1. ASPHYXIA NEONATORUM/HIE
DR BINOD KUMAR SINGH
Associate Professor, NMCH, Patna
CIAP Executive Board Member 2015
NNF State President-2014
IAP State Secretary ,Bihar
NNF State Secretary , Bihar
Chief Consultant:-
Shiv Shishu Hospital
K P C Colony ,Hanuman Nagar,
Patna -
web site :-

2. ASPHYXIA NEONATORUM
D Defined as impaired respiratory gas exchange accompanied by the development of acidosis

4. Definition of perinatal asphyxia
WHO :
A failure to initiate and sustain breathing at birth.
NNF :
Moderate asphyxia
Slow gasping breathing or an apgar score of 4-6 at 1 minute of age
Severe asphyxia
No breathing or an apgar score of 0-3 at 1 minute of age

5. HOW DOES ASPHYXIA OCCUR?
Interruption of umbilical cord blood flow, eg: cord compression during labour
Failure of exchange across the placenta, eg: abruption
Inadequate perfusion of maternal side of placenta, eg: maternal hypotension
Compromised fetus who cannot tolerate transient intermittent hypoxia of normal labour
Failure to inflate lungs

6. CHARACTERSITICS OF PERINATAL ASPHYXIA
Profound metabolic acidosis (pH<7.00)
Persistence of an Apgar score of 0 to 3 beyond 5 minutes
Clinical neurologic sequelae in the immediate neonatal period
Evidence of of multiorgan system dysfunction in the immediate neonatal period
- derived from the 1992 joint statement of the AAOP and ACOG and the 1999 International Cerebral Palsy Task Force

7. TO ASSESS THE SEVERITY OF ASPHYXIA - Apgar Scores
Signs
Colour Blue/pale Blue peripheries Pink
Heart rate 0 <100 >100
Respiration 0 Weak, gasping Regular
Suction response 0 Slight Cries
Tone Fair Active
A -Appearance P- Pulse G- Grimace A-Activity R-Respiration

8. Quiz:
At birth, a newborn infant is noted to have the following findings: heart rate – 70/min, respiratory effort – poor and irregular, limp, no reflex irritability, blue all over the body.
The Apgar score of the baby at this point is?
HR 1, RR 1, Tone 1, reflex 0, color 0
APGAR=3

9. PREDISPOSING FACTORS Maternal Causes
Medical conditions eg Pulmonary hypertension Chronic Hypertension
Antenatal conditions eg Abnormal uterine contraction Antepartum haemorrhage Prolapsed cord Malpositions etc

10. PREDISPOSING FACTORS Fetal Causes Multiple pregnancies
Big baby with CPD
Fetal anomalies - Congenital abnormalities
of the lung

11. PATHOPHYSIOLOGY
Fetal adaptation to oxygen lack 1. Preferential flow to heart, brain and adrenals aerobic  anaerobic metabolism
glucose  pyruvic acid  lactic acid  Acidosis
Acidosis  failure of autoregulation  impaired perfusion
increasing acidosis  Death unless resuscitated

12. PATHOPHYSIOLOGY 2. Primary and Secondary apnoea
Occur as an attempt to minimize metabolic work
3.Fetal response to asphyxia
Respiratory  metabolic acidosis
4. EEG changes
Loss of faster rhythm  iso-electric rhythms
Prolonged voltage suppression with burst of spike
waves indicating risk of significant brain damage

13. CLINICAL FEATURES Apnoea, bradycardia
Altered respiratory pattern - grunting, gasping
Cyanosis
Pallor-shock
Hypotonia
Unresponsiveness

14. ORGANS INVOLVED IN ASPHYXIA (1)
Asphyxia results in alteration in blood flow to various organs, hence multiple organ injury
Kidney abnormalities occur in 50% of asphyxiated infants. CNS abnormalities in 30% & CVS & pulmonary abnormalities in 25%
Renal abnormalities - Oliguria, elevated β2 microglobulin,
azotaemina, elevated serum creatinine, acute tubular necrosis

15. ORGANS INVOLVED IN ASPHYXIA (2)
CNS abnormalities - HIE, PV-IVH
CVS abnormalities - Ventricular failure (R > L)
Tricuspid regurgitation
Hypotension
Pulmonary abnormalities –Decreased Pulmonary reserve, pulmonary haemorrhage
GIT abnormalities - bleeding GIT, NEC
Bone marrow abnormalities - Thrombocytopenia etc

16. PATHOLOGY OF BRAIN DAMAGE
Acidosis alteration in cell membrane
permeability fluid shift cerebral edema
Anoxia chromatolytic changes in neuron
neuron necrosis and neuroglia reactions
Neuron necrosis may be focal, multifocal or
diffuse over the cerebral cortex, brainstem,
thalamus, basal ganglia etc

18. Potential pathways for brain injury after hypoxia-ischemia.
Pathophysiology
Potential pathways for brain injury after hypoxia-ischemia.
Perlman J M Pediatrics 2006;117:S28-S33
©2006 by American Academy of Pediatrics

19. PATHOLOGY OF BRAIN DAMAGE
Extent of damage depends on:
duration of asphyxia
severity of asphyxia
gestational age
alteration in cerebral blood flow
changes in glucose/glycogen metabolism
in vulnerable areas of brain.

