Tuberculosis infection and stillbirth in Ethiopia-A prospective cohort study

PLoS One. 2022 Apr 11;17(4):e0261972. doi: 10.1371/journal.pone.0261972. eCollection 2022.

Abstract

Background: Tuberculosis is among the leading causes of death among infectious diseases. Regions with a high incidence of tuberculosis, such as sub-Saharan Africa, are disproportionately burdened by stillbirth and other pregnancy complications. Active tuberculosis increases the risk of pregnancy complications, but the association between latent tuberculosis infection (LTBI) and pregnancy outcomes is unknown. We explored the effect of latent tuberculosis infection on the risk of stillbirth in women attending antenatal care clinics in Ethiopia, a country with >170 000 annual cases of active tuberculosis.

Method: Pregnant women were enrolled from antenatal care at three health facilities in Adama, Ethiopia, during 2015-2018, with assessment for previous and current active tuberculosis and testing for LTBI using QuantiFERON-TB-GOLD-PLUS. Proportions of stillbirth (≥ 20 weeks of gestation) and neonatal death (< 29 days of birth) were compared with respect to categories of maternal tuberculosis infection (tuberculosis-uninfected, LTBI, previous-, and current active tuberculosis). Multivariable logistic regression was performed for stillbirth.

Results: Among 1463 participants enrolled, the median age was 25 years, 10.2% were HIV-positive, 34.6% were primigravidae, and the median gestational age at inclusion was 18 weeks. Four (0.3%) were diagnosed with active tuberculosis during pregnancy, 68 (4.6%) reported previous treatment for active tuberculosis, 470 (32.1%) had LTBI, and 921 (63.0%) were tuberculosis-uninfected. Stillbirth was more frequent in participants with LTBI compared to tuberculosis-uninfected participants, although not reaching statistical significance (19/470, 4.0% vs 25/921, 2.7%, adjusted [for age, gravidity and HIV serostatus] odds ratio 1.38, 95% confidence interval 0.73-2.57, p = 0.30). Rates of neonatal death (5/470, 1.1% vs 10/921, 1.1%) were similar between these categories.

Conclusion: Latent tuberculosis infection was not significantly associated with stillbirth or neonatal death in this cohort. Studies based on larger cohorts and with details on causes of stillbirth, as well as other pregnancy outcomes, are needed to further investigate this issue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Ethiopia / epidemiology
  • Female
  • Humans
  • Infant, Newborn
  • Latent Tuberculosis* / complications
  • Latent Tuberculosis* / diagnosis
  • Latent Tuberculosis* / epidemiology
  • Perinatal Death*
  • Pregnancy
  • Pregnancy Complications*
  • Prospective Studies
  • Stillbirth / epidemiology
  • Tuberculosis* / complications
  • Tuberculosis* / diagnosis
  • Tuberculosis* / epidemiology

Grants and funding

This study was supported by the Swedish Heart-Lung Foundation (PB, grant number 20170258, url https://www.hjart-lungfonden.se/), the Swedish Research Council (SH, grant number 2018-04840, url https://www.vr.se), the Crafoord Foundation (PB, grant number 20170537, url https://www.crafoord.se), Governmental funding of clinical research within the National Health Services, Sweden (JW and PB, url https://www.medicin.lu.se/), Region Skåne research grants (PB, url www.skane.se), Alfred Österlund Foundation (PB, url www.alfredosterlundsstiftelse.se), and a private donation to Lund University, Sweden (PB). Additional grants were obtained from the John and Hedda Forssman Foundation (JW, url https://www.fysiografen.se); and the Folke Nordbring Foundation (JW, url https://www.sls.se/lil). Qiagen (url https://www.qiagen.com) donated the QuantiFERON-TB GOLD PLUS kits used that were used in this cohort. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.