Basics
Description
A neonatal neurologic diagnosis notable for depressed level of consciousness with or without seizures. This is a nonspecific term with many etiologies, most commonly hypoxic ischemic encephalopathy (HIE). ‚
Epidemiology
- Most commonly term infants
- Incidence in developed countries 2.5 per 1,000 live births
- 50 " “80% of cases secondary to HIE
Risk Factors
- Variable depending on etiology
- HIE
- Sentinel event (placental abruption, uterine rupture, cord accident, etc.)
- Maternal factors: advanced age, obesity, diabetes, severe preeclampsia, infertility treatments, maternal thyroid disease, and placental abnormalities
Pathophysiology
- Hypoxic ischemic event leading to brain injury with energy failure and ongoing secondary injury, leading to encephalopathy and possibly seizures
- Ongoing injury involves excitotoxic glutamate accumulation in synapses, alterations in cellular calcium management, free radical production and nitrosative/oxidative damage, mitochondrial failure, activation of proteases, and other death cascades, cellular death, with both acute and delayed cytokine production and inflammation.
- Other etiologies include various metabolic disorders, hypoglycemia, kernicterus, nonketotic hyperglycinemia, intracranial infection, perinatal arterial ischemic stroke (PAIS), and sinovenous thrombosis.
Diagnosis
History
- Sentinel event (uterine rupture, placental abruption, cord accident, cardiorespiratory arrest in delivery room)
- Low Apgar scores
- Advanced resuscitation required in delivery room (intubation, chest compressions, medications)
Physical Exam
- Altered level of consciousness (hyperalert or lethargic/obtunded)
- Initial hypotonia
- Weak or absent reflexes
- Decerebrate posturing
- Distal flexion, complete extension
- Abnormal autonomic nervous system:
- Constricted or unreactive pupils
- Deviated/dilated pupils
- Bradycardia
- Periodic breathing/apnea
- Possible seizure activity: Importantly, seizures may continue but be subclinical (electrical only) after loading dose of an antiepileptic drug (AED).
Diagnostic Tests & Interpretation
Lab
- Umbilical cord gas (HIE)
- Glucose (hypoglycemia)
- Electrolytes (metabolic abnormalities)
- Bilirubin (kernicterus)
- Lactate and ammonia (HIE and metabolic abnormalities)
- Plasma amino acids and urine organic acids (metabolic abnormalities)
Imaging
- Head ultrasound (cerebral edema associated with HIE, intracranial hemorrhage)
- MRI with DWI (structural anomalies, stigmata of various encephalopathies, stroke, intracranial hemorrhage)
Diagnostic Procedures/Other
- EEG (seizures, electrographic background " ”specifically discontinuity, burst suppression patterns)
- Amplitude-integrated EEG (if available)
- Lumbar puncture (cell count for infection, metabolic workup including neurotransmitters)
Differential Diagnosis
- HIE
- Metabolic disorder
- Intracranial hemorrhage or PAIS
- Hypoglycemia
- Kernicterus
- Nonketotic hyperglycinemia
- Epileptic syndromes/seizure disorder
- Infection (meningitis, encephalitis)
Treatment
Medication
- Antiepileptic medications for seizures
- Phenobarbital or levetiracetam, depending on clinical preference. Multiple other AED are used based on clinical experience and preference.
- No conclusive data available to guide choice of AED currently. Developing a consensus on treatment with neonatal and neurology consultants is recommended.
Additional Therapies
- Hypothermia therapy (HT) for moderate to severe HIE (significantly decreased risk of death or moderate to severe disability when treated)
- Criteria for initiation of HT in newborns:
- Specific management of metabolic disorder or electrolyte/glucose abnormality
- Time of appearance of symptoms in relationship to birth and presence or absence of a perinatal sentinel event often provides important clues to presence of a metabolic disorder.
- Immediate recognition and treatment of hypoglycemia, hyponatremia, and hypocalcemia with further investigation into causality and prevention of recurrence
- Recognition of hyperammonemia is emergent.
- Lactate/pyruvate ratios, plasma amino acids, urine organic acids, and possibly CSF neurotransmitter levels are often helpful and diagnostic.
