Pertussis infection in critically ill infants: meta-analysis and validation of a mortality score

Abstract

Background: Despite widespread vaccination programs, pertussis continues circulating within populations and remains a life-threatening infection in infants. While several mortality risk factors have been described, a comprehensive synthesis is lacking. We conducted a meta-analysis of studies investigating mortality risk factors in Pertussis infections and validated those factors in a large cohort.

Methods: Observational studies published in English were systematically searched in PubMed, EMBASE, and LiSSa databases from 01/2000 to 06/2024. The search yielded 816 unique citations. The primary outcome was mortality before discharge from the Pediatric Intensive Care Unit (PICU). Two independent reviewers assessed the risk of bias and extracted data. A REML-random effect model was used to calculate pooled prevalence and conduct the analysis. The identified risk factors were subsequently evaluated in a monocentric cohort of patients admitted to a tertiary hospital's PICU for severe pertussis between January 1996 and December 2020. Data analysis was conducted between June and August 2024.

Results: Seventeen studies, including 2,725 patients, met the inclusion criteria. The pooled prevalence of mechanical ventilation, continuous renal replacement therapy, and Extracorporeal Membrane Oxygenation support were 55% (95% CI: 40-70; I² = 98), 15% (95% CI: 3-27; I² = 95), and 8% (95% CI: 3-12; I² = 93), respectively. The pooled mortality incidence was 19% (95% CI:12-26; I² = 96). Identified mortality risk factors included elevated heart rate, presence of pulmonary hypertension, presence of seizures, and elevated white blood cell (WBC) count. Validation in an 83-patient cohort (median age: 45 days, IQR: 30-55) revealed a mortality rate of 12%. Risk factors identified in the meta-analysis were significantly associated with non-survival in the cohort. A mortality prediction score was developed incorporating age < 30 days, heart rate > 200/min, and WBC > 30 G/l, achieving an area under the curve of 0.92 (95% CI: 0.86-0.99).

Conclusion: This meta-analysis identified a simple yet effective score to assess the severity of pertussis infection in infants admitted to PICU. Accurate risk stratification may enable timely treatment of critically ill patients, potentially improving outcomes.

Trial registration: The study protocol was registered on PROSPERO: CRD42024582057.

Keywords: Bordetella pertussis; Malignant pertussis; Metanalysis; Mortality.

Fig. 1

Preferred reporting items for systematic reviews and meta-analysis flow diagram

Fig. 2

Forrest plot of included studies reporting the severity of severe Bordetella pertussis infection. A Mechanical ventilation pooled prevalence. 16/17 studies reported mechanical ventilation. B Continuous renal replacement therapy (CCRT) pooled prevalence. 5/17 studies reported CRRT. C Extracorporeal membrane oxygenation (ECMO) pooled prevalence and 11/17 studies reported ECMO. D Mortality pooled prevalence, 15/17 reported mortality. CI, confidence interval

Fig. 3

Forrest plot of included studies reporting clinical risk factors for non-survival. A Mean difference for heart rate, favoring non-survival. 5/17 studies included. B Pooled odds ratio of the presence of pulmonary arterial hypertension, favoring non-survival. 10/17 studies included. C Pooled odds ratio of the presence of seizure, favoring non-survival. 9/17 studies included. D Pooled odds ratio of the presence of apnea. 8/17 studies included. CI, confidence interval

Fig. 4

Forrest plot of included studies reporting biological risk factors for non-survival. A Mean difference for admission total white blood cell count, favoring non-survival. 8/17 studies included. B Mean difference for peak total white blood cell count, favoring non-survival. 8/17 studies included. CI, confidence interval