Birth asphyxia, or lack of oxygen during birth, is one of the leading causes of neonatal mortality globally. It can result in hypoxic-ischemic encephalopathy (HIE), where the brain is damaged from lack of oxygen and blood flow. The presentation of HIE can range from mild to severe, with signs including abnormal consciousness, muscle tone, reflexes, and seizures. Diagnosis is based on metabolic acidosis, low Apgar scores, multi-organ dysfunction, and neurologic symptoms. Treatment focuses on supportive care and stabilization in the delivery room, followed by monitoring for complications like seizures or cerebral palsy. HIE remains a major public health challenge, especially in low-to-middle income countries

1. Birth Asphyxia:
What we should know?
What we should do?
DR AMIN ALI
FCPS Paediatrics
Fellowship in Neonatology (AKUH)
Assistant Professor DUHS

2. OBJECTIVES
• This lecture will cover following;
• Definitions
• Epidemiology
• Pathophysiology and Risk factors
• Apgar Score and staging of HIE
• Clinical features and Diagnosis
• Treatment and recent advances
• Complications and prognosis

3. DEFINATIONS
• Anoxia is a term used to indicate the consequences of complete lack
of oxygen as a result of a number of primary causes
• Hypoxemia – Abnormally low blood oxygen levels in the blood
• Hypoxia refers Abnormally low blood oxygen levels in the body tissue
• Ischemia refers to blood flow to cells or organs that is insufficient to
maintain their normal function

4. • Perinatal Asphyxia – Condition of impaired gas exchange or
inadequate blood flow that leads to persistent hypoxemia and
hypercarbia that occurs during labour (peripartum) and delivery
(intrapartum)
• Acidemia-------increased concentration of hydrogen ions in blood
• Acidosis--- increased concentration of hydrogen ions in tissue

5. DEFINATION OF HIE
• Hypoxic-ischemic encephalopathy (HIE) is a type of newborn brain
damage caused by oxygen deprivation and limited blood flow.
• Is an abnormal neurobehavioral state in which the predominant
pathogenic mechanism is impaired cerebral blood flow that may
result in neonatal death or be manifested later as cerebral palsy or
mental deficiency.
• Disturbed neurological function in a neonate (>35 weeks) with
abnormal level of consciousness and any combination of seizures,
difficulty initiating and maintaining respiration, abnormal tone or
reflexes, or disturbances of suck or swallowing

6. HYPOXIC ISCHEMIC
ENCEPHALOPATHY

7. • GUIDELINES FOR HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)
• Profound metabolic or mixed acidemia (pH < 7)
• Persistence of an Apgar score of 0-3 for longer than 5 minutes
• Neonatal neurologic sequelae (eg, seizures, coma, hypotonia)
• Multiple organ involvement (eg, kidney, lungs, liver, heart, intestines

8. Epidemiology
• Birth Asphyxia WHO  One of the 10 leading causes deaths
• HIC 0.5-1.5/1000
• LMIC 12-14/1000
• Recent incidence reduction in European studies due to improving
prenatal and perinatal care
• Wales - 1/1000 in 2007 to <0.5/1000 in 2015
• The Netherlands - 1.56/1000 in 2000-2007
• to 0.86/1000 in 2008-2013

9. • Globally, 1.15 Million Neonates (8.5/1000) Developed NE Associated
With Intrapartum Events
96% In LMICs
• Sentinel events associated with Birth
Asphyxia
• Maternal (eg hypotension)
• Cord (eg prolapse)
• Placenta (abruption)
• Uterus (rupture)
• Postnatal collapse

10. • Birth asphyxia is caused of 23% of all neonatal deaths worldwide.
• It is one of the top 20 leading causes of burden of diseases in all age
group by the World Health Organization
• It is the the fifth largest cause of death of children younger than 5
years (8%)
• More than a million children who survive birth asphyxia develop
problems such as cerebral palsy, mental retardation, learning
difficulties, and other dis abilities

11. • In severe hypoxic-ischemic encephalopathy, the mortality rate is
reportedly 23-30%
• As many as 80% who survive hypoxic-ischemic encephalopathy
develop serious complications, 10-20% develop moderately serious
disabilities, as many as 10% are healthy.
• The infants who survive moderately severe hypoxic-ischemic
encephalopathy, 30-50% may have serious long term complications,
and 10-20% have minor neurological morbidities.
• Infants with mild hypoxic-ischemic encephalopathy tend to be free
from serious CNS complications.

