Perinatal asphyxia and hypoxic-ischemic encephalopathy

What is the primary cause of perinatal asphyxia according to the summary?

Compromised placental or pulmonary gas exchange. Summary 1

What are the physiological consequences of persisting impaired blood gas exchange in perinatal asphyxia?

Oxygen deficiency, hypercapnia, and blood acidosis, potentially compromising cell function in various tissues (e.g., heart, muscle, brain). Summary 2

Which organ is most vulnerable to damage in perinatal asphyxia?

The brain. Summary 3

What is a potential neurological consequence of perinatal asphyxia in the brain?

The development of hypoxic-ischemic encephalopathy (HIE). Summary 4

What is the primary acute intervention for eligible patients with perinatal asphyxia to minimize brain damage?

Therapeutic hypothermia over a period of 72 hours. Summary / Tx 5

How can depressed myocardial function exacerbate ischemia in perinatal asphyxia?

It can exacerbate ischemia and cause subsequent short-term complications with end-organ damage in other tissues (e.g., kidneys, lung, liver, GI tract, bone marrow). Summary / Patho 6

What are potential long-term complications of perinatal asphyxia?

Irreversible neurological damage, cerebral palsy, and periventricular leukomalacia. Summary / Compl 7

How is perinatal asphyxia defined?

A condition characterized by fetal oxygen deprivation that occurs in close temporal proximity to birth, potentially leading to impaired cell function and end-organ damage. Definitions 8

What is neonatal encephalopathy defined as?

A syndrome of CNS dysfunction in the early newborn period characterized by altered consciousness/seizures, difficulty initiating/maintaining respiration, poor tone, and/or depressed reflexes. Definitions 9

What is Hypoxic-Ischemic Encephalopathy (HIE) defined as, and how does it relate to neonatal encephalopathy?

HIE is a diffuse disruption of brain function/structure caused by inadequate tissue oxygenation (e.g., due to perinatal asphyxia). It is the most common subtype of neonatal encephalopathy. Definitions 10

What is the approximate global annual number of fetal deaths attributed to perinatal asphyxia?

Approximately 900,000 fetal deaths per year (worldwide). Epidemiology 11

What is the approximate incidence of Hypoxic-Ischemic Encephalopathy (HIE) in live births in the US?

Approximately 1.5 per 1,000 live births in the US. Epidemiology 12

Name two fetal cardiovascular or pulmonary abnormalities that are perinatal risk factors for asphyxia.

Cardiovascular: congenital heart defects. Pulmonary: decreased surfactant (prematurity), aspiration (amniotic fluid, meconium), persistent pulmonary hypertension. Etiology 13

Which period (antepartum, intrapartum, or perinatal) poses the biggest risk for factors leading to perinatal asphyxia?

Antepartum risk factors play the biggest role. Etiology 14

Name two antepartum placental abnormalities or congenital infections that are risk factors for perinatal asphyxia.

Placental: fetal vascular malperfusion, thrombosis. Infections: congenital infections. Etiology 15

List two maternal conditions or substance uses during antepartum period that are risk factors for perinatal asphyxia.

Substance use: alcohol, cocaine, amphetamines. Maternal conditions: diabetes mellitus, preeclampsia, congestive heart failure, abnormal maternal oxygenation (trauma, hypotension, severe anemia). Etiology 16

Name two intrapartum traumatic delivery events or placental perfusion issues that are risk factors for perinatal asphyxia.

Traumatic delivery: shoulder dystocia, emergency C-section, failed vacuum. Placental perfusion: placental abruption, abnormal uterine contractions, uterine rupture. Etiology 17

List two intrapartum maternal oxygenation/hemodynamic issues or umbilical cord problems that risk perinatal asphyxia.

Maternal oxygenation: pulmonary edema in preeclampsia. Maternal hemodynamic: amniotic fluid embolus. Umbilical cord: prolapse, nuchal cord, umbilical cord knot. Etiology 18

What is the initial physiological response to hypoxia in terms of sympathetic activity and circulation in perinatal asphyxia?

Hypoxia leads to increased sympathetic activity, causing circulatory centralization to maintain perfusion of vital organs (brain, adrenals, heart), reducing supply to peripheral organs. Pathophysiology 19

What happens if hypoxia is prolonged in perinatal asphyxia, regarding myocardial function and peripheral organs?

Compromised myocardial cell function and ischemia lead to decreased myocardial contractility and cardiac output, worsening ischemia in peripheral organs. Pathophysiology 20

What is "primary energy failure" in the pathophysiology of brain damage in perinatal asphyxia?

Insufficient oxygen supply to organ tissue leads to brain tissue acidosis (due to CNS susceptibility), osmotic dysregulation in cells, cellular edema, and apoptosis. Pathophysiology 21

What occurs during the "latency period" after primary energy failure in brain damage due to perinatal asphyxia?

Reperfusion and recovery of some brain cells, lasting several hours. Pathophysiology 22

What is "secondary energy failure" (6-48h post-injury) in brain damage due to perinatal asphyxia?

Distribution of toxic neurotransmitters, oxidative stress, and inflammation lead to widening of the affected brain area. Pathophysiology 23

What characterizes the long-term "brain injury" phase (months-years) after perinatal asphyxia?

Persistent inflammation, impaired neurogenesis, reduced axonal growth, leading to reduced neural plasticity, myelin deficits, and brain cell death. Pathophysiology 24

What are the signs of short-term asphyxia (primary apnea)?

Cyanosis (blue asphyxia), decreased heart rate, and peripheral vasoconstriction (maintains blood pressure/circulation). Clinical Features 25

What are the signs of prolonged asphyxia (secondary apnea)?

