1. PerinatalAsphyxia Dr. C.S.N.Vittal

2. Definitions • Anoxia: – Complete lack of oxygen. • Hypoxia: – Decreased availability of oxygen • Hypoxemia: – Decreased arterial concentration of oxygen. • Ischemia: – Insufficient blood flow to cells or organ resulting in interrupted metabolism and death of the cell or organ affected.

3. PerinatalAsphyxia (PA) Def: The Perinatal Asphyxia may be defined as hypoxic insult to the fetus during the first and second stage of labor severe enough to cause metabolic acidosis, neonatal encephalopathy, and multiorgan system dysfunction. AAP & ACOG ( 2004) CriteriaofBirthAsphyxia 1. PersistanceofanApgarscore: 0-3 forlongerthan 5 min 2. Profoundmetabolicormixedacidosis (CordbloodpH < 7.0) 3. Neonatal Encephalopathy (as seizures, hypotoniaorcoma) & 4. E/o. multiorgan systemdysfunction

4. Some Terminology • Neonatal encephalopathy: is clinically defined as a disturbance in neurologic function demonstrated by difficulty in maintaining respirations, hypotonia, altered level of consciousness, depressed or absent primitive reflexes, seizures, and poor feeding. • NE does not imply HIE. NE may represent a metabolic disorder, infection, drug exposure, or neonatal stroke, but it is the preferred terminology to describe a depressed newborn from any cause at the time of birth • Hypoxic-ischemic encephalopathy (HIE) • A term that describes clinical evidence of encephalopathy as defined earlier, with objective data to support a hypoxic-ischemic (HI) mechanism as the underlying cause for the encephalopathy.

5. Criteria to decide acute intrapartum hypoxic event to be considered a cause of cerebral palsy (CP) :- (AAP, AACOG) • Evidence of a metabolic acidosis in fetal umbilical cord arterial blood obtained at delivery (pH <7 and base deficit ≥12 mmol/L). • Early onset of severe or moderate neonatal encephalopathy in infants born at 34 or more weeks of gestation. • CP of the spastic quadriplegic or dyskinetic type. • Exclusion of other identifiable etiologies, such as trauma, coagulation disorders, infectious conditions, or genetic disorders.

6. Criteria that collectively suggest an acute intrapartum hypoxic event • A sentinel hypoxic event occurring immediately before or during labor • A sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the presence of persistent, late, or variable decelerations, usually after a hypoxic sentinel event when the pattern was previously normal • Apgar scores of 0–3 beyond 5 minutes • Onset of multisystem involvement within 72 hours of birth • Early imaging showing evidence of acute non-focal cerebral abnormality

7. Incidence: • 25 per 1000 term live births and 73 per 1000 preterm live births, with 15 and 50% moderate to severe cases, respectively (2001) • Overall incidence of NE attributable to perinatal asphyxia was ~1.6 per 10,000 live births in the absence of preconception or antepartum abnormalities.

8. Causes of Asphyxia • Prenatal • Perinatal • Postnatal

9. Pathophysiology • Primary energy failure. • Cerebral ischemia, which precipitates an immediate drop in cellular high-energy phosphate levels, termed primary energy failure. • Glutamate, an excitatory amino acid, is also released in substantial amounts due to cellular depolarization • N-methyl-d-aspartate (NMDA) receptors are subsequently overstimulated by glutamate and result in increased intracellular calcium and necrotic cell death. • Reperfusion period • Cerebral blood flow is restored with normalization of cellular energy levels within 2–3 hours after the insult • Latent phase • follows and lasts 6–15 hours, during which oxidative metabolism returns to baseline, but secondary inflammation and cellular apoptosis are initiated.

10. Pathophysiology • Secondary energy failure. • Without intervention, the latent phase can progress to characterized by cellular excitotoxicity, oxidative damage, and neuronal death within 3 days. • Neurodevelopmental outcomes have specifically been correlated with the degree of secondary energy failure. • Current neuroprotective therapies are therefore designed to intervene within the latent phase and before the onset of secondary energy failure.

11. Adaptive responses of the fetus or newborn to asphyxia • Impairment of cerebrovascular autoregulation. • Majority of neuronal disintegration • Major circulatory changes during asphyxia (reperfusion phase): • a. Loss of cerebrovascular autoregulation • Increase in cerebral blood flow • In prolonged asphyxia, there is a decrease in cardiac output, hypotension, and a corresponding fall in CBF. • The postasphyxianewborn is in a persistent state of vasoparalysis and cerebral hyperemia. Cerebrovascular hemorrhage may occur on reperfusion of the ischemic areas of the brain.

