Africa); Susan Purchase (Stellenbosch University, South Africa).

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Methodology

Methodology

Development of the TB component of the toolkit for inclusion of pregnant and lactating in clinical trials was informed by the WHO-led global consensus process on the earlier and optimal inclusion of pregnant and lactating women in TB research, conducted between October 2023 and February 2025. Five thematic working groups covering preclinical research, TB therapeutics, TB vaccines, maternal TB surveillance and advocacy met throughout 2024 to identify evidence gaps and develop proposed approaches. Evidence reviews were commissioned to address key gaps identified during this process, and the proposed approaches were subsequently discussed and refined through the consensus process.

To support development of the toolkit, this work was supplemented by a rapid, targeted review of relevant evidence and practical resources. Relevant published literature, guidance and normative documents, reports and meeting proceedings, trial protocols and registration records, and other practical research resources were identified based on their relevance to the topics covered by the toolkit. The identified materials were used alongside the outputs of the consensus process to develop the draft content. The draft was subsequently reviewed and refined by members of the relevant working groups and additional subject-matter experts.

Management of declarations of interest

All external experts signed declarations of interest, disclosing to the WHO any potential conflicts of interest that might influence or could reasonably be perceived to influence their objectivity and independence in relation to the content of the TB-specific toolkit. WHO thoroughly reviewed each declaration and determined that none posed an actual or reasonably perceived conflict of interest concerning any aspect of the toolkit.

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