Guidelines for the prevention and management of mother-to-child transmission of tuberculosis

Introduction

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that can affect almost any organ system. Maternal TB can lead to congenital TB via vertical transmission (e.g., intrauterine infection) or to acquired TB through close postpartum contact (e.g., respiratory transmission). TB in neonates and infants is characterized by rapid disease progression, frequent delays in diagnosis, and high rates of mortality and disability, endangering survival and long-term quality of life. A proportion of exposed individuals develop latent TB infection (LTBI) and remain at risk of progression to active disease when immune defenses decline. Systematic prevention and control of mother-to-child transmission (MTCT) are therefore crucial to safeguard maternal and child health and to reduce the long-term burden of diseases.

Current knowledge on preventing and managing MTCT of TB is dispersed across multiple fields [TB in pregnancy, congenital TB, pediatric TB, breastfeeding, Bacille Calmette-Guérin (BCG) vaccination], contributing to inconsistent diagnosis, treatment, and newborn care. This guideline integrates multidisciplinary evidence to provide practical and actionable recommendations for comprehensive prevention and control of MTCT.

Guideline development methods

Registration and process standardization

This guideline was registered in Chinese and English on the Practice Guideline Registration and Transparency (PREPARE) platform (Registration No. IPGRP-2022CN104), with the protocol publicly available. Development followed the WHO Handbook for Guideline Development (2nd edition), and reporting adhered to the Reporting Items for Practice Guidelines in Health Care (RIGHT) checklist (1,2).

Guideline panel composition and declaration of interests

The guideline development panel comprised a multidisciplinary team from different regions, including specialists in TB, obstetrics and gynecology, neonatology, infectious diseases, preventive healthcare, hospital infection management, and methodology. All members completed conflict of interest declarations to ensure objectivity and independence.

Evidence integration and consensus formation

Clinical data were collected via expert discussions, questionnaires, and individual interviews. Systematic searches were performed in both Chinese and English databases [China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Weipu, PubMed, Embase, Cochrane Library, Web of Science] from database inception to June 2025 using Boolean operators (AND/OR/NOT) and keywords such as “assisted reproductive technologies”, “pregnancy”, “fetus”, “newborn”, “tuberculosis”, “breastfeeding”, and “treatment”. Evidence quality and recommendation strength were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework (3). Draft recommendations were developed based on evidence synthesis and refined through multiple rounds of a modified Delphi process and face-to-face panel discussions. The final guideline was approved by the steering committee following external expert review.

Scope and target users

The guideline primarily applies to women with active TB who are planning pregnancy, are pregnant, or develop active TB within one year postpartum, and their neonates/infants. It provides comprehensive guidance on screening, diagnosis, treatment, and nursing management for healthcare professionals working in obstetrics, neonatology, pediatrics, TB services, maternal and child health institutions, and TB control programs.

Epidemiological characteristics

According to WHO estimates, there were 10.7 million new TB cases globally in 2024. Of these, adult women accounted for 35% (3.7 million) and children/adolescents accounted for 11% (1.2 million) (4). Approximately 200,000 pregnant or postpartum women develop active TB each year (5). In high-burden countries, the prevalence of active TB among pregnant and postpartum women exceeds 60 per 100,000 population (6). Increasing use of in vitro fertilization and embryo transfer (IVF-ET) and the ongoing human immunodeficiency virus (HIV) epidemic may contribute to a rising incidence of TB during pregnancy.

Delayed diagnosis and inadequate treatment during pregnancy markedly increase adverse outcomes. A systematic review reported that pregnant women with TB had a 2.8-fold higher risk of adverse outcomes than those without TB, including higher risks of maternal anemia, cesarean delivery, perinatal mortality, miscarriage, preterm birth, low birth weight, and acute fetal distress (7). A U.S. nationwide hospitalization analysis (4,053 TB-affected pregnancies) showed significantly higher risks of severe preeclampsia, eclampsia, postpartum hemorrhage, placenta previa, and sepsis. The in-hospital mortality rate among pregnant women with TB was 37 times higher than that in women without TB (8).

Maternal TB can cause neonatal/infant infection via intrauterine transmission or postpartum respiratory exposure. About 50% of infected neonates/infants develop active disease within one year. Due to immune immaturity, they are more likely to develop severe forms (disseminated TB, TB meningitis) (9,10). In 2019, approximately 230,000 children died of TB globally, and the case-fatality rate of neonatal TB was as high as 40–60% (11). Even with treatment, TB in infants may cause irreversible damage (e.g., neurological sequelae after TB meningitis, spinal deformity after spinal TB, skeletal developmental abnormalities after bone TB, and pulmonary fibrosis/bronchiectasis after pulmonary TB) (12). The WHO recommends integrating TB screening into routine reproductive health services in settings with a high burden of HIV/TB (13).

Preconception TB screening

Screening population

Although it is uncertain whether pregnancy per se increases TB incidence, TB clearly contributes to adverse perinatal outcomes (14-16). Individuals at increased risk—and thus candidates for preconception screening—include those with suspected pulmonary or extrapulmonary TB; a history of TB without standardized treatment; close contacts of infectious pulmonary TB; residence in or travel to high‑burden settings; immunosuppression (e.g., HIV infection, prolonged immunosuppressant use, poorly controlled diabetes); people with substance use disorders; those living in poor conditions (homelessness or overcrowded housing); and those with malnutrition [body mass index (BMI) <18.5 kg/m²] (17,18).

Extrapulmonary TB, predominantly female genital tuberculosis (FGTB), warrants special attention and enhanced screening. FGTB may reactivate or worsen during pregnancy and is associated with adverse perinatal outcomes (7,19,20). In low- and middle-income or high-burden settings, women with primary/secondary infertility, chronic pelvic infections, or hydrosalpinx with poor response to standard therapy should be screened for possible FGTB (21,22). In a prospective cohort of 202 infertile women with FGTB, 77.2% had primary infertility, 22.77% had secondary infertility, and 34.15% had a history of miscarriage (23). Previous studies have shown that infertility occurs in 40–80% of women with FGTB (24), and the prevalence of FGTB among infertile women can reach as high as 20% in high-burden countries such as India and Pakistan (25,26).

