9. Effect estimates, intervention versus other active interventions.

Outcomes	Paracetamol versus Ibuprofen Jasani 2022	Morphine versus midazolam Bellù 2021	Morphine versus diamorphine Bellù 2021	Morphine versus fentanyl Bellù 2021
Any GMH‐IVHa	RR 1.17, 95% CI 0.31 to 4.34; 1 RCT, 30 infants	RR 0.28, 95% CI 0.09 to 0.87; 1 RCT, 46 infants	RR 0.65, 95% CI 0.40 to 1.07; 1 RCT, 88 infants	Not reported
Severe IVHb	RR 2.65, 95% CI 0.12 to 60.21; 1 RCT, 30 infants	RR 0.08, 95% CI 0.00 to 1.43; 1 RCT, 46 infants	Not reported	RR 0.59, 95% CI 0.18 to 1.95; 1 RCT, 163 infants
Neonatal deathc	Not reported	RR 0.31, 95% CI 0.01 to 7.16; 1 RCT, 46 infants	RR 1.17, 95% CI 0.43 to 3.19; 1 RCT, 88 infants	Not reported
Major neurodevelopmental disabilityd	Not reported	Not reported	Not reported	Not reported
Death during initial hospitalizatione	RR 0.88, 95% CI 0.14 to 5.42; 1 RCT, 30 infants	Not reported	Not reported	RR 1.21, 95% CI 0.43 to 3.45; 1 RCT, 163 infants
Any ROPf	RR 4.41, 95% CI 0.24 to 84.79; 1 RCT, 30 infants	Not reported	Not reported	Not reported
Severe ROPg	Not reported	Not reported	Not reported	Not reported
Cerebellar hemorrhageh	Not reported	Not reported	Not reported	Not reported
PVLi	Not reported	RR 0.23, 95% CI 0.03 to 1.90; 1 RCT, 46 infants	Not reported	Not reported
Brain MRI abnormalitiesj	Not reported	Not reported	Not reported	Not reported

Studies comparing morphine versus midazolam, diamorphine, or fentanyl: their results are shown in this table; I² was not applicable because there was only one study in each analysis.

List of outcomes

^aAny germinal matrix hemorrhage‐intraventricular hemorrhage: any GMH‐IVH, ultrasound diagnosis grade 1 to 4 (according to Papile classification (Papile 1978)).
^bSevere intraventricular hemorrhage (IVH), ultrasound diagnosis grade 3 and 4 (according to Papile classification (Papile 1978)).
^cAll‐cause neonatal death (death within 28 days of birth).
^dMajor neurodevelopmental disability: cerebral palsy, developmental delay (Bayley Mental Developmental Index (Bayley 1993; Bayley 2006) or Griffiths Mental Development Scale assessment (Griffiths 1954) more than two SD below the mean), intellectual impairment (IQ more than two standard deviations below mean), blindness (vision < 6/60 in both eyes), or sensorineural deafness requiring amplification (Jacobs 2013). We planned to evaluate each of these components as a separate outcome and to extract data on this long‐term outcome from studies that evaluated children after 18 months of chronological age. We planned to assess separately data on children aged 18 to 24 months and those aged three to five years.
^eAll‐cause death during initial hospitalization.
^fAny retinopathy of prematurity: any stage (ICROP 1984).
^gSevere retinopathy of prematurity: stage 3 or greater (ICROP 1984).
^hCerebellar hemorrhage at brain ultrasound in the first month of life (yes/no, Graça 2013).
ⁱCystic periventricular leukomalacia at brain ultrasound in the first month of life (yes/no); or at term equivalent age (yes/no).
^jBrain magnetic resonance imaging (MRI) abnormalities at term equivalent age (yes/no), defined as white matter lesions (i.e. cavitations; Rutherford 2010) and punctate lesions (Cornette 2002); GM‐IVH (Parodi 2015); or cerebellar hemorrhage (Limperopoulos 2007).

CI = confidence interval; GMH‐IVH = germinal matrix hemorrhage‐intraventricular hemorrhage; MRI = magnetic resonance imaging; PVL = periventricular leukomalacia; ROP = retinopathy of prematurity; RR = risk ratio