20. Penumbra
Accepted definition for penumbra describes the area as "ischemic tissue potentially destined for infarction but it isn't irreversibly injured and the target of any acute therapies."
The original definition of the penumbra referred to areas of the brain that were damaged but not yet dead, and offered promise to rescue the brain tissue with the appropriate therapies

22. Pathology Severity and distribution is dependent on several factors
Certain vulnerable areas
- cerebral cortex , hippocampus , basal ganglia, thalamus, brain stem, subcortical and periventricular white matter
In full term infants gray matter structures affected and in premature infants white matter
Four basic and clinically important lesions
- Neuronal necrosis, status marmoratus, para-sagittal cerebral injury, periventricular leucomalacia

23. In hypoxic-ischaemic encephalopathy, as the
cerebral edema develops, the brain function is
affected in descending order.

24. PATHOCLINICAL CORRELATION
Full term infant
Pathology Clinical Signs
Parasagittal cortical and Spastic quadriplegia
subcortical neurosis especially arms
Intellectual deficits
Cerebellum Ataxia
Brainstem Bulbar palsy

25. PATHOCLINICAL CORRELATION
Preterm infant
Pathology Clinical Signs
Periventricular leukomalacia Spastic diplegia
Status marmoratus of
Basal ganglia choreoathetosis,Dystonia
Thalamus Mental retardation
Cerebral Cortex Mental retardation

26. SEVERITY OF HIE - SARNAT & SARNAT STAGE
Stage I Stage II Stage III
Consciousness Hyperalert Lethargic Stuporose
Muscle Tone NAD Mild Hypotonia Flaccid
Reflexes active Reflexes active intermittent
decerebration
Primitive Reflexes Present Incomplete Absent
sucking weak suck weak or -ve suck -ve
Autonomic Function Sympathetic Parasympathetic Both depressed depressed depressed
Seizures None Common None
EEG Normal Seizure, Isopotential
background burst
mildly abnormal suppression

27. Mild HIE Muscle tone may be increased slightly
Deep tendon reflexes may be brisk during the first few days.
Transient behavioral abnormalities, such as poor feeding, irritability, or excessive crying or sleepiness, may be observed.
By 3-4 days of life, the CNS examination findings become normal.

28. Moderate HIE Lethargic, significant hypotonia
Diminished deep tendon reflexes.
Grasp, Moro, and sucking reflexes may be sluggish or absent.
Occasional periods of apnea.
Seizures may occur within the 1st 24 hours of life.
Full recovery within 1-2 weeks is possible and is associated with a better long-term outcome.

29. Severe HIE Stupor or coma is typical.
may not respond to any physical stimulus.
Breathing may be irregular, and the infant often requires ventilatory support.
Generalized hypotonia and depressed deep tendon reflexes are common.
Neonatal reflexes (e.g., sucking, swallowing, grasping, Moro) are absent.
Disturbances of ocular motion, such as a skewed deviation of the eyes, nystagmus, bobbing, and loss of "doll's eye" (i.e., conjugate) movements may be revealed by cranial nerve examination.
Pupils may be dilated, fixed, or poorly reactive to light.

30. Preventing asphyxia Perinatal assessment Perinatal management
Regular antenatal check ups
High risk approach
Anticipation of complications during labour
Timely intervention ( eg. LSCS)
Perinatal management
Timely referral
Management of maternal complications Prevention,

31. PREVENTION Recognition of at risk pregnancies Antenatal monitoring
fetal movements, fetal growth
CTG for change in baseline, loss of variability, decelerations
fetal scalp pH
< immediate delivery
repeat in 1 hour
normal
Co-ordinated care at delivery by paediatrician

32. MANAGEMENT-Investigations
Hx - of pregnancy and resuscitation
O/E to exclude other abnormality
Metabolic tests - sugar, Ca/P04/Mg, cord BG, ABG, metabolic screen
CSF - to exclude infection; assay brain specific creatine kinase
EEG - to help with seizure Dx and prognosis
Tech. scan - for abnormal uptake in damaged area

33. MANAGEMENT U/S - to exclude PV-IVH
CT scan - to exclude IVH/trauma, demonstrate severity of edema and for prognosis
MRI scan
Supportive care
Monitor B/p, To, blood sugar, correct acidosis and electrolyte inbalance
Care of renal failure - low fluid, dialysis
Care of cardiac failure - Dopamine, restrict fluid
Management of inappropriate ADH secretion - prevent overhydration

34. MANAGEMENT-1
BASIC CARE :Should be a daily routine in the management of all these babies -
1. Strict asepsis.
2. Ensure neutral thermal environment.
3. Monitor vital parameters – HR,RR,BP,and Pulse Oximetry.
4. Urine output.
5. Daily weight.
6. Nutrition.

35. 1. Management of shock
1.Hypovolumic shock needs replacement with fluids, plasma, or blood.
2.Cardiogenic shock warrants use of pressors like dopamine and / or dobutamine. In case of refractory shock inspite of use of pressors of 20 microgram/kg/mt steroids may be tried.
3.Septic shock should be suspected based on intrapartum risk factors for sepsis, core axillary mismatch and results of sepsis screen.

