Association between iron deficiency anemia and the risk of new-onset TB infection [TBN 077]

1. Who

• Population: Adult patients aged ≥18 years from the TriNetX Research Network.
• Sample size:
  • Initial cohorts: 177,846 patients with iron deficiency anemia (IDA) and 309,662 control patients with dermatitis.
  • Final matched cohort after 1:1 propensity score matching: 160,928 patients.
• Demographics:
  • Mean age after matching: ~51 years.
  • Male proportion: ~27–29%.
  • Predominantly White participants (46–48%), with smaller Black/African American (~12–15%) and Asian (~5%) populations.
• Inclusion criteria:
  • Adults with IDA (ICD-10 D50) and at least one additional IDA diagnosis within 2 years.
• Exclusion criteria:
  • Prior tuberculosis (TB), latent TB, TB exposure, anti-TB medication use, HIV infection, organ transplantation, immunosuppressive therapy, glucocorticoid use, antineoplastic use, and other anemias.
• Subgroups analyzed:
  • Sex (male vs female).
  • Age (18–50 years vs >50 years).

---

2. What

• Research focus:
  To determine whether iron deficiency anemia is associated with an increased risk of incident tuberculosis, including pulmonary and extrapulmonary TB.
• Primary outcome:
  Incident tuberculosis within 5 years after index diagnosis.
• Secondary outcomes:
  • TB incidence during years 5–10.
  • Positive control outcomes: pneumonia and reactive thrombocytosis.
• Key findings:
  • IDA was associated with higher TB risk within 5 years:
    • HR 1.48 (95% CI 1.10–2.00, p=0.010).
  • No significant association during 5–10 years:
    • HR 1.17 (95% CI 0.63–2.17, p=0.627).
  • Pulmonary TB:
    • HR 1.71 (95% CI 1.30–2.24, p<0.001).
  • Extrapulmonary TB:
    • HR 3.01 (95% CI 1.73–5.22, p<0.001).
  • Stronger associations were observed in:
    • Men: HR 2.06.
    • Younger adults (18–50 years): HR 2.42.
  • Positive controls confirmed expected associations:
    • Pneumonia HR 1.87.
    • Reactive thrombocytosis HR 3.68.
• Authors’ conclusions:
  IDA was independently associated with increased short-term TB risk, particularly extrapulmonary TB, suggesting that iron metabolism and nutritional status may influence susceptibility to mycobacterial infection.
• Practical implications:
  Patients with IDA may warrant closer monitoring for TB symptoms, especially in high-risk settings or populations.

---

3. When

• Study period: January 1, 2010 to December 31, 2020.
• Follow-up duration:
  • Primary analysis: within 5 years after index date.
  • Secondary analysis: 5–10 years post-index.

---

4. Where

• Data source: TriNetX Research Network.
• Geographic coverage: Multinational healthcare organizations from:
  • United States
  • Australia
  • Belgium
  • Brazil
  • Bulgaria
  • Estonia
  • France
  • Germany
  • Ghana
  • Israel
  • Italy
  • Japan
  • Lithuania
  • Malaysia
  • Poland
  • Singapore
  • Spain
  • Taiwan
  • UAE
  • United Kingdom
  • and others.
• Institutional oversight:
  Approved by Chi Mei Medical Center IRB (Taiwan).

---

5. Why

• Rationale:
  Prior evidence linking IDA with TB susceptibility was limited by small sample sizes, restricted populations, and insufficient subtype analyses.
• Knowledge gap addressed:
  Whether IDA independently increases TB risk across diverse multinational populations and whether associations differ by TB subtype.
• Objective:
  To evaluate the association between IDA and incident TB using a large multinational electronic health record database with robust matching and subtype analysis.

---

6. How

• Study design:
  Retrospective matched cohort study (observational).
• Data source:
  Federated electronic health records from TriNetX.
• Comparator group:
  Patients with unspecified dermatitis (ICD-10 L30).
• Matching method:
  1:1 propensity score matching using greedy nearest-neighbor algorithm.
• Covariates included:
  • Age
  • Sex
  • Race
  • BMI
  • Comorbidities
  • Laboratory values
  • Diabetes medications
• Statistical analyses:
  • Kaplan–Meier survival analysis
  • Cox proportional hazards regression
  • Schoenfeld residual testing
  • Subgroup analyses
• Positive controls:
  Pneumonia and reactive thrombocytosis.
• Major limitations:
  • Residual confounding cannot be excluded.
  • Lack of race-stratified subgroup analysis due to low event counts.
  • Reliance on ICD-10 coding may introduce misclassification.
  • Observational design cannot establish causality.
  • TB incidence remained relatively low despite large sample size.
• Level of evidence:
  Moderate observational evidence (retrospective propensity-matched cohort study).
• Funding/conflict of interest:
  Not specified in the provided text.

Source: Chen IW, Chang LC, Chang YJ, Lai YC, Hung KC. Association between iron deficiency anemia and the risk of new-onset tuberculosis infection: a matched cohort analysis. Frontiers in Nutrition. 2026 Jan 20;13:1727992. https://benangmerah.net/record/96/association-between-iron