Summary of findings 1. Tramadol compared to no treatment or placebo for postoperative pain in neonates.

Tramadol compared to no treatment or placebo for postoperative pain in neonates
Patient or population: postoperative pain in preterm and term infants  Setting: neonatal intensive care unit Intervention: tramadol  Comparison: no treatment or placebo
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with no treatment or placebo	Risk with tramadol
Pain assessed with validated methods during the administration of selected drugs	‐		‐	‐	‐	This outcome was not reported.
Major neurodevelopmental disability in children aged 18 to 24 months	‐		‐	‐	‐	This outcome was not reported.
Major neurodevelopmental disability in children aged three to five years	‐		‐	‐	‐	This outcome was not reported.
Cognitive and educational outcomes in children more than five years old	‐		‐	‐	‐	This outcome was not reported.
All‐cause mortality during initial hospitalization	Study population		RR 0.32 (0.01 to 7.70) RD ‐0.03, (‐0.10 to 0.05)	71 (1 RCT)	⊕⊝⊝⊝ Very low 1	The evidence is very uncertain about the effect of tramadol on this outcome compared to placebo.
	29 per 1000	9 per 1000 (0 to 220)
Severe retinopathy of prematurity (defined as stage 3 or greater)	‐		‐	‐	‐	This outcome was not reported.
Severe intraventricular hemorrhage (grade 3 or greater) on cranial ultrasound, as per Papile classification	‐		‐	‐	‐	This outcome was not reported.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; OR: odds ratio; RCT: randomized controlled trial; RD: risk difference; RR: risk ratio;
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

¹Downgraded one level for study limitations: unclear selection and reporting bias; downgraded two levels for imprecision: one small trial with wide confidence of interval