All Clinical Signs in WHO IMCI Predictive of Sepsis and Mortality in Young Infants: JAMA
Researchers have found in a new systematic review and meta-analysis that all seven clinical signs in the WHO IMCI possible serious bacterial infection (SBI) algorithm were significantly associated with sepsis or mortality in infants aged 0–59 days. Notably, prolonged capillary refill and central cyanosis, which showed strong associations, are not currently included in IMCI. These findings support further research into expanding clinical criteria and exploring non-checklist approaches, including machine learning, to improve identification and management of serious bacterial infections in young infants. The study was published in JAMA Pediatrics by Sophie D. and colleagues.
Sepsis is one of the major causes of neonatal and infant deaths globally. Early diagnosis is essential, but most peripheral health facilities make diagnoses based on clinical presentations rather than laboratory results. The purpose of this study was to systematically review the available evidence on the relationship and accuracy of clinical presentations in diagnosing sepsis or predicting mortality in young infants aged 0 to 59 days.
The review searched MEDLINE, Embase, CINAHL, Global Index Medicus, and the Cochrane CENTRAL Register from inception to May 2023, and updated searches were carried out on September 5, 2024. Moreover, an umbrella review of systematic reviews was undertaken in January 2024 to make sure that all existing evidence was covered. The studies eligible for inclusion provided data on 24 predefined infant clinical signs, based on current WHO IMCI and hospital algorithms, and included odds ratios (ORs), risk ratios, sensitivity, and specificity.
Data extraction was performed independently by two authors. Quality assessment of studies was done using the Newcastle-Ottawa Scale, QUADAS-2, and the Quality Assessment of Prognostic Accuracy Studies (QUAPAS) scales. Statistical analysis was carried out between July and September 2025, and ORs were pooled using random-effects models. A total of 52 studies with 140 885 infants were included after screening 7641 studies.
Key findings
A total of 16 clinical signs were significantly associated with mortality, 11 signs with culture-confirmed sepsis, and 13 signs with clinical sepsis.
For mortality, the strongest associations were observed for:
Weak, abnormal, or absent cry: OR 20.48 (95% CI, 6.59–63.67)
Not able to feed at all: OR 18.32 (95% CI, 6.00–55.97)
Not feeding well: OR 13.39 (95% CI, 6.97–25.72)
Drowsiness or unconsciousness: OR 12.46 (95% CI, 6.06–25.62)
Prolonged capillary refill: OR 12.06 (95% CI, 2.77–52.53)
For culture-confirmed sepsis, the top associated signs were:
Not feeding well: OR 4.52 (95% CI, 1.10–18.59)
Prolonged capillary refill: OR 3.59 (95% CI, 2.05–6.28)
Lethargy: OR 3.44 (95% CI, 1.89–6.26)
Drowsiness or unconsciousness: OR 3.07 (95% CI, 2.01–4.68)
Feeding intolerance: OR 2.95 (95% CI, 1.67–5.21)
In infants aged 0 to 59 days, clinical signs alone can be used to accurately predict sepsis and mortality without laboratory confirmation. All existing WHO IMCI signs were validated, and new signs were also found that could improve the detection of life-threatening conditions. These results support the improvement of clinical sign algorithms to increase infant survival in resource-limited areas.
Reference:
Driker S, Mathias S, Fung A, et al. Clinical Signs Associated With Mortality and Sepsis in Young Infants: A Systematic Review and Meta-Analysis. JAMA Pediatr. Published online February 02, 2026. doi:10.1001/jamapediatrics.2025.5967
