Background. Management of pain in very low birth weight infants is limited by a lack of empiric knowledge about the multiple determinants of biobehavioral reactivity in infants receiving neonatal intensive care.Objective. To examine relationship of early neonatal factors and previous medication exposure to subsequent biobehavioral reactivity to acute pain of blood collection.Design. Prospective cohort study.Methods. One hundred thirty-six very low birth weight (≤1500 g) infants who underwent heel lance for blood collection at 32 weeks' postconceptional age formed the study sample, after excluding those with significant cerebral lesions (periventricular leukomalacia or cerebral parenchymal infarction [grade 4 intraventricular hemorrhage]) on cranial ultrasound. Pain reactions were assessed using the Neonatal Facial Coding System, infant state, and spectral analysis of change in heart rate variability from baseline to reaction to invasive stimulation. Factor analysis was used to provide an empirical basis for deriving summary pain scores, one factor was primarily behavioral and the other primarily autonomic.Results. A normal reaction to procedural pain is characterized by facial grimacing and heightened cardiac sympathetic activity. The most significant factors associated with altered behavioral and autonomic pain reactivity at 32 weeks' postconceptional age were a greater number of previous invasive procedures since birth and gestational age (GA) at birth, both of which were related to a dampened response. After controlling for these variables, exogenous steroid exposure made an independent contribution to both the behavioral and autonomic pain scores, also in the direction of dampening the response. Conversely, previous exposure to morphine was associated with “normalized” (ie, increased) rather than diminished responses. In addition, higher mean heart rate at baseline was associated with lower GA at birth and longer time on mechanical ventilation.Conclusion. Early pain exposure at very low GA may alter the autonomic substrate, resulting in infants who are in a perpetual state of stress. The results of this study suggest that the judicious use of analgesia may ameliorate these effects on later pain reactivity. However, although early morphine exposure may “normalize” subsequent pain reaction, this study did not examine its effects on neurodevelopment.
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