Perinatal & Pediatric
Infant Clinical Signs Associated with Mortality and Bacteremia in Young Infants Aged 0-59 Days: A Systematic Review and Meta-analysis Sophie Driker* Sophie Driker Alastair Fung Suci Ardini Widyaningsih Naomi Schmeck Yumin Kim Jana Adnan Anum S. Hussaini Sitarah Mathias Tessa Kehoe Yasir Shafiq Carrie G. Wade Anne CC Lee
Background: Certain clinical signs are early indicators of infection and may be associated with mortality or bacteremia in young infants. Understanding these associations is important to optimize clinical algorithms to identify the highest-risk infants.
Aim: To systematically review evidence on the association of various individual infant clinical signs with mortality or bacteremia among young infants aged 0-59 days.
Methods: We searched Medline, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Register in September 2024 for studies evaluating the association of individual signs with all-cause mortality or bacteremia. We used Cochrane methods for study screening, data extraction, and performed quality assessment using QUADAS, QUAPAS, and Newcastle-Ottawa Scales. We reviewed clinical signs in the current WHO integrated management of childhood illness (IMCI) algorithm for management of sick young infants, plus 7 additional signs.
Results: Of 6701 studies identified, 37 were included. Of 21 clinical signs reviewed, 13 signs were significantly associated with mortality and 8 with bacteremia. The 5 clinical signs with the highest risk of mortality were weak or absent cry, prolonged capillary refill, altered consciousness (defined as “no movement when stimulated, movement only when stimulated, drowsy, unconscious, or lethargic”), not feeding well, and severe abdominal distension. The top 5 clinical signs associated with bacteremia were bulging fontanelle, prolonged capillary refill, not feeding well, fever, and altered consciousness.
Conclusion: Several infant clinical signs included in the current WHO IMCI algorithm are significantly associated with mortality and bacteremia. Bulging fontanelle and prolonged capillary refill were significantly associated with mortality and bacteremia in this review and are not included in the current IMCI algorithm. Future analyses will additionally assess the prevalence and predictive accuracy of individual infant clinical signs.
