Subacute Hypoxia-Ischemia and the Timing of Injury in Treatment With Therapeutic Hypothermia

Objective: This study aims to categorize infants treated with therapeutic hypothermia who presented with suspected subacute hypoxia-ischemia-that is, injury that likely occurred well before delivery and thus beyond the 6-hour window for therapeutic hypothermia-and to contrast the clinical characteristics with infants who suffered a known acute hypoxia-ischemia event.

Design: A retrospective chart review was undertaken of infants treated with therapeutic hypothermia at our center during a 6-year period. Suspected subacute injury is defined as decreased fetal movement greater than 6 hours before delivery or severe depression at birth without need for cardiopulmonary resuscitation. Acute injury is defined as an acute perinatal event including placental abruption, ruptured uterus, or umbilical cord abnormalities. Abnormal outcome is defined as death, cognitive delay, or spastic quadriplegia at follow-up.

Results: Infants with subacute (n = 7) versus acute injury (n = 26) were less likely to require cardiopulmonary resuscitation, were less acidotic at birth on cord gases with no significant difference in initial postnatal pH or base deficit, were more severely encephalopathic with severe amplitude electroencephalogram suppression, and demonstrated universal adverse outcome.

Conclusions: These data demonstrate greater benefit of therapeutic hypothermia for those infants with acute versus subacute injury. Early initiation of therapeutic hypothermia relative to the presumed onset of hypoxia-ischemia is critical. Early severe encephalopathy in the absence of a known acute perinatal event should raise concern in some cases for a subacute insult where the effect of therapeutic hypothermia is unlikely to be of benefit.