White asphyxia, decreased blood pressure, severely decreased heart rate, decreased muscle tone, and decreased reflexes. Clinical Features 26

What are the features of MILD neonatal encephalopathy (HIE Stage 1)?

Mental status: hyperalert. Muscle tone: normal or slightly increased. Respiration: normal. Reflexes: weak sucking, diminished DTRs. Seizures: none. Other: temporary behavioral abnormalities (poor feeding, irritability). Clinical Features 27

What are the features of MODERATE neonatal encephalopathy (HIE Stage 2)?

Mental status: lethargic. Muscle tone: hypotonia. Respiration: periodic apnea. Reflexes: weak/absent neonatal, depressed DTRs. Seizures: may occur within 24h (usually generalized). Recovery possible in 1-2 weeks. Clinical Features 28

What are the features of SEVERE neonatal encephalopathy (HIE Stage 3)?

Mental status: comatose/stuporous. Muscle tone: hypotonia, flaccidity. Respiration: irregular. Reflexes: absent neonatal. Seizures: increase after 24-48h. Ocular motor disturbances, pupillary abnormalities. Clinical Features 29

When should neonatal assessment for perinatal asphyxia be performed in newborns with signs of encephalopathy?

Within the first 6 hours of life, as neuroprotective treatment is time-sensitive. Diagnosis 30

What APGAR score at 5 and 10 minutes suggests a hypoxic-ischemic etiology for neonatal encephalopathy?

APGAR score < 5 at 5 minutes and 10 minutes. Diagnosis 31

What fetal umbilical artery pH and base deficit suggest a hypoxic-ischemic etiology for neonatal encephalopathy?

Fetal umbilical artery pH < 7.0 and/or arterial base deficit ≥ 12 mmol/L. Diagnosis 32

What other neonatal signs support a hypoxic-ischemic etiology for neonatal encephalopathy?

Neuroimaging evidence of acute brain injury and/or presence of multisystemic organ failure consistent with HIE. Diagnosis 33

Name two birth-related events that might lead to hypoxic-ischemic complications.

Uterine rupture, severe abruptio placentae, umbilical cord prolapse, severe/prolonged maternal hypoxia/hypotension, maternal cardiovascular collapse, fetal exsanguination. (Any 2) Diagnosis 34

What is the most sensitive imaging tool for detecting hypoxic-ischemic brain injury in neonates?

Cranial MRI. Diagnosis 35

What are MRI patterns consistent with HIE?

Deep nuclear gray matter injury, parasagittal injury of the cerebral cortex, and watershed cortical injury. Diagnosis 36

When is CNS ultrasound used for suspected HIE, and what can it evaluate?

Alternative if MRI unavailable; less sensitive. Evaluates perfusion, morphological changes (hemorrhages, ventricular size, edema, severe white-matter damage). Diagnosis 37

When is echocardiography indicated in suspected HIE, and what might it show?

If myocardial injury is suspected. May show decreased ventricular contractility, valve dysfunction, or heart enlargement. Diagnosis 38

What is the purpose of EEG monitoring in neonates with suspected HIE?

Conducted on first day (continued for ≥24h) to evaluate seizure activity and background electrical activity. Diagnosis 39

What is the current standard of care for neonates with moderate to severe HIE?

Therapeutic hypothermia. Treatment 40

What is the target temperature and duration for therapeutic hypothermia in HIE?

Treatment at 33-35°C for 72 hours. Treatment 41

What is the therapeutic window for initiating therapeutic hypothermia in HIE?

Within the first 6 hours of life. Treatment 42

What are the eligibility criteria for therapeutic hypothermia regarding gestational age and age at initiation?

Gestational age ≥ 36 weeks AND ≤ 6 hours of age. Treatment 43

What are the pH/base deficit criteria for therapeutic hypothermia eligibility?

pH ≤ 7 OR base deficit of ≥ 16 mmol/L. Treatment 44

What additional criteria (APGAR/resuscitation OR encephalopathy) are needed for therapeutic hypothermia eligibility?

EITHER APGAR score at 10 min: ≤ 5 OR Ongoing resuscitation at 10 min OR Clinically moderate or severe encephalopathy. Treatment 45

List three supportive measures in the management of HIE.

Ensure sufficient oxygenation/ventilation, maintain adequate organ perfusion, maintain electrolyte/glucose homeostasis, anticonvulsive treatment. Treatment 46

Why should volume overload be avoided in children with HIE?

Due to the possible subsequent development or worsening of brain edema. Treatment 47

Name three CNS complications of perinatal asphyxia/HIE.

Cerebral palsy (spastic quadriplegia, dyskinetic), periventricular leukomalacia (PVL), epilepsy, specific learning disorders, ADHD, intellectual developmental disorder, hearing/visual impairment. (Any 3) Complications 48

What is a common cardiac complication of perinatal asphyxia/HIE?

Impaired myocardial contractility. Complications 49

What is a common renal complication of perinatal asphyxia/HIE, and what is a potential long-term risk?

Acute renal failure. Increased risk for chronic kidney disease later in life. Complications 50

Name two other organ system complications (besides CNS, cardiac, renal) of perinatal asphyxia/HIE.

Hematopoietic (bone marrow suppression, thrombocytopenia, DIC), Liver (elevated transaminases, injury), GI (necrotizing enterocolitis), Lungs (NRDS, pulmonary hypertension). (Any 2) Complications 51

What is the typical prognosis for mild neonatal encephalopathy?

Usually normal development. Prognosis 52

What is the general prognosis for moderate to severe neonatal encephalopathy?

Long-term neurologic manifestations are common; severe abnormalities on MRI/EEG are associated with poor outcome. Prognosis 53