Perinatal Asphyxia

DR AMAR
MODERATORS: DR LOKESH/DR RAMESH KONANKI/DR NIKIT

Definition

It refers to a condition during first and second stage of labour in

which impaired gas exchange leads to fetal hypoxemia and
hypercarbia.

Hypoxic ischemic encephalopathy (HIE) is a term that describes

encephalopathy with objective data to support a hypoxic
ischemic mechanism as the underlying cause for the
encephalopathy.

Causes
1)Maternal Factors:

Hypotension from acute blood loss, spinal anesthesia, or

compression of the vena cava and aorta by the gravid uterus
hypertension( acute or chronic)

Infection including chorioamnionitis

Hypoxia from anaesthesia ,pulmonary or cardiac disorders

Maternal Diabetes

Maternal Vascular disease

Causes
2)Placental factors: abnormal placentation,abruption,infarction and
fibrosis..
3) Uterine factors: Uterine Rupture, uterine tetany caused by the
administration of excessive oxytocin.
4) Umbilical cord accidents: prolapse,entanglement,compression
5))Abnormalities of umbilical vessels
6) Fetal factors: Anaemia, infection,cardiomyopathy,hydrops
fetalis,severe cardiac or circulatory insufficiency.
7) Neonatal factors: Cyanotic heart disease ,PPHN,
cardiogenic/septic shock interfering with o2 transport, massive
blood loss, and intracranial or adrenal haemorrhage.

Pathophysiology

The topography of injury typically correlates with areas of

decreased cerebral blood flow.

After an episode of hypoxia and ischemia, anaerobic metabolism

occurs and generates increased amounts of lactate and inorganic
phosphates.

Excitatory and toxic amino acids, particularly glutamate,

accumulate in the damaged tissue.

Increased amounts of intracellular sodium and calcium may

result in tissue swelling and cerebral oedema.

There is also increased production of free radicals and nitric

oxide in these tissues.

Pathophysiology

The initial circulatory response of the fetus is increased shunting

through the ductus venosus, ductus arteriosus, and foramen
ovale, with transient maintenance of perfusion of the brain,
heart, and adrenals in preference to the lungs, liver, kidneys, and
intestine.

But with prolonged asphyxia this compensation is lost and

ultimately leads to hypoxic injury to brain.

Pathophysiology

Cell death occurs in three forms.

1)

Immediate neuronal death( Necrosis): due to intracellular

osmotic overload of Na+, Ca2+, ion pump failure, excitatory
neurotransmitters acting on inotropic receptors

2)

Delayed neuronal death(Apoptosis): secondary to uncontrolled

activation of enzymes( eg: Ca2+ dependant lipases, proteases,
caspases ), generation of free radicals and leukotrenes,
generation of NO, depletion of energy stores

3)

Reperfusion Injury: formation of excessive reactive oxygen

species( superoxide,H2O2), release of injurious cytokines(eg;IL 1
beta,TNF alpha etc..)

Location of Injury and Sequale

AREA OF INJURY

LOCATION OF INJURY

CLINICAL CORRELATE(S)

LONG-TERM SEQUELA(E)

Cognitive delay
Cerebral palsy
Dystonia
Seizure disorder
Ataxia
Bulbar and pseudobulbar palsy

Selective neuronal necrosis

Entire neuroaxis, deep cortical area,

brainstem and pentocubicular

Stupor or coma
Seizures
Hypotonia
Oculomotor abnormalities
Suck/swallow abnormalities

Parasagittal injury

Cortex and subcortical white matter

Parasagittal regions, especially posterior

Proximal limb weakness

Upper extremities affected more than
lower extremities

Spastic quadriparesis
Cognitive delay
Visual and auditory processing difficulty

Focal ischemic necrosis

Cortex and subcortical white matter

Vascular injury (usually middle cerebral
artery distribution)

Unilateral findings
Seizures common and typically focal

Hemiparesis
Seizures
Cognitive delays

Periventricular injury

Injury to motor tracts, especially lower

extremity

Bilateral and symmetric weakness in

lower extremities
More common in preterm infants

Spastic diplegia

Clinical.

At delivery, the presence of meconium-stained amniotic fluid is evidence

that fetal distress has occurred.

At birth, affected infants may be depressed and may fail to breathe

spontaneously.

During the ensuing hours, they may remain hypotonic or change from a
hypotonic to a hypertonic state, or their tone may appear normal.

Pallor, cyanosis, apnoea, a slow heart rate, and unresponsiveness to

stimulation are also signs of HIE.

Cerebral oedema may develop during the next 24hr and result in profound
brainstem depression. During this time, seizure activity may occur; it may
be severe and refractory to the usual doses of anticonvulsants.

Though most often a result of the HIE, seizures in asphyxiated newborns

may also be due to hypocalcemia, hypoglycemia, or infection.

