BIRTH ASPHYXIA AND HYPOXIC- ISCHEMIC

ENCEPHALOPATHY: NURSING ROLE IN EARLY INTERVENTION

PRESENTED BY: IBEKWE CHIDIMMA
E046361

LECTURER IN CHARGE: DR LUCIA OJEWALE

SUBMITTED TO THE FACULTY TY OF NURSING

SCIENCE, UNIVERSITY OF IBADAN.

MAY 2025
DEDICATION:
TABLE OF CONTENTS:
CONTENTS. PAGES
Title Page. i
Dedication. ii
Acknowledgement iii
• Table of Contents CHAPTER ONE: INTRODUCTION
• 1.1 Key Mechanisms of Hypoxic-Ischemic Injury in Neonates 1
• 1.1.1 Phase I: Primary Energy Failure
• 1.1.2. Phase II: Excitotoxicity
• 1.1.3 Phase III: Latent Phase
• 1.1.4 Phase IV: Reperfusion Injury
• 1.1.5 Phase V: Delayed Apoptosis
• 1.2 Clinical Implications
• 1.3 Epidemiology
• 1.4. Risk Factors
• 1.5 Significance of the Article
• 1.6 Operational Definition of Terms
• Chapter Two: Anatomy of Affected Organ – The Neonatal Brain
• 2.0 Introduction 17
• 2.1 Structural Anatomy 18
• 2.2 Vulnerable Neural Structures 20
• 2.3 Pathophysiological Changes in HIE 24
• 2.4 Clinical Presentation and Grading 26
• 2.5 Diagnostic Approaches 28
• 2.6 MRI vs CT Imaging 30
• 2.7 Signs and Symptoms of Birth Asphyxia 33
•
• Chapter Three: Current Medical and Therapeutic Interventions
• 3.0 Introduction 36
• 3.1 Standard Treatments 37
• 3.2 Emerging Therapies 41
• 3.3 Comparative Summary of Therapies 44
• 3.4 Long-Term Outcomes
•
• Chapter Four: Nursing Role in Early Intervention
• 4.1 Nursing Role in Resuscitation
• 4.2 Comprehensive Nursing Monitoring
• 4.3 Family Integration
• 4.4 Integrating Technology
• 4.5 Documentation
• 4.6 Hypothermia Management
• 4.7 Skin Protection and Pressure Injury
• 4.8 Vital Signs and Complication Monitoring
•
• Chapter Five: Summary, Conclusion and Recommendations
• 5.1 Introduction
• 5.2 Summary of Major Findings
• 5.2.1 Pathophysiology and Clinical Presentation
• 5.2.2 Nursing Roles in Acute Management
• 5.2.3 Long-Term Follow-Up and Developmental Support
• 5.2.4 Challenges in Low-Resource Settings
• 5.3 Gaps in Literature
• 5.4 Conclusion
• 5.5 Recommendations
• 5.6 Final Remarks
• 5.7 Suggestions for future research
LIST OF FIGURES:
CONTENT PAGE
Fig 2.1 Prenatal development of the human brain————— 11
Fig 2.2 Schematic representation of HIE phases. ———-16
Fig 2.3 Pathogenesis of hypoxic-ischemic encephalopathy——-17
Fig 2.4 Apgar Scoring Chart ———————— ———-22
1.0 INTRODUCTION:
Birth asphyxia, now more accurately termed perinatal asphyxia,
represents one of the most critical emergencies in neonatal
medicine. This condition occurs when a fetus or newborn
experiences impaired oxygen delivery (hypoxia) and compromised
blood flow (ischemia) before, during, or immediately after birth.
The shift in terminology from "birth" to "perinatal" asphyxia
reflects our modern understanding that oxygen deprivation can
occur at any point during the peripartum period, not just during
delivery. What this simply means is that :
Antepartum factors (e.g., placental insufficiency, maternal
hypotension)
Intrapartum events (e.g., cord compression, prolonged labor)
Postnatal transitions (e.g., failure to establish respiration), can all
contribute to hypoxic ischemic insult that characterizes this
condition (WHO, 2023)
The transition to perinatal asphyxia also aligns with diagnostic criteria requiring
evidence of:
Metabolic acidosis (umbilical cord pH <7.0 or base deficit ≥12 mmol/L)
Neurological dysfunction (altered consciousness, seizures, hypotonia)
Multiorgan involvement (kidney, liver, or myocardial injury) (AAP, 2023)
The progression from perinatal asphyxia to hypoxic-ischemic encephalopathy
(HIE) represents one of the most consequential sequences in neonatal medicine.
When oxygen deprivation is severe enough to compromise cellular viability,
typically defined by umbilical cord pH <7.0 and persistent Apgar scores ≤3 at 10
minutes the stage is set for HIE, a distinct neurological syndrome characterized by
encephalopathy, seizures, and long-term neurodevelopmental impairment (AAP,
2023).
The path from oxygen deprivation to permanent brain damage involves a
precisely timed cascade of cellular events that this paper will explore in depth,
with particular attention to:
The biochemical transitions from hypoxia to neuronal death
Clinical manifestations across the severity spectrum
Neuroprotective strategies where nursing care proves pivotal
1.1 Key mechanisms of hypoxic-ischemic injury in neonates.

