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Updated: Dec 18, 2025
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
The Cerebral Hemodynamic Response to Pain in Preterm Infants With Fetal Growth Restriction
Laura M L Dix1,2,3, Kelsee Shepherd1, Graeme R Polglase1
1Department of Paediatrics, The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, VIC, Australia.
Insights
Preterm infants small for gestational age (FGR) show altered cerebral hemodynamics and reduced stroke volume compared to appropriately grown infants (AGA). However, both groups exhibit similar cerebral responses to painful heel lances, with FGR infants less likely to show vasoconstriction.
Area of Science:
- Neonatal neuroscience
- Developmental pediatrics
- Clinical neurophysiology
Background:
- Preterm infants in intensive care experience painful procedures like heel lance.
- Understanding cerebral hemodynamic responses to pain is crucial for preterm brain development.
- Fetal growth restriction (FGR) impacts brain development, potentially altering pain responses compared to appropriately grown (AGA) infants.
Purpose of the Study:
- To compare the cerebral hemodynamic response to painful heel lance stimuli in preterm FGR and AGA infants.
- Investigate differences in neurovascular and cortical pain processing between FGR and AGA preterm infants.
Main Methods:
- Near-infrared spectroscopy (NIRS) monitored cerebral oxygenation (TOI) and hemoglobin changes (ΔO2Hb, ΔHHb, ΔTHb) in preterm FGR (n=20) and AGA (n=15) infants (28-32 weeks gestation).
- Echocardiography assessed ductus arteriosus and stroke volume at baseline.
- Cerebral hemodynamic responses during heel lance were analyzed in contralateral and ipsilateral hemispheres.
Main Results:
- FGR infants had lower baseline tissue oxygenation index (TOI) and stroke volume than AGA infants.
- Most infants in both groups showed increased NIRS parameters in the contralateral hemisphere post-heel lance.
- AGA infants were more likely to exhibit decreased total hemoglobin (ΔTHb) post-stimulus (p=0.016); FGR infants showed greater contralateral oxygenated hemoglobin (ΔO2Hb) increase (p=0.05).
Conclusions:
- Preterm FGR infants exhibit reduced stroke volume and lower cerebral oxygenation in early postnatal life compared to AGA infants.
- Cerebral hemodynamic responses to noxious stimuli are comparable between FGR and AGA preterm infants.
- FGR infants demonstrate a reduced likelihood of cerebral vasoconstriction, potentially linked to in-utero placental insufficiency and brain-sparing effects.
Abstract:
Background: Preterm infants undergoing intensive care often experience painful procedures such as heel lance for blood sampling. Knowledge of the cerebral hemodynamic response to painful stimuli contributes to understanding of cortical pain processing and the neurovascular network in the preterm brain. Previous research has demonstrated cerebral hemodynamic responses using near-infrared spectroscopy (NIRS) after noxious stimuli in infants appropriately grown for age (AGA). But this has not been studied in infants born small for gestational age after fetal growth restriction (FGR). FGR infants differ in brain development due to utero-placental insufficiency leading to the intrauterine growth restriction, and cerebral response to pain may be altered. Objectives: We aimed to compare the cerebral hemodynamic response to painful stimuli (heel lance) in FGR and AGA infants. Methods: Preterm FGR infants (n = 20) and AGA infants (n = 15) born at 28-32 weeks' gestation were studied at mean ± SD postnatal age of 11.5 ± 2.4 and 10.5 ± 2.4 days, respectively. Infants had baseline echocardiographic assessment of ductus arteriosus and stroke volume. They were monitored with NIRS for changes in tissue oxygenation index (TOI, %), and oxygenated, deoxygenated, and total hemoglobin (ΔO2Hb, ΔHHb, and ΔTHb) in contralateral and ipsilateral cerebral hemispheres, during a heel lance. Results: At baseline, FGR infants had significantly lower TOI, higher heart rate, and lower stroke volume compared to AGA infants. Most infants in both groups showed increase in each of the NIRS parameters in the contralateral hemisphere following heel lance. However, more AGA infants (6/15) showed decreased ΔTHb compared to FGR infants (1/20) (p = 0.016). The magnitude of cerebral hemodynamic response and time to response did not differ between FGR and AGA infants. FGR infants showed larger ΔO2Hb in the contralateral compared to ipsilateral cortex (p = 0.05). Conclusion: Preterm FGR infants have reduced stroke volume and lower cerebral oxygenation compared to AGA infants in the second to third week of life. FGR infants show similar cerebral hemodynamic responses to noxious stimuli compared to AGA infants. However, FGR infants are less likely to have a cerebral vasoconstrictive response, possibly due to cerebrovascular changes following placental insufficiency and brain sparing in-utero.
