Chain of brain preservation-A concept to facilitate early identification and initiation of hypothermia to infants at high risk for brain injury

Background: Therapeutic hypothermia has been associated with improved outcomes in term infants particularly in those who present with moderate hypoxic-ischemic encephalopathy (HIE). However, in the three major studies the time to initiate cooling was at approximately 4.5 postnatal hours. Objective: To determine in term infants who meet criteria for therapeutic hypothermia whether specific clinical and/or biochemical parameters might identify those high risk infants destined for abnormal neurodevelopmental outcome even sooner than is currently possible. Design/methods: Retrospective chart review for the following parameters: gestational age, birth weight, sex, labor complications, mode of delivery, 10 min Apgar ≤ 3, cardio-pulmonary resuscitation in the delivery room, cord arterial pH and base deficit, initial postnatal pH and base deficit obtained within 1 h, aEEG, Sarnat staging and seizures at enrollment. Abnormal outcome included death and neurodevelopmental deficits. Results: At a single tertiary care center in a metropolitan area, 45 term infants with moderate to severe HIE were treated with selective head cooling initiated at a mean of 4.69 ± 0.79 h of life; 43/45 (96%) were outborn. Five (11%) infants died and of survivors 26 (58%) are normal and 14 (31%) infants are abnormal at follow-up ranging from 12 to 26 months. Infants with abnormal vs. normal outcome were of comparable gestational age, birth weight with no differences in any parameters between groups except that in infants with abnormal vs. normal outcome the postnatal pH obtained within the first postnatal hour was lower, i.e. 6.87 ± 0.15 vs. 7.00 ± 0.22 (p= 0.02) and abnormal infants were more likely to present with severe encephalopathy, i.e. 15/19 (79%) vs. 6/26 (23%) (p= 0.0002) and clinical seizures, i.e. 14/19 (74%) vs.10/26 (38%) (p= 0.03) on admission. Conclusions: High risk infants who become candidates for therapeutic hypothermia and ultimately have an abnormal outcome may be identified by an additional early postnatal biochemical marker, i.e. the presence of profound metabolic acidosis. An earlier induction of hypothermia that currently occurs particularly in infants with severe encephalopathy may potentially improve outcome. Given that most infants are outborn, a time sensitive education metaphor termed Chain of Brain Preservation may facilitate early recognition of high risk infants and thus earlier treatment.