36. 2-MANAGEMENT of Cerebral Oedema
Minimise cerebral edema
Ventilation - to prevent apnoea and maintain PC02 of mmHg
Ensure adequate oxygenation
Restrict fluid intake
Mannitol ?/frusemide - if urine output is established

37. 3-Manangement of seizures
Not all seizures require treatment. Only if seizures are more than 3 in a hour or lasting for 3 mts or more they warrant anticonvulant.
Phenobarbitone,Phenytoin,initially by loading dose followed by maintenance dose are the first line drugs.
In refractory seizures use of drip of midazolam or lorazepam may be required.
sodium valproate or Leviterecetam is occasionally used.
Use of newer anticonvulants like lamotrigene,clobazam,gabapentin etc is not used well known in neonates.

38. 4-MANAGEMENT OF KIDNEY FAILURE
1.Urine output is by itself not a reliable marker renal parameters need to be monitored.
2.Fluid restriction is required once renal failure sets in. A careful evaluation of electrolytes would direct the fluid management.
3.Daily monitoring of urine output, urine specific gravity, and body weight are adjuvant to basic care.
4.Rarely peritoneal dialysis is required in case of persistent oliguria

39. 5-Management of metabolic derangement
1.Hypoglycemia needs to be corrected by 10 % D.Only if it is symptomatic it warrants a bolus otherwise in asymptomatic cases maintenance infusion is all that is required.
2.Only symptomatic hypocalcemia needs correction.Evaluate for hypomagnesemia in case of persistent hypocalcemia.
3.Hyponatremia should be anticipated and prevented by restricted fluid administration.

40. Newer modalities Hypothermia
Antagonists of excitotoxic neurotransmitter receptors
- NMDA receptor blockers
Free radical inhibitors / scavengers
- vitamin E, superoxide dismutase
Ca channel blockers
Nitric oxide synthetase inhibitors
Erythropoitin
Stem cell transplantation
Hypothermia

41. Management - Hypothermia
Has become standard of care
Whole-body and head-cooling available
Unclear if one regimen is superior to the other - currently either one is utilized, based on availability
Aim to get core (rectal) temperature to 33-35º C for 72 hours
based on Cool Cap and NICHD Neonatal Research Network trials

42. Inclusion criteria for hypothermia
Gestational age>=36 week, wt >= 2000g
Within 6 hrs of age
Abnormal aEEG with minimum 20 min recording severely abnormal – upper margin<10 microV moderate- upper>10, lower < 5micro V
Evidence of fetal and neonatal distress

43. Exclusion criteria Wt less than 2000gm,Gestation less than 36 wks
After 6 hrs,aEEG< 5micro V
Lethal chromosomal anomaly – trisomy 13,18
Severe congenital anomaly
Symptomatic systemic congenital viral infection
Bleeding diathesis
Major intracranial hemorrhage

44. Hypothermia - Mechanism of Action
Reduces cerebral metabolism, prevents edema
Decreases energy utilization
Reduces/suppresses cytotoxic amino acid accumulation and nitric oxide
Inhibits platelet-activating factor, inflammatory cascade
Suppresses free radical activity
Attenuates secondary neuronal damage
Inhibits cell death
Reduces extent of brain damage
DEATH OR SEVERE DISABILITY AT 18 MONTHS OF AGE SIGNIFICANTLY REDUCED!!

45. Hypothermia as a Treatment for HIE
Studies have shown that hypoxic ischemic injury can be reduced by brain cooling.
Favorable effect on many of the pathways contributing to brain injury
Excitatory amino acids
Cerebral energy state
Cerebral blood flow and metabolism
Nitric oxide production
Apoptosis

46. Selective Head Cooling
Whole Body Hypothermia

47. OUTCOME Stage I 0% 0% Stage II 5% 21% Stage III 75% 100%
Death CNS sequelae
Stage I 0% %
Stage II % %
Stage III 75% %
Outcome generally good in those who do not reach stage III and spend < 5/7 in stage II

48. DIFFERENTIAL DIAGNOSIS
Drug depression - maternal drugs, GA
Prematurity
Trauma - tentorial tear
Anaemia
Neuromuscular disorder
Infection
Inborn error of metabolism - Pyridoxine Dependency
Respiratory tract malformation

49. Prognosis based on Apgar score
Score at 1, 5 minutes does not give prognosis indicator
The longer the score remains lower, the greater its significance
0-3 at 1min has mortality of 5-10%
may be increased to 53% if at 20min apgar score 0-3
0-3 at 5min , CP risk app. 1%
may be increased to 9% if APS is 0-3 for 15min
dramatic rise to 57% CP risk if APS is 0-3 for 20min

50. Predictors of poor neuro-developmental outcome
Failure to establish resp. by 5 minutes
Apgar score of 3 or less at 5 minutes
Onset of seizures with in 12 hours
Refractory seizures
Inability to establish oral feeds by 1 wk
Abnormal EEG, neuro-imaging