Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 weeks' postconceptional age

Background. Management of pain in very low birth weight infants is limited by a lack of empiric knowledge about the multiple determinants of biobehavi oral reactivity in infants receiving neonatal intensive care. Objective. To examine relationship of early neonatal factors and previous m edication exposure to subsequent biobehavioral reactivity to acute pain of blood collection. Design. Prospective cohort study. Methods. One hundred thirty-six very low birth weight (less than or equal t o 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 pare nchymal infarction [grade 4 intraventricular hemorrhage]) on cranial ultras ound. Pain reactions were assessed using the Neonatal Facial Coding System, infant state, and spectral analysis of change in heart rate variability fr om baseline to reaction to invasive stimulation. Factor analysis was used t o provide an empirical basis for deriving summary pain scores, one factor w as primarily behavioral and the other primarily autonomic. Results. A normal reaction to procedural pain is characterized by facial gr imacing and heightened cardiac sympathetic activity. The most significant f actors associated with altered behavioral and autonomic pain reactivity at 32 weeks' postconceptional age were a greater number of previous invasive p rocedures since birth and gestational age (GA) at birth, both of which were related to a dampened response. After controlling for these variables, exo genous steroid exposure made an independent contribution to both the behavi oral and autonomic pain scores, also in the direction of dampening the resp onse. Conversely, previous exposure to morphine was associated with "normal ized" (ie, increased) rather than diminished responses. In addition, higher mean heart rate at baseline was associated with lower GA at birth and long er time on mechanical ventilation. Conclusion. Early pain exposure at very low GA may alter the autonomic subs trate, resulting in infants who are in a perpetual state of stress. The res ults of this study suggest that the judicious use of analgesia may ameliora te these effects on later pain reactivity. However, although early morphine exposure may "normalize" subsequent pain reaction, this study did not exam ine its effects on neurodevelopment.