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Updated: Apr 17, 2026
Electrophysiological Measurements and Analysis of Nociception in Human Infants
Published on: December 20, 2011
Multidimensional response to vaccination pain in very preterm, moderate- to-late preterm and full-term infants at age
Katrin Mehler1, Lisa Ulbrich1, Sarah Börner1
1University Hospital of Cologne, Department of Neonatology, Germany.
Insights
Early life pain and stress alter brain development and pain sensitivity. Very preterm infants exhibit reduced behavioral and physiological responses to pain at three months, indicating altered hypothalamic-pituitary-adrenal (HPA) axis reactivity.
Area of Science:
- Neonatal development
- Pain perception
- Neuroendocrinology
Background:
- Early life pain and stress can impact brain development and pain sensitivity.
- Premature infants often experience numerous early postnatal adverse events.
- Altered behavioral and hypothalamic-pituitary-adrenal (HPA) axis reactivity are observed in infants with adverse early life experiences.
Purpose of the Study:
- To compare the multidimensional response to vaccination in three-month-old infants.
- To investigate varying pain and stress exposure in very preterm, moderate to late preterm, and full-term infants.
Main Methods:
- Infant reactivity to intramuscular immunization at three months was evaluated.
- Included 61 very preterm, 30 moderate to late preterm, and 30 full-term infants.
- Assessed heart rate recovery, Bernese Pain Score, salivary cortisol, flexor withdrawal reflex, and Prechtl's General Movements, alongside potential influencing factors.
Main Results:
- Significant differences in pain reactivity were observed across all infant groups.
- Very preterm infants demonstrated lower behavioral and physiological reactivity.
- Early pain/stress exposure correlated with a reduced cortisol increase in very preterm infants.
Conclusions:
- At three months, very preterm infants display altered HPA axis reactivity.
- Minimizing pain and stress in premature infants is crucial.
- Early life adversity impacts neonatal pain processing and HPA axis function.
Background:
Very early life pain exposure and stress induces alterations in the developing brain and leads to altered pain sensitivity. In premature infants with a history of numerous early postnatal adverse events, behavioral responsiveness and hypothalamic-pituitary-adrenal (HPA) axis reactivity may show alterations as well.
Aims:
We compared a multidimensional response to a painful situation (vaccination) in three month old infants. The study involved very preterm, moderate to late preterm infants and full-term infants with varying exposure to pain and stress within the first weeks of life.
Study Design:
At the age of three months, we evaluated the infants' reactivity to intramuscular injections for immunization.
Subjects:
The study included 61 very preterm infants, 30 moderate to late preterm infants and 30 full-term infants.
Outcome Measures:
We assessed heart rate recovery, Bernese pain Score and increase of salivary cortisol following vaccination. We also evaluated the flexor withdrawal reflex threshold as well as Prechtl's General Movements. Secondly, we assessed factors potentially influencing pain reactivity such as exposure to pain/stress, gender, use of steroids or opioids and mechanical ventilation.
Results:
Very preterm, moderate to late preterm and full-term infants showed different reactivity to pain in all analyzed aspects. Very preterm infants showed a lower level of behavioral and physiologic reactivity and exposure to pain/stress predicted lower cortisol increase.
Conclusion:
At three months of age, very preterm infants show an altered level of HPA axis reactivity. Efforts aiming at minimizing pain and stress in premature infants should be taken.
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