Does parenchymal brain injury affect biobehavioral pain responses in very low birth weight infants at 32 weeks' postconceptional age?
OBJECTIVE
Children with neurologic impairments have shown diminished pain response compared with control subjects; however, it remains unclear what mechanisms underlie this response or when it develops. If this were also true with premature infants who undergo neonatal intensive care, then infants with parenchymal brain injury (PBI) would be at increased risk of underrecognition and undertreatment of procedural pain. The purpose of this study was to determine whether infants with PBI display altered responses to acute procedural pain at 32 weeks' postconceptional age (PCA), compared with control subjects.


METHODS
We compared responses to blood collection by heel lance at 32 weeks' PCA in 12 very low birth weight infants (mean [range] birth weight: 876 g [630-1240 g]; gestational age: 26.3 weeks (24-28 weeks) who had sustained PBI in the neonatal period, with 12 control subjects matched for gestational age at birth and gender (838 g [625-990 g]; 26.3 weeks [24-28 weeks[) who had normal neonatal brain imaging. PBI was defined as cerebral parenchymal infarction (grade 4 intraventricular hemorrhage) or cystic periventricular leukomalacia on serial cranial ultrasound scans conducted in the neonatal period. Biobehavioral responses to pain were measured using facial activity (Neonatal Facial Coding System) and measures of heart rate (HR) variability (low-frequency [LF] power [0.04-0.15], high-frequency [HF] power [0.15-0.8 Hz], and LF/HF ratio) as a measure of cardiac autonomic modulation. Neurodevelopmental follow-up was undertaken at 18 months.


RESULTS
The infants with PBI had significantly higher illness severity scores at day 1 compared with day 3 (Score of Neonatal Acute Physiology II: 32.1 vs 19.8) but similar previous pain experiences (109 vs 115) and total morphine exposure (0.29 vs 0.30 mg/kg). Both groups of children mounted similar responses to heel lance at 32 weeks' PCA with no difference in facial response or HR variability. Mean HR and facial action scores increased from baseline to the lance, whereas LF, HF, and the LF/HF ratio decreased significantly. No group differences were found. The only statistically significant difference between groups was that infants with PBI had more tongue protrusion at lance. Neurodevelopmental follow-up showed 8 of 11 toddlers with PBI had cerebral palsy compared with 0% of control toddlers. Psychomotor Developmental Index score on the Bayley Scales of Infant Development II was significantly lower in the PBI group. Five of 11 toddlers with PBI had Mental Developmental Index score <2 standard deviations below mean compared with 0% of the control toddlers.


CONCLUSIONS
Contrary to expectations, we did not find any evidence of an altered pain response pattern in infants with proven brain injury in the neonatal period. Although most infants with PBI developed cerebral palsy, these findings suggest that cerebral injury predominantly to the central white matter leaves brainstem responses intact in the neonatal period. Furthermore, it seems that the injured brain of the preterm infant has not yet expressed the identifiable differences in pain display and the functional impairment observed at later ages.
Biobehavioral Research Unit, Centre for Community Child Health Research, B.C. Research Institute for Children's and Women's Health, Vancouver, British Columbia, Canada. toberlander@cw.bc.ca
Tim F
TF
Oberlander
Ruth E
RE
Grunau
Colleen
C
Fitzgerald
Michael F
MF
Whitfield
D020520:Brain Infarction / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D005260:Female; D005865:Gestational Age; D006339:Heart Rate; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007235:Infant, Premature, Diseases / Q000503:physiopathology*; D019102:Infant, Very Low Birth Weight / Q000502:physiology*; D007969:Leukomalacia, Periventricular / Q000503:physiopathology; D008297:Male; D009460:Neurologic Examination; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D011597:Psychomotor Performance; D012720:Severity of Illness Index