12. 1. Maternal Factors: • DM • Toxemia • Hypertension • Cardiac disease • Collagen vascular disease • Infections • Iso-immunization • Drug addiction 2. Obstetric Factor: • Placenta Previa • Cord prolapse • PROM • Polyhidramnios • Placenta insufficiency • Chorioamnionitis A. Antepartumconditions

13. Abnormal presentation • Precipitate delivery • Prolonged delivery • Difficult delivery • Post term delivery • Forceps delivery • Vacuum delivery B. Intrapartum Conditions

14. Prematurity • Respiratory distress syndrome • Meconium aspiration syndrome • Sepsis • Pneumonia • Hemolytic disease • Cardiac or pulmonary anomalies C. Fetal or neonatal conditions

15. How does a baby receive O2 before birth ? • O2 diffuse across the placental membrane from the mother’s blood to the baby blood • Only a small fraction of the fetal blood passed through the fetal lungs • Alveoli are filled with fluid • The blood vessels in the fetal lungs are markedly constricted • Most of the blood flow through the ductus arteriosus into the aorta

16. After Birth: • No connection to the placenta • A baby get oxygen from the lung 1. The fluid in the alveoli is absorbed into the lungs tissue and replace by air 2. The umbilical arteries and vein clamped  increases systemic blood pressure 3. O2 ↑ in the alveoli  relaxation of blood vessel in the lungs 4. The ductus arteriosus begin to constrict  more blood flow trough the lungs  O2 ↑ to tissues

17. PATHOPHYSIOLOGY OF ANTEPARTUM ASPHYXIA • When babies become asphyxiated (either in utero or after delivery), they undergo a well defined sequence of events, i.e. primary apnea followed by secondary apnea.

18. PATHOPHYSIOLOGY OF ANTEPARTUM ASPHYXIA • Cardiac output is maintained early, but changes radically • Selective vasocontrictor to gut, kidneys, muscles, skin • Pulmonary blood flow ↓ by hypoxia and acidosis • Respiration center is depressed • Severe stage of asphyxia  O2 ↓to the heart & brain  - myocardial function ↓  O2 ↓↓ to the vital organ - brain injury

19. Effects of perinatal asphyxia • Hypoxic damage to most of infant’s organs, esp Brain • Developmental delay • Intellectual disability • Spasticity • Motor deficit • Cerebral palsy

21. Pathophysiology of PA Acidosis Myocardial depression Ischemia + Hypoxia Reduced COP ↓ Blood flow to brain Hypotension

23. Perinatal Asphyxia • Diving Reflex • LUNG • BOWEL • KIDNEY • SPLEEN • SKIN • MUSCULATURE • BRAIN • MYOCARDIUM • ADRENAL GLAND ↑ HR, ↑ BP, ↑ CVP↑ const. CO and const. BRAIN PERFUSION

24. Perinatal Asphyxia Re-perfusion Asphyxia Ischemia Apoptosish Pro-inflammatory cells h Oxidative radicals h MINUTES - HOURS HOURS - DAYS MINUTES THERAPEUTIC WINDOW

25. Pathophysiology • Significant increases in the IL1β, IL6, and TNFα mRNA and serum levels compared with those in healthy newborns at birth. Additionally, the S100 mRNA and serum levels were significantly increased in the HIE neonates compared with the healthy controls • Severe brain damage stimulates the release of TNF-αand inflammatory molecules, including interleukins and Intracellular Adhesion Molecule 1 (ICAM-1), into systemic circulation. • Certain attacks on the brain are accompanied by increased permeability of the blood brain barrier

26. Pathophysiology • Amoeboid microglia in the brain respond to hypoxia and accumulate in injured tissue.Activation of glial cells caused by hypoxic-ischemic oxygen deprivation results in the release of inflammatory mediators, including IL-6, TNF-α, IL-1α, IL-1β, interferon-γ, NO, glutamate and ROS, leading to oligodendrocyte death, axonal degeneration, disruption of the immature blood brain barrier, and neuronal death • Activation astrocyte support of neurons after a stroke can be achieved by several mechanisms, including the release of glutathione and superoxide dismutase, enhanced extra-synaptic glutamate uptake, and the maintenance of ion gradients, such as potassium gradients

27. Neurological Patterns of hypoxic ischemic encephalopathy • Premature newborns • Selective subcortical neuronal necrosis • Periventriculr leukomalacia • Focal and multifocal ischemic necrosis • Term newborns • Selective cortical neuronal necrosis • Status marmoratus of basal ganglia and thalamus • Parasagittal cerebral atrophy • focal and multifocal ischemic cerebral necrosis

28. APGAR Score Assigned at 1 and 5 minute after birth, If < 7  every 5 minute – 20 minute

29. Newborn Resuscitation

30. Neonatal Resuscitation Equipment 1.Suction Equipment • Bulb Syringe/ mechanical suction and tubing, • suction catheter 5F or 6 F, 10 F or 12 F • 8 F feeding tube and 20 ml syringe meconium aspirator 2. Bag and mask equipment 3. Intubation equipment 4. Medications : • Epinephrine 1/10.000 • Isotonic crystaloid • Dextrose 10 % • Normal saline • Umbilical Vessel catheterization supplies 5. Miscellaneous • Gloves, radiant warmer, linens, stethoscope, oropharyngeal airway

