This document discusses perinatal asphyxia and hypoxic ischemic encephalopathy. It defines related terms like anoxia, hypoxia, and ischemia. It describes the physiology of asphyxia, risk factors for it like placental insufficiency, and the potential effects on the infant like hypoxic ischemic brain damage. The clinical features of mild, moderate and severe hypoxic ischemic encephalopathy are outlined. Investigations and management approaches are also summarized, including supportive therapies, anticonvulsants, and monitoring the infant.

1. Perinatal Asphyxia
&
Hypoxic Ischemic Encephalopathy
DR. M. S. PRASAD
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2. Definitions
• Anoxia:
– Complete lack of oxygen.
• Hypoxia:
– Decreased availability of oxygen
• Hypoxemia:
– Decreased arterial concentration of oxygen.
• Ischemia:
– Insufficient blood flow to cells or organ resulting in interrupted
metabolism and death of the cell or organ affected.
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3. Perinatal Asphyxia (PA)
Perinatal asphyxia, neonatal asphyxia,
or birth asphyxia is the medical
condition resulting from
deprivation of oxygen to a
newborn infant that causes
physical harm, mainly to the brain.
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4. Definition
The Perinatal Asphyxia may be
defined as hypoxic insult to the
fetus severe enough to cause
metabolic acidosis, neonatal
encephalopathy, and multiorgan
system dysfunction.
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5. Perinatal Asphyxia
The NNF of India has defined
asphyxia as “gasping or
ineffective breathing or lack of
breathing at one minute of life”
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6. AAP Criteria
• Umbilical artery blood pH < 7.0.
• 5 minute apgar score < 3,
• Neonatal Encephalopathy manifesting as
seizures, hypotonia or coma in the immediate
neonatal period.
• Evidence of multiorgan dysfunction.
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7. Birth Asphyxia
• Birth Asphyxia = Perinatal
Asphyxia = Neonatal Asphyxia.
• Incidence: 1 – 6 /1000 live births.
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8. Perinatal Asphyxia
• Perinatal Asphyxia is the leading cause of
neonatal death (along with infection,
prematurity and LBW).
• It is the leading cause of neurodevelopmental
disability in children.
• The term perinatal asphyxia is preferred to
Birth Asphyxia as asphyxia may occur before,
during and after birth.
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9. Why it is important?
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10. 10
Primary cause of death: NNPD
Cause Deaths
(n = 1800)
Prematurity 27 %
Infection 17 %
Perinatal hypoxia 29 %
Malformation 09 %
Other causes 18 %
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11. 11
4 million newborn deaths – Why?
almost all are due to preventable conditions
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12. 12
Causes of neonatal death
(n=258)
Not
established
14.7%
Others
10.7% Birth asphyxia
20.9%
Infection
33.2%
Prematurity
15.2%
Congenital
malformation
5.4%
Others: Hypothermia, RD, Jn, Pulm. Haemorrhage, Seizure etc. ICMR 2006
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13. Physiology of Asphyxia
When babies become asphyxiated (either in utero or
after delivery), they undergo a well defined sequence
of events, ie primary apnea followed by secondary
apnea.
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14. Primary Apnea
• When an infant is deprived of oxygen, an initial
brief period of rapid breathing occurs.
• If the asphyxia continues, the respiratory
movements cease, the HR begins to fall, muscle
tone gradually diminishes, and the infant enters a
period of apnea known as primary apnea.
• The initial steps will induce breathing.
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15. Secondary Apnea
• If the asphyxia continues, the infant develops
deep gasping respiration, the HR continues to
decrease, the BP begins to fall, and the infant
becomes nearly flaccid.
• The respirations become weak and weaker until
the infant takes a last gasp and enters a period of
apnea called secondary apnea.
• During secondary apnea the infant does not
respond to initial steps.
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16. Effects of PA
• Hypoxic damage to most of the infant's organs
(heart, lungs, liver, gut, kidneys), but brain
damage is of most concern and perhaps the least
likely to heal.
