What interventions are recommended for an infant with moderate hypoxic‑ischemic encephalopathy (HIE)?

Interventions for Moderate Hypoxic-Ischemic Encephalopathy

Therapeutic hypothermia to 33-34°C for 72 hours initiated within 6 hours of birth is the mandatory standard of care, followed by enrollment in multidisciplinary follow-up with early cerebral palsy-specific motor interventions starting as soon as neurological deficits are identified. 1

Acute Neuroprotective Intervention

Therapeutic Hypothermia Protocol

Therapeutic hypothermia reduces death or major neurodevelopmental disability by 22-33%, with one fewer infant dying or having significant disability for every 5-7 infants treated. 1 For moderate HIE specifically, this intervention provides a 33% reduction in death or major neurodevelopmental disability (RR 0.67; 95% CI 0.56-0.81). 1

Critical protocol requirements:

• Initiation within 6 hours of birth (efficacy decreases significantly after this window) 2, 1
• Target core temperature of 33-34°C maintained continuously for 72 hours 2, 1
• Rewarming over at least 4 hours at approximately 0.5°C per hour 2, 1
• Strict temperature control throughout the entire protocol 2

Required Facility Capabilities

Cooling must only occur in facilities with:

• Intravenous therapy and respiratory support with mechanical ventilation 2, 1
• Continuous pulse oximetry and hemodynamic monitoring 2, 1
• Anticonvulsant medications and antibiotics 2, 1
• Transfusion services and radiology including ultrasound 1
• Pathology testing capabilities 2, 1

Supportive Care During Cooling

Maintain physiological stability throughout:

• Adequate ventilation with target PaCO₂ of 4.5-5.0 kPa 1
• Systolic blood pressure >110 mmHg 1
• Intravenous glucose infusion 1
• Active monitoring and treatment of complications including seizures 1

Seizure Management and Discontinuation

If seizures occur during the acute phase, antiseizure medications should be discontinued strategically once seizure activity resolves:

Stop levetiracetam first (abruptly or over 24-48 hours) while maintaining phenobarbital. 3 This is because phenobarbital's half-life of 45-500 hours in neonates provides prolonged anticonvulsant coverage, whereas levetiracetam's half-life is only ~5 hours. 3

• Observe clinically for 24-48 hours after stopping levetiracetam while phenobarbital continues 3
• If no seizure recurrence, discontinue phenobarbital (abruptly or brief taper) 3
• Do not discharge on phenobarbital alone without documented ongoing seizure activity—this represents ineffective prophylactic use 3
• Minimum 48 hours continuous EEG monitoring detects approximately 94% of electrographic seizures 3

Early Intervention and Follow-Up Programs

Enrollment in Multidisciplinary Follow-Up

All infants with moderate HIE must be enrolled in multidisciplinary follow-up programs to detect impairments, initiate early intervention, and provide family support. 4, 5 This is critical because even with hypothermia, HIE still has significant impact on neurodevelopment and quality of life. 4

Cerebral Palsy-Specific Early Intervention

Task-specific, motor training-based early intervention (such as GAME and CIMT) represents the new paradigm of care because these interventions induce neuroplasticity and produce functional gains. 2 Early intervention maximizes neuroplasticity and minimizes deleterious modifications to muscle and bone growth. 2

Before commencing intervention, identify whether cerebral palsy is unilateral versus bilateral, as treatments and long-term musculoskeletal outcomes differ. 2

Motor and Cognitive Interventions

Physical and occupational therapy should use:

• Child-initiated movement and task-specific practice 2
• Environmental adaptations that stimulate independent task performance 2
• Goals-Activity-Motor Enrichment (GAME) for all subtypes—provides better motor and cognitive skills at 1 year than usual care 2
• Constraint-induced movement therapy (CIMT) or bimanual therapy for hemiplegia 2
• Learning Games Curriculum for diplegia 2

Improvements are better when intervention occurs at home because children learn best in supported natural settings where training is personalized to their enjoyment. 2

Communication Interventions

Speech language pathology should:

• Foster parent-infant transactions 2
• Provide compensation when speech is inadequate (1 in 4 are nonverbal) 2
• Implement Hanen "It Takes Two to Talk" and "More Than Words" programs 2
• Provide alternative and augmentative communication as needed 2

Surveillance for Secondary Complications

Regular surveillance and intervention prevent:

• Hip displacement, contracture, and scoliosis (1 in 3 have hip displacement) 2
• Chronic pain management (3 in 4 have chronic pain) 2
• Epilepsy monitoring (1 in 4 have epilepsy) 2
• Vision and hearing deficits (1 in 10 are blind, 1 in 25 are deaf) 2
• Sleep disorders (1 in 5) and bladder control problems (1 in 4) 2

Timeline for Assessments

Early assessments at 4-8 months focus on head growth, general health, and motor neurodevelopment. 5 Assessments at 12-24 months focus on cognitive skills and language development. 5 Preschool assessments are strongly recommended to identify children requiring early education programs. 5

Prognostic Indicators Guiding Intervention Intensity

Use neuroimaging and EEG to stratify intervention needs:

• Normal/mildly abnormal neonatal EEG with normal neuroimaging correlates with favorable outcome (negative predictive value 91.6%) 6
• Moderate/severely abnormal EEG and multifocal/diffuse cortical or deep gray matter lesions correlate with poor outcome 6
• MRI sensitivity is 83.3% for predicting adverse outcomes 6

Family Support

Provide emotional support and counseling for parents/caregivers to reduce stress, anxiety, and depression. 2 Family concern is a valid reason to trigger formal diagnostic investigations and intervention referrals. 2

Common Pitfalls to Avoid

• Do not delay hypothermia beyond 6 hours—efficacy decreases significantly after this window 1
• Do not rewarm rapidly—must occur over at least 4 hours to prevent complications 2, 1
• Do not continue antiseizure medications without documented seizure activity—this adds unnecessary drug burden without proven benefit 3
• Do not stop phenobarbital before levetiracetam—phenobarbital's long half-life provides essential coverage during levetiracetam withdrawal 3
• Do not delay early intervention referrals—infants who do not actively use their motor cortex risk losing cortical connections and dedicated function 2