DR. TAI AL AKAWY
Perinatal asphyxia, more appropriately known
as hypoxic-ischemic encephalopathy, is
characterized by clinical and laboratory
evidence of acute or subacute brain injury due
The primary causes of this condition are
systemic hypoxemia and/or reduced cerebral
blood flow (CBF).
Birth asphyxia causes 23% of all neonatal
Severe hypoxia results in anaerobic glycolysis
and lactic acid production first in the peripheral
tissues (muscle and heart) and then in the
Ischemia (lack of sufficient blood flow to all or
part of an organ) is both a cause and a result
Hypoxia and acidosis can depress myocardial
function, leading to hypotension and ischemia.
Ischemia can impair oxygen delivery, causing
further compromise, as well as disrupt delivery
of substrate and removal of metabolic and
respiratory by-products (eg, lactic acid, carbon
TIMING OF INJURY
Asphyxia can occur before, during, or after
birth. Based on a review of multiple studies
that have examined the temporal relationship
of obstetric events and neonatal outcomes,
predominantly HIE in term infants, the
proportion of conditions that occurs in each
time period can be estimated
Antepartum events, such as maternal
hypotension or trauma, account for 4 to 20
percent of cases.
Intrapartum events, such as placental
abruption or umbilical cord prolapse, are seen
in 56 to 80 percent.
In approximately 10 percent of cases, a
postnatal insult occurs, usually caused by
severe cardiopulmonary abnormalities or
associated with prematurity.
However, the timing of injury often is difficult to
establish for an individual infant
Neonatal encephalopathy is a heterogeneous
syndrome characterized by signs of central
nervous system dysfunction in newborn
Clinical suspicion of neonatal encephalopathy
should be considered in any newborn
exhibiting an abnormal level of consciousness,
seizures, tone and reflex abnormalities,
apnea, aspiration and feeding difficulties
"Neonatal encephalopathy" has emerged as
the preferred term to describe central nervous
system dysfunction in the newborn period
The terminology does not imply a specific
underlying pathophysiology since the nature of
brain injury causing neurologic impairment in a
newborn is poorly understood.
While neonatal encephalopathy was once
automatically ascribed to hypoxia-ischemia
It is now known that hypoxia-ischemia is only
one of many possible contributors to neonatal
Whether a particular newborn's
encephalopathy can be attributed to hypoxic-
ischemic brain injury is often unclear.
Some investigators require stringent criteria
for using the term neonatal encephalopathy,
such as two or more symptoms of
encephalopathy lasting over 24 hours ,while
others require no more than a low five minute
However, the use of Apgar scores alone is
problematic, as Apgar scores may be low due
to maternal analgesia or prematurity, or can
be normal in the presence of acute hypoxia-
Given that the underlying nature of brain injury
causing neurologic impairment in a newborn is
often poorly understood, "neonatal
encephalopathy" has emerged as the
preferred terminology to describe central
nervous system dysfunction in the newborn
period, as it does not imply a specific
The incidence of neonatal encephalopathy
depends on how the syndrome is defined, but
varies between two to nine per 1000 term
As the term “neonatal encephalopathy” has
become increasingly favored, it has been
shown that the diagnosis of "birth asphyxia"
has declined over the past decade
Despite major advances in monitoring
technology and knowledge of fetal and
neonatal pathologies, perinatal asphyxia or,
more appropriately, hypoxic-ischemic
encephalopathy (HIE), remains a serious
condition that causes significant mortality and
Brain hypoxia and ischemia due to systemic
hypoxemia, reduced cerebral blood flow
(CBF), or both are the primary physiological
processes that lead to hypoxic-ischemic
The initial compensatory adjustment to an
asphyxial event is an increase in CBF due to
hypoxia and hypercapnia.
This is accompanied by a redistribution of
cardiac output to essential organs, including
the brain, heart, and adrenal glands.
A blood pressure (BP) increase due to
increased release of epinephrine further
enhances this compensatory response.