With the increasing use of IVF-ET, adverse maternal and infant outcomes related to FGTB have increased. Comparative studies have shown that, among women who developed TB during pregnancy, those who conceived through IVF-ET had significantly higher risks than those who conceived naturally, including TB-related critical illness, miliary TB, and TB meningitis. Even after excluding induced abortion, this population remained at increased risk of infant mortality (19). Early screening and standardized treatment of FGTB are therefore essential (27).

• Recommendation 1. Preconception TB screening is recommended for high-risk populations, including individuals with suspected active TB, prior TB without completed treatment, close contacts of infectious pulmonary TB, HIV-infected or otherwise immunocompromised individuals, and those with malnutrition (B, 1). For individuals with primary/secondary infertility, recurrent miscarriage, or poor response to treatment for chronic pelvic inflammatory disease, screening for genital TB is suggested, particularly before IVF-ET and in those with prior failed IVF-ET (B, 1).

Screening methods

Preconception TB screening follows the same approach as for the general population (28,29). Screening includes symptom assessment, immunologic testing [tuberculin skin test (TST), Mtb antigen-based skin test (TBST), interferon-gamma release assay (IGRA)], and chest imaging. Site-specific evaluation is required for suspected extrapulmonary TB. Positive screens should be confirmed by microbiology (smear, molecular testing, culture) and/or pathology.

There is no single gold standard for diagnosing FGTB. Clinical manifestations are often atypical or absent. Infertility is common (43–74%), and other symptoms may include oligomenorrhea, amenorrhea, dysmenorrhea, and abdominal pain (30). Prior extragenital TB and TB exposure are frequent (25,26). Imaging specificity is limited: about half of tubal lesions detected on hysterosalpingography are TB-related, and up to 57.1% of FGTB patients have normal uterine cavity imaging (31). Microbiological and histopathological positivity rates are low due to cyclical endometrial shedding and low tissue bacillary load (32,33).

A comprehensive diagnostic approach combining medical history, smear/culture, molecular testing, histopathology, hysteroscopy/laparoscopy, and imaging (hysterosalpingography, gynecologic ultrasonography) improves diagnostic accuracy compared with singlemodality strategies (34). Minimally invasive specimens (e.g., blood, vaginal secretions) can be tested with molecular assays such as polymerase chain reaction (PCR) or Xpert MTB/RIF (21,35,36). Pelvic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) helps identify early lesions (e.g., tubal occlusion, hydrosalpinx, intrauterine adhesions, calcification, pelvic masses/abscesses) and supports differential diagnosis (37). Imaging is valuable not only for lesion detection but also for defining disease extent, guiding invasive sampling, and supporting fertility-related decision-making in women preparing for pregnancy or assisted reproductive treatment (37). For highly suspected but unconfirmed cases, hysteroscopy/laparoscopy with multi-site sampling is advised.

• Recommendation 2. For preconception screening, perform one of the following: TST/TBST/IGRA, plus chest imaging. For suspected extrapulmonary TB, conduct site-specific evaluation and confirm positive screens with microbiologic and/or pathological testing (D, 1).
• Recommendation 3. For suspected FGTB, in addition to the above, obtain hysterosalpingography, gynecologic ultrasonography, and abdominal contrast-enhanced CT/MRI as indicated, and perform molecular testing on vaginal discharge/menstrual blood/endometrium. Hysteroscopy/laparoscopy should be considered when clinically indicated (C, 2).

Management before pregnancy

For women diagnosed with TB preconception, treatment should be guided by drug susceptibility. Relapse rates among women cured of TB during pregnancy and postpartum are similar to those in non-pregnant women (38). Women cured of TB without evidence of relapse may proceed with pregnancy per routine guidance, with close monitoring during pregnancy and breastfeeding.

Active TB during pregnancy confers substantial maternal-fetal risks (7,39). WHO family planning guidance advises pregnancy monitoring for women on TB therapy; if pregnant, manage as TB in pregnancy; if not, counsel on risks of conceiving during treatment and complete therapy before conception, using effective contraception compatible with the regimen (40-42).

• Recommendation 4. Individuals diagnosed with TB before pregnancy should complete anti-TB treatment and use effective contraception until cure before attempting conception (B, 1). Women cured of TB with no relapse on preconception screening may proceed with pregnancy, with close monitoring during pregnancy and breastfeeding (D, 2).

TB during pregnancy

Diagnosis

Typical TB symptoms may be masked by pregnancy (e.g., weight loss obscured by gestational gain; fatigue, night sweats, anorexia, dyspnea attributed to pregnancy). Approximately 20% of pregnant women with TB may be asymptomatic, and in 60–70% of congenital TB cases, maternal TB is identified only after the newborn’s diagnosis (43). Avoidance of imaging due to fetal concerns can further delay diagnosis.

Among women who have undergone IVF-ET or who are immunocompromised, pregnancy TB more often presents as miliary (hematogenous) TB with acute onset and rapid progression, frequently complicated by respiratory failure, acute respiratory distress syndrome (ARDS), or TB meningitis (19). Fetal risks include miscarriage, preterm birth, intrauterine growth restriction, stillbirth, and increased congenital TB (44-47).

TST and IGRA can be used to screen for TB infection in pregnancy. Positive results indicate infection and warrant evaluation for active disease. Negative results are less reliable in individuals with HIV infection, immunosuppression, or renal failure (45-49). IGRA may be more sensitive than TST in high-burden settings (50).

