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Meta-Analysis
. 2020 Jan 27;1(1):CD011219.
doi: 10.1002/14651858.CD011219.pub4.

Paracetamol (acetaminophen) for prevention or treatment of pain in newborns

Arne Ohlsson  1   2 , Prakeshkumar S Shah  3
Affiliations
Meta-Analysis

Paracetamol (acetaminophen) for prevention or treatment of pain in newborns

Arne Ohlsson et al. Cochrane Database Syst Rev. .

Abstract

Background: Newborn infants have the ability to experience pain. Hospitalised infants are exposed to numerous painful procedures. Healthy newborns are exposed to pain if the birth process consists of assisted vaginal birth by vacuum extraction or by forceps and during blood sampling for newborn screening tests.

Objectives: To determine the efficacy and safety of paracetamol for the prevention or treatment of procedural/postoperative pain or pain associated with clinical conditions in neonates. To review the effects of various doses and routes of administration (enteral, intravenous or rectal) of paracetamol for the prevention or treatment of pain in neonates.

Search methods: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1966 to 9 May 2016), Embase (1980 to 9 May 2016), and CINAHL (1982 to 9 May 2016). We searched clinical trials' databases, Google Scholar, conference proceedings, and the reference lists of retrieved articles.

Selection criteria: We included randomised and quasi-randomised controlled trials of paracetamol for the prevention/treatment of pain in neonates (≤ 28 days of age).

Data collection and analysis: Two review authors independently extracted data from the articles using pre-designed forms. We used this form to decide trial inclusion/exclusion, to extract data from eligible trials and to request additional published information from authors of the original reports. We entered and cross-checked data using RevMan 5 software. When noted, we resolved differences by mutual discussion and consensus. We used the GRADE approach to assess the quality of evidence.

Main results: We included nine trials with low risk of bias, which assessed paracetamol for the treatment of pain in 728 infants. Painful procedures studied included heel lance, assisted vaginal birth, eye examination for retinopathy of prematurity assessment and postoperative care. Results of individual studies could not be combined in meta-analyses as the painful conditions, the use of paracetamol and comparison interventions and the outcome measures differed. Paracetamol compared with water, cherry elixir or EMLA cream (eutectic mixture of lidocaine and prilocaine) did not significantly reduce pain following heel lance. The Premature Infant Pain Profile score (PIPP) within three minutes following lancing was higher in the paracetamol group than in the oral glucose group (mean difference (MD) 2.21, 95% confidence interval (CI) 0.72 to 3.70; one study, 38 infants). Paracetamol did not reduce "modified facies scores" after assisted vaginal birth (one study, 119 infants). In another study (n = 123), the Échelle de Douleur et d'Inconfort du Nouveau-Né score at two hours of age was significantly higher in the group that received paracetamol suppositories than in the placebo suppositories group (MD 1.00, 95% CI 0.60 to 1.40). In that study, when infants were subjected to a heel lance at two to three days of age, Bernese Pain Scale for Neonates scores were higher in the paracetamol group than in the placebo group, and infants spent a longer time crying (MD 19 seconds, 95% CI 14 to 24). For eye examinations, no significant reduction in PIPP scores in the first or last 45 seconds of eye examination was reported, nor at five minutes after the eye examination. In one study (n = 81), the PIPP score was significantly higher in the paracetamol group than in the 24% sucrose group (MD 3.90, 95% CI 2.92 to 4.88). In one study (n = 114) the PIPP score during eye examination was significantly lower in the paracetamol group than in the water group (MD -2.70, 95% CI -3.55 to 1.85). For postoperative care following major surgery, the total amount of morphine (µg/kg) administered over 48 hours was significantly less among infants assigned to the paracetamol group than to the morphine group (MD -157 µg/kg, 95% CI -27 to -288). No adverse events were noted in any study. The quality of evidence according to GRADE was low.

Authors' conclusions: The paucity and low quality of existing data do not provide sufficient evidence to establish the role of paracetamol in reducing the effects of painful procedures in neonates. Paracetamol given after assisted vaginal birth may increase the response to later painful exposures. Paracetamol may reduce the total need for morphine following major surgery, and for this aspect of paracetamol use, further research is needed.

PubMed Disclaimer

Conflict of interest statement

Dr Arne Ohlsson is a co‐author of one of the included trials (Shah 1998).

Dr Prakeshkumar Shah reports no conflicts of interest.

Figures

1
1
Study flow diagram: review update
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 2 Heel lance ‐ paracetamol (oral) vs glucose (oral), outcome: 2.1 PIPP (maximum score within 3 minutes following lancing).
5
5
Forest plot of comparison: 6 Eye examination ‐ paracetamol (oral) vs placebo (sterile water) for eye examination, outcome: 6.4 PIPP score during eye examination.
6
6
Forest plot of comparison: 7 Eye examination ‐ paracetamol (oral) vs 24% sucrose (oral), outcome: 7.1 PIPP score in first 45 seconds of eye examination.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Härmä 2016 {published data only}
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Ohlsson 2015
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