Fetal response to asphyxia illustrating the initial redistribution of blood
flow to vital organs. With prolonged asphyxial insult and failure of
compensatory mechanisms, cerebral blood flow falls, leading to ischemic
In adults, CBF is maintained at a constant
level despite a wide range in systemic BP.
This phenomenon is known as the cerebral
autoregulation, which helps maintain cerebral
In human adults, the BP range at which CBF is
maintained is 60-100 mm Hg.
Limited data in the human fetus and the
newborn infant suggest that CBF is stable
over much narrower range of BPs
Some experts have postulated that, in the
healthy term newborn, the BP range at which
the CBF autoregulation is maintained may be
only between 10-20 mm Hg (compared with
the 40 mm Hg range in adults)
In addition, the autoregulatory zone may also
be set at a lower level, about the midpoint of
the normal BP range for the fetus and
However, the precise upper and lower limits of
the BP values above and below which the
CBF autoregulation is lost remain unknown for
the human newborn.
In the fetus and newborn suffering from acute
asphyxia, after the early compensatory
adjustments fail, the CBF can become
pressure-passive, at which time brain
perfusion depends on systemic BP
As BP falls, CBF falls below critical levels, and
the brain injury secondary to diminished blood
supply and a lack of sufficient oxygen occurs.
This leads to intracellular energy failure.
During the early phases of brain injury, brain
temperature drops, and local release of
neurotransmitters, such as gamma-
aminobutyric acid transaminase (GABA),
These changes reduce cerebral oxygen
demand, transiently minimizing the impact of
At the cellular level, neuronal injury in hypoxic-
ischemic encephalopathy is an evolving
The magnitude of the final neuronal damage
depends on duration and severity of the initial
insult combined to the effects of reperfusion
injury, and apoptosis.
At the biochemical level
Excitatory amino acid (EAA) receptor
overactivation plays a critical role in the
pathogenesis of neonatal hypoxia-ischemia.
During cerebral hypoxia-ischemia, the uptake
of glutamate (the major excitatory
neurotransmitter of the mammalian brain) is
This results in high synaptic levels of
glutamate and EAA receptor overactivation,
including N-methyl-D-aspartate (NMDA),
propionate (AMPA), and kainate receptors.
NMDA receptors are permeable to Ca++
, whereas AMPA and kainate receptors are
permeable to Na+
Accumulation of Na+
coupled with the failure of
energy dependent enzymes such as Na+/
-ATPase leads to rapid cytotoxic edema and
necrotic cell death.
Activation of NMDA receptor leads to
accumulation and further
pathologic cascades activation.
EAAs accumulation also contributes to
increasing the pace and extent of programmed
cell death through secondary Ca++
Finally, developing oligo/dendroglia is uniquely
susceptible to hypoxia-ischemia, specifically
excito-toxicity and free radical damage.
This white matter injury may be the basis for
the disruption of long-term learning and
memory abilities in infants with hypoxic-
During the reperfusion period, free radical
production increases due to activation of
enzymes such as cyclooxygenase, xanthine
oxidase, and lipoxygenase.
Free radical damage is further exacerbated in
the neonate because of immature antioxidant
Free radicals can lead to lipid peroxidation as
well as DNA and protein damage and can
Finally, free radicals can combine with nitric
oxide (NO) to form peroxynitrite a highly toxic
This excessive NO production plays an
important role in the pathophysiology of
perinatal hypoxic-ischemic brain injury.
Inflammatory mediators (cytokines and
chemokines) have been implicated in the
pathogenesis of HIE and may represent a final
common pathway of brain injury.
Following the initial phase of energy failure
from the asphyxial injury, cerebral metabolism
may recover following reperfusion, only to
deteriorate in a secondary energy failure
This new phase of neuronal damage, starting
at about 6-24 hours after the initial injury, is
characterized by mitochondrial dysfunction,
and initiation of the apoptotic cascade.
This phase has been called the "delayed
phase of neuronal injury."
The duration of the delayed phase is not
precisely known in the human fetus and
newborn but appears to increase over the first
24-48 hours and then start to resolve
In the human infant, the duration of this phase
is correlated with adverse neurodevelopmental
outcomes at 1 year and 4 years after insult.