Ultrasound and MRI are preferred during pregnancy, whereas X-ray and CT require careful risk-benefit assessment consistent with imaging guidelines in pregnancy (51). In clinical practice, ultrasonography is the first-line imaging modality for obstetric and fetal assessment; non-contrast MRI may serve as a complementary tool when sonographic findings are inconclusive or deep pelvic, abdominal, spinal, or central nervous system (CNS) TB is suspected. Available evidence has not demonstrated increased adverse fetal or childhood outcomes from non-contrast MRI, including first-trimester exposure; however, when imaging is not urgent, MRI may be deferred until after the first trimester if this is clinically feasible. Gadolinium contrast crosses the placenta and should generally be avoided during pregnancy unless the expected diagnostic benefit is substantial and cannot be replaced by non-contrast imaging (52-54). Microbiological testing (smear, culture, molecular assays) should be prioritized. Molecular tests are highly sensitive/specific, yield rapid results, and can detect drug resistance, thereby improving positivity rates and reducing time to diagnosis/treatment compared with smear and conventional culture-based methods (55-60).

• Recommendation 5. In pregnant individuals with suspected active pulmonary TB, prioritize sputum molecular testing for Mtb (A, 1). TST/IGRA may be used as adjuncts. When imaging is clinically indicated, ultrasonography is preferred for obstetric and fetal assessment, and non-contrast MRI may be used when additional evaluation is needed; chest X-ray or CT should be used cautiously after risk–benefit assessment, and contrast agents (such as gadolinium-based agents) should generally be avoided during pregnancy (D, 2).

Treatment

Timing

Early initiation of therapy substantially reduces adverse outcomes. Initiating anti-TB treatment in the first trimester is associated with lower rates of preterm birth, stillbirth, and low birth weight compared with delayed treatment (7). The risks posed by untreated active TB far outweigh the potential risks of anti-TB therapy during pregnancy (60,61).

• Recommendation 6. Initiate anti-TB treatment immediately once TB in pregnancy is diagnosed (B, 1).

Drug selection

Pregnancy alters pharmacokinetics (absorption, distribution, clearance), affecting maternal-fetal efficacy and safety. Data remain limited because pregnant individuals are often excluded from trials, and shared decision-making is advised.

First-line drugs—isoniazid, rifampin, ethambutol, and pyrazinamide—are generally acceptable in pregnancy and support favorable outcomes in drug-sensitive TB (61-63). Monitor for hepatotoxicity (isoniazid, rifampin, pyrazinamide); supplement vitamin B6 with isoniazid to prevent neurotoxicity; consider vitamin K with rifampin to reduce the risk of bleeding. Aminoglycosides are, in principle, contraindicated due to oto-/nephrotoxicity.

For multidrug resistance/rifampicin resistance pulmonary TB, maternal benefits of effective therapy generally outweigh potential fetal risks. Evidence supports regimens including bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx), and clofazimine (C) (64). WHO 2024 guidance recommends a 6-month BDLLfxC regimen and three 9-month options (BLMZ, BLLfxCZ, BDLLfxZ) (65). If adverse events require changes, or in cases of drug-resistant TB, select a personalized regimen guided by drug susceptibility testing and relevant guidelines.

Detailed safety information, precautions, and monitoring requirements for the use of second-line drugs during pregnancy have been described in previous publications (61,66).

• Recommendation 7. Select anti-TB drugs during pregnancy by balancing efficacy and fetal risk (C, 1); avoid aminoglycosides in principle (D, 1).

Assessment and management of infant TB after birth

Assessment

Infants born to mothers with TB during pregnancy are at a significantly increased risk of congenital TB and therefore require early evaluation (67). Vertical transmission occurs via hematogenous placental spread (to fetal liver/lungs) or aspiration/ingestion of infected amniotic fluid in utero/during delivery. Accordingly, neonatal assessment should include chest and abdominal imaging, microbiologic analysis of respiratory/gastric/stool specimens, and microbiologic/histologic examination of the placenta, amniotic fluid, and umbilical cord. Cantwell’s diagnostic criteria are based on this framework (68).

A systematic review reported abnormal chest X-rays in 93% and hepatic lesions on ultrasound in 89% of congenital TB cases, underscoring the value of imaging and multi-specimen microbiology (69). These findings further support imaging as a core component of neonatal evaluation, not only for detection but also for localization of organ involvement and assessment of disease severity, particularly in hepatic, splenic, pulmonary, and CNS disease. Recommended assessment includes the following: symptoms/signs with serial weight monitoring; chest X-ray and abdominal ultrasound (especially when maternal risk for vertical transmission is high: miliary TB, TB meningitis, pleural TB, genital/pelvic TB); for symptomatic infants, at least two respiratory or gastrointestinal specimens (gastric aspirates, nasopharyngeal secretions, or stool) for molecular testing and culture; and cerebrospinal fluid studies plus neuroimaging (preferably contrastenhanced MRI; CT as alternative) when CNS TB is suspected. Gastric aspirates should be prioritized because they yield higher rates in infants (70,71). Where testing is unavailable, expedited referral is recommended; if referral risks undue delay, initiate treatment based on clinical diagnosis (69). If the mother has LTBI without evidence of active TB, routine newborn care suffices.

• Recommendation 8. Infants born to mothers with TB during pregnancy should be assessed for active TB after birth, including at least a chest X-ray and an abdominal ultrasound (C, 2).

Management

If congenital (active) TB is diagnosed, initiate anti-TB treatment immediately, which dramatically reduces mortality (69,72). If congenital TB is excluded, practice regarding TB preventive treatment (TPT) varies. Given the risk of intrauterine transmission and the lack of reliable LTBI screening in neonates, this guideline recommends TPT for exposed neonates, with close monitoring: every 2 weeks for the first 3 months, then monthly through 6 months (67,69,73,74).

Since neonatal TST is unreliable (e.g., only 2/14 congenital TB cases were TST-positive) (75), perform TST at 3–6 months of age after initiating TPT. If induration <5 mm (and HIV antibody negative), administer BCG at the standard dose; if ≥5 mm, withhold BCG, conduct further evaluation, and—if active TB is excluded—complete the planned TPT (74,76).