• In more pronounced cases, an infant will survive,
but with damage to the brain manifested as
either mental or physical disability, such as
developmental delay or intellectual disability, or
physical, such as spasticity
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17. Effects (continued)
• Mental Disability:
– Developmental Delay,
– Intellectual Disability.
• Physical Disability:
– Spasticity,
– Motor Deficit.
• Cerebral Palsy.
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18. What to do?
Baby Cried immediately after birth
Yes
Routine Care
No
NNR
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19. Routine Care
• Dry,
• Provide warmth,
• Clear airway, if needed,
• Initiate Breastfeeding, and
• Monitor Breathing, Heart-Rate and Color.
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20. NNR (Neonatal Resuscitation)
• Initial Steps,
• Assisted Ventilation,
– Bag & Mask,
– Endotracheal Intubation.
• Chest Compression,
• Medication.
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21. Global Hypoxic Ischemic Insult
Global Hypoxic Ischemic Insult of Brain
Hypoxic Ischemic Encephalopathy (HIE)
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22. Hypoxic-Ischemic Encephalopathy (HIE)
• The HIE refers to the characteristic neurological
manifestations in term and near-term newborns
which develop soon after birth following
perinatal asphyxia.
• Incidence: 3-5 per 1000 full-term live births.
• Half of them progress to moderate to severe HIE.
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23. HIE
• The encephalopathy resulting from hypoxia
(low oxygen) and ischemia (low blood flow)
mainly to the brain.
• The HIE refers to the characteristic
neurological manifestations in term and near-
term newborns which develop soon after birth
following perinatal asphyxia.
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24. Pathology
• Lack of adequate breathing  lack of
oxygen supply to heart  Inability of heart
to pump adequate blood  hypoxia +
ischemia to organs (particularly brain).
• Longer Arrest  Infarct  Brain Death.
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25. Brain Regions vulnerable for damage
• Hippocampus,
• Purkinje Neurons in Cerebellum,
• Basal Ganglia, and
• Brain-stem.
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26. Pathogenesis
• Poorly understood,
• Hypoxic Ischemic insult can damage
periventricular white matter tracks.
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27. Etiology
• Perinatal Asphyxia,
• Drowning,
• Airway Obstruction,
• Trauma,
• Hanging,
• Infection
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28. Outcome
• Immediate outcome: Death.
• Late outcome (if survived):
–Cerebral Palsy,
–Developmental Delay,
–Mental Retardation.
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29. Further Outcome (complications)
• Death,
• Vegetative State,
• Severe Disability,
• SIRS,
• Multiple Organ Dysfunction Syndrome.
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30. Etiology of Perinatal Asphyxia
• Multifactorial,
• Antepartum:
– Placental Insufficiency.
• Intrapartum, and
• Postpartum period.
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31. Placental Insufficiency
• Impaired maternal oxygenation,
• Decreased blood flow from the mother to the
placenta,
• Decreased blood flow from placenta to fetus,
• Impaired gas exchange across placenta or fetal
tissues,
• Increased fetal oxygen requirement.
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32. Impaired Maternal Oxygenation
• Anemia,
• Pulmonary, or
• Cardiac, or
• Neurologic disease in mother.
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33. Decreased Blood Flow from
the mother to the placenta
• Maternal Infection,
• Shock,
• Dehydration, and
• Hypotension.
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34. Decreased Blood Flow from
the Placenta to the Fetus
• Placental abruption,
• Cord Prolapse,
• Cord Entanglement,
• True Knot,
• Cord Compression,
• Abnormality of the
umbilical vessels.
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35. Impaired Gas Exchange across placenta or fetal tissues
• Maternal Hypertension,
• Vascular Disease,
• Diabetes,
• Drug Abuse,
• Post-Maturity,
• Placental Calcification, infarct or fibrosis.
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36. Increased Fetal Oxygen Requirement
• Fetal Anemia,
• Fetal Infection, or
• IUGR
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37. Causes
• Before Birth (Maternal Causes).
– Inadequate oxygenation of maternal blood.
– Low Maternal Blood Pressure.
• At Birth (Fetal or Neonatal Causes).
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38. Inadequate Oxygenation of maternal blood
• Hypoventilation during anesthesia,
• Cyanotic Heart Disease,
• Respiratory Failure,
• CO Poisoning.
