Clinical presentation, diagnostics, and outcomes of infants with congenital and postnatal tuberculosis: a multicentre cohort study of the Paediatric Tuberculosis Network European Trials Group (ptbnet)
Götzinger, Florian Caprile, Alejandra Alonso Noguera-Julian, Antoni Lo Vecchio, Andrea Baquero-Artigao, Fernando Rosal, Teresa Del Brinkmann, Folke Mouchet, Françoise Velizarova, Svetlana Kötz, Karsten
Götzinger, Florian
Caprile, Alejandra Alonso
Noguera-Julian, Antoni
Lo Vecchio, Andrea
Baquero-Artigao, Fernando
Rosal, Teresa Del
Brinkmann, Folke
Mouchet, Françoise
Velizarova, Svetlana
Kötz, Karsten
Affiliation
Vienna Healthcare Group; Austrian Reference Centre for Childhood Tuberculosis; Medical University of Vienna; Guy's & St. Thomas' NHS Foundation Trust; Hospital Sant Joan de Déu; Center for Biomedical Network Research on Epidemiology and Public Health Madrid; Universitat de Barcelona; University of Naples Federico II; La Paz Hospital; Ruhr University Bochum; Centre Hospitalier Universitaire Saint-Pierre; Medical University Sofia; Sahlgrenska University Hospital; Children's Hospital of Central Switzerland; University of Basel Children's Hospital; Royal Children's Hospital Melbourne; University of Melbourne; Fondazione Policlinico Universitario A. Gemelli IRCCS; University of Oxford; Oxford University Hospitals NHS Foundation Trust; Queen Mary University of London; University of Helsinki; University Medical Center Hamburg-Eppendorf; National Academy of Medical Sciences of Ukraine; University Hospitals Birmingham NHS Foundation Trust; Klinikum Bremen-Nord; Newcastle upon Tyne Hospitals NHS Foundation Trust; Newcastle University; Karolinska University Hospital; Hospital Universitario 12 de Octubre; Great Ormond Street Hospital for Children NHS Foundation Trust; University College London
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Publication date
2025-04-19
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Abstract
Background: According to estimates, globally more than 200,000 pregnant women develop tuberculosis (TB) annually. Despite this, data on perinatal TB remain scarce. This study aimed to describe perinatal TB, comprising congenital (cTB) and postnatal (pTB) TB, in a European setting.
Methods: Retrospective cohort study via the Paediatric Tuberculosis Network European Trials Group (ptbnet) capturing and comparing cases of cTB and pTB diagnosed at 104 participating European healthcare institutions between 1995 and 2019.
Findings: Forty-six cases reported by 20 centres were included in the final analysis (cTB, n = 27; pTB, n = 19). Median age at symptom onset was one week in cTB (IQR: 0-1 weeks), and 12 weeks in pTB patients (IQR: 5-18 weeks). Prematurity was more common in cTB than pTB patients [57.9% (11/19); 95% CI: 36.3-76.9% vs. 21.1% (4/19); 95% CI: 8.5-43.3%; p = 0.049], and the average birth weight was significantly lower [1680 g; IQR: 932-2805 g vs. 2890 g; IQR: 2461-3400 g; p = 0.0043]. Microbiological confirmation was achieved in most patients [85.2% (23/27); 95% CI: 67.5-94.1% vs. 78.9% (15/19); 95% CI: 56.7-91.5%; p = 0.70]. The sensitivity of interferon-gamma release assays was poor in both groups [25.0% (3/12) 95% CI: 8.9-53.2% vs. 35.7% (5/14) 95% CI: 16.3-61.2%; p = 0.68]; in contrast, the sensitivity of the tuberculin skin tests (at 5 mm cut-off) was significantly higher in pTB patients [16.7% (2/12) 95% CI: 4.7-44.8% vs. 66.7% (10/15); 95% CI: 41.7-84.8%; p = 0.0185]. Approximately half of the patients required intensive care support [51.9% (14/27) 95% CI: 34.0-69.3% vs. 47.4% (9/19); 95% CI: 27.3-68.3%; p > 0.99]. Four (4/46; 8.7%) patients died, and four (4/46; 8.7%) had severe long-term sequelae.
Interpretation: There was substantial mortality and morbidity in this patient cohort, despite the high-resource setting. cTB was associated with premature birth and low birth weight. In contrast to microbiological tests, immunological tests perform poorly in perinatal TB, and should therefore not be used as rule-out tests.
Citation
Götzinger F, Caprile AA, Noguera-Julian A, Lo Vecchio A, Baquero-Artigao F, Rosal TD, Brinkmann F, Mouchet F, Velizarova S, Kötz K, Ritz N, Buonsenso D, Song R, Roy RB, Nieminen T, Rau C, Chechenieva V, Welch S, Kaiser-Labusch P, Emonts M, Buxbaum C, Blázquez-Gamero D, Bamford A, Tebruegge M, Martinez-Alier N; Paediatric Tuberculosis Network European Trials Group (ptbnet). Clinical presentation, diagnostics, and outcomes of infants with congenital and postnatal tuberculosis: a multicentre cohort study of the Paediatric Tuberculosis Network European Trials Group (ptbnet). Lancet Reg Health Eur. 2025 Apr 19;53:101303. doi: 10.1016/j.lanepe.2025.101303.
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Article