BIRTH ASPHYXIA

Birth asphyxia (perinatal asphyxia) denotes clinic- pathological consequences of perinatal hypoxic-ischemic injury, due to late fetal, obstetrical or immediate postnatal causes.

Diagnostic criteria for birth asphyxia depend on the purpose of diagnosis.

For the purpose of long-term outcome, American Academy of Pediatrics suggests following essential diagnostic criteria for perinatal asphyxia:

• Persistence of Apgar score 3 at 5 minutes,

• Fetal acidosis, i.e. cord blood pH lt;7.0,

• Signs of hypoxic-ischemic encephalopathy, e.g. seizures, coma, hypotonia, etc.

• Signs of multi-organ dysfunction.

Pathophysiology of birth asphyxia is multifactorial and complex—the common denominator being lack of oxygen supply to various fetal tissues during intrauterine, peripartum or immediate postnatal period. Intrauterine hypoxia is perhaps more important than the intrapartum asphyxia in causation of hypoxic-ischemic injury.

Immediate response to hypoxia in fetus or newborns is similar to that seen in older children, i.e. bradycardia and hypertension (diving-seal reflex), followed by a series of compensatory or protective events as follows:

a. Re-distribution of blood flow from less vital to vital organs, e.g. brain, heart and adrenals. Intra-cerebrally

HIE: Hypoxic-ischemic encephalopathy, IVH/PVH: Intra/peri ventricular hemorrhage, SIADH: Syndrome of inappropriate ADH secretion, RDS: Respiratory distress syndrome

too, blood flow is re-distributed towards brainstem from cerebral cortex.

b. Compensatory autonomic response which is primarily sympathetic in term babies (#8593;HR, BP) and para­sympathetic (#936; HR, BP) in preterms.

c. Compensatory metabolic responses, i.e. switch-over from aerobic to anaerobic metabolism.

However, prolonged hypoxia and consequent acidosis leads to many adverse pathophysiological changes, responsible for multi-organ dysfunction (Table 12.16). Diagnosis of birth asphyxia may be evident even before the delivery with signs of fetal hypoxia, e.g. bradycardia, altered fetal movements, meconium stained liquor, etc.

Postnatally, these cases are either apneic or have inadequate spontaneous breathing with persistently low Apgar score (3), cyanosis or pallor (Asphyxia livida or Asphyxia pallida), bradycardia and poor peripheral perfusion or hypotension.

Neurological damage in asphyxiated newborns varies according to the gestation age, generally presenting as Hypoxic-ischemic encephalopathy (HIE) in term neonates, and Intraventricular-periventricular hemorrhage (IVH/PVH) in preterms, as follows:

Hypoxic-ischemic encephalopathy (HIE): The term HIE refers to various quot;neuro-pathological changes and their clinical consequences in asphyxiated newborns, especially in term or near-term babies”.

Pathogenesis of HIE is complex but main contributory factors include:

• Increased neuronal cell permeability due to hypoxia and acidosis.

• Immature autoregulation of cerebral blood flow, i.e. parallel changes with systemic blood pressure, leading to cortical hemorrhage in hypertensive states or ischemia/infarcts in hypotensive states.

• Secondary necrosis in hemorrhagic/ischemic areas, leading to neuronal loss and gliosis.

• Late development of focal/multicystic leukomalacia, porenchephalic cysts, cortical atrophy and status marmoratus (gliosis with hypermyelination) amongst survivors, with long-term sequelae.

*or Isoelectric

Neuropathological changes in HIE also vary with gestational age, usually limited to watershed area (border-zones between areas supplied by different cerebral vessels) in fullterms, e.g.

Clinical manifestations of HIE may be apparent at birth or develop gradually, depending on the timing and severity of hypoxic insult. Common indicators of HIE include:

• Unresponsiveness to stimulation with sluggish reflexes,

• Hypotonia that may persist or change to hypertonia in a few hours, and

• Seizures, which may be multifocal, recurrent and/ or refractory.

Severity of HIE may be graded according to Sarnat and Sarnat classification (Table 12.17) for prediction of outcome.

Diagnosis of HIE is mainly clinical in a full-term newborn with history of birth asphyxia, supported by:

• Neuroimaging studies, e.g. USG, CT/MRI. MRI is the preferred investigation and early neuroimaging findings include—(a) cortical infarcts, (b) cerebral edema, (c) intraventricular hemorrhage; while later studies may reveal, and (d) cortical atrophy and (e) focal/multicystic leukomalacia and/or porencephalic cysts.

• EEG has a prognostic significance with presence of isoelectric or burst-suppression patterns suggestive of moderate to severe HIE.

• Lumbar puncture is used to exclude meningitis and subarachnoid/intraventricular hemorrhage. Brain­specific creatinine kinase level (CK-BB) in CSF is a useful indicator of the severity of neuronal injury.

Management of HIE is supportive and involves:

• Cardiopulmonary support to ensure adequate ventilation (O₂, assisted ventilation) and perfusion (vasopressors,

volume expanders). A systemic mean arterial blood pressure of 45-50 mm Hg in term babies (35-40 mm in babies weighing 1-2 kg and 30-35 mm in those lt; 1 kg) is advisable.

