Table 1.

GRADE summary combining quality of evidence and summary of findings^*

Question: What clinical signs best identify severe illness in young infants aged 0–59 days?

Settings: Primary healthcare settings in resource-poor settings

Diagnostic criteria: Clinical signs (clinical referral algorithms)

Quality assessment							Summary of findings
No of studies	No of infants	Design	Limitations	Inconsistency	Indirectness	Imprecision	ORs† (Range)	Quality (GRADE)	Importance
Cyanosis§
3 4 6 13	13 428	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–25.8	HIGH	Critical
Change in level of activity‡
3 6 11 13	15 759	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–15.1	HIGH	Critical
Fast breathing (respiratory rate ≥60 bpm)
3 4 6 13	13 428	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–3.1	MODERATE	Critical
Grunting
2 6 13	12 192	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–2.9	MODERATE	Critical
History of convulsions
2 6 13	12 192	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–15.4	HIGH	Critical
History of difficulty feeding
3 4 6 13	13 428	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–10.0	HIGH	Critical
Severe chest indrawing
4 4 6 12 13	13 939	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–8.9	MODERATE	Critical
Temperature (axillary) ≥37.5°C or <35.5°C
3 4 6 13	13 428	Observational studies	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	1.5–9.2	HIGH	Critical

^*Quality of evidence—the extent to which we can be confident that an estimate of effect or association is correct. The judgements are based on the: study design (randomised vs observational studies); likelihood of bias; consistency of the results across the studies; precision (wide or narrow CIs) of overall estimates and; directness of the evidence with respect to the populations, interventions and settings where the proposed intervention may be used

^†ORs of signs or symptoms calculated by multivariable analyses

^‡History of reduced activity, showing no spontaneous movement, stiff limbs, limps becoming limp

^§Bluish or greyish discoloration of the tongue

Quality of evidence is categorised as ‘high’, ‘moderate’, ‘low’ or ‘very low’

• HIGH : Further research is very unlikely to change our confidence in the estimate of effect.
• MODERATE : Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
• LOW: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
• VERY LOW : We are very uncertain about the estimate.