Pathophysiology of hypoxic-ischemic brain injury in the developing brain. During the
initial phase of energy failure, glutamate mediated excitotoxicity and Na+/K+ ATPase
failure lead to necrotic cell death. Aftertransient recovery of cerebral energy
metabolism, a secondary phase of apoptotic neuronal death occurs.(ROS = Reactive
In the United States and in most advanced
countries, the incidence of hypoxic-ischemic
encephalopathy is 1-8 cases per 1000 births.
The incidence of HIE is reportedly high in
countries with limited resources; however,
precise figures are not available.
Birth asphyxia is the cause of 23% of all
neonatal deaths worldwide.
In severe hypoxic-ischemic encephalopathy,
the mortality rate is reportedly 25-50%. Most
deaths occur in the first week of life due to
multiple organ failure.
Some infants with severe neurologic
disabilities die in their infancy from aspiration
pneumonia or systemic infections.
80% of infants who survive severe hypoxic-
ischemic encephalopathy develop serious
10-20% develop moderately serious
as many as 10% are healthy.
The 1996 guidelines from the AAP and ACOG for
(HIE) indicate that all of the following must be present
for the designation of perinatal asphyxia severe
enough to result in acute neurological injury:
Profound metabolic or mixed acidemia (pH < 7) in an
umbilical artery blood sample, if obtained
Persistence of an Apgar score of 0-3 for longer than 5
Neonatal neurologic sequelae (eg, seizures, coma,
Multiple organ involvement (eg, kidney, lungs, liver,
Mild hypoxic-ischemic encephalopathy
Muscle tone may be slightly increased and
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.
The neurologic examination findings normalize
by 3-4 days of life.
Moderately severe hypoxic-
The infant is lethargic, with significant
hypotonia and diminished deep tendon
The grasping, Moro, and sucking reflexes may
be sluggish or absent.
Occasional periods of apnea.
Seizures may occur within the first 24 hours of
Full recovery within 1-2 weeks is possible and
is associated with a better long-term outcome.
An initial period of well-being or mild hypoxic-
ischemic encephalopathy may be followed by
sudden deterioration, suggesting ongoing
brain cell dysfunction, injury, and death;
seizure intensity might increase.
Stupor or coma is typical. The infant 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 (eg, sucking, swallowing,
grasping, Moro) are absent.
Disturbances of ocular motion. The pupils may
be dilated, fixed, or poorly reactive to light
Seizures occur early and often and may be
initially resistant to conventional treatments.
The seizures are usually generalized, and
their frequency may increase during the 24-48
hours after onset, correlating with the phase of
As the injury progresses, seizures subside and
the EEG becomes isoelectric or shows a burst
At that time, wakefulness may deteriorate
further, and the fontanelle may bulge,
suggesting increasing cerebral edema.
Irregularities of heart rate and blood pressure
(BP) are common , as is death from
Infants who survive severe
The level of alertness improves by days 4-5 of
Hypotonia and feeding difficulties persist,
requiring tube feeding for weeks to months.
Multiorgan systems involvement is a hallmark
of hypoxic-ischemic encephalopathy.
May present as reduced myocardial
contractility, severe hypotension, passive
cardiac dilatation, and tricuspid regurgitation.
Patients may have severe pulmonary
hypertension requiring assisted ventilation.
Renal failure presents as oliguria, leading to
significant water and electrolyte imbalances.
Elevated liver function test results,
hyperammonemia, and coagulopathy can be
Necrotizing enterocolitis is rare
Disturbances include increased nucleated
RBCs, neutropenia or neutrophilia,
thrombocytopenia, and coagulopathy.
Lack of reflex activity mediated by the cranial
nerves can indicate brainstem dysfunction.
Neurologic examination may be difficult in the
small premature infant, but weakness of the
lower extremities sometimes reflects the
neuropathologic substrate of periventricular
The pupil starts reacting to light around 30
weeks, but the light reflex is not consistently
assessable until the gestational age of 32-35
weeks. Pupillary reflexes are reliably present
Patients with mild HIE often have mydriasis.