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39. Low Maternal BP
• Acute Blood Loss,
• Spinal Anesthesia,
• Great Vessels compression by gravid uterus.
• Uterine Tetany (oxytocin induced)
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40. Low Maternal BP (continued)
• Premature separation of placenta,
• Compression of knotting of umbilical cord,
• Placental insufficiency due to toxemia or
postmaturity.
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41. At Births
• Failure of oxygenation:
– Fetal Cyanotic Congenital Heart Disease,
– Severe Pulmonary Distress.
• Severe Anemia
– Severe Hemorrhage,
– Hemolytic Disease.
• Shock
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42. Shock
• Sepsis,
• Massive Blood Loss,
• Intra-Cranial Hemorrhage,
• Adrenal Hemorrhage.
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43. Pathophysiology
Hypoxia
Ischemia
Anaerobic Metabolism
Lactate Inorganic Phosphate
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44. Vulnerable Organ
• Brain,
• Neonatal Brain has very high requirements for
oxygen and baseline blood flow.
• Hypoxic insult to the fetus initiates diving
seal reflex.
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45. Diving Seal Reflex
• Shunting of blood to brain, heart and adrenals
and away from lungs, gut, kidneys, liver,
spleen and skin, in an attempt to maintain
perfusion to more vital organs.
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46. Pathophysiology
• Accumulation of excitatory and toxic
amino acids (glutamate) in the
damaged tissue.
• Increased production of free radicals
and NO in damaged tissue.
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47. Pathophysiology
Accumulation of AA (glutamate) in damaged tissue.
Increased amount of intracellular Na & Ca
Tissue Swelling Cerebral Oedema
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48. Fetal Hypoxia & Ischemia
Term
Cortical Atrophy
Preterm
1. PVL
2. IVH
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49. Biochemical Changes
• Hypoxia impairs cerebral oxidative metabolism
 
– Increase in lactate,,
– Fall in pH (acidosis), and
– Decrease in ATP level.
• Acidosis   Myocardial Depression  
Reduced Cardiac Output.
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50. Acidosis
Myocardial
Depression
Reduced Cardiac Output
Hypotension
Reduced Blood-Flow to Brain
Ischemia +
Hypoxia
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51. Energy Failure
Impaired ion-pumps
Intracellular
Na++, Cl-, H2O, Ca++
Extracellular
K+, Glutamate, Aspartate
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52. Reperfusion of ischemic tissue
Generation of oxygen free radicals
Neuronal Damage
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53. Brain Damage
• Term Newborn:
–Cerebral Cortex, and
–Basal Ganglia
• Preterm Newborn:
–Periventricular White Matter.
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54. Circulatory Response of Fetus
• Increased shunting through Ductus
Venosus, Ductus Arteriosus and Foramen
Ovale.
• Inadequate perfusion of periventricular
white matter    PVL
(periventricular leucomalacia).
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55. Causes of Hypotension
• Myocardial Dysfunction,
• Capillary Leak Syndrome, and
• Hypovolemia.
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56. Clinical
Features
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57. Clinical Features
• Perinatal Asphyxia (no breathing or difficult
breathing at birth).
• IUGR,
• MSAF (Fetal Distress), Meconium Stained Amniotic Fluid
• Hypotonic State.
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58. Clinical Features
• Mild HIE,
• Moderate HIE, and
• Severe HIE.
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59. Mild HIE
• Transient abnormalities,
• Poor Feeding,
• Irritability, or excessive crying, or sleepiness,
• Slightly increased muscle-tone,
• Brisk DTR.
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60. Moderate HIE
• Lethargic,
• Significant hypotonia,
• Diminished DTR,
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61. Moderate HIE (continued)
• Sluggish or absent Grasp, Moro and
Sucking Reflexes.
• Occasional Apnea,
• Seizures.
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62. Severe HIE
• Coma,
• Difficult breathing requiring ventilator support,
• Decreased Tone,
• Depressed DTR,
• Absent neonatal reflexes.