The Threshold of Injury: When Asphyxia Crosses Into Encephalopathy

The transition from transient perinatal hypoxia to full-blown hypoxic-ischemic
encephalopathy (HIE) represents one of the most critical distinctions in neonatal
neurology. The neonatal brain exhibits remarkable but finite adaptive capacities
during oxygen deprivation.
This pathophysiological cascade, unfolding over hours to days, explains why some
infants recover completely from birth asphyxia while others develop the
devastating neurological sequelae of hypoxic-ischemic encephalopathy (HIE).
Understanding these mechanisms forms the foundation for timely clinical
intervention and targeted neuroprotection.
The transition from perinatal asphyxia to hypoxic-ischemic encephalopathy (HIE)
represents a critical juncture in neonatal brain injury that is determined by the
complex interplay of ischemic duration, metabolic factors, and individual
susceptibility. This threshold phenomenon explains why some neonates recover
completely from oxygen deprivation while others develop permanent neurological
injury.
The duration and severity of hypoxia-ischemia are primary determinants of
whether the injury remains reversible or progresses to encephalopathy. During
brief hypoxic episodes lasting less than five minutes, the neonatal brain activates
several compensatory mechanisms that often prevent permanent damage. These
include cerebral autoregulation that maintains adequate perfusion through
peripheral vasoconstriction, metabolic suppression reducing cerebral oxygen
demand by 30-40%, and activation of anaerobic glycolysis to sustain limited ATP
production. However, when hypoxia persists beyond approximately ten minutes,
these protective mechanisms become overwhelmed, leading to complete ATP
depletion, failure of cerebral autoregulation, and profound intracellular acidosis
with pH levels falling below 6.5.
A critical factor in this transition is the effectiveness of reperfusion following the
hypoxic insult. Even after systemic oxygenation is restored, many neonates
experience incomplete reperfusion at the microvascular level due to the "no-
reflow" phenomenon. This occurs when swollen endothelial cells, activated
leukocytes, and microthrombi obstruct capillaries, particularly in vulnerable
watershed regions of the brain. Advanced neuroimaging techniques have
demonstrated that approximately 40% of asphyxiated neonates show persistent
hypoperfusion in critical brain areas despite normal systemic oxygenation
parameters.
Individual variability plays a significant role in determining the injury threshold.
Several factors influence an infant's susceptibility to progressing from asphyxia to
encephalopathy, including antenatal glucocorticoid exposure that enhances
ischemic tolerance, the presence of hypoxic preconditioning that upregulates
neuroprotective proteins, and genetic polymorphisms affecting antioxidant
enzymes. Conversely, conditions such as intrauterine growth restriction and
prematurity reduce metabolic reserves and impair autoregulatory capacity,
lowering the threshold for permanent injury.
Clinically, the crossing of this pathophysiological threshold manifests through
distinct neurological changes. The initial period of transient depression gives way
to persistent encephalopathy, often accompanied by the emergence of seizures
typically occurring 6-24 hours post-insult and evolving abnormalities in muscle
tone. Biochemical markers including elevated CSF lactate levels above 4.0 mmol/L
at 12 hours and plasma GFAP levels exceeding 0.3 ng/mL at 24 hours provide
objective evidence of threshold crossing, as does the appearance of a burst-
suppression pattern on EEG.
Understanding this transition has direct therapeutic implications. The recognition
that there is a window of opportunity before secondary energy failure becomes
established has led to the emphasis on initiating hypothermia therapy within six
hours of the insult. Maintenance of adequate mean arterial pressure above 40
mmHg helps overcome microvascular obstruction and improve cerebral perfusion.
Emerging neuroprotective strategies specifically target the microvascular
dysfunction that characterizes the no-reflow phenomenon.
This pathophysiological framework explains the clinical observation that
only about 60% of neonates with severe acidosis (pH <6.8) develop HIE,
while some infants with less severe biochemical markers may show
significant neurological injury. It underscores the importance of
comprehensive assessment incorporating biochemical, physiological, and
neurological parameters to accurately identify infants who have crossed the
threshold into encephalopathy and who may benefit most from targeted
neuroprotective interventions. The concept of an injury threshold rather
than a simple dose-response relationship to hypoxia has fundamentally
shaped our approach to both the prediction and prevention of permanent
neurological injury following perinatal asphyxia.
1.1.1 Phase I: The Initial Insult - Primary Energy Failure

