Importance:

Venipuncture is among the most common neonatal painful procedures. While several analgesic interventions (non-pharmacologic and pharmacologic) have been studied in the last two decades, their comparative efficacy is unknown.

Objective:

To compare the efficacy and safety of different interventions for analgesia during venipuncture in neonates by a systematic review and network meta-analysis (NMA).

Data sources:

Medline, the Cochrane Central Register of Controlled Trials, Embase, and CIHAHL were searched from inception until March 2023.

Study selection:

Randomized and quasi-randomized clinical trials that evaluated different pharmacological and non-pharmacological interventions for analgesia during venipuncture were included.

Data extraction and synthesis:

Data from the included trials were extracted in duplicate. An NMA with frequentist random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE.

Main outcomes and measures:

Pain scores during and 30 s after the venipuncture.

Results:

Of 95 full texts, 37 trials comparing 18 different analgesic measures were included. Three trials had a low risk of overall bias, 21 had some concerns and 13 had a high risk of overall bias. Among the 18 interventions for pain during the venipuncture, breastfeeding (including breastmilk; SMD −1.9 (−0.83, −3)) followed by non-nutritive sucking (SMD −1.69 (−0.27, −3.1)) had a high certainty of evidence (CoE) to reduce pain scores when compared to no intervention. Glucose and swaddling had low certainty of evidence to reduce pain scores.

Conclusions and relevance:

Among various non-pharmacological and pharmacological analgesics to reduce pain during and after the venipuncture in neonate, breastfeeding (including breast milk) was the best intervention to reduce pain during venipuncture, followed by NNS. Both these are feasible interventions in all settings.