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63. Severe HIE (continued)
• Disturbance of ocular motions,
• Loss of “doll’s eye” movement,
• Dilated and fixed pupils with poor LR,
• Seizures,
• Full & bulging AF,
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64. Investigations
• No confirmatory laboratory tests to
diagnose perinatal asphyxia,
• Tests are helpful to assess the severity of
brain injury and to monitor the
functional status of systemic organs.
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65. Investigation
• Blood Sugar,
• ABG,
• SpO2
• US in preterm,
• Serum Electrolytes,
• Diffuse mediated MRI,
• CT,
• aEEG
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66. Investigations (continued)
• Renal Function Tests:
– Blood Urea,
– Serum Creatinine.
• Liver Function Tests,
• Coagulation Profile
– PT and
– PTT.
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67. Management
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68. Goal of Treatment
• Maintain TABC,
• Optimize Cardiac Output and Cerebral
Perfusion,
• Maintain SpO2
• Treat / Prevent Hypoglycemia,
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69. Principles of Management
• Supportive Therapy,
• Anticonvulsants,
• Cerebroprotective interventions, and
• Monitoring.
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70. Supportive Therapy
• IV Fluid:
– 10% Dextrose,
– 60 ml/kg/day.
• Treat Hypotension:
– Dobutamine, and
– Dopamine.
• Temperature:
– Cool Therapy (33-340 C)
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71. Supportive Therapy (continued)
• Glucose:
– Treat hypoglycemia,
– Maintain BS at 75 to 100 mg/dl.
• Calcium:
– Calcium level should be kept in the normal range
(9 – 11 mg/dl)
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72. Anticonvulsants
• Control Seizures:
– Phenobarbitone:
• Loading Dose: 20 mg/kg slowly
• Maintenance Dose: 5 mg/kg/day
– Phenytoin as a second line drug
– Lorazepam
• (0.05-0.1 mg/kg/dose I. V.) for seizures not responding
to Phenobarbitone and/or Phenytoin.
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73. Cerebroprotective Interventions
• Therapeutic Hypothermia (cool therapy),
• Free Radical Scavengers,
• Antagonists of excitotoxic amino acids,
• Calcium Channel Blockers.
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74. Caution!
• Drugs like mannitol, steroids,
and furosemide used in past
are no longer recommended.
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75. Treatment
• Selective Cerebral or Whole Body Therapeutic
Hypothermia (Cool Therapy),
• Control Seizures,
– Phenobarbitone/Phenytoin/Midazolam.
• Mechanical Ventilation, (or ECMO),
• Volume Expansion,
• Pressure Amines.
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76. Monitoring
• Regular clinical assessment,
• Biochemical monitoring,
• SpO2.
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77. Clinical Assessment
• Respiratory Rate,
• Heart Rate,
• CRT,
• BP
• Temperature,
• Oxygen Saturation,
• Urine Output.
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78. Prognosis
• Early Treatment   Better Prognosis.
• Bad Prognosis:
– Initial cord or initial blood pH < 6.7,
– Low Apgar Score (0-3),
– High Base Deficit,
– Decrebrate Posture,
– Lack of spontaneous activity.
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79. Mortality
• Moderate Encephalopathy:
–10 to 30%
• Severe Encephalopathy:
–Mortality: 60%
–Disability: 100%.
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80. Long Term Handicaps
• Developmental Delay,
• Cerebral Palsy,
• Microcephaly,
• Seizures
• Blindness,
• Deafness,
• Problems with
cognition, memory, fine
motor skills and
behaviour.
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81. Staging of HIE
Stage-I Stage-II Stage-III
Level of consciousness Hyper-alert Lethargic Stupor/coma
Muscle Tone Normal Hypotonic Flaccid
Posture Normal Flexion Decerebrate
DTR/Clonus Hyperactive Hyperactive Absent
Myoclonus Present Present Absent
Moro Reflex Strong Weak Absent
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82. HIE Staging
Stage-I Stage-II Stage-III
Pupils Dilated Constricted Unequal
Seizures None Common Decerebrate
Duration < 24 hrs 24 hrs-14 d Days & Weeks
Outcome Good Variable Death or Severe Deficit
EEG Normal Low Voltage Bursts
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