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Updated: Oct 8, 2025
Electrophysiological Measurements and Analysis of Nociception in Human Infants
Published on: December 20, 2011
Premature infants display discriminable behavioral, physiological, and brain responses to noxious and nonnoxious
Marianne van der Vaart1, Caroline Hartley1, Luke Baxter1
1Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK.
Insights
Assessing pain in preterm infants is difficult. This study shows that infant responses to pain are distinguishable and change with age, improving pain assessment for premature babies.
Area of Science:
- Neonatal care
- Neuroscience
- Developmental pediatrics
Background:
- Pain assessment in preterm infants is challenging due to less sensitive measures compared to term infants.
- Understanding noxious-evoked responses is crucial for improving pain management in premature infants.
- Multimodal pain assessment offers a more comprehensive approach.
Purpose of the Study:
- To investigate the discriminability of multimodal noxious-evoked responses in preterm infants.
- To examine the developmental patterns of these responses from 28 to 40 weeks postmenstrual age.
- To enhance pain assessment tools for premature infants.
Main Methods:
- A classifier was trained using facial expression, brain activity, heart rate, and limb withdrawal data.
- Responses to noxious heel lance were compared against non-noxious stimuli.
- The model was tested on two independent cohorts totaling 97 infants.
Main Results:
- The classifier accurately discriminated noxious from non-noxious stimuli (0.76-0.84 accuracy).
- Accuracy remained high in younger infants (28-31 weeks: 0.78-0.79).
- Distinct developmental patterns were observed, including a novel brain activity stage.
Conclusions:
- Infant responses to noxious and non-noxious stimuli are discriminable in prematurity.
- Noxious-evoked responses exhibit significant developmental changes.
- Findings support improved multimodal pain assessment in preterm infants.
Abstract:
Pain assessment in preterm infants is challenging as behavioral, autonomic, and neurophysiological measures of pain are reported to be less sensitive and specific than in term infants. Understanding the pattern of preterm infants' noxious-evoked responses is vital to improve pain assessment in this group. This study investigated the discriminability and development of multimodal noxious-evoked responses in infants aged 28-40 weeks postmenstrual age. A classifier was trained to discriminate responses to a noxious heel lance from a nonnoxious control in 47 infants, using measures of facial expression, brain activity, heart rate, and limb withdrawal, and tested in two independent cohorts with a total of 97 infants. The model discriminates responses to the noxious from the nonnoxious procedure with an overall accuracy of 0.76-0.84 and an accuracy of 0.78-0.79 in the 28-31-week group. Noxious-evoked responses have distinct developmental patterns. Heart rate responses increase in magnitude with age, while noxious-evoked brain activity undergoes three distinct developmental stages, including a previously unreported transitory stage consisting of a negative event-related potential between 30 and 33 weeks postmenstrual age. These findings demonstrate that while noxious-evoked responses change across early development, infant responses to noxious and nonnoxious stimuli are discriminable in prematurity.
