Perinatal asphyxia, Definition, cause, pathophysiology and management

1. Perinatal Asphyxia
Dr. Prakash. I

2. Introduction
Brain:
2% of body mass
Consumes: 15% of energy generated
Grows by about 1% per day for the next
three months
Incidence:
Between 4 and 9 million newborns develop
birth asphyxia each year
1/1000 to 6/1000 live births

3. Definition
• Birth asphyxia: Impaired gas exchange, due to interruption of
placental blood flow, with progressive hypoxemia, hypercapnia, and
acidosis
• Perinatal asphyxia: Asphyxia that occurred during period
immediately before, during, or after the birth process
• Anoxia: Complete lack of oxygen
• Hypoxia: Decreased availability of oxygen
• Hypoxemia: Decreased arterial concentration of oxygen
• HIE: Effect of perinatal asphyxia on neurologic function

4. Etiology
Based on stage- 90% Antepartum + Intrapartum
10% Post partum
Based on disease factor-
• Maternal – Hypertension (Chronic, Pre-
eclampsia)
Diabetes, anemia, malnutrition
Pulmonary , cardiac disease
Hypotension, Intrauterine infection
Prolonged and difficult 2nd stage of
labor
• Placental –Infarction, fibrosis, abruption
• Cord accidents – Prolapse, true knots ,
compression
• Neonatal- Cong anomalies, CNS disorders,
Infection, severe cardiopulmonary disease

5. Pathophysiology
Features suggestive of acute asphyxia
include:
1.CTG: Sudden and sustained fetal
bradycardia, or the absence of fetal heart
rate variability with persistent late or
persistent variable decelerations when the
pattern was previously normal
2.Apgar scores: <5 at 5 and 10 minutes, need
for prolonged resuscitation
3.Cord gas: Acidemia PH ≤ 7, base deficit ≥
10
4.Evidence of multiorgan dysfunction

6. Pathophysiology
Features suggestive of chronic asphyxia
include:
1. Episode of loss of fetal movements for
12 or more hours
2. CTG: Loss of fetal heart rate variability
or persistent nonreactive heart rate
tracing
3. Oligohydramnios
4. IUGR
5. Meconium staining of fetal membranes,
placenta, and neonatal nails and skin
6. Often these babies do not require
extensive resuscitation, with Apgar
scores ≥ 5 and mild academia

7. Sequence of
Events Basic
Resus

8. Pathophysiology
Diving reflex
• Shunting of blood
Progressive asphyxia
• Hypoxia, hypercapnia,
acidosis, ↑ PVR, ↓HR,
CO, BP, right to left
shunt

9. Pathophysiology- Organ affected
CNS-28%, CVS-25%, Lung-23%, Kidney-50%, Others (GIT, Blood, Endocrine, Metabolic)

10. Pathophysiology: Primary energy failure (0 to
6 hrs)
Decreased
perfusion
Ischemia,
Hypoxia,
Hypoglycaemia,
Metabolic
acidosis,
Intracellular
derange-
ments
Increased
intracellular
calcium, Na-
K Channel
Edema,
cell death
Continued
destruction of
proteins,
membrane
lipids, other
cellular
contents
Cell
necrosis

11. Pathophysiology – Secondary energy failure
(6 hrs to 12 to 48hrs)
• Inflammation
• Apoptosis
• Oxidative injury
• Decreased growth factors
• Impaired protein synthesis
Secondary energy failure phase begin approximately 12 to 36 hours after the initial injury and may last 7 to 14 days

12. Pathophysiology- Brain

13. Pathology – pattern
of Brain injury
• Selective neuronal necrosis-
cerebral and cerebellar
cortex, Thalamus, Brain
stem nuclei
• Focal and multifocal cortical
necrosis
• Watershed infarct
• Parasagittal cerebral injury
• PVL
• Status murmoratus