12. Pathophysiology
• Pathophysiology depends upon the organ affected and the severity of
insult.
• The onset of asphyxia is followed by:
• Metabolic acidosis
• Hypoglycaemia
• Hypotension
• And alteration in cerebral blood flow.

13. • Alteration in cerebral blood flow accompany these metabolic changes
and includes:
• Initial increase in cerebral blood flow
• Loss of vascular autoregulation
• Reduction in cardiac output
• Hypotension , and
• Reduction in cerebral blood flow.

14. • In CNS  increased capillary permeability cerebral edema and cell
death.
• Acceleration of glycolysis increase in brain lactate levels
• Reduction in high energy phosphate concentration  failure of
energy dependent ionic pumps  Leakage from cells of the normally
intracellular potassium and influx of sodium, chloride and calcium.
• As a consequence, membrane depolarization occur with release of
the exitotoxic neurotransmitters, glutamate and aspartate, these
activates N-methyl-D-Aspartate receptors which play critical role in
neuronal damage

15. • The pathologic changes observed in the brain reflect the combined
effects of metabolic derangements that are occurring in the context
of cerebral hypoperfusion.
• Full term infants shows cortical necrosis and para sagaital ischemic
injury, whicih results in focal or multifocal infarcts that produce focal
seizures and hemiplegia.
• Preterm infants demonstrate periventricular leukomalacia (later
spastic diplegia), basal ganglia damage and IVH

18. FETAL HYPOXIA CAUSED BY VARIOUS DISORDERS IN
MOTHER
• Inadequate oxygenation of maternal blood from hypoventilation during anesthesia, cyanotic
heart disease, respiratory failure, or carbon monoxide poisoning;
• Low maternal blood pressure from acute blood loss, spinal anesthesia, or compression of the
vena cava and aorta by the gravid uterus;
• Inadequate relaxation of the uterus to permit placental filling as a result of uterine tetany caused
by the administration of excessive oxytocin;
• Premature separation of the placenta;
• Impedance to the circulation of blood through the umbilical cord as a result of compression or
knotting of the cord; and
• Placental insufficiency from toxemia or postmaturity.

19. • DIAGNOSTIC CRITERIA
American Academy of Pediatrics, the following criteria must be present in order
to diagnose HIE resulting from perinatal asphyxia:
o Metabolic acidosis with pH <7.0
o on an umbilical cord gas measurement (arterial or venous) or
o within 1 hour of birth on infant arterial blood gas measurement
o Base deficit ≥12 mEq/L
o Apgar score ≤5 at 10 minutes with continued need for resuscitation
o Presence of multiple organ system dysfunction
o Clinical evidence of encephalopathy (hypotonia, abnormal oculomotor or
pupillary movements, weak or absent suck, apnea, hyperpnea, or clinical
seizures).

20. Apgar Score
• The Apgar score is a test given to newborns soon after birth. This test
checks a baby's heart rate, muscle tone, and other signs to see if extra
medical care or emergency care is needed. The test is usually given
twice: once at 1 minute after birth, and again at 5 minutes after birth.

21. APGAR Score:
APGAR sign 2 1 0
Appearance Normal color all over Only hands and feet are
bluish
Bluish-gray or pale all
over
Pulse >100 <100 No pulse
Grimace Pulls away, sneezes,
coughs, or cries with
stimulation
Facial movement only
(grimace) with
stimulation
Absent (no response to
stimulation)
Activity Active, spontaneous
movement
Arms and legs flexed
with little movement
No movement, “floppy”
tone
Respiration Normal rate and effort
good cry
Slow or irregular
breathing, weak cry
Absent (no breathing)

22. STAGING FOR HIE

23. Points in History and Examination
 Maternal history
• A thorough maternal history (prior pregnancy loss, thyroid disease, fever, drug use, infection)
and family history (thromboembolic disorders, seizure disorder) can help identify causes of NE
other than HIEs.
 Fetal heart rate (FHR) patterns
 Umbilical cord blood gases
 Placental pathology
 Apgar scores
 Sarnat staging
 Altered state of consciousness (irritability, unresponsiveness to stimulation)
 Abnormal tone (hypo/hypertonia, abnormal posturing, decerebrate rigidity, extensor response
to painful stimulus)
 Seizures
 Weak/ absent suck
 Hypo/hyperventilation

