Neuroprotective Strategies for Extremely Preterm Neonates in Clinical Practice
Delayed umbilical cord clamping for at least 30 seconds is the most important neuroprotective strategy for extremely preterm infants who do not require immediate resuscitation at birth. 1 This practice should be combined with other evidence-based interventions to form a comprehensive neuroprotection bundle.
Antenatal Neuroprotective Strategies
Maternal Interventions
- Antenatal corticosteroids: Should be administered to women at risk of preterm birth to reduce respiratory distress syndrome and improve neonatal outcomes
- Magnesium sulfate: Should be given to women at risk of preterm birth before 32 weeks for fetal neuroprotection 2
- Transfer to appropriate facility: Whenever possible, periviable births should occur in centers with level III-IV NICU capabilities 1
Delivery Room Management
Cord Management
- Delayed cord clamping: Wait at least 30 seconds before clamping the umbilical cord in preterm infants not requiring immediate resuscitation 1
- Cord milking: Not recommended for infants born at less than 29 weeks gestation outside of research settings due to insufficient evidence for long-term outcomes 1
Temperature Management
- Maintain normothermia: Temperature of preterm infants should be maintained between 36.5°C and 37.5°C after birth 1
- Prevention strategies:
- Use radiant warmers and plastic wrap with cap
- Consider thermal mattresses for infants <32 weeks
- Use warmed humidified resuscitation gases
- Increase delivery room temperature 1
Respiratory Support
- Initial oxygen concentration: Begin resuscitation with low oxygen concentration (21%-30%) rather than high oxygen (65%-100%) 1
- Non-invasive ventilation: Use early CPAP with selective surfactant administration rather than routine intubation 3
- Lung-protective ventilation: If mechanical ventilation is necessary, use lower tidal volumes (3.5-5 mL/kg) 3
NICU Management
Pharmacological Interventions
- Caffeine therapy: Administer caffeine citrate to prevent apnea of prematurity with loading dose of 20 mg/kg followed by maintenance dose of 5 mg/kg daily 4
- Benefits include improved respiratory outcomes and potential neuroprotection
- Mechanism involves stimulation of respiratory center, increased minute ventilation, and antagonism of adenosine receptors 4
Hemodynamic Management
- Minimize hypotension treatment: Avoid unnecessary use of inotropes and fluid boluses, which are associated with increased risk of brain injury 5
- Maintain cerebral perfusion: Avoid rapid fluctuations in blood pressure
Positioning and Handling
- Midline head positioning: Maintain neutral head position to optimize cerebral venous drainage 5
- Minimal handling: Implement clustered care to reduce stress and physiological instability 5
Neuroprotection Care Bundle
Implementation of a structured neuroprotection care bundle has been shown to significantly reduce death or severe brain injury in extremely preterm infants (adjusted odds ratio 0.34; 95% CI 0.20-0.59) 5. Key components include:
- Minimal handling protocols
- Midline head positioning
- Delayed cord clamping
- Protocolized hemodynamic management
- Standardized respiratory management
Monitoring and Follow-up
- Regular cranial ultrasound screening to detect intraventricular hemorrhage
- Monitor for signs of post-hemorrhagic hydrocephalus in infants with IVH
- Long-term neurodevelopmental follow-up, as infants with unilateral periventricular hemorrhagic infarction have better outcomes than those with bilateral lesions 1
Pitfalls and Caveats
- Hyperthermia: Avoid temperatures >38.0°C due to potential associated risks 1
- Cord milking in extremely preterm infants: Current evidence suggests against routine use in infants <29 weeks gestation outside research settings 1
- Prolonged resuscitation: Decision to continue or discontinue resuscitative efforts must consider multiple factors including gestational age, adequacy of resuscitation, and availability of advanced neonatal care 1
- Oxygen management: Avoid both hypoxia and hyperoxia; titrate oxygen based on saturation targets
The implementation of these neuroprotective strategies requires a multidisciplinary approach involving obstetric and neonatal teams. When applied systematically, these interventions can significantly improve neurological outcomes for extremely preterm infants.