• Recommendation 9. Do not administer BCG to newborns with active TB, and initiate anti-TB treatment immediately (B, 1). For infants born to mothers with TB during pregnancy, initiate TPT with close monitoring once congenital TB has been excluded (D, 2).
• Recommendation 10. For infants on TPT, perform TST after 3 months of age. TST-negative infants (HIV-negative) should receive BCG, whereas TST-positive infants should not receive BCG and require further evaluation. If active TB is diagnosed, treat accordingly; if excluded, complete TPT (D, 2).

Postpartum protection and feeding management

Indications for mother-infant separation

If the mother has received anti-TB treatment for ≥2 months at delivery and has negative sputum smear and multiple negative cultures, separation is not required. If sputum is positive, adherence is poor, or drug resistance is suspected, separate mother and infant or require a medical protective/N95 mask until non-infectious (61,77,78).

If the infant has active TB and is receiving treatment, or has LTBI and has started TPT, separation is unnecessary, but the mother should wear a medical protective or surgical mask correctly and perform strict hand hygiene (61,78,79). In China, masks should comply with GB 19083-2023 (80,81). Additional measures: optimize ventilation and use UV/air disinfection; handle secretions and disinfect the environment appropriately; and screen close contacts for infectious TB per the national infection prevention and control handbook (80). Mothers should undergo monthly sputum smear and culture; at least two consecutive negative samples, separated by ≥30 days, define non-infectiousness. Persistent positivity warrants assessment of adherence and drug resistance.

• Recommendation 11. For mothers with infectious pulmonary TB, separate the newborn from the mother, or the mother should wear a medical protective mask (e.g., N95-equivalent) until non-infectiousness is confirmed (D, 1).

Feeding decisions and risk control

Breastmilk is optimal for infant nutrition and immunity and is encouraged when safe. Risk assessment should consider respiratory transmission, breast involvement, and drug exposure via Breastmilk.

Respiratory transmission: if therapy <2 months at delivery or sputum remains positive, close contact during feeding poses a risk.

Transmission via breastmilk: rare overall, but active breast TB (swelling, ulceration, necrosis, sinus tract, or bacteriologic positivity) poses a risk (82,83).

Drug exposure: first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide) appear at low concentrations in breastmilk and are generally compatible with breastfeeding. Concerns exist for some second-line medicines (e.g., bedaquiline: high breastmilk levels/QTc prolongation/hepatotoxicity; linezolid: hematologic toxicity; fluoroquinolones: cartilage toxicity; aminoglycosides: ototoxicity; ethionamide: thyroid dysfunction/hepatic toxicity) (61).

Operational guidance: for drug-sensitive TB mothers: if <2 months of therapy or ongoing sputum positivity without 2 consecutive negative results at least 30 days apart, recommend formula feeding. If not feasible, the mother should wear a compliant protective/surgical mask during breastfeeding, or expressed breastmilk may be given to the infant by another caregiver (61,80,81). For drugresistant TB mothers: Given limited lactational safety data for most second-line agents and the difficulty balancing maternal control with infant safety, formula feeding throughout treatment is recommended (84). Active breast TB: Do not breastfeed from the affected breast until cure (82,83).

• Recommendation 12. Mothers who remain infectious should not breastfeed, use formula instead. If formula is not feasible, the mother may breastfeed with a medical protective mask or express breastmilk for administration by another caregiver. For drug‑resistant TB, recommend formula feeding throughout treatment. For active breast TB, avoid feeding from the affected side until the condition is cured (D, 1).

Pregnancy and LTBI

TPT and early initiation of antiretroviral therapy are essential to prevent TB in pregnant women living with HIV (44,85). Even during pregnancy, the benefits of TPT outweigh potential risks (16). A systematic review (12 studies; n=8,578) showed that TPT reduced the risk of active TB among individuals with LTBI by 32% [relative risk 0.68; 95% confidence interval (CI): 0.54–0.85] (86). Centers for Disease Control and Prevention/American Thoracic Society (CDC/ATS) and others recommend prompt TPT for pregnant women with recent exposure to infectious pulmonary TB—even in the first trimester—to prevent hematogenous placental spread. High-risk factors for progression include HIV infection, TB infection within the past 2 years, significant immunosuppression, and injection drug use (87). For women with high-risk factors, initiate TPT promptly once active TB is excluded, regardless of whether LTBI is identified before or during pregnancy. For those without high-risk factors, the likelihood of progression during pregnancy is relatively low; TPT may be deferred until the postpartum period, with close monitoring during pregnancy (44,88).

Atypical or subtle symptoms during pregnancy can delay TB diagnosis. In one study, among 170 infants with congenital TB, 121 mothers were diagnosed postpartum, and 39 mothers were asymptomatic during pregnancy (72). TB detection within 3 months postpartum is higher than that during pregnancy (89), and the risk of TB within 6 months postpartum is higher than in the non-pregnant state (incidence rate ratio 1.95, 95% CI: 1.24–3.07) (90). Thus, postpartum imaging and microbiological testing are recommended to exclude active TB in women with LTBI.

• Recommendation 13. For HIV-infected individuals with LTBI, initiate TPT promptly regardless of pregnancy status (B, 1). For individuals with LTBI and other high-risk factors (recent close contact with infectious pulmonary TB, severe immunosuppression, severe malnutrition), initiate TPT after excluding active TB (D, 2).
• Recommendation 14. All pregnant women with LTBI should undergo postpartum imaging and microbiologic testing to exclude active TB (C, 2).

Infertility and embryo transfer

Infertile women—especially those planning IVF-ET—should undergo TB screening. Performing IVF-ET in patients with untreated active TB carries a risk of disease dissemination, with potentially fatal consequences for both mother and fetus (87,91). Contributing factors include the following: (I) ovarian stimulation with marked estrogen/progesterone elevations suppressing T-cell function and cellular immunity; (II) potential disturbance of pelvic TB lesions during oocyte retrieval; and (III) pregnancy-related immune shifts. These factors may reactivate prior TB or lead to progression from LTBI to active TB, and in severe cases, may result in acute hematogenous dissemination (92,93).