When oxygen supply is interrupted, the neonate's brain, a metabolically

active organ consuming nearly 60% of the body's oxygen is plunged into
crisis. Within minutes, the collapse of oxidative phosphorylation leads
to catastrophic ATP depletion. This energy bankruptcy manifests in the
failure of the sodium-potassium pump, that normally maintain
electrochemical gradients.
As the pumps falter, sodium and water flood into cells, creating the
characteristic cytotoxic edema visible on early MRI scans. Meanwhile,
the desperate switch to anaerobic metabolism becomes inadequate,
generating only 2 ATP molecules per glucose molecule (compared to 38
via aerobic metabolism) while accumulating lactic acid. This acidosis,
once considered merely a marker of injury, is now recognized as an
active contributor to cellular damage, denaturing proteins and
disrupting enzyme function.
 1.1.2 Phase II: The Glutamate Storm - Excitotoxicity
Unleashed
As energy failure progresses, the brain's delicate neurotransmitter balance
collapses. Astrocytes, normally responsible for glutamate reuptake, become
dysfunctional, allowing this excitatory neurotransmitter to accumulate to toxic
levels in synaptic clefts. The resulting overstimulation of NMDA and AMPA
receptors triggers catastrophic calcium influx, a single neuron may admit enough
calcium to raise intracellular concentrations 10,000-fold above baseline.
This calcium tsunami activates a host of destructive enzymes, which includes:
Phospholipases ( which dismantle cell membranes, releasing arachidonic acid),
Proteases (which degrade cytoskeletal proteins),
Endonucleases (which fragment DNA)
Nitric oxide synthase, which generates reactive nitrogen species
The mitochondria, overwhelmed by calcium, undergo permeability transition,
their membranes become sieve-like, leaking cytochrome c and other pro-
apoptotic factors. This marks the transition from potentially reversible injury to
irreversible cell death.
This sequence explains why therapeutic interventions must target early stages of
the cascade to prevent the point-of-no-return in cellular injury.
 1.1.3 Phase III: The Latent Phase
Following successful resuscitation, neonates frequently demonstrate a period
of apparent clinical stabilization lasting approximately 1-6 hours (Gunn et al.,
2023). During this latent phase, key metabolic parameters may normalize
transiently, including pH correction and stabilization of vital signs (Chalak et al.,
2023). This interval represents a critical therapeutic window preceding the
onset of secondary energy failure and reperfusion injury (NIH, 2023).
Therapeutic hypothermia demonstrates maximal efficacy when initiated during
this phase, primarily through two mechanisms: reduction of cerebral metabolic
rate by approximately 5-7% per 1°C cooling (Volpe, 2023) and preservation of
endogenous cellular repair processes (ICN, 2023). Experimental models
indicate this intervention attenuates both apoptotic pathways and
inflammatory cascades when applied within this timeframe (Davidson et al.,
2022).
This period of temporary metabolic stabilization is characterized by partial
recovery of oxidative phosphorylation and transient normalization of cerebral
energy metabolism (Wintermark et al., 2020). However, ongoing cellular
dysfunction persists at the molecular level, including mitochondrial membrane
potential abnormalities and accumulating reactive oxygen species (Ferriero,
2021). The clinical significance of this phase lies in its potential for therapeutic
intervention before the establishment of irreversible cellular injury (ACOG,
2023).
1.1.4 Phase IV: Reperfusion Injury and Oxidative Stress

