Perinatal asphyxia

| What is the fundamental definition of perinatal asphyxia?

| An insult to the fetus or newborn involving inseparable hypoxia and ischemia, which both contribute to tissue injury. | Definitions | 1 |

| According to ACOG/AAP, how is perinatal asphyxia defined?

| "Marked impairment of gaseous exchange in the fetus leading to progressive hypoxemia, hypercabia and significant metabolic acidosis if prolonged with umbilical cord artery pH<7.0". | Definitions | 2 |

| According to the WHO, how is perinatal asphyxia defined?

| "Failure to initiate and sustain breathing at birth". | Definitions | 3 |

| What is a functional definition of perinatal asphyxia in terms of its consequences?

| Prolonged hypoxemia and ischemia in the fetus/newborn resulting in multi-organ and multi-system dysfunction. | Definitions | 4 |

| What are the four essential criteria for diagnosing perinatal asphyxia?

| 1. Prolonged metabolic/mixed acidemia (pH < 7.00) on umbilical cord blood. 2. Persistent Apgar score of 0-3 for >5 mins. 3. Neurological dysfunction (seizure, hypotonia, coma, HIE). 4. Multi-organ/system dysfunction. | Diagnosis | 5 |

| How is Hypoxic Ischemic Encephalopathy (HIE) defined?

| An abnormal state of neurobehavior comprising altered level of consciousness, abnormal brainstem and motor function as a result of prolonged hypoxemia and ischemia. | Definitions | 6 |

| What is the rank of term Hypoxic Ischemia (HI) as a cause of global childhood death?

| Term HI is the 3rd leading cause of global childhood death. | Epidemiology | 7 |

| Annually, how many newborns die from perinatal asphyxia and how many develop acute cerebral dysfunction (NE)?

| Each year, 0.7 million affected newborns die, and 1.15 million develop acute cerebral dysfunction (Neonatal Encephalopathy - NE). | Epidemiology | 8 |

| What is the rank of Neonatal Encephalopathy (NE) as a cause of childhood neurodisability?

| Neonatal Encephalopathy is the 2nd commonest cause of childhood neurodisability. | Epidemiology | 9 |

| What is the incidence of perinatal asphyxia in Western countries versus typical developing countries?

| Incidence in Western countries is 1-1.5 per 1000 live births, while in typical developing countries it is 10%. | Epidemiology | 10 |

| What percentage of neonatal deaths worldwide does birth asphyxia account for?

| Birth asphyxia accounts for 23% of neonatal deaths worldwide. | Epidemiology | 11 |

| What are the three main categories of risk factors for perinatal asphyxia?

| 1. Poor maternal oxygenation and/or circulation. 2. Poor placental perfusion. 3. Impaired flow of blood in the umbilical cord. | Etiology | 12 |

| What percentage of perinatal asphyxia cases are due to intrapartum/antepartum versus postpartum causes?

| 90% of cases are due to intrapartum or antepartum causes (placental/cord insufficiency), while 10% are due to postpartum causes (pulmonary, cardiovascular, neurologic insufficiency). | Etiology | 13 |

| List two maternal factors that can cause perinatal asphyxia.

| Chronic hypertension or a pulmonary/cardiac disorder causing hypoxia. | Etiology | 14 |

| List two placental or umbilical cord factors that can cause perinatal asphyxia.

| Placental factors like abruption or infection, or umbilical cord accidents. | Etiology | 15 |

| List two fetal or neonatal factors that can cause perinatal asphyxia.

| Fetal factors (infection, severe anemia, cardiac abnormalities) or neonatal factors (severe congenital heart/pulmonary disease, severe septicemia with shock, neurologic abnormalities). | Etiology | 16 |

| What are the diagnostic criteria for perinatal asphyxia regarding Apgar score and resuscitation need?

| Persistent low Apgar score ≤ 5 for over 10 minutes, or need for resuscitation beyond 10 minutes. | Diagnosis | 17 |

| What neurological manifestations occurring within 12-14 hours are criteria for diagnosing perinatal asphyxia?

| Seizures or coma, hypotonia or hypertonia. | Diagnosis | 18 |

| According to Sarnat staging, what are the features of Stage 1 (Mild) HIE?

| Consciousness: Hyperalert. Muscle Tone: Normal. Stretch Reflexes: Overactive. Seizures: None. Suck: Weak. Heart Rate: Tachycardia. Pupils: Mydriasis. | Clinical Features / Staging | 19 |

| According to Sarnat staging, what are the features of Stage 2 (Moderate) HIE?