Anti-TB treatment before IVF-ET improves reproductive parameters. Compared with untreated patients, women with FGTB who received anti-TB therapy before IVF-ET required lower gonadotropin doses, had greater endometrial thickness and increased subendometrial blood flow on the day of embryo transfer, and achieved higher numbers of retrieved oocytes and high-quality embryos, suggesting improved endometrial receptivity and ovarian reserve (94). Women with LTBI had lower clinical pregnancy and live birth rates after intrauterine insemination compared with women without LTBI (95).

Therefore, women with active TB should complete standard treatment and achieve a cure before IVF-ET. For LTBI, TPT is recommended before embryo transfer to reduce the risk of TB during pregnancy and to improve embryo transfer success and pregnancy outcomes. It should be noted that TPT does not eliminate the risk of TB. Close monitoring during pregnancy is essential, and new symptoms (fever, cough, sputum, dyspnea, headache, nausea, vomiting) should prompt immediate TB evaluation.

• Recommendation 15. In infertile women with TB who require IVF-ET, complete TB treatment and achieve cure before IVF-ET (C, 1). In infertile women with LTBI who require IVF-ET, initiate TPT after active TB has been thoroughly excluded, proceed with IVF-ET following preventive therapy, and monitor closely during pregnancy (D, 2).

Future directions and prospects

Despite recent progress, evidence remains limited due to the unique characteristics of this population. Priority gaps include early screening strategies; optimal regimen for drug-resistant TB in pregnancy; breastfeeding safety in complex scenarios; neonatal prevention treatment (composition and duration of TPT); and earlier detection of genital TB in infertility. Pregnancy-related immune changes complicate screening and diagnosis, and consensus on breastfeeding under specific conditions is lacking. Establishing effective MTCT management models—particularly in low-resource settings—also remains challenging. Future research should target these key issues to optimize prevention and treatment strategies, curb TB transmission, and improve maternal and neonatal health outcomes.

Acknowledgments

None.