- EEG combined with pyridoxine supplementation can be diagnostic as well.
- DW-MRI may reveal important diagnostic clues for metabolic encephalopathies.
Ongoing Care
Follow-up Recommendations
- Developmental pediatrician
- Pediatric neurologist
- Geneticist (if applicable)
Prognosis
- Widely variable depending on etiology, severity (if HIE), and treatment
- Of patients with moderate to severe HIE treated with hypothermia: at 6 " “7 years of age, death or an IQ score below 70, 47%; death, 28%; death or severe disability, 41%; moderate or severe disability, 35%; attention " “executive dysfunction, 4%; visuospatial dysfunction, 4%
- Perinatal arterial stroke: cerebral palsy (58%), epilepsy (39%), language delay (25%), and behavioral abnormalities (22%)
Additional Reading
- Badawi ‚ N, Kurinczuk ‚ JJ, Keogh ‚ JM, et al. Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ. 1998;317(7172):1549 " “1553. ‚ [View Abstract]
- Graham ‚ EM, Ruis ‚ KA, Hartman ‚ AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol. 2008;199(6):587 " “595. ‚ [View Abstract]
- Jacobs ‚ S, Hunt ‚ R, Tarnow-Mordi ‚ W, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2007;(4):CD003311. ‚ [View Abstract]
- Raju ‚ TN, Nelson ‚ KB, Ferriero ‚ D, et al. Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Pediatrics. 2007;120(3):609 " “616. ‚ [View Abstract]
- Sarnat ‚ HB, Sarnat ‚ MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696 " “705. ‚ [View Abstract]
- Shankaran ‚ S, Laptook ‚ AR, Ehrenkranz ‚ RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574 " “1584. ‚ [View Abstract]
- Miller ‚ SP, Ferriero ‚ DM. Hypoxic-ischemic brain injury in the term newborn. In: Swaiman ‚ KF, Ashwal ‚ S, Ferriero ‚ DM, et al, eds. Swaiman 's Pediatric Neurology: Principles and Practice. 5th ed. Philadelphia: Saunders; 2012:47 " “58.
- Volpe ‚ JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012;72(2):156 " “166. ‚ [View Abstract]
Codes
ICD09
- 768.70 Hypoxic-ischemic encephalopathy, unspecified
- 768.71 Mild hypoxic-ischemic encephalopathy
- 768.72 Moderate hypoxic-ischemic encephalopathy
- 768.73 Severe hypoxic-ischemic encephalopathy
ICD10
- P91.60 Hypoxic ischemic encephalopathy [HIE], unspecified
- P91.61 Mild hypoxic ischemic encephalopathy [HIE]
- P91.62 Moderate hypoxic ischemic encephalopathy [HIE]
- P91.63 Severe hypoxic ischemic encephalopathy [HIE]
SNOMED
- 95628005 Neonatal encephalopathy
- 703300001 Hypoxic ischemic encephalopathy (disorder)
- 703301002 Mild hypoxic ischemic encephalopathy (disorder)
- 703302009 Moderate hypoxic ischemic encephalopathy (disorder)
- 703303004 Severe hypoxic ischemic encephalopathy (disorder)
FAQ
- Q: Is neonatal encephalopathy secondary to HIE always associated with an acute perinatal event?
- A: No. Neonatal encephalopathy may be secondary to an ongoing process in utero and not associated with an acute event. There may be signs prenatally such as decreased fetal movement or abnormalities in fetal heart tracings.
- Q: Does the infant have to be less than 6 hours old to be a candidate for hypothermia therapy?
- A: Yes. Current research has shown that in order to prevent the secondary energy failure and further brain injury, hypothermia should be initiated as soon as possible and within 6 hours of birth. If there is concern for encephalopathy in the delivery room, according to the Neonatal Resuscitation Program, the radiant warmer may be turned off and the infant may be passively cooled until further evaluation can be performed. If applicable, consultation with a referral center that provides hypothermia therapy should be performed as soon as possible. Research trials will determine if there is any value in a more delayed application of the therapy.