Evidence map›Paper›PMID 26763312›Full record

ArticleThe Journal of pediatrics2016

Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine.

Jill G Zwicker, Steven P Miller, Ruth E Grunau, Vann Chau, Rollin Brant, Colin Studholme, Mengyuan Liu, Anne Synnes, Kenneth J Poskitt, Mikaela L Stiver and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pediatrics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 6 pooled it
45.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 6 syntheses or guidelines pooled it, 210 citations in OpenAlex.

  1. Opioid equipotency conversions for hospitalized infants: a systematic review.Journal of perinatology : official journal of the California Perinatal Association · 2024
    Pooled it
  2. Pooled it
  3. Systemic opioid regimens for postoperative pain in neonates.The Cochrane database of systematic reviews · 2023
    Pooled it
  4. Pooled it
  5. Systemic opioid regimens for postoperative pain in neonates.The Cochrane database of systematic reviews · 2023
    Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Article
  10. Observational
  11. Article
  12. Associations between opioid exposure and brain size among extremely preterm infants.Journal of perinatology : official journal of the California Perinatal Association · 2026
    Article
  13. Review
  14. Review
  15. Article
  16. Cumulative exposure to opioids and benzodiazepines in extremely preterm neonates.Journal of perinatology : official journal of the California Perinatal Association · 2026
    Article
  17. Article
  18. Opioid exposure on the preterm brain: qualitative and quantitative MRI analysis.Intensive care medicine. Paediatric and neonatal · 2026
    Article
  19. Article
  20. Review

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Jill G ZwickerDepartment of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, Vancouver, Canada. Electronic address: jill.zwicker@ubc.ca.
Steven P MillerDepartment of Pediatrics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, Vancouver, Canada; Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada.
Ruth E GrunauDepartment of Pediatrics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, Vancouver, Canada; British Columbia Women's Hospital, Vancouver, Canada.
Vann ChauDepartment of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada.
Rollin BrantChild and Family Research Institute, Vancouver, Canada; Department of Statistics, University of British Columbia, Vancouver, Canada.
Colin StudholmeDepartments of Bioengineering and Pediatrics, University of Washington, Seattle, WA.
Mengyuan LiuDepartments of Bioengineering and Pediatrics, University of Washington, Seattle, WA.
Anne SynnesDepartment of Pediatrics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, Vancouver, Canada; British Columbia Women's Hospital, Vancouver, Canada.
Kenneth J PoskittChild and Family Research Institute, Vancouver, Canada; Department of Radiology, University of British Columbia, Vancouver, Canada.
Mikaela L StiverDepartment of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada.
Emily W Y TamDepartment of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada.
University of British Columbia · CAUniversity of Toronto · CAUniversity of Washington · US

Funding

Motion Robust Mapping of Human Brain Microstructure and Macrostructure In-UteroR01NS055064 · NINDS · UNIVERSITY OF WASHINGTON · PI STUDHOLME, COLIN · 2006 to 2017
$4.1M
PAIN IN PRETERM INFANTS--DEVELOPMENT AND EFFECTSR01HD039783 · NICHD · UNIVERSITY OF BRITISH COLUMBIA · PI GRUNAU, RUTH E · 2001 to 2012
$1.8M
Mapping Patterns of Brain Tissue Growth in Premature NeonatesR01NS061957 · NINDS · UNIVERSITY OF WASHINGTON · PI STUDHOLME, COLIN · 2009 to 2013
$1.7M
CIHR MOP79262CIHR MOP86489NICHD NIH HHS R01 HD039783NINDS NIH HHS R01 NS055064NINDS NIH HHS R01 NS061957
6 · The paper itself

Abstract

objectiveTo examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). STUDY

designA prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes.

resultsA 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth.

conclusionsMorphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.

Indexed as

Analgesics, OpioidCerebellumCerebrumDevelopmental DisabilitiesFemaleHumansInfant, NewbornInfant, PrematureMagnetic Resonance ImagingMaleMorphineNervous System MalformationsProspective StudiesAnalgesics, OpioidMorphine

Identifiers

PMID26763312
PMCPMC5462546
OpenAlexW2224598932

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.