Footnote

Funding: This work was supported by Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (No. 2025ZD01907900), the Shenzhen Medical Research Fund (Nos. C2405002 and D250403009), the National Natural Science Foundation of China (No. 32394014), and the Shenzhen Natural Science Foundation in Basic Research Fund (No. JCYJ20250604144008011).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-0570/coif). S.L. reports receiving support from Shenzhen Medical Research Fund, National Natural Science Foundation of China, and Shenzhen Natural Science Foundation in Basic Research Fund. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. WHO handbook for guideline development, 2nd Edition. Geneva: World Health Organization; 2014.
2. Chen Y, Yang K, Marušic A, Qaseem A, Meerpohl JJ, Flottorp S, et al. A Reporting Tool for Practice Guidelines in Health Care: The RIGHT Statement. Ann Intern Med 2017;166:128-32. [Crossref] [PubMed]
3. The GRADE Working Group; Holger Schünemann, Jan Brożek, Gordon Guyatt, Andrew Oxman. GRADE Handbook. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. Updated October 2013. Available online: https://gdt.gradepro.org/app/handbook/handbook.html
4. Global tuberculosis report 2025. Geneva: World Health Organization; 2025.
5. Optimal and early inclusion of pregnant and lactating women in tuberculosis research: consensus statement. Geneva: World Health Organization; 2025.
6. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2014;2:e323-33. [Crossref] [PubMed]
7. Sobhy S, Babiker Z, Zamora J, Khan KS, Kunst H. Maternal and perinatal mortality and morbidity associated with tuberculosis during pregnancy and the postpartum period: a systematic review and meta-analysis. BJOG 2017;124:727-33. [Crossref] [PubMed]
8. Dennis EM, Hao Y, Tamambang M, Roshan TN, Gatlin KJ, Bghigh H, Ogunyemi OT, Diallo F, Spooner KK, Salemi JL, Olaleye OA, Khan KZ, Aliyu MH, Salihu HM. Tuberculosis during pregnancy in the United States: Racial/ethnic disparities in pregnancy complications and in-hospital death. PLoS One 2018;13:e0194836. [Crossref] [PubMed]
9. Bekker A, Du Preez K, Schaaf HS, Cotton MF, Hesseling AC. High tuberculosis exposure among neonates in a high tuberculosis and human immunodeficiency virus burden setting. Int J Tuberc Lung Dis 2012;16:1040-6. [Crossref] [PubMed]
10. Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med 2012;367:348-61. [Crossref] [PubMed]
11. Di Comite A, Esposito S, Villani A, Stronati M. the Italian Pediatric TB Study Group. How to manage neonatal tuberculosis. J Perinatol 2016;36:80-5. [Crossref] [PubMed]
12. Igbokwe V, Ruby LC, Sultanli A, Bélard S. Post-tuberculosis sequelae in children and adolescents: a systematic review. Lancet Infect Dis 2023;23:e138-50. [Crossref] [PubMed]
13. Tuberculosis in women. Geneva: World Health Organization; 2015.
14. Hui SYA, Lao TT. Tuberculosis in pregnancy. Best Pract Res Clin Obstet Gynaecol 2022;85:34-44. [Crossref] [PubMed]
15. Miele K, Bamrah Morris S, Tepper NK. Tuberculosis in Pregnancy. Obstet Gynecol 2020;135:1444-53. [Crossref] [PubMed]
16. Mnyani CN, McIntyre JA. Tuberculosis in pregnancy. BJOG 2011;118:226-31. [Crossref] [PubMed]
17. General Office of the National Health Commission. Notice of the General Office of the National Health Commission on Issuing the Technical Specifications for Tuberculosis Prevention Work in China (2020 Edition). 2020-04-02.
18. Nguyen HT, Pandolfini C, Chiodini P, Bonati M. Tuberculosis care for pregnant women: a systematic review. BMC Infect Dis 2014;14:617. [Crossref] [PubMed]
19. Xia L, Mijiti P, Liu XH, Hu ZD, Fan XY, Lu SH. Association of in vitro fertilization with maternal and perinatal outcomes among pregnant women with active tuberculosis: A retrospective hospital-based cohort study. Front Public Health 2022;10:1021998. [Crossref] [PubMed]
20. Wang K, Ren D, Qiu Z, Li W. Clinical analysis of pregnancy complicated with miliary tuberculosis. Ann Med 2022;54:71-9. [Crossref] [PubMed]
21. Ahmed MAE, Mohammed AAA, Ilesanmi AO, Aimakhu CO, Bakhiet AO, Hamad SBM. Female Genital Tuberculosis Among Infertile Women and Its Contributions to Primary and Secondary Infertility: A systematic review and meta-analysis. Sultan Qaboos Univ Med J 2022;22:314-24. [Crossref] [PubMed]
22. Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. Am J Reprod Immunol 2011;66:410-5. [Crossref] [PubMed]
23. Bhanothu V, Theophilus JP, Rozati R. Use of endo-ovarian tissue biopsy and pelvic aspirated fluid for the diagnosis of female genital tuberculosis by conventional versus molecular methods. PLoS One 2014;9:e98005. [Crossref] [PubMed]
24. Bose M. Female genital tract tuberculosis: how long will it elude diagnosis? Indian J Med Res 2011;134:13-4.
25. Sharma JB. Current Diagnosis and Management of Female Genital Tuberculosis. J Obstet Gynaecol India 2015;65:362-71. [Crossref] [PubMed]
26. Shahzad S. Investigation of the prevalence of female genital tract tuberculosis and its relation to female infertility:An observational analytical study. Iran J Reprod Med 2012;10:581-8.
27. Gleeson LE, Varghese C, Ryan E, Kane M, McDonald C, Gleeson N, McLaughlin AM, Butler K, Gavin P, Keane J. Untreated chronic tuberculous salpingitis followed by successful in vitro fertilization conception and congenital tuberculosis. QJM 2015;108:899-901. [Crossref] [PubMed]
28. Chinese Medical Association. Clinical Diagnose and Treatment Instructions: Tuberculosis. Beijing: People’s Medical Publishing House; 2005.
29. National Health and Family Planning Commission of the People's Republic of China. Diagnostic Criteria for Pulmonary Tuberculosis (WS 288-2017). Electronic Journal of Emerging Infectious Diseases (Chinese) 2018;3:59-61.
30. Tjahyadi D, Ropii B, Tjandraprawira KD, Parwati I, Djuwantono T, Permadi W, Li T. Female Genital Tuberculosis: Clinical Presentation, Current Diagnosis, and Treatment. Infect Dis Obstet Gynecol 2022;2022:3548190. [Crossref] [PubMed]
31. Sharma JB, Pushparaj M, Roy KK, Neyaz Z, Gupta N, Jain SK, Mittal S. Hysterosalpingographic findings in infertile women with genital tuberculosis. Int J Gynaecol Obstet 2008;101:150-5. [Crossref] [PubMed]
32. Goel G, Khatuja R, Radhakrishnan G, Agarwal R, Agarwal S, Kaur I. Role of newer methods of diagnosing genital tuberculosis in infertile women. Indian J Pathol Microbiol 2013;56:155-7. [Crossref] [PubMed]
