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Updated: May 21, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Neonatal pain in relation to postnatal growth in infants born very preterm
Jillian Vinall1, Steven P Miller, Vann Chau
1Department of Neuroscience, University of British Columbia, Vancouver, BC, Canada Developmental Neurosciences & Child Health, Child & Family Research Institute, Vancouver, BC, Canada Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Insights
Neonatal procedural pain in very preterm infants is linked to reduced early postnatal growth, including weight and head circumference. This suggests pain impacts growth during a critical developmental window in the neonatal intensive care unit.
Area of Science:
- Neonatology
- Developmental Pediatrics
- Pain Research
Background:
- Procedural pain in preterm infants is a concern for neurodevelopment.
- The impact of neonatal pain-related stress on postnatal growth in very preterm infants is not well understood.
- Animal studies suggest early stress hinders growth, but human data is limited.
Purpose of the Study:
- To investigate the relationship between neonatal pain exposure and postnatal growth in infants born very preterm (≤ 32 weeks gestational age).
- To assess growth in terms of weight and head circumference (HC) percentiles early in life and at term-equivalent age.
- To adjust for potential medical confounders influencing growth.
Main Methods:
- Prospective follow-up of 78 infants born ≤ 32 weeks gestational age.
- Measurement of infant weight and HC at birth, early in life (32 weeks postconceptional age), and at term-equivalent age (40 weeks).
- Calculation of weight and HC percentiles using sex-specific British Columbia population data; statistical adjustment for confounders.
Main Results:
- Greater neonatal pain exposure predicted lower weight and HC percentiles at 32 weeks postconceptional age.
- These findings remained significant after adjusting for birth weight percentile and other postnatal risk factors.
- Neonatal infection, however, predicted lower weight percentile at term-equivalent age.
Conclusions:
- Repetitive procedural pain in physiologically immature very preterm infants appears to negatively impact early postnatal growth.
- Pain may trigger stress signaling pathways affecting growth within the neonatal intensive care unit.
- Further research is needed to elucidate the mechanisms linking neonatal pain and growth outcomes.
Abstract:
Procedural pain is associated with poorer neurodevelopment in infants born very preterm (≤ 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born ≤ 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald χ(2)=7.36, P=0.01) and HC (Wald χ(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald χ(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.