• Fluid restriction to reduce cerebral edema and manage SIADH, preferably with 60 ml/kg/day of DW 10%.

• Anticonvulsants to prevent seizures and further neurological damage.

• Monitoring and control of other complications, e.g. hypothermia, hypoglycemia, hypocalcemia, dys­electrolytemia and coagulation abnormalities.

• Therapeutic hypothermia to maintain the core tem­perature at 33.5°C during first 48-72 hours of birth, has been reported to reduce the mortality or neurodevelopmental morbidity in HIE, due to decrease in release of neurotoxic mediators, e.g. glutamate, free radicals, nitric oxide, lactate, etc. Complications include thrombocytopenia, bradycardia, subcutaneous fat necrosis and overcooling with cold-injury syndrome.

While emerging as a preferred intervention for HIE in developed countries, efficacy and safety of induced hypothermia has not been established in Indian settings and NNF recommends that it should be used only in a tertiary care setting under supervision by a trained team and only in selected group of newborns.

Efficacy of newer therapeutic modalities, e.g. free radical scavengers/removers, e.g. allopurinol or vitamin E; cerebral flow stabilizing agents, e.g. phenobarbital or calcium channel blockers, etc. is still in experimental stage.

Outcome depends on the severity of HIE, gestational age and co-existing complications. While most cases with Grade I HIE recover fully, grade II and III disease has progressively higher mortality (~ 5% and ~75%) and late neurological sequelae (~20% and ~100%).

Important neurological sequelae are—(a) cognitive deficits or mental retardation, (b) motor deficits, e.g. cerebral palsy, (c) epilepsy, (d) visual or hearing loss, and (e) hydrocephalus.

Apart from clinical staging, other poor prognostic indicators include—(a) HIE in a preterm baby, (b) low Apgar score or absence of spontaneous respiration at 20 minutes, (c) persistence of abnormal neurological signs at 2 weeks of age, and (d) abnormal EEG or CT scan.

IntraZperiventricular hemorrhage (IVH/PVH) is primarily a neurological complication of birth asphyxia in preterms, with incidence being inversely related to gestational age and birth weight, i.e. 60-70% in babies lt;1000 gm, 10-20% between 1000-1500 gm and rare in newborns gt;1500 gm or 34 weeks.

Pathogenesis: IVH is rarely present at birth and usually develops during first 3 days of life. Subependymal germinal matrix, i.e. lining of the ventricular walls, is susceptible for rupture and bleeding in preterms due to—(a) higher vascularity, (b) poor tissue support to vasculature, and (c) immature autoregulation of cerebral blood flow—a protective mechanism that prevents sudden changes in cerebral perfusion pressure on systemic pressure changes in sick babies. Bleeding in germinal matrix may extend into ventricles (IVH) to cause obstructive hydrocephalus, and/ or outwards into cerebral parenchyma (PVH). PVH or periventricular infarcts due to ischemic/reperfusion injury may later progress to develop as periventricular leukomalacia (PVL). Clinical manifestations depend on the severity of IVH/ PVH and ~25% cases are asymptomatic. Others may present on 2-3rd day, with:

• Early signs, e.g. sluggish/absent Moro reflex, sluggish activity and hypotonia. Progressive pallor or sudden drop in hematocrit is an early indicator of IVH/PVH.

• Recurrent apneic spells, acidosis and shock.

• Feeble or high-pitched shrill cry, seizures, bulging anterior fontanel and progressive coma in severe cases. While mild cases recover in a few days, others may progressively deteriorate or have a waxing and waning course, due to re-bleeds.

Diagnosis may be confirmed and classified (Table 12.18) on USG, which is routinely indicated in all high-risk preterms lt;1500 gm on 3^rd day and 2^nd week of life.

CT/MRI is indicated only in—(a) suspected cases with intra-parenchymal bleed/infarcts, and (b) term infants with more chances of subdural/subarachnoid hemorrhage.

Management includes: (a) supportive measures, e.g. control of seizures, shock and anemia, (b) reduction of intraventricular pressure by repeated lumbar punctures or ventriculostomy, and (c) evacuation of subdural hematoma, if present.

TABLE 12.18: USG criteria for severity of IVH (Volpe's Classification)

Grade USG finding

I Bleeding limited to periventricular area (germinal matrix)

II IVH filling 10-50% of ventricle

III IVH filling gt;50% of ventricle or ventricular dilatation IV* IVH with periventricular hemorrhagic infarct

*not a part of Volpe classification

Prognosis depends on the severity and location of bleed. Apart from early death, complications include- (a) post-hemorrhagic hydrocephalus, and (b) residual sequelae due to PVL/porencephalic cysts, e.g. motor deficit, e.g. cerebral palsy, mental retardation, seizures, etc. Posthemorrhagic hydrocephalus, though develops in 10-15% babies with IVH, often gets arrested after a few days/ weeks and most cases do not require shunting.

12.10.2