Progression of the disease may produce
miosis responsive to light, and in severe cases
(stage 3 of Sarnat classification), the pupils
are small or midpositioned and poorly reactive
to light, reflecting sympathetic or
The lack of pupillary, eye movement, corneal,
gag, and cough reflexes may reflect damage
to the brainstem, where the cranial-nerve
nuclei are located.
Decreased respiratory drive or apnea can be
from lesions of the respiratory center or
medullary reticular formation.
Ventilatory disturbances in HIE may manifest
as periodic breathing apnea or just decreased
Begin the motor examination of an infant with
suspected HIE by qualitatively and
quantitatively observing his posture and
Specific patterns of motor weakness indicate
cerebral injury patterns
Se iz ure s
HIE is often reported to be the most frequent
cause of neonatal seizures
They usually occur 12-24 hours after birth and
are difficult to control with anticonvulsants.
Tonic, unilateral, or focal seizures consistently
have an EEG signature.
Subtle seizures may be a part of the HIE
Sarnat Staging System
The staging system proposed by Sarnat in
1976 is often useful in classifying the degree
Stages I, II, and III correlate with the
descriptions of mild, moderate, and severe
Badawi et al investigated risk factors of neonatal
encephalopathy in the Western Australian case
Of the 164 infants with moderate-to-severe
neonatal encephalopathy, preconceptual and
antepartum risk factors were identified in 69% of
24% of infants had a combination of antepartum
and intrapartum risk factors,
whereas only 5% of infants had only intrapartum
In this study, 5% had no identifiable risk factors.
There are nor specific tests to confirm or
exclude a diagnosis of hypoxic-ischemic
encephalopathy (HIE) because the diagnosis
is made based on the history, physical and
neurological examinations, and laboratory
As always, the results of the tests should be
interpreted in conjunction with the clinical
history and the findings from physical
Serum electrolyte levels
In severe cases, daily assessment of serum
electrolytes are valuable until the infant's
Markedly low serum sodium, potassium, and
chloride levels in the presence of reduced
urine flow and excessive weight gain may
indicate acute tubular damage or syndrome of
inappropriate antidiuretic hormone (SIADH)
secretion, particularly during the initial 2-3
days of life.
Renal function studies
Serum creatinine levels, creatinine clearance,
and BUN levels suffice in most cases.
Cardiac and liverenzymes
These values are an adjunct to assess the
degree of hypoxic-ischemic injury to these
Coagulation system evaluation
This includes prothrombin time, partial
thromboplastin time, and fibrinogen levels.
Blood gas monitoring is used to assess acid-
base status and to avoid hyperoxia and
hypoxia as well as hypercapnia and
Following initial resuscitation and stabilization,
treatment of (HIE) is largely supportive and
should focus on adequate ventilation and
careful fluid management,
avoidance of hypoglycemia and
treatment of seizures. Intervention strategies
aim to avoid any further brain injury in these
Supportive Care in Patients with
Most infants with severe hypoxic-ischemic
encephalopathy need ventilatory support
during first days of life.
Hypocapnia in particular may lead to severe
brain hypoperfusion and cellular alkalosis and
has been associated with worse
Of note, recent evidence indicates that
increased FiO2 in the first 6 hours of life is a
significant risk factor for adverse outcomes
Infants with hypoxic-ischemic encephalopathy
are also at risk for pulmonary hypertension
and should be monitored.
Perfusion and Blood Pressure
Studies indicate that a mean blood pressure
(BP) above 35-40 mm Hg is necessary to
avoid decreased cerebral perfusion.
Hypotension is common in infants with severe
HIE 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
Fluid and Electrolytes
Because of the concern for acute tubular
necrosis (ATN) and syndrome of inappropriate
antidiuretic hormone (SIADH) secretion, fluid
restriction is typically recommended for these
infants until renal function and urine output
can be evaluated.
