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Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary results from the NEOPAIN trial
  1. G Menon1,
  2. E M Boyle1,
  3. L L Bergqvist2,
  4. N McIntosh3,
  5. B A Barton4,
  6. K J S Anand5
  1. 1
    Department of Neonatology, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK
  2. 2
    Neonatal Research Unit, Karolinska Institute, Astrid Lindgren's Children's Hospital, Stockholm, Sweden
  3. 3
    University of Edinburgh, Edinburgh, Scotland, UK
  4. 4
    Maryland Medical Research Institute, Baltimore, Maryland, USA
  5. 5
    Department of Pediatrics, University of Arkansas for Medical Sciences College of Medicine and Arkansas Children’s Hospital, Little Rock, Arkansas, USA
  1. Dr G Menon, Department of Neonatology, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SA, Scotland, UK; gopi.menon{at}


Objective: To investigate the influence of morphine therapy and other factors on the attainment of full enteral feeds and on acquired gastrointestinal pathology in preterm infants.

Design: Secondary data analysis from a randomised, placebo controlled trial.

Setting: 16 neonatal intensive care units in USA, Sweden, France and UK.

Patients: 898 infants (treatment group 449, control 449). Gestation (median (range)): 27 (23–32) weeks; birth weight (median (range)): 985 (420–2440) g.

Interventions: Morphine (M) or placebo (Pl) given pre-emptively by intravenous loading dose (100 μg/kg of morphine) and infusion (10–30 μg/kg/h depending on gestation) while infants were ventilated, for up to 14 days. “Open-label” morphine (A) could be given if clinically indicated.

Main outcome measures: Age at full enteral feeds and major acquired gastrointestinal pathology.

Results: The group randomised to morphine was later in attaining full feeds (median days (quartiles): M 20 (13–29), Pl 17 (12–26); p = 0.003), and in starting feeds (median days (quartiles): M 5 (3–8), Pl 4 (2–7)). In a linear regression model, age at full feeds was independently associated with birth weight, a score of neonatal morbidities, neonatal dexamethasone use and cumulative morphine dose. There was no relationship between morphine use and acquired gastrointestinal pathology (M 9/449, Pl 8/449; χ2 p = 0.81).

Conclusions: Morphine delays the attainment of full enteral feeds, partly by delaying the start of feeding, but does not discernibly increase gastrointestinal complications. The attainment of full feeds is influenced by morphine dose, but other factors seem to be important, including birth weight and neonatal morbidity.

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  • Funding: The NEOPAIN study (Neurologic Outcomes and Pre-emptive Analgesia in Neonates) was funded by grants from the following: the National Institute for Child Health and Human Development in the USA; the Chief Scientist’s Office of the Scottish Executive; and the Swedish Research Council, Vardal Foundation, and Free Masons, Sweden, the fondation pour la Santé CNP, France, and the Örebro University Hospital Research Foundation, Sweden.

  • Competing interests: None.

  • Ethics approval: Ethical approval was obtained.