Multiorgan effects of Hypoxia

SYSTEM

EFFECT(S)

Central nervous system

Hypoxic-ischemic encephalopathy, infarction, intracranial hemorrhage, seizures, cerebral edema, hypotonia,

hypertonia

Cardiovascular

Myocardial ischemia, poor contractility, cardiac stunning, tricuspid insufficiency, hypotension

Pulmonary

Pulmonary hypertension, pulmonary haemorrhage, respiratory distress syndrome

Renal
Adrenal

Acute tubular or cortical necrosis

Adrenal hemorrhage

Gastrointestinal

Perforation, ulceration with hemorrhage, necrosis

Metabolic

Inappropriate secretion of antidiuretic hormone, hyponatremia, hypoglycemia, hypocalcemia, myoglobinuria

Integument

Subcutaneous fat necrosis

HIE Stages
SIGNS

STAGE 1

STAGE 2

STAGE 3

Level of consciousness

Hyperalert

Lethargic

Stuporous, coma

Muscle tone
Posture

Normal
Normal

Hypotonic
Flexion

Flaccid
Decerebrate

Tendon reflexes/clonus

Hyperactive

Hyperactive

Absent

Myoclonus
Moro reflex
Suck
Pupils
Autonomic Dysfunction
Seizures

Present
Strong
weak
Mydriasis
sympathetic
None

Present
Weak
Weak or absent
Miosis
Parasympathetic
Common

Absent
Absent
Absent
Unequal, poor light reflex
Both systems soppressed
Decerebration

Electroencephalographic findings

Normal

Low voltage changing to

seizure activity

Burst suppression to isoelectric

Duration

<24hr if progresses;
otherwise, may remain
normal

24hr-14 days

Days to weeks

About 100% normal

80% normal; abnormal if

symptoms more than 5-7
days

About 50% die, remaining have severe sequelae

Outcome

Doppler assesment

Intrauterine growth restriction with increased vascular resistance

may be the 1st indication of fetal hypoxia.

During labour, the fetal heart rate slows and beat-to-beat

variability declines.

Continuous heart rate recording may reveal a variable or late

deceleration pattern.

Diagnosis

Asphyxia may be suspected and HIE is reasonably included in the

differential diagnosis when there is:

1)Prolonged (>1 hr ) antenatal acidosis with PH< 7.0 and base

deficit > 16 mmol/L.
2)Fetal heart rate < 60/min
3)Apgar score<3 at 10 minutes
4)Need for PPV for > 1 min or first cry delayed> 5 minutes
5)Seizures with in 12 to 24 hours of birth.
6)Burst suppression pattern in EEG.

Labs

Decreased cell lines mainly platelets due to hypoxic BM suppression

Elevated urea and creat levels due to renal dysfunction

Liver dysfunction causes elevated liver enzymes, bleeding

manifestations due to poor production of clotting factors, DIC,
Hypoglycemia, altered metabolism

Cardiac- Elevated cardiac troponins I and T. CK-MB fraction is

elevated by > 5 to 10%. ECG shows ST depression and T- wave
inversion in the left leads. 2D echo shows decreased left ventricular
contractility, elevated ventricular end diastolic pressure etc

Neurological- CK-BB is elevated with in 12 hours of life.

Gastrointestinal- Signs of NEC can be seen in X ray abd in cases of

severe bowel ischemia.

Brain Imaging

Diffusion-weighted MRI is the preferred imaging modality in neonates

with HIE because of its increased sensitivity and specificity early in
the process and its ability to outline the topography of the lesion

SWI Mri useful for detection of haemorrhagic injury.

MR angio or venography is done if there is suspicion of vascular

anomalies, thromboembolic disease

CT scans are helpful in identifying focal hemorrhagic lesions, diffuse

cortical injury, and damage to the basal ganglia; CT has limited
ability to identify cortical injury during the 1st few days of life.

Ultrasonography has limited utility in evaluation of hypoxic injury in

the term infant; it is the preferred modality in evaluation of the
preterm infant.

Treatment

Selective cerebral or whole body (systemic) therapeutic hypothermia reduces mortality

or major neurodevelopmental impairment in term and near-term infants with HIE.

Hypothermia decreases the rate of apoptosis and suppresses production of mediators

known to be neurotoxic, including extracellular glutamate, free radicals, nitric oxide, and
lactate.

The neuroprotective effects are thought to be secondary to downregulation of the

secondary mediators of injury resulting from cerebral oedema, accumulation of
cytokines, and seizures.

Animal data suggest that the intervention is most effective when implemented within
6hr of the event.

Several clinical trials and a meta-analysis demonstrate that either isolated cerebral
cooling or systemic hypothermia to a core temperature of 33.5 C within the 1st 6hr after
birth reduces mortality and major neurodevelopmental impairment at 18mo of age.