However, fluid and electrolyte management
must be individualized on the basis of clinical
course, changes in weight, urine output, and
the results of serum electrolyte and renal
The role of prophylactic theophylline, given
early after birth, in reducing renal dysfunction
after HIE has been evaluated in 3 small
randomized controlled trials
A single dose of theophylline (5-8 mg/kg)
given within 1 hour of birth resulted in (1)
decreased severe renal dysfunction (2)
increased creatine clearance; (3) increased
glomerular filtration rate (GFR); and (4)
decreased b2 microglobulin excretion.
Fluid and glucose homeostasis should be
Avoid hypoglycemia and hyperglycemia
because both may accentuate brain damage
Hyperthermia management :
Hyperthermia has been shown to be
associated with increased risk of adverse
outcomes in neonates with moderate-to-
Treatment of Seizures
Hypoxic-ischemic encephalopathy is the most
common cause of seizures in the neonatal
Seizures are generally self-limited to the first
days of life
Current therapies include phenobarbital,
phenytoin, and benzodiazepines
Extensive experimental data suggest that mild
hypothermia (3-4°C below baseline
temperature) applied within a few hours (no
later than 6 h) of injury is neuroprotective
The neuroprotective mechanisms are not
Possible mechanisms include
(1) reduced metabolic rate and energy
(2) decreased excitatory transmitter release;
(3) reduced alterations in ion flux;
(4) reduced apoptosis due to HIE; and
(5) reduced vascular permeability, edema, and
disruptions of blood-brain barrier functions
The clinical efficacy of therapeutic
hypothermia in neonates with moderate-to-
severe hypoxic-ischemic encephalopathy has
been evaluated in 7 randomized controlled
Evidence of acute event around the time of
birth - Apgar score of 5 or less at 10 minutes
Evidence of moderate to severe
encephalopathy at birth - Clinically determined
at least 2 of the following:
lethargy, stupor, or coma;
abnormal tone or posture;
abnormal reflexes [suck, grasp, Moro, gag,
decreased or absent spontaneous activity;
autonomic dysfunction [including bradycardia,
abnormal pupils, apneas];
and clinical evidence of seizures, moderately or
severely abnormal amplitude (aEEG)
the results of the trials
No difference in composite outcome of death
or severe disability were noted between the
However, the study found that moderate
hypothermia for 72 hours improved neurologic
outcomes in survivors.
Surviving infants who were cooled were more
likely to be free of neurologic abnormalities
These clinical studies have been reassuring
regarding safety and applicability of
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 HIE
hypothermia and its side effects
include coagulation defects,
worsening of metabolic acidosis, and
abnormalities of cardiac rhythm, especially
What is the optimal timing of
initiation of hypothermia therapy?
Cooling must begin early, within 6 hours of
injury. However (the earlier the better )
Simplified method using widely available
icepacks is an effective way to provide
hypothermia therapy in referring centers while
awaiting transfer to a tertiary NICU
On the other hand, a favorable outcome may
be possible if the cooling begins beyond 6
hours after injury.
A current National Institute of Child Health
and Human Development (NICHD) study is
evaluating the efficacy of delayed hypothermia
therapy for infants presenting at referral
centers beyond 6 hours of life or with evolving
What is the optimal duration of
The greater the severity of the initial injury, the
longer the duration of hypothermia needed for
The optimal duration of brain cooling in the
human newborn has not been established
What is the best method?
Two methods have been used in clinical trials:
selective head cooling and whole body
selective head cooling
In selective head cooling, a cap (CoolCap)
with channels for circulating cold water is
placed over the infant's head, and a pumping
device facilitates continuous circulation of cold
Rectal temperature is then maintained at 34-
35°C for 72 hour
whole body hypothermia
In whole body hypothermia, the infant is
placed on a commercially available cooling
blanket, through which circulating cold water
flows, so that the desired level of hypothermia
is reached quickly and maintained for 72
What is the optimal rewarming
Rewarming is a critical period.
In clinical trials, rewarming was carried out
gradually, over 6-8 hours.