| Consciousness: Lethargic/Obtunded. Muscle Tone: Mild hypotonia. Stretch Reflexes: Overactive. Seizures: Common. Suck: Weak or absent. Heart Rate: Bradycardia. Pupils: Miosis. | Clinical Features / Staging | 20 |

| According to Sarnat staging, what are the features of Stage 3 (Severe) HIE?

| Consciousness: Stupor or coma. Muscle Tone: Flaccid. Stretch Reflexes: Decreased or absent. Seizures: Uncommon. Suck: Absent. Heart Rate: Variable. Pupils: Variable. | Clinical Features / Staging | 21 |

| According to Levene's classification, what are the features of Mild HIE?

| Consciousness: Irritable. Tone: Hypotonia. Seizure: No. Sucking/Respiration: Poor Suck. | Clinical Features / Staging | 22 |

| According to Levene's classification, what are the features of Moderate HIE?

| Consciousness: Lethargy. Tone: Marked. Seizure: Yes. Sucking/Respiration: Unable to suck. | Clinical Features / Staging | 23 |

| According to Levene's classification, what are the features of Severe HIE?

| Consciousness: Comatose. Tone: Severe. Seizure: Prolonged. Sucking/Respiration: Unable to sustain spontaneous respiration. | Clinical Features / Staging | 24 |

| What is the initial event in the HIE injury cascade following acute hypoxic ischemia?

| A decrease in O2 and glucose leads to a drop in ATP production. | Pathophysiology | 25 |

| In the HIE injury cascade, what is the consequence of ATP failure?

| Failure of the Na+/K+ pump. | Pathophysiology | 26 |

| In the HIE injury cascade, what happens after failure of the Na+/K+ pump?

| Neuronal depolarization, which causes the synaptic cleft to flood with glutamate. | Pathophysiology | 27 |

| In the HIE injury cascade, what does the flooding of glutamate in the synaptic cleft lead to?

| Activation of NMDA and AMPA receptors, causing a calcium influx into the cell. | Pathophysiology | 28 |

| In the HIE injury cascade, what are the consequences of calcium influx into the cell?

| Activation of NO synthase, neurotoxicity/inflammation, and cell edema. | Pathophysiology | 29 |

| What is the final step in the primary HIE injury cascade?

| Mitochondrial disruption, release of free radicals (O3), and reduction in glutathione. | Pathophysiology | 30 |

| What is the 'Latent Period' following an HIE insult, and how long does it last?

| A period where cell destruction is abating. The duration (2-8 hours) is inversely proportional to the severity of the injury. It is the therapeutic window. | Pathophysiology | 31 |

| What occurs during the 'Secondary Energy Failure' phase (6-24 hrs) after an HIE insult?

| A decrease in cerebral metabolism resulting in cytotoxic edema, seizures, raised cytokine levels, and mitochondrial failure. | Pathophysiology | 32 |

| What is the 'diving reflex' during hypoxia and what is its initial effect?

| Shunting of blood to vital organs (brain, adrenals, heart) and away from lungs, kidney, gut, and skin, resulting in little initial brain/heart injury. | Pathophysiology | 33 |

| If asphyxia continues, what happens to circulation within the brain?

| Shunting occurs within the brain, where the anterior circulation suffers while the posterior circulation is maintained, leading to cerebral cortical lesions. | Pathophysiology | 34 |

| What pattern of brain injury occurs in 'near-total asphyxia' (e.g., cord accidents)?

| Abrupt and severe hypoxia with no time for compensation, resulting in thalamus and brain stem injury, while the cortex is spared. | Pathophysiology | 35 |

| Which organs are most commonly affected by perinatal asphyxia, and their rates of involvement?

| Kidneys (50%), Brain (28%), Heart (25%), Lung (23%), Liver/Bowel/Bone marrow (<5%). | Pathology | 36 |

| What patterns of neuropathological injury are seen in term babies with HIE?

| Selective neuronal necrosis (Spastic CP), Status Marmoratus (Chorea, Athetoid, Dystonia), Parasagittal cerebral injury (Proximal Spastic Quadriparesis), Focal/multifocal ischemic injury (Hemiparesis, seizure). | Pathology | 37 |

| What is the predominant pattern of neuropathological injury in preterm babies with HIE?

| Periventricular leukomalacia. | Pathology | 38 |

| List three pathological effects of free radical (O3) accumulation in perinatal asphyxia.

| DNA strand breakage → membrane damage → cell death; Lipid peroxidation → release of proteases/prostaglandins → tissue damage; Neutrophil accumulation → phagocytosis & PMN plugging → ischemia. (Any 3 paths) | Pathophysiology | 39 |

| What are the five main categories of clinical manifestations of HIE?

