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Updated: May 5, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Internalizing behaviours in school-age children born very preterm are predicted by neonatal pain and morphine
M Ranger1, A R Synnes, J Vinall
1Department of Paediatrics, University of British Columbia, Vancouver, Canada; Developmental Neurosciences & Child Health, Child & Family Research Institute, Vancouver, BC, Canada.
Insights
Neonatal pain in very preterm infants may impact school-age internalizing behaviors. Morphine use in ventilated infants was linked to increased internalizing behaviors, highlighting the need for careful pain management.
Area of Science:
- Neonatal care
- Developmental psychology
- Pediatric pain management
Background:
- Neonatal pain is linked to internalizing behaviors in preterm infants.
- The persistence of this link into school age is unknown.
- Morphine's role in modulating pain's behavioral effects needs clarification.
Purpose of the Study:
- To investigate the association between neonatal pain-related stress and internalizing behaviors at age 7 in very preterm children.
- To determine if morphine exposure influences this relationship.
Main Methods:
- 101 very preterm infants (gestation ≤32 weeks) assessed at ~7.7 years.
- Parent-completed Parenting Stress Index and Child Behavior Checklist.
- Neonatal pain-related stress (skin-breaking procedures) analyzed in relation to internalizing behavior, stratified by ventilation and morphine exposure.
Main Results:
- In non-ventilated infants, more procedures and higher parenting stress correlated with increased internalizing behaviors.
- In ventilated infants, greater morphine exposure was associated with higher child internalizing scores.
Conclusions:
- Judicious morphine use is crucial in ventilated very preterm children.
- Morphine may mitigate pain effects on nociception but potentially worsen school-age internalizing behaviors.
- Addressing procedural pain in the NICU is vital to prevent long-term behavioral issues.
Background:
Greater neonatal pain is associated with higher internalizing behaviours in very preterm infants at 18 months corrected age, but it is unknown whether this relationship persists to school age. Moreover, it is unclear whether morphine ameliorates or exacerbates the potential influence of neonatal pain/stress on internalizing behaviours. We examined whether neonatal pain-related stress is associated with internalizing behaviours at age 7 years in children born very preterm, and whether morphine affects this relationship.
Methods:
One hundred one children born very preterm (≤32 weeks gestation) were seen at mean age 7.7 years. A parent completed the Parenting Stress Index and Child Behavior Checklist questionnaires. Neonatal pain-related stress (the number of skin-breaking procedures adjusted for clinical factors associated with prematurity) was examined in relation to internalizing behaviour, separately in subjects mechanically ventilated and exposed to both pain and morphine (n = 57) and those never mechanically ventilated, exposed to pain but not morphine (n = 44).
Results:
In the non-ventilated group, higher skin-breaking procedures (p = 0.037) and parenting stress (p = 0.004) were related to greater internalizing behaviours. In the ventilated group, greater morphine exposure (p = 0.004) was associated with higher child internalizing scores.
Conclusions:
In very preterm children who undergo mechanical ventilation, judicious use of morphine is important, since morphine may mitigate the negative effects of neonatal pain on nociception but adversely affect internalizing behaviours at school age. Management of procedural pain needs to be addressed in very preterm infants in the neonatal intensive care unit, to prevent long-term effects on child behaviour.
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