14. Asphyxia continues Shunting within the
brain
Anterior circulation >
posterior affected;
Brainstem less
affected
Cerebral cortical lesions
Abrupt and severe hypoxia
Thalamus and brain stem injury,
Cortex spared
No time for compensation

15. Definition
AAP and the ACOG consider all of the following criteria in diagnosing
asphyxia:
• Profound metabolic or mixed acidemia (pH <7.00) in umbilical
artery blood sample, if obtained,
• Persistence of an Apgar score of 0–3 for longer than 5 min
• Neonatal neurologic sequelae (e.g., seizures, coma, hypotonia)
and
• Multiple organ involvement
Clinically, this type of brain injury is called HIE

16. Cooling criteria
Inclusion criteria:
• Infants > 35 completed week’s gestation (best obstetric estimate) who meet the
following criteria:
Any 2 of the following criteria:
• Apgar score < 5 at 10 minutes
• Cord pH or postnatal blood gas pH < 7.0 within one hour of age
• Base deficit of > 12 meq/L on cord gas or on any postnatal arterial blood gas (within one hour of
age)
• At least 10 minutes of Positive Pressure Ventilation
• Highest Serum Lactate greater than 7.5 mmol/lit in the first hour of age
AND
• Evidence of moderate to severe encephalopathy defined as clinical seizures
OR
• Presence of at least ONE sign in at 3 least of these 6 categories in modified Sarnat scoring
system

17. Sarnat Staging-1976
Total score ranging from 6 to 18.

18. Exclusion criteria
• >6 hours of age at the time of initiating hypothermia
• Presence of known chromosomal anomaly/ major congenital
anomalies
• GA< 35 weeks
• Severe intrauterine growth restriction (weight <2 kg)
• Uncontrolled severe clinical coagulopathy
• Evidence of head trauma or intracranial hemorrhage

19. Therapeutic hypothermia
Aimed at
• Decreased cerebral metabolism, prevents oedema
• Decreases energy utilization
• Inhibit inflammatory cascades
• Suppresses free radical activity
• Attenuates secondary energy failure
• Inhibits apoptosis
• Reduces extent of brain injury
Reduce
injury to
brain

20. Therapeutic hypothermia
Benefits
• Reduction in infarct size
• Decrease in neuronal cell loss
• Retention of sensory/ motor function
• Preservation of hippocampal structures
• Recovery of EEG activity
• Decreases risk of death and major neurodevelopmental disabilities at 18
mo of age in neonates with moderate to severe HIE(Cool cap study)
Benefits to
Brain

21. INTERVENTIONS & THERAPIES
Whole body cooling (33-34°C)
Selective head cooling with mild systemic
hypothermia (Rectal temp 34-35°C)
Goal: Lower temp of the vulnerable deep brain structures, the basal ganglia to 32-34°C.

22. Therapeutic hypothermia
• Must be initiated within 6 hours of birth
• Includes passive cooling
• All external heat sources off
• Desired temp 33.5°C + 0.1°C
• Monitor Temp Q15 min
• Vitals & urine output monitoring
• Neurological assessment
• Therapy for 72 hrs

23. Management
• Ventilation + Sedation
• Antibiotics
• Maintain cerebral perfusion
• CVS stabilization
• Renal management
• Temperature maintenance
• Electrolytes and blood glucose levels
• Management of seizures
• Feeding +/-
↑HR, Shivering,
difficult ventilation

24. Labs/ Radiological study
• Glucose
• Septic markers
• Cardiac markers
• Coagulation profile
• Arterial Blood Gases
• LFTs
• BUSS
• aEEG monitoring
• MRI Brain Day 5-7

25. Changes during therapeutic hypothermia
Cooling
• Decreased heart rate
• Increased blood
pressure
• Increase in urine output
• Decrease in calcium,
magnesium, phosphorus
and potassium
• Labile glucose levels
Rewarming
• Increase in heart rate
• Decrease in blood pressure
• Decrease in urine output
• Electrolyte shifts (renal and
liver clearance rates change)
• Emergence of seizure