33. Shrivastava G, Bajpai T, Bhatambare GS, Patel KB. Genital tuberculosis: Comparative study of the diagnostic modalities. J Hum Reprod Sci 2014;7:30-3. [Crossref] [PubMed]
34. Saxena R, Shrinet K, Rai SN, Singh K, Jain S, Jain S, Singh D, Anupurba S, Jain M. Diagnosis of Genital Tuberculosis in Infertile Women by Using the Composite Standard. Dis Markers 2022;2022:8078639. [Crossref] [PubMed]
35. Chaubey L, Kumar D, Prakash V, Nath G. Menstrual Blood versus Endometrial Biopsy in Detection of Genital Tuberculosis by Using Nested Polymerase Chain Reaction in an Endemic Region. J Hum Reprod Sci 2019;12:35-9. [Crossref] [PubMed]
36. Gurjar K, Meena KL, Rajoria L, Sharma N. Comparison of diagnostic efficacy of USG, Tuberculin test, Nucleic acid amplification test (PCR) & histopathology for diagnosis of genital tuberculosis in infertile women, assuming culture as gold standard. International Multispeciality Journal of Health 2018;4:138-43.
37. Aggarwal A, Das CJ, Manchanda S. Imaging Spectrum of Female Genital Tuberculosis: A Comprehensive Review. Curr Probl Diagn Radiol 2022;51:617-27. [Crossref] [PubMed]
38. Schaefer G, Zervoudakis IA, Fuchs FF, David S. Pregnancy and pulmonary tuberculosis. Obstet Gynecol 1975;46:706-15.
39. Nguyen Y, McNabb KC, Farley JE, Warren N. Examining family planning and adverse pregnancy outcomes for women with active tuberculosis disease: a systematic review. BMJ Open 2022;12:e054833. [Crossref] [PubMed]
40. Quality of care in the provision of sexual and reproductive health services. Geneva: World Health Organization; 2011.
41. Freyder M, Craig L, Kaji A. Monitoring the Integration of Family Planning and HIV Services: A Manual to Support the Use of Indicators to Measure Progress toward PEPFAR’s 90–90-90 Targets and Protect Women’s Reproductive Rights. North Carolina: Chapel Hill; 2016.
42. Family Health International, Uniter States Agency for International Development. Strategic considerations for strengthening the linkages between family planning and HIV/AIDS policies, programs, and services. Geneva: World Health Organization; 2009.
43. Yu T, Wang B, Duan X, Peng Y. Imaging diagnosis and differential diagnosis of hematogenous disseminated pulmonary tuberculosis in children. Chinese Journal of Applied Clinical Pediatrics 2020;35:733-7.
44. Getahun H, Sculier D, Sismanidis C, Grzemska M, Raviglione M. Prevention, diagnosis, and treatment of tuberculosis in children and mothers: evidence for action for maternal, neonatal, and child health services. J Infect Dis 2012;205:S216-27. [Crossref] [PubMed]
45. Loto OM, Awowole I. Tuberculosis in pregnancy: a review. J Pregnancy 2012;2012:379271. [Crossref] [PubMed]
46. Dong S, Zhou R, Peng E, He R. Analysis of Clinical Features and Risk Factors in Pregnant Women With Miliary Pulmonary Tuberculosis After In Vitro Fertilization Embryo Transfer. Front Cell Infect Microbiol 2022;12:885865. [Crossref] [PubMed]
47. WHO consolidated guidelines on tuberculosis: Module 5: Management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
48. Centers for Disease Control and Prevention. Clinical Testing Guidance for Tuberculosis: Interferon Gamma Release Assay. (2024, May 9). Available online: https://www.cdc.gov/tb/hcp/testing-diagnosis/interferon-gamma-release-assay.html
49. Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O'Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis 2017;64:111-5. [Crossref] [PubMed]
50. Malhamé I, Cormier M, Sugarman J, Schwartzman K. Latent Tuberculosis in Pregnancy: A Systematic Review. PLoS One 2016;11:e0154825. [Crossref] [PubMed]
51. The American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice. Committee Opinion No. 723: Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Obstet Gynecol 2017;130:e210-e216.
52. Puris G, Chetrit A, Katorza E. Fetal Safety in MRI During Pregnancy: A Comprehensive Review. Diagnostics (Basel) 2025;15:208. [Crossref] [PubMed]
53. Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes. JAMA 2016;316:952-61. [Crossref] [PubMed]
54. Tercanli S, Prüfer F. Fetal Neurosonogaphy: Ultrasound and Magnetic Resonance Imaging in Competition. Ultraschall Med 2016;37:555-7. [Crossref] [PubMed]
55. Gomathi NS, Singh M, Singh UB, Myneedu VP, Chauhan DS, Sarin R, Mohan A, Bhatnagar A, Khangembam JS, Kannan T, Rao MVV, Logani J, Dey B, Gangakhedkar RR, Swaminathan S, Tripathy S. Multicentric validation of indigenous molecular test Truenat MTB for detection of Mycobacterium tuberculosis in sputum samples from presumptive pulmonary tuberculosis patients in comparison with reference standards. Indian J Med Res 2020;152:378-85. [Crossref] [PubMed]
56. Lee JH, Garg T, Lee J, McGrath S, Rosman L, Schumacher SG, Benedetti A, Qin ZZ, Gore G, Pai M, Sohn H. Impact of molecular diagnostic tests on diagnostic and treatment delays in tuberculosis: a systematic review and meta-analysis. BMC Infect Dis 2022;22:940. [Crossref] [PubMed]
57. Liang C, Tang SJ. Annual progress on molecular biological diagnosis of tuberculosis 2022. Zhonghua Jie He He Hu Xi Za Zhi 2023;46:176-82. [Crossref] [PubMed]
58. WHO operational handbook on tuberculosis. Module 2: screening- Systematic screening for tuberculosis disease. Geneva: World Health Organization; 2021.
59. WHO consolidated guidelines on tuberculosis: Module 3: diagnosis e rapid diagnostics for tuberculosis detection 2021 update. Geneva: World Health Organization; 2021.
60. Centers for Disease Control and Prevention. Tuberculosis Clinical Care and Treatment During Pregnancy. (2025, April 17). Available online: https://www.cdc.gov/tb/hcp/clinical-care/pregnancy.html
61. Maugans C, Loveday M, Hlangu S, Waitt C, Van Schalkwyk M, van de Water B, Salazar-Austin N, McKenna L, Mathad JS, Kalk E, Hurtado R, Hughes J, Eke AC, Ahmed S, Furin J. Best practices for the care of pregnant people living with TB. Int J Tuberc Lung Dis 2023;27:357-66. [Crossref] [PubMed]
62. Denti P, Martinson N, Cohn S, Mashabela F, Hoffmann J, Msandiwa R, Castel S, Wiesner L, Chaisson RE, McIlleron H, Dooley KE. Population Pharmacokinetics of Rifampin in Pregnant Women with Tuberculosis and HIV Coinfection in Soweto, South Africa. Antimicrob Agents Chemother 2015;60:1234-41. [Crossref] [PubMed]