Systemic hypothermia may result in more uniform cooling of the brain and deeper CNS
structures.

Cooling Inclusions and Exclusions

Inclusions are:

1)Gestational age>36 wks and birth weight >2 kg

2)Evidence of fetal distress by atleast one of the following:
a) History of acute perinatal event Eg: abruption placenta,cord prolapse,fetal
heartrate abnormaity etc..
b)Biophysical profile <6/10 within 6 hrs of birth
c)Cord PH< 7.0 or base deficit>16 meq/l
3)Evidence of neonatal distress by atleast one of the following:
a)Apgar score < 5 at 10 min
b)Postnatal blood gas PH at < 1 hr is < 7.0 or base deficit>16 meq/l
c)Continued need for ventilation initiated at birth and continued for atleast 10 min

Inclusions
4) Evidence of neonatal encephalopathy by physical exam
5)Abnormal EEG with min 20 min of recording atleast one of
following
a)Severely abnormal: Upper margin >10 microvolt
b)Moderately abnormal: Upper margin > 10 microvolt and lower
margin <5 mocrovolt
c)Seizures identified by an EEG

Exclusions
1)Normal initial EEG tracing, lower margin > 5 microvolt
2)Inability to initiate cooling by 6 hours of age
3)Presence of lethal chromosomal anamoly (eg: Trisomy 13 or 18)
4)Presence of severe congenital anamolies( Complex cyanotic heart
disease, major CNS anamoly etc..)
5)Symptomatic systemic congenital viral infection (HSM,
microcephaly)
6) 5)Symptomatic systemic bacterial infection (meningoencephalitis
, DIC etc..)
7)Bleeding diathesis( Plt < 50 k, spontaneous clinical bleeding)
8)Major intracranial bleed.

Rx..
1)

Ventilation: Co2 should be maintained in normal range(35-40).

Hypercapnoea can cause cerebral acidosis and vasodilatation
which can lead to steal phenomenon. Hypocapnoea can cause
decreased cerebral flow.

2)

Oxygenation: O2 levels should be in normal range(60-80).

Hyperoxia can lead to decreased CBF and exacerbate free
radical damage.

3)

Temperature: therapeutic hypothermia is generally advised.

4)

Perfusion: Cardiovascular stability and adequate mean arterial

BP are important to maintain adequate cerebral perfusion
pressure.

5)

Maintain normal glucose, calcium levels.

RX
6)Judicious fluid management: Fluid management is important in cases of SIADH
(restriction) ATN
7)Seizures: controlling seizures agressively is very important part of RX and may
warrant the use of continuous EEG monitoring.
Phenobarbitone is the drug of choice. Loading with 20 mg/ kg
Additional loading doses of 5-10 mg/kg can be given if recurrence
Maintenance of 3- 5 mg/kg/day after 12 hours of laoding.
Therapeutic serum levels are 15-40mg/dl (Doses to be adjusted in hepatic dysfunction)
Phenytoin 20 mg/kg loading followed by 4-8mg/kg/day is given if seizures not
controlled with phenobarbital.
Therapeutic serum levels 15-20mg/dl.
Benzodiazepines for acute seizure control
Leviteracetam is being used recently because of relative safety and efficacy.

Rx for other target organ injury

1)Cardiac: Correction of hypoxemia,acidosis,hypoglycaemia,avoding fluid overload,
inotropic support, monitoring ABP, CVP
2)Renal: In presence of oliguria , avoid fluid overload by limiting total volume of
fluids to 60cc/kg/day and consider using low dose dopamine infusion(2.5
microgram/kg/min)
If low or no urine output 10-20 ml/kg fluid challenge followed by loop diuretic can
be useful.
3) Gastrointestinal: Feeding should be withheld till hemodynamically stable, active
bowel sounds are present. Trophic feeds are encouraged.
4) Hematological: PRBC, Platelets, FFP are used as per need.
5)Liver: Frequent monitoring of liver functions and levels of drugs metabolised by
liver should be monitored.
6)Lung: Management of pulmonary effects of asphyxia depends on specific etiology.

Prognosis

Over all mortality is 20% and risk of neurodevelopmental sequelae is 30%

Stage I HIE -98 to 100% newborns have normal outcome

Stage II HIE-20 to 37% die or have abnormal outcome. Approximately 80%

have good outcome if encephalopathy less than 5-7 days and there is no
other system involvement.

Stage III HIE-> 50% death and remaining have severe sequelae.

Seizures with in 12 hrs of birth increase mortality and morbidity risk

EEG showing persistent burst suppression or isoelectric background have

poor outcome.

MRI showing injury to cortex and subcortical nuclei is associated with both
motor and cognitive delay while discrete lesions in the subcortical nuclei
have normal cognition with motor delay.