• The restoration of oxygen following hypoxia paradoxically contributes to

secondary brain injury through oxidative stress pathways (NIH, 2023).
Xanthine oxidase, which is particularly abundant in neonatal endothelial
cells, catalyzes the conversion of accumulated hypoxanthine to uric acid
while generating superoxide radicals (Chalak et al., 2023). These reactive
oxygen species (ROS) induce molecular damage through several
mechanisms: lipid peroxidation of cellular membranes, oxidative
modification of proteins, and direct DNA damage (Volpe, 2023).
• Concurrently, this oxidative stress triggers a robust neuroinflammatory
response (Davidson et al., 2022). Activated microglia release pro-
inflammatory cytokines including TNF-α, IL-1β, and IL-6 (ICN, 2023). The
compromised blood-brain barrier permits neutrophil infiltration, while
complement system activation marks otherwise viable cells for
destruction (Wintermark et al., 2020). Importantly, this inflammatory
cascade persists for several weeks post-injury, contributing to ongoing
neurodegeneration even after resolution of the initial hypoxic insult
(Ferriero, 2021).
1.1.5 Phase V: Delayed Apoptosis

• Days after the initial injury, a wave of programmed cell death sweeps through
vulnerable brain regions. Following the initial hypoxic-ischemic insult, a delayed
wave of programmed cell death emerges days later, predominantly affecting
vulnerable brain regions (Northington et al., 2023). This apoptotic process is
initiated through mitochondrial release of cytochrome c, which activates
caspase-3, the primary effector enzyme of apoptosis (Volpe, 2023). The
penumbral region, marginally perfused tissue surrounding the core injury zone,
is particularly susceptible to this delayed cell death (Chalak et al., 2023).
• The neonatal brain demonstrates distinct regional vulnerability patterns based
on developmental stage:
• In term infants, injury predominantly affects metabolically active grey matter
structures including the basal ganglia, thalamus, and sensorimotor cortex (NIH,
2023). This reflects the high metabolic demand and glutamate receptor density
in these regions (Ferriero, 2021).
• Preterm infants primarily exhibit white matter injury, manifesting as
periventricular leukomalacia (ICN, 2023). This results from the particular
vulnerability of pre-oligodendrocytes to oxidative stress and excitotoxicity (Back
et al., 2022).
• Watershed zones between major arterial territories show heightened
susceptibility due to their tenuous perfusion and limited collateral circulation
(Wintermark et al., 2020).
1.2 Clinical Implications:

• The 6-hour therapeutic window for hypothermia corresponds to the

latent phase preceding secondary energy failure (Gunn et al., 2023).
• Seizure peaks at 24-48 hours reflect maximal excitotoxic and
inflammatory activity during secondary energy failure (Glass et al.,
2021).
• Outcome variability stems from both injury pattern and duration,
with grey matter injury carrying different prognostic implications
than white matter injury (ACOG, 2023).
• Nursing management plays a pivotal role in interrupting this
pathological cascade through:
• Continuous monitoring for autonomic instability and abnormal
movements
• Precise implementation of therapeutic hypothermia protocols
• Timely identification and management of seizure activity
• Careful hemodynamic monitoring to maintain adequate cerebral
perfusion
1.3 EPIDEMIOLOGY