31. Initial Steps Routine care

32. Initial Steps • Provide warm therapy • Position, clear airway (as necessary) • Dry, stimulate, reposition • Give oxygen (as necessary): Free-flow O2 & Tactile stimulation

33. Newborn Resuscitation Algorithm.

34. Meconium Staining if baby is vigorous: - strong respiratory efforts - good muscle tone - heart rate > 100 / minute ...no change in approach

35. If the baby is not vigorous  direct suction of the trachea soon after delivery : • Insert a laryngoscope and use a 12 F or 14 F catheter to clear the mouth & posterior pharynx • Attack the endotracheal tube to a suction source • Apply suction as tube is slowly with drawn • Repeat as necessary until clear

36. POSITIVE PRESSURE VENTILATION Indication: 1. Apnea or gasping breath 2. Heart rate < 100 bpm 3. Persistent central cyanosis despite FI O2 100% Use : 1. Flow inflating bag volume 240 – 750 mL 2. Self inflating bag Rate : 40 – 60 breath per minute Pressure : 30 – 40 am H2O and then ↓ Mask : - Face Mask : - Full term - Pre term - Round - Anatomical shape - With cushioned rim

37. Appropriate PPV is followed by : • Increase of heart rate • Improved in color • Spontaneous breathing

38. Chest Compressions IF HR < 60 BPM DESPITE 30 SECOND OF EFFECTIVE PPV Provided by : - The thumb technique - The two finger technique Place : on the sternum above xyphoid Rate : 90 per minute Ratio chest compression to ventilator 3 : 1 Depth : 1/3 the depth of the chest

39. Endotracheal Intubation Indications : 1. to suction meconium 2. to improve ventilation in bag andmask ventilation in effective 3. To coordinate ventilation and chest compression 4. To administration medication such as epinephrine 5.When prolonged ventilation is needed 6. Administer surfactant 7. When congenital diaphragmatic hernia is suspected.

40. Equipment 1. Endotracheal tube : - uniform type - size : 2,5 – 3,5 mm 2. Laryngoscope - small handle - blade handle no : - 1 = full term - 0 = preterm - 00 = extremelly preterm

41. Medications 1. Epinephrine Indications : HR < 60 bpm after 30 sec of PPV and mother 30 sec of PPV + chest compressions How : - ET - Umbilical vein Doze : 0.1 – 0.3 mL / kg of a 1 : 10.000 sol ( UV ) 0.3 – 1.0 mL / kg of a 1 : 10.000 sol ( ET ) Repeat every 3 – 5 minutes 2. IV normal saline / ringer lactate 10 mL/ kgBB

42. Sequalae of Birth Asphyxia I.Early sequalae: 1. Metabolic a. Metabolic acidosis b. Inappropriate anti diuretic hormone secretion 2. Respiratory a. RDS : increase severity of RDS b. Transient tachypnoea of the new born c. Respiration of meconium antenatally may lead to MAS

43. 3. Cardiac a. myocardial ischemia b. Persistent pulmonary hypertension of the new born c. PDA 4. CNS : hypoxic ischemia encephalopathy (HIE) 5. Renal Impairment : ATN 6. Hematological : DIC 7. Gastrointestinal : NEC II. Late Sequalae Depend on the severity of asphyxia. Clinical severityof HIE is a better predictor of long outcome

44. Discontinuation of Resuscitation Discontinuation of resuscitation of despite all step resuscitation heart beat remain absent after 10 minute  stop resuscitation

45. Hypoxic ischemic encephalopathy (HIE) • Hypoxia • Ischemia • Clinical neurological syndrome • Brain stem and cranial nerve abnormalities • Seizures • Motor abnormalities • Raised ICP

46. Sarnat and Sarnat Classified HIE

47. Levene’s Staging of HIE

48. Thompson Scoring mild-to-severe hypoxic–ischemic encephalopathy (Thompson score ≥7)

49. Multi-organ system dysfunction that maybe caused by neonatal asphyxia • Kidney - Acute tubular necrosis: • oliguria, hematuria, polyuria • Cardiomyopathy: • hypotension • Persistent pulmonary hypertension: • tachypnea, hypoxemia • Hematologic • DIC, platelet dysfunction

50. Multi-organ system dysfunction that maybe caused by neonatal asphyxia • Hepatic necrosis: • ↑ ammonia, jaundice, • ↑ AST/ ALT • GI : NEC: • distention, bloody stool • Adrenal insufficiency: • ↓ glucose, ↓ Na, BP ↓ • Inappropriate secretion of ADH • oliguria, ↓ Na