63. Abdelwahab MT, Leisegang R, Dooley KE, Mathad JS, Wiesner L, McIlleron H, Martinson N, Waja Z, Letutu M, Chaisson RE, Denti P. Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV. Antimicrob Agents Chemother 2020;64:e01978-19. [Crossref] [PubMed]
64. Conradie F. High rate of successful outcomes treating RR TB with a delamanid-bedaquiline regimen in BEAT Tuberculosis: an interim analysis. Paper presented at the Union World Conference on Lung Health Virtual Conference, 2022-11-12.
65. Key updates to the treatment of drug-resistant tuberculosis: rapid communication. Geneva: World Health Organization; 2024.
66. Alene KA, Jegnie A, Adane AA. Multidrug-resistant tuberculosis during pregnancy and adverse birth outcomes: a systematic review and meta-analysis. BJOG 2021;128:1125-33. [Crossref] [PubMed]
67. Pediatric Tuberculosis Committee, Chinese Society for Tuberculosis, Chinese Medical Association. National Children's Medical Center; Beijing Children's Hospital, Capital Medical University. Expert consensus on screening and preventive treatment of latent Mycobacterium tuberculosis infection in children. Chinese Journal of Tuberculosis and Respiratory Diseases 2020;43:345-9.
68. Cantwell MF, Shehab ZM, Costello AM, Sands L, Green WF, Ewing EP Jr, Valway SE, Onorato IM. Brief report: congenital tuberculosis. N Engl J Med 1994;330:1051-4. [Crossref] [PubMed]
69. Hasan N, Nourse C, Schaaf HS, Bekker A, Loveday M, Alcântara Gabardo BM, Coulter C, Chabala C, Kabra S, Moore E, Maleche-Obimbo E, Salazar-Austin N, Ritz N, Starke JR, Steenhoff AP, Triasih R, Welch SB, Marais BJ. Management of the infant born to a mother with tuberculosis: a systematic review and consensus practice guideline. Lancet Child Adolesc Health 2024;8:369-78. [Crossref] [PubMed]
70. Lu S, Huang G, Xu X. Diagnostic value of collecting gastric juice by different methods for culturing Mycobacterium tuberculosis in children with pulmonary tuberculosis. Chinese Journal of Tuberculosis and Respiratory Diseases 1998;21:615-6.
71. WHO operational handbook on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
72. Peng W, Yang J, Liu E. Analysis of 170 cases of congenital TB reported in the literature between 1946 and 2009. Pediatr Pulmonol 2011;46:1215-24. [Crossref] [PubMed]
73. Song B, Lu S. Strategies for preventing mother-to-child transmission of tuberculosis. Electronic Journal of Emerging Infectious Diseases (Chinese) 2017;2:138-42.
74. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: World Health Organization; 2018.
75. Hageman J, Shulman S, Schreiber M, Luck S, Yogev R. Congenital tuberculosis: critical reappraisal of clinical findings and diagnostic procedures. Pediatrics 1980;66:980-4.
76. Pickering L. Red book: 2012 Report of the Committee on Infectious Diseases. 29th edition. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
77. Kodadhala V, Gudeta A, Zerihun A, Lewis O, Ahmed S, Gajjala J, Thomas A. Postpartum Tuberculosis: A Diagnostic and Therapeutic Challenge. Case Rep Pulmonol 2016;2016:3793941. [Crossref] [PubMed]
78. Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee. 4th edition. Geneva: World Health Organization; 2010.
79. Reid M, Agbassi YJP, Arinaminpathy N, Bercasio A, Bhargava A, Bhargava M, et al. Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis. Lancet 2023;402:1473-98. [Crossref] [PubMed]
80. Wang L. Handbook of Tuberculosis Infection Prevention and Control in China. Beijing: Peking Union Medical College Press, 2010.
81. National Medical Products Administration. Medical Protective Masks (GB19083-2023). 2023.
82. Babamahmoodi F, Babamahmoodi A, Barzegar R, Sadr M, Rezaei M, Marjani M. Breast Tuberculosis in Iran: A Comprehensive Review. Int J Mycobacteriol 2024;13:1-6. [Crossref] [PubMed]
83. Uçan ES, Alpaydın AÖ, Gündüz Karayazı D, Kapkaç M, Takar B, Zekioğlu O, Balcı P, Yılmaz MR. Tuberculous mastitis: A masquerading face of granulomatous mastitis. Tuberk Toraks 2022;70:271-8. [Crossref] [PubMed]
84. WHO operational handbook on tuberculosis. Module 4: treatment and care. Geneva: World Health Organization; 2025.
85. Getahun H, Granich R, Sculier D, Gunneberg C, Blanc L, Nunn P, Raviglione M. Implementation of isoniazid preventive therapy for people living with HIV worldwide: barriers and solutions. AIDS 2010;24:S57-65. [Crossref] [PubMed]
86. Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev 2010;2010:CD000171. [Crossref] [PubMed]
87. Cao W, Fu X, Li H, Bei J, Li L, Wang L. Tuberculosis in pregnancy and assisted reproductive technology. Drug Discov Ther 2024;18:80-8. [Crossref] [PubMed]
88. Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000;161:S221-S247.
89. Bothamley GH, Ehlers C, Salonka I, Skrahina A, Orcau A, Codecasa LR, Ferrarese M, Pesut D, Solovic I, Dudnyk A, Anibarro L, Denkinger C, Guglielmetti L, Muylle I, Confalonieri M. Pregnancy in patients with tuberculosis: a TBNET cross-sectional survey. BMC Pregnancy Childbirth 2016;16:304. [Crossref] [PubMed]
90. Zenner D, Kruijshaar ME, Andrews N, Abubakar I. Risk of tuberculosis in pregnancy: a national, primary care-based cohort and self-controlled case series study. Am J Respir Crit Care Med 2012;185:779-84. [Crossref] [PubMed]
91. Mir N, Pal L. Genital tuberculosis, infertility and assisted reproduction. Curr Opin Obstet Gynecol 2023;35:263-9. [Crossref] [PubMed]
92. Cheng MP, Butler-Laporte G, Parkes LO, Bold TD, Fritzler MJ, Behr MA. Prevalence of Auto-antibodies in Pulmonary Tuberculosis. Open Forum Infect Dis 2019;6:ofz114. [Crossref] [PubMed]
93. Burke RM, Rickman HM, Singh V, Corbett EL, Ayles H, Jahn A, Hosseinipour MC, Wilkinson RJ, MacPherson P. What is the optimum time to start antiretroviral therapy in people with HIV and tuberculosis coinfection? A systematic review and meta-analysis. J Int AIDS Soc 2021;24:e25772.
94. Dam P, Shirazee HH, Goswami SK, Ghosh S, Ganesh A, Chaudhury K, Chakravarty B. Role of latent genital tuberculosis in repeated IVF failure in the Indian clinical setting. Gynecol Obstet Invest 2006;61:223-7. [Crossref] [PubMed]
95. Chu Y, Chen Y, Yao W, Wang L, Zhang B, Jin L, Yue J. The Effect of Latent Tuberculosis Infection on Ovarian Reserve and Pregnancy Outcomes among Infertile Women Undergoing Intrauterine Insemination: A Retrospective Cohort Study with Propensity Score Matching. J Clin Med 2023;12:6398. [Crossref] [PubMed]