Does hypothermia therapy result in
Several meta-analysis have been conducted
and indicate that therapeutic hypothermia is
beneficial to term newborns with hypoxic-
In a Cochrane review, Jacobs et al found that
therapeutic hypothermia results in significant
reduction in the following:
Combined outcome of mortality or major
neurodevelopmental disability at age 18
Neurodevelopmental disability in survivors
They also found a significant increase in
thrombocytopenia, although it was not
Benign sinus bradycardia
Hypothermia therapy should be conducted
under strict protocols and reserved to regional
referral centers offering comprehensive
multidisciplinary care and planning to conduct
long-term neurodevelopmental follow-up.
Summary of potential neuroprotective strategies
Promising avenues include the
Prophylactic barbiturates: high-dose
phenobarbital (40 mg/kg) was given over 1
hour to infants with severe hypoxic-ischemic
Treated infants had fewer seizures
Treated infants also had fewer neurological
deficits at age 3 years
Erythropoietin: In a recent study, low-dose
erythropoietin (300-500 U/kg) administered for
2 weeks starting in the first 48 hours of life
decreased the incidence of death or moderate
and severe disability at age 18 months
Subgroup analysis indicated that only infants
with moderate disability benefited from this
Allopurinol: Slight improvements in survival
and cerebral blood flow (CBF) were noted in a
small group of infants tested with this free-
radical scavenger in one clinical trial.
Excitatory amino acid (EAA) antagonists: (MK-
801, an EAA antagonist), has shown
promising results in experimental animals and
in a limited number of adult trials.
However, this drug has serious cardiovascular
Providing standard intensive care support,
correcting metabolic acidosis, close monitoring
of the fluid status, and seizure control are the
main elements of treatment in patients with
Anticonvulsants are the only specific drugs
used often in this condition.
Close physical therapy and developmental
evaluations are needed prior to discharge in
patients with (HIE).
Ferriero DM. Neonatal brain injury. NEng lJ Me d. Nov 4 2004;351(19):1985-95. [Medline].
Perlman JM. Brain injury in the term infant. Se m in Pe rinato l. Dec 2004;28(6):415-24. [Medline].
Grow J, Barks JD. Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current
concepts.Clin Pe rinato l. Dec 2002;29(4):585-602, v. [Medline].
Srinivasakumar P, Zempel J, Wallendorf M, Lawrence R, Inder T, Mathur A. Therapeutic
hypothermia in neonatal hypoxic ischemic encephalopathy: electrographic seizures and
magnetic resonance imaging evidence of injury. JPe diatr. Aug 2013;163(2):465-70. [Medline].
Shankaran S. The postnatal management of the asphyxiated term infant. Clin Pe rinato l. Dec
Stola A, Perlman J. Post-resuscitation strategies to avoid ongoing injury following intrapartum
hypoxia-ischemia. Se m in Fe talNe o natalMe d. Dec 2008;13(6):424-31. [Medline].
Laptook A, Tyson J, Shankaran S, et al. Elevated temperature after hypoxic-ischemic
encephalopathy: risk factor for adverse outcomes. Pe diatrics . Sep 2008;122(3):491-
9. [Medline]. [Full Text].
[Guideline] American Academy of Pediatrics. Relation between perinatal factors and neurological
outcome. In: Guidelines for Perinatal Care. 3rd ed. Elk Grove Village, Ill: American Academy of
[Guideline] Committee on fetus and newborn, American Academy of Pediatrics and Committee
on obstetric practice, American College of Obstetrics and Gynecology. Use and abuse of the
APGAR score.Pe diatr. 1996;98:141-142. [Medline].
Papile LA, Rudolph AM, Heymann MA. Autoregulation of cerebral blood flow in the preterm fetal lamb.Pe dia tr
Re s. Feb 1985;19(2):159-61. [Medline].
Rosenkrantz TS, Diana D, Munson J. Regulation of cerebral blood flow velocity in nonasphyxiated, very low birth
weight infants with hyaline membrane disease. JPe rinato l. 1988;8(4):303-8. [Medline].
Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physio lRe v. Jan
Roth SC, Baudin J, Cady E, Johal K, Townsend JP, Wyatt JS. Relation of deranged neonatal cerebral oxidative
metabolism with neurodevelopmental outcome and head circumference at 4 years. De v Me d Child Ne uro l. Nov
Berger R, Garnier Y. Pathophysiology of perinatal brain damage. Brain Re s Brain Re s Re v. Aug 1999;30(2):107-
Rivkin MJ. Hypoxic-ischemic brain injury in the term newborn. Neuropathology, clinical aspects, and
neuroimaging. Clin Pe rinato l. Sep 1997;24(3):607-25. [Medline].
Vannucci RC. Mechanisms of perinatal hypoxic-ischemic brain damage. Se m in Pe rinato l. Oct 1993;17(5):330-
Vannucci RC, Yager JY, Vannucci SJ. Cerebral glucose and energy utilization during the evolution of hypoxic-
ischemic brain damage in the immature rat. JCe re b Blo o d Flo w Me tab. Mar 1994;14(2):279-88.[Medline].
de Haan HH, Hasaart TH. Neuronal death after perinatal asphyxia. Eur JO bste t Gyne co lRe pro d Bio l. Aug
McLean C, Ferriero D. Mechanisms of hypoxic-ischemic injury in the term infant. Se m in Pe rinato l. Dec
Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in children. Lance t. Mar
26-Apr 1 2005;365(9465):1147-
A male , post term (42)W , NVD, AGA , BW
3.625, admitted to our NICU at 12:15 am with
a diagnosis of HIE.
The mother is a 34yr old multipara G3 P2
A1,low socioeonomic status and suferred from
raised blood pressure and UTI during the last
trimester for which she received oral therapy .
Iron deficieny anaemia started during 2nd
trimester and 3rd
for which she received oral
Spontaneous vaginal delivery , spont. Rupture
of memb.,clear amnion , vertex presentation ,
fetal monitoring : absent +ve data.
APGAR score 1st
min is 1 and immediat
resuscitation started in the delivery room ,
drying ,warming , positioning and AMBU bag
5 min and 10 min apgar was 5 , intubation
and transfere to NICU
Whole body cooling was started at 12:30 am
(within 15 min of birth)
Monitoring of pulse, temp, bl press and ECG
cardiac monitor and other aspect of incubator
care were started prompetly
IV fluid , broad spectrum antibiotic and
complete panil of initial investigations including
CBC , electrolyte , pt, ptt, liver enz , BUN and
creatinin together with CK and LDH
COOLING for 72hr
On D 2 : prolonged PT 50 sec and PTT 2 min
for which plasma trnsfusion was given
Erythropoietin inj. are Started
Convulsion occured , generalized colonic ,
phenobarbiton inj was given (loading and
D3: convulsions un controlled , add Epanutin
D4: Gradual rewarming was started
D5: significant apnea attacks , PTV was given
then NCPAP ( peep 5 , fio2 30%)
Hypoactive , poor reflexes
BP monitoring showed rising MAP :88 , 72, 90.
D7: nasal pronge ( stop NCPAP)
Full fontanelle: CSF analysis (bloody tap)
Cr U/S : free
MRI : pic. Of cerebral oedema and hypoxic
Reduced total fluid intake with gradual
introduction of NG feeding
D8: ECG monitor multiple premature
ventricular contractions associated with
generalized tonic convulsions treated with IV
D11 : Off o2
D24: stable , transfered to bed , nasogastric
full feeding , stop IV fluid and antibiotics
Convulsions controlled , maintenance
sominaletta and epanutin orally
Educate the parent about NG feeding with
gradual stimulation of oral suckling ( pacifiers)
Follow up at Neonatal outpt clinic and blood
Gradual withdrawal of anti convulsant under
supervision of ped. Neurology clinic
F/u of MRI after 3 month of discharge
Cont. care and support in pediat outpt clinic
Fundus exam and hearing assessment to
exclude potential handicap
Follow up of developmental mile stones