• The World Health Organization (WHO) estimates that approximately 2 million intrapartum-
related neonatal deaths and stillbirths occur annually, with birth asphyxia contributing
significantly to these outcomes, particularly in low- and middle-income countries (WHO,
2023). HIE, resulting from perinatal asphyxia, is responsible for long-term disabilities such as:
• Cerebral palsy
• Epilepsy
• Hearing and visual impairments
• Cognitive deficits
• Globally, birth asphyxia contributes to approximately 23% of the 2.4 million annual neonatal
deaths, with an estimated 1 million survivors developing long-term neurodevelopmental
disabilities (WHO, 2023). The incidence shows marked geographical variation, ranging from
0.5-1.2 cases per 1,000 live births in high-income countries like Sweden to 5-15 cases per
1,000 in low-resource settings (ACOG, 2023). This tenfold difference primarily reflects
disparities in access to quality obstetric and neonatal care, particularly regarding fetal
monitoring during labor and neonatal resuscitation capacity.
• The African continent bears a disproportionate burden, accounting for 38% of global neonatal
deaths from asphyxia despite representing only 17% of the world's births (WHO AFRO, 2023).
Our analysis of regional data demonstrates that sub-Saharan Africa has a neonatal mortality
rate of 27 deaths per 1,000 live births, with birth asphyxia responsible for nearly one-third of
these deaths. The high prevalence correlates strongly with limited healthcare infrastructure,
as evidenced by only 52% of deliveries being attended by skilled birth attendants across the
region, compared to 99% in high-income countries (UNICEF, 2023).
Nigeria presents a particularly concerning case study, contributing 10% of global
neonatal deaths with birth asphyxia as the second leading cause (NHREC, 2023).
National prevalence studies indicate an incidence of 8-12 cases per 1,000 live
births, though with significant regional variation. Northern states report higher
rates (15/1,000) compared to southern regions (6/1,000), reflecting differences in
healthcare access and cultural birth practices (Ogunlesi et al., 2023). Tertiary
hospital data reveals mortality rates of 25-35% among HIE cases, with long-term
neurological sequelae in 40-60% of survivors (BMC Pediatrics, 2023).
In Ibadan, a major referral center in southwest Nigeria, review of hospital records
shows an HIE incidence of 7.5 cases per 1,000 live births (Adekanmbi et al., 2023).
The 18% mortality rate among these cases, while lower than national averages,
still far exceeds rates in resource-rich settings. Two critical factors emerge from
this local data: first, the median 4.2-hour delay in hospital presentation after
delivery significantly impacts outcomes, and second, the limited availability of
therapeutic hypothermia (currently only two facilities in Ibadan offer this
treatment) restricts access to evidence-based care.
1.4 Risk Factors for Birth Asphyxia and Hypoxic-Ischemic
Encephalopathy (HIE)
Birth asphyxia and its neurological consequence, hypoxic-ischemic
encephalopathy (HIE), result from a complex interplay of maternal, fetal, and
delivery-related factors.
Maternal Risk Factors
Maternal health status significantly influences fetal oxygenation and the
likelihood of birth asphyxia. These factors can be categorized into medical
conditions, sociodemographic factors, and pregnancy-related complications.
Medical Conditions
Hypertensive Disorders
1. Preeclampsia/eclampsia is a leading cause of placental insufficiency, reducing
blood flow to the fetus. Studies indicate that preeclampsia increases the risk of
birth asphyxia fourfold due to impaired uteroplacental perfusion (ACOG, 2023).
2. Chronic hypertension exacerbates vascular dysfunction, further
compromising fetal oxygenation (WHO, 2023).
3. Diabetes Mellitus (Gestational and Pregestational): Poorly controlled
diabetes leads to macrosomia (fetal overgrowth), increasing the risk of
shoulder dystocia and traumatic birth asphyxia (NIH, 2023). Diabetic
vasculopathy also contributes to placental dysfunction, reducing oxygen and
nutrient transfer (Lee et al., 2023).
Maternal Anemia
Severe anemia (Hb <7 g/dL) reduces oxygen-carrying capacity, increasing the risk of
fetal hypoxia during labor (UNICEF, 2023). In sub-Saharan Africa, where 55% of
pregnant women are anemic, this is a major contributor to birth asphyxia (WHO AFRO,
2023).
Chronic Illnesses (Cardiac, Respiratory, or Renal Disease): Conditions such as
congenital heart disease or severe asthma impair maternal oxygenation, indirectly
affecting fetal oxygen supply (Ferriero, 2021).
Sociodemographic Factors
1. Low Socioeconomic Status: Associated with poor antenatal care attendance,
malnutrition, and higher rates of infection (UNICEF, 2023). In Nigeria, women in rural
areas are three times more likely to experience birth asphyxia due to limited healthcare
access (NHREC, 2023).
2. Extremes of Maternal Age: Adolescent pregnancies (<18 years): Higher risk of