24. CLINICAL PRESENTATION
• Pallor, cyanosis, apnea, a slow heart rate and unresponsiveness to
stimulation are non specific initial signs of HIE.
ENCEPHALOPATHY
• Newborns with HIE must have depressed consciousness whether mild
moderate or severe.
MOTOR ABNORMALITIES
• There is generally greater hypotonia, weakness and abnormal posture
with lack of flexor tone which is usually symmetric, with severe HIE
primitive reflexes MORO or GRASP may be diminished.
SEIZURES
• Occurs in upto 50% of newborns with HIE and usually starts within
24 hrs after HIE insult ,seizures may be subtle, tonic or clonic.

25. Investigations:
• Complete blood,
• blood culture,
• serum electrolytes, blood urea nitrogen, creatinine,
• cardiac enzymes,
• liver enzymes,
• a coagulation panel, blood gases should be obtained at time of admission and
serially monitored as indicated,
• Cranial ultrasound, Electroencephalography (EEG) and MRI of brain.

26. DIAGNOSIS
• MRI is the most sensitive modality for detecting hypoxic brain injury in neonate,
• CT scans may be helpful in ruling out focal hemorrhagic lesions or large arterial
ischemic strokes
• Loss of gray white differentiation and injury to basal ganglia in more severe HIE can
be detected on CT,U/s has limited modality in evaluating hypoxic injury.
ESSENTIAL CRITERIA FOR DIAGNOSIS OF HIE:
• Metabolic acidosis ph<7.0
• Early onset of encephalopathy
• Persistence of an Apgar score of 0-3 for longer than 5 minutes
• Neonatal neurologic sequelae (eg, seizures, coma, hypotonia)
• Multiple organ involvement (eg, kidney, lungs, liver, heart, intestines

28. TREATMENT
• Delivery room management follows standard Neonatal Resuscitation
Program (NRP) guidelines. Close attention should be paid to
appropriate
oxygen delivery, perfusion status, and avoidance of hypoglycemia and
hyperthermia.
• After the initial steps of neonatal resuscitation, management of an
asphyxiated infant includes: assisting the infant to obtain adequate
ventilation, oxygenation, pulmonary perfusion, and cardiac output,
minimizing body heat loss and maintaining peripheral circulation.

29. • 1. Glucose: Provide a continuous infusion of glucose to maintain serum blood
glucose greater than or equal to 60 mg/dl.
• 2. Oxygen: Provide oxygen to avoid hypoxemia, maintain PaO2 60-80 and SpO2
>94%
• 3. Carbon dioxide: Avoid hypo-or hypercarbia maintain carbon dioxide levels in
the normal to low normal range to prevent excess cerebral blood flow to
potentially injured and ischemic areas.
• 4. Fluid balance and renal function: Initial fluid restriction is recommended as
HIE infants are predisposed to a fluid overload state from renal failure secondary
to acute tubular necrosis (ATN) and SIADH. Restrict total fluid intake to 60-80
cc/kg/day. The avoidance of volume overload helps averts cerebral edema.

30. Therapeutic hypothermia
• HIE is managed using a treatment called therapeutic hypothermia where
the baby’s brain or body is cooled down below normal temperatures of
33.5.C or 92.3;F to slow the cascade effect that causes widespread
damage.
• This allows the baby’s brain to recover and reduces the level of disability
they may have as they grow. According to current guidelines, the
treatment must be given within six hours of birth, although there
is some evidence to suggest it may be beneficial when given up to 24
hours.
• Therapeutic hypothermia lasts for around 72 hours, allowing the baby’s
metabolic rate to slow. This prevents further damage known
as reperfusion injury, which occurs when normal oxygenation and blood
flow are restored too quickly to the brain’s cells.
• Hypothermia treatment works to stabilize the brain’s cells and prevent
or limit damaging inflammation.