| Altered consciousness, tone problems, seizure activity, autonomic disturbances, and abnormalities of peripheral and stem reflexes. | Clinical Features | 40 |

| What are the three main principles for preventing further injury in HIE management?

| 1. Maintain adequate perfusion, oxygenation & ventilation. 2. Correct & maintain normal metabolic & acid-base milieu. 3. Prompt management of complications. | Management | 41 |

| What are the key components of the initial management of an infant with perinatal asphyxia?

| Admit to newborn unit, maintain temperature, check vital signs, check hematocrit/sugar/ABG/electrolytes, place IV line, consider volume expander, give Vit K, perform stomach wash, monitor urine volume. | Management | 42 |

| What are the key elements of the subsequent management of HIE?

| Oxygenation & ventilation, adequate perfusion, normal glucose & calcium, normal hematocrit, and treatment of seizures. | Management | 43 |

| What is the first step in treating seizures in HIE?

| Correction of hypoglycemia, hypocalcemia, and electrolyte imbalances. | Management | 44 |

| What is the therapeutic dose for Phenobarbitone in HIE seizures?

| 20 mg/kg as a loading dose, followed by 5 mg/kg/day for maintenance. | Management | 45 |

| Which benzodiazepine is recommended for HIE seizures, and which should be avoided?

| Lorazepam (0.05-0.1 mg/kg) is recommended; Diazepam is to be avoided. | Management | 46 |

| How is cerebral edema managed in an infant with HIE?

| Avoid fluid overload (due to SIADH, ATN), raise the head 30°, and maintain PaCO2 at 25-30 mmHg in ventilated infants. (Mannitol use is questioned). | Management | 47 |

| What are the principles of perfusion management in HIE?

| Maintain MAP to maintain CBF, maintain CVP (5-8mmHg Term, 3-5mmHg Preterm), avoid fluid/colloid/blood boluses, and replace volume slowly. | Management | 48 |

| What is the main 'recent advance' in supportive care for HIE?

| Therapeutic Hypothermia. | Treatment | 49 |

| Name two potential therapeutic strategies for HIE that involve blockade of free-radical generation.

| Xanthine oxidase inhibitors (Allopurinol, Oxypurinol) or scavenging of oxidants with antioxidant enzymes (SOD, Catalase, Glutathione) or radical scavengers (N-Acetylcysteine, α-Tocopherol). | Treatment | 50 |

| What are the mechanisms of action of Therapeutic Hypothermia (TH) in HIE?

| Reduces cerebral metabolism, attenuates excitatory injury, alleviates oxidative cascade, suppresses inflammation, suppresses apoptosis, and expands the therapeutic window. | Treatment | 51 |

| List four prerequisites for initiating Therapeutic Hypothermia in an infant with HIE.

| Gestation ≥36wks; Apgar ≤5 & resus >10min; Acidosis (pH<7.0); Neuro signs; Age ≤6hrs from birth; Abnormal aEEG; Moderate/severe asphyxia; Ability to provide care; Absence of major congenital abnormalities. (Any 4) | Treatment | 52 |

| What are the principles of performing Therapeutic Hypothermia (TH)?

| Achieve rectal temp of 33-34°C in 3-4hrs; maintain target of 33.5°C for 72hrs; rewarm at 0.5°C/hr until 37°C is attained; monitor closely until 80hrs; continue supportive NICU care. | Treatment | 53 |

| How is the total daily Thompson score interpreted for HIE severity?

| 0-10: Mild HIE; 11-14: Moderate HIE; ≥15: Severe HIE. | Diagnosis / Staging | 54 |

| What factors are associated with a good outcome in perinatal asphyxia?

| Grade I asphyxia, absence of seizures in the first 24 hours, resolution of seizures by day 7, and ability to suck and swallow by one week of age. | Prognosis | 55 |

| What risk of severe disability or death is associated with Grade II and Grade III HIE?

| Grade II HIE: 20-25% risk. Grade III HIE: 75-90% risk. | Prognosis | 56 |

| List three predictors of a poor neurodevelopmental outcome following perinatal asphyxia.

| Failure to establish respiration by 5 min, Apgar ≤3 at 5 min, seizure onset within 12h, refractory convulsion, Stage III HIE, inability to feed by 1 wk, abnormal EEG, abnormal imaging. (Any 3) | Prognosis | 57 |

| According to meta-analysis, what is the risk of death and severe disability for Severe HIE?

| Risk of Death: 61%; Risk of Severe Disability: 72%. | Prognosis | 58 |

| According to meta-analysis, what is the risk of death and severe disability for Moderate HIE?

| Risk of Death: 5.6%; Risk of Severe Disability: 20%. | Prognosis | 59 |