Cover image: Ellie Remus lies on a specially designed cooling pad in the neonatal intensive care unit at Women & Children’s Hospital in April. The photo was taken by her father. | Davis, H., & News, T. (2013). Cooling newborns to save their lives. The Buffalo News. Retrieved 21 May 2018, from http://buffalonews.com/2013/11/30/cooling-newborns-to-save-their-lives/

Introduction

Insult to the fetus/newborn due to a lack of oxygen (hypoxia) and/or a lack of perfusion (ischemia) to various organs.

• Associated with tissue lactic acidosis & hypercarbia

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Epidemiology

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Aetiology

Risk factors:

• Elderly/young mothers
• Prolonged rupture of membranes
• Meconium-stained fluid
• Multiple births
• Lack of antenatal care
• LBW infants
• Malpresentation
• Augmentation of labour with oxytocin
• Antepartum haemorrhage
• Severe eclampsia and pre-eclampsia
• Antepartum/intrapartum anemia

Cause:

• Inadequate oxygenation of maternal blood
  • Due to hypoventilation during anaesthesia, heart diseases, pneumonia, respiratory failure
• Low maternal blood pressure
  • Due to hypotension e.g. compression of vena cava and aorta, excess anaesthesia
• Inadequate relaxation of uterus
  • Due to excess oxytocin
• Premature separation of placenta
• Placental insufficiency
• Knotting of umbilical cord around the neck of infant

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Pathophysiology

Neuropathology:

• Premature newborns:
  • Selective subcortical neuronal necrosis
  • Periventricular leukomalacia(PVL)
    • Due to hypoxic-ischemic insult leading to coagulative necrosis and infarction of periventricular white matter (watershed area between various arteries)
  • Focal and multifocal ischemic necrosis
  • Periventricular haemorrhage/infarction
• Term newborns:
  • Selective cortical neuronal necrosis
  • Status marmoratus of basal ganglia and thalamus
    • Variant of selective neuronal necrosis involving basal ganglia and thalamus, having longterm sequelae
  • Parasagittal cerebral injury
  • Focal and multifocal ischemic cerebral necrosis

Other lesions (due to small infarcts secondary to blocking of end arteries):

• Porencephaly
• Hydrancephaly
• Multicysticencephalomalacia

Multiorgan dysfunction:

• CNS: Hypoxic ischemic encephalopathy, cerebral oedema, long-term neurological sequelae
• Pulmonary: Pulmonary hypertension, meconium aspiration, surfactant disruption
• Renal: Acute renal failure
• Metabolic: Metabolic acidosis, hypoglycemia, hypocalcemia, hyponatremia
• GI: Necrotizing enterocolitis, hepatic dysfunction
• Haematological: Thrombocytopenia, disseminated intravascular coagulation

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Clinical features

Selective neuronal necrosis:

• Diminished consciousness
• Seizures
• Abnormalities of feeding, breathing, etc

Parasagittal cerebral injury:

• Spastic quadriparesis

Status marmoratus:

• Long-term sequelae:
  • Choreoathetosis
  • Spastic quadriparesis
  • Retardation

Periventricular leukomalacia (PVL):

• Long-term sequelae:
  • Spastic diplegia
  • Quadriplegia (lower limbs >upper limbs)
  • Visual impairment

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Diagnosis

Clinical criteria

American Academy of Pediatrics Committee on Fetus and Newborn:

• Prolonged metabolic or mixed acidemia (pH <7.0) on an umbilical arterial blood sample
• Persistence of Apgar score of 0-3 for >5 min
  • National Neonatology Forum of India (NNF) and WHO:
    • Apgar of 0-3 and 4-7, at 1 min
• Neurological manifestations:
  • e.g. seizures, coma, hypotonia or hypoxic-ischemic encephalopathy (HIE) in the immediate neonatal period
• Evidence of multiorgan dysfunction in the immediate neonatal period

Levene classification for HIE (hypoxic-ischemic encephalopathy) staging:

For babies of gestational age > 36 weeks

Feature	Mild	Moderate	Severe
Consciousness	Irritability	Lethargy	Comatose
Tone	Hypotonia	Marked hypotonia	Severe hypotonia
Seizures	No	Yes	Prolonged
Sucking/respiration	Poor suck	Unable to suck	Unable to sustain spontaneous respiration

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Management

Medical management

Admit to NICU

• Indications:
  • Need for positive pressure ventilation for ≥ 30 seconds, chest compression or adrenaline
  • Apgar <7 at 5 minutes

Temperature:

• Maintain normal temperature of the baby
• Avoid hyperthermia
• Resourceful setting:
  • Moderate induced hypothermia (core temperature of 33°-34° C)

Ventilation:

• Oxygen saturation (90-95%)
• CO₂ concentration (40-50 mm Hg)

Perfusion:

• Systemic mean arterial pressure:
  • 45-50 mm Hg (term)
  • 35-40 (1-2 kg weight)
  • 30-35 mm Hg (<1 kg weight)

Metabolic profile:

• Look for hypocalcemia and electrolyte disturbances
• Glucose: 75-100 mg/ dl
• Seizures:
  • Antiepileptic drugs (AEDs)
    • Phenobarbitone
    • Phenytoin

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Prognosis

Poor prognosis if:

• Lack of spontaneous respiratory effort within 20-30 minutes of birth is associated with almost uniform mortality
• HIE stage 3
• Abnormal neurological findings persisting beyond the first 7-10 days of life
• Oliguria (<1 ml/kg/ day) during the first 36 hr