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Updated: Sep 10, 2025

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
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Neurodevelopmental effects of opioids in preterm infants - A systematic review and meta-analysis of randomised and

Maya Rakshasbhuvankar1, Chandra Rath2, Sachin Agrawal2

  • 1General Paediatrics, Perth Children's Hospital, Western Australia, Australia; Neonatology, King Edward Memorial Hospital for Women, Perth, Western Australia, Australia.

Early Human Development
|August 20, 2025
PubMed

Insights

Opioid use in preterm infants does not appear to increase neurodevelopmental impairment risk. However, evidence is very limited, with some studies suggesting potential negative impacts on motor skills.

Area of Science:

  • Neonatalogy
  • Developmental Pediatrics
  • Pharmacology

Background:

  • Opioids are frequently administered to preterm infants for pain and distress management in neonatal intensive care units.
  • Concerns exist regarding the potential adverse effects of opioid exposure on infant neurodevelopment.

Purpose of the Study:

  • To systematically review randomized controlled trials (RCTs) and observational studies (OSs) investigating the impact of opioids on neurodevelopmental outcomes in preterm infants.

Main Methods:

  • A systematic review adhering to Cochrane Collaboration guidelines was performed.
  • Included randomized controlled trials (RCTs) and observational studies (OSs).
  • Quantitative synthesis (pooling) was used where possible; qualitative synthesis for other data.

Main Results:

  • The review encompassed 16 studies (13 OSs, 3 RCTs) with 3173 infants.
  • No increased risk of neurodevelopmental impairment was found (very low certainty evidence).
  • Lower motor scores were observed in opioid-exposed infants at 2-3 years; qualitative analysis showed variable effects of opioids.

Conclusions:

  • The current evidence regarding opioid effects on preterm infant neurodevelopment is inconclusive.
  • The certainty of the available evidence is rated as 'very low'.
Abstract

Keywords:
InfantNeurodevelopmentOpioidsPreterm

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