26. When to stop therapeutic hypothermia
• Hypotension despite inotropic support
• PPHN with hypoxemia despite adequate treatment
• Clinically significant coagulopathy, despite treatment
• Severe Intracranial hemorrhage noted on BUSS

27. Complications of cooling
• Arrhythmias
• Bradycardia
• Ventricular tachycardia
• Persistent Acidosis
• Bleeding
• Subcutaneous fat necrosis
• Death

28. Rewarming
• Rewarm slowly after 72 hours
• Monitor very closely
• Increase temp by 0.5°C Q hour
• Hemodynamic unstable/ seizures: Slower rewarming
• Once temp reaches 36.5°C for 1 hour
• Turn on radiant warmer
• Return to standard servo control protocol

29. Some facts from studies
Fluid:
• Prevent Fluid OVERLOAD & Cerebral Edema
• Avoid fluid boluses
• Do not worry about lack of urine output for DOL 1–2 (BMC Pediatrics 2011)
PaCO2: Infants with HIE and Low PaCO2 Have Poor Outcomes (Lingappan et al 2016)
Blood glucose: Prevent & treat hyper/hypoglycemia ( Arch Ds Child Fetal Neonatal Ed
2015)
Seizures: Treat seizures early (Miller J Pediatr 2009)

30. Promising therapies in management of HIE by
mechanism
Mechanism Clinical trials Pre-clinical studies
Endogenous • Erythropoietin
• Darbepoetin
• Stem cells
• Melatonin
• Remote ischemic
postconditioning
• Endocannabinoids
Exogenous • Monosialogangliosides
• Xenon
• Allopurinol
• Topiramate
• Magnesium sulphate
• Argon
• Azithromycin

31. Follow-up
• Developmental Pediatrics Consult & evaluation
• Neurology Clinic
• Brain MRI at 1 year of age
• Developmental Clinic
• Full Bayley exam

32. Neurological sequelae
• Cerebral Palsy
• Spastic diplegia
• Spastic quadriplegia
• Spastic hemiplegia
• Dystonia
• Choreo-athetosis
• Mental retardation
• Epilepsy
• Auditory, visual, language abnormalities

33. Prognosis
• Overall mortality: 10 to 20%
• Neurological Sequelae: 20 to 45%
• Subtle school problems: 18 to 35%
• Sarnat stage:
• Stage I: 100% Normal
• Stage II: 80% Normal
• Stage III: 50% Death, 50% Severe neurological disorder
Risk of death: 10% for moderate and 60% for severe grade
Risk of disability: 30% for moderate and 100% for severe grade

34. What the evidence says
• Therapeutic Hypothermia is Beneficial
• Cooling improves survival without increasing major disability in survivors
• Therapeutic hypothermia should be used in infants ≥35 weeks with moderate-to
severe HIE if begun within 6 hours of age
• Therapeutic hypothermia resulted in reduction in……….
• Combined outcome of mortality or major ND disability [Cochrane Review
Cooling for Newborns with HIE]

35. References
• Neonatal Therapeutic Hypothermia (Mohamed Sakr; Palanikumar Bala
Sundaram)(National library of medicine)
• Shankaran, S., Laptook, A.R., Ehrencranz, R.A., Tyson, J.E., McDonald,
S.A., Donovan, E.F., et al. (2005). National Institute of Child Health and
Development Neonatal Research Network. Whole-body hypothermia for
neonates with hypoxic-ischemic encephalopathy. New England Journal of
Medicine. 353. 1574-1584
• Jacobs S.E., Berg M., Hunt R., Tarnow Mordi W.O., Inder T.E., Davis P.G.
(2013). Cooling for newborns with hypoxic ischemic encephalopathy.
Cochrane Database Systematic Review.
• 15.6. Mosalli, R. (2012) Whole Body Cooling for Infants with Hypoxic
Ischemic Encephalopathy. Journal of Clinical Neonatology. Perinaltal
asphyxia WHO

36. Thank You