32. HYPOTHERMIA THERAPY
• Mild hypothermia (3-4°C below baseline temperature) applied within a few hours
(no later than 6 h) of injury is neuroprotective. Possible mechanisms include
• Reduced metabolic rate and energy depletion
• Decreased excitatory transmitter release;
• Reduced alterations in ion flux;
• Reduced apoptosis due to hypoxic-ischemic encephalopathy; and
• Reduced vascular permeability, edema, and disruptions of blood-brain barrier
functions.
• Therapeutic hypothermia when applied within 6 hours of birth and maintained for
48-72 hours is a promising therapy for mild-to-moderate cases of hypokic-ischemic
encephalopathy.

33. COMPLICATION OF INDUCED HYPOTHERMIA
• Thrombocytopenia
• Reduced heart rate
• Subcutaneous fat necrosis (sometimes associated with
hypercalcemia)
• Bleeding

34. SUPPORTIVE CARE
• ENCEPHALOPATHY
• Most infants with severe hypoxic-ischemic encephalopathy need
ventilator support during first days of life.
• The role of mechanical ventilation is to maintain the blood gases and
acid-base status in the physiological ranges and prevent
hypoxia, hyperoxia, hypercapnia, and hypocapnia.
• Infants with hypoxic-ischemic encephalopathy are also at risk for
pulmonary hypertension and should be monitored.

35. PERFUSION AND BLOOD PRESSURE MANAGEMENT
• A mean blood pressure (BP) above 35-40 mm Hg is necessary to avoid
decreased cerebral perfusion.
• Hypotension is common in infants with severe hypoxic-ischemic
encephalopathy and is due to myocardial dysfunction, capillary leak
syndrome, and hypovolemia; hypotension should be promptly treated.
• Dopamine or dobutamine can be used to achieve adequate cardiac
output in these patients. Avoiding iatrogenic hypertensive episodes is also
important.

36. TREATMENT OF SEIZURES
• Hypoxic-ischemic encephalopathy is the most common cause
of seizures in the neonatal period.
• Current therapies available to treat neonates with seizures
include phenobarbital, phenytoin, and benzodiazepines.
• Phenobarbital has been shown to be effective in only 29-50%
of cases.
• Phenytoin only offers an additional 15% efficacy.
• Benzodiazepines, particularly lorazepam, may offer some
additional efficacy

37. DIET
• In most cases, the infant is restricted to nothing by mouth (NPO)
during the first 3 days of life or until the general level of alertness and
consciousness improves.
• In addition, infants undergoing hypothermia therapy should remain
NPO until rewarmed. Enteral feeds should be carefully initiated and
the use of trophic feeds is initially advisable (about 5 ml every 3-4 h).
• Infants should be monitored carefully for signs and symptoms of
necrotizing enterocolitis, for which infants with perinatal asphyxia are
at high risk.

38. POOR PREDICTIVE VALUES FOR DEATH
AND DISABILIY AFTER HIE
• Low (0-3)10 min APGAR Score
• Presence of multiorgan failure especially oilgurea.
• Delayed onset of spontaneous breathing (>20min)of
spontaneous breathing
• Early onset Seizure <12 hr or difficult to treat
• Abnormal MRI in 1st 24 to 72 hours.
• Persistant abnormalties of brain stem functions
• Abnormal neurologic exam >15 days
• Microcephaly at 3 months of age

39. PROGNOSIS:
• The likelihood and extent of brain damage is related to the severity of
encephalopathy.
• Most infants with mild encephalopathy develop normally
• infants with moderate to severe encephalopathy are more likely to develop long-
term neurologic morbidity.
• Severe brain MRI abnormalities are usually associated with marked
electroencephalogram (EEG) abnormalities and poor outcome.

40. Reference:
• 1. Cloherty and Starks Manual of Neonatal Care- 2021
• 2. Gomella's Neonatology: Management, Procedures, On-Call Problems, Diseases, and
• Drugs.
• 3. https://pedsinreview.aappublications.org/content/33/9/387
• 4. Neonatal Guidelines 2019-2021 West Midlands Neonatal Operational Delivery network.
• 5. https://kidshealth.org/en/parents/apgar.html
• 6. https://obgynkey.com/hypoxic-ischemic-encephalopathy/
• 7. Wu Y, Nordli DR, Weisman LE, Dashe JF. Clinical features, diagnosis, and treatment of neonatal
encephalopathy.