Infant Outcomes, Risk Factors, and Diagnostic Yield After a Brief Resolved Unexplained Event: A Systematic Review and Meta-Analysis
After a brief resolved unexplained event, serious illness is uncommon, death is rare, and routine testing usually adds little.
*Systematic review and meta-analysis of cohort studies; Level 2a.
Citation
Nama N, Liebert S, Abaji M, et al. Infant Outcomes, Risk Factors, and Diagnostic Yield After a Brief Resolved Unexplained Event: A Systematic Review and Meta-Analysis. JAMA Pediatrics. 2026;180(3):250-262. doi:10.1001/jamapediatrics.2025.5858
Background
Brief resolved unexplained events in infants often prompt testing and hospital care, despite limited evidence that broad testing improves outcomes. This review aimed to clarify prognosis, risk factors, and which tests are useful.
Patients
Infants younger than 12 months meeting 2016 American Academy of Pediatrics criteria. Studies were excluded if events were not clinically verified or could not be distinguished from other episodes.
Intervention
Assessment of clinical risk factors and common diagnostic tests after the event.
Control
Infants without the risk factor, or comparison with the overall tested group.
Outcome
Serious underlying diagnosis, recurrent event, 3-month death, and diagnostic test yield.
Follow-up Period
Up to 3 months for recurrence and death; serious diagnoses within 1 year.
Results
| Finding | Result |
|---|---|
| Serious diagnosis (primary) | 6.0% (95% CI, 4.6%-7.9%) |
| Death within 3 months (primary) | 1 per 1851 infants |
| Recurrent event | 13.6% (95% CI, 11.1%-16.7%) |
| Higher-risk features for serious diagnosis | Multiple events +3.7%; prematurity +2.6%; abnormal medical history +3.1% |
| Routine tests | Metabolic panels 0% yield; electrocardiograms 0.2%; chest radiographs 0.4% |
| More selective test | Brain wave testing yield 5.5%; number needed to test 18 |
CI = confidence interval.
Age 60 days or younger was not linked to serious diagnosis. Most studies were observational, not treatment trials.
Limitations
Most studies were retrospective, single-center, and from high-income countries. Test yield may be overestimated because clinicians selected which infants were tested.
Funding
Seattle Children’s Research Institute awards; no industry funding reported.
Clinical Application
Reassure most families and avoid routine testing; target evaluation to infants with multiple events, prematurity, or abnormal history.
Discussion
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In this systematic review/meta-analysis of mostly observational BRUE studies, routine ECGs had 0.2% diagnostic yield (NNT 623) and serious underlying diagnosis prevalence was 6.0%; how valid and applicable is shifting from blanket testing to targeted risk-informed evaluation in your practice? In this meta-analysis, chest radiographs after BRUE had a pooled diagnostic yield of 0.4% and a number needed to test (NNT) of 256. What is the best interpretation of this NNT?