preterm birth and obstructed labor due to underdeveloped pelvises (WHO, 2023).
Advanced maternal age (>35 years): Increased incidence of hypertension, diabetes, and
placental insufficiency(ACOG, 2023).
3. Substance Use (Tobacco, Alcohol, Drugs): Smoking causes vasoconstriction, reducing
placental blood flow (NIH, 2023). Alcohol and illicit drugs impair fetal brain
development and increase hypoxia risk (Volpe, 2023).
Pregnancy related factors
1. Placental Abruption: Placental abruption is a serious complication where the placenta detaches
from the uterine wall before delivery. This separation disrupts the flow of oxygen and nutrients from
the mother to the fetus. The extent of oxygen deprivation depends on how much of the placenta
detaches and how quickly delivery occurs. If not managed urgently, it can lead to severe birth
asphyxia, stillbirth, or neonatal brain damage.
2. Placenta Previa:In placenta previa, the placenta partially or completely covers the cervix. During
labor, this can cause heavy bleeding and obstruct the baby's passage through the birth canal. Reduced
oxygen supply may occur if delivery is prolonged or if the placenta begins to separate during labor.
Emergency cesarean section is often required to prevent fetal distress and asphyxia (Cunningham et
al., 2022).
3. Uterine Rupture: Uterine rupture is a life-threatening condition where the uterine wall tears,
usually during labor, especially in women with a previous cesarean scar. This rupture can cause
massive bleeding and a sudden drop in oxygen delivery to the fetus. Immediate surgical intervention
is essential to save both mother and baby, as birth asphyxia can occur within minutes.
4. Umbilical Cord Complications: Conditions like cord prolapse (when the cord slips out before the
baby), nuchal cord (cord wrapped around the baby’s neck), or cord compression (due to tight loops
or knots) can severely restrict oxygen flow during labor. These complications often result in variable
decelerations on fetal monitoring and may lead to birth asphyxia if not corrected quickly.
5. Prolonged or Obstructed Labor: Labor that is excessively long or obstructed puts prolonged
pressure on the fetus, leading to reduced oxygenation. As the uterus contracts for extended periods
without effective delivery, oxygen transfer through the placenta can be compromised, raising the risk
of birth asphyxia and subsequent complications like hypoxic-ischemic encephalopathy.
6. Maternal Hypotension or Hypertension: Low maternal blood pressure (hypotension),
often due to anesthesia or hemorrhage, can reduce uteroplacental blood flow. On the
other hand, high blood pressure (as seen in preeclampsia or eclampsia) can impair
placental function. Both scenarios reduce the amount of oxygen reaching the fetus, making
birth asphyxia more likely, especially during the stress of labor.
7. Intrauterine Growth Restriction (IUGR): Babies with IUGR are often affected by placental
insufficiency, which limits their oxygen and nutrient supply throughout pregnancy. These
fetuses are more vulnerable to oxygen deprivation during labor because they already have
lower reserves. As a result, they are at higher risk for birth asphyxia and related
complications.
8. Chorioamnionitis: Chorioamnionitis, an infection of the amniotic sac and fluid, can lead
to inflammation and fever in the mother, increasing the fetal metabolic rate and oxygen
demands. At the same time, the infection may impair placental function. This mismatch
between oxygen demand and supply may lead to fetal distress and birth asphyxia if labor is
not expedited.
9. Multiple Gestation; In pregnancies with twins or more, complications such as twin-to-
twin transfusion syndrome, cord entanglement, or limited intrauterine space can impair
one or more babies’ access to adequate oxygen. Labor in multiple pregnancies is also often
complicated, further increasing the risk of asphyxia.
10. Post-term Pregnancy: After 42 weeks of gestation, the placenta may begin to age and
function less efficiently. This “placental insufficiency” can reduce oxygen delivery to the
fetus, especially during labor when contractions intermittently compress the placenta and
cord. Babies born post-term are therefore at greater risk for birth asphyxia if labor is
prolonged or not carefully monitored.
1.5 Significance of the article

This term paper holds critical importance in neonatal medicine

as it addresses key challenges and advancements in managing
birth asphyxia and HIE, particularly in preterm infants—a
population with unique vulnerabilities. By exploring diagnostic
difficulties, neuropathological variations, and evolving
treatment strategies, this research contributes to evidence-
based clinical decision-making, ultimately enhancing survival
rates and long-term neurodevelopmental outcomes.
Additionally, it underscores the need for tailored therapeutic
approaches across different gestational ages, helping clinicians
optimize care while minimizing risks.
1.6 Operation Definition of Terms