ABE is an acute state of elevated bilirubin in the central nervous system. Clinically, it encompasses a wide range of symptoms. These include lethargy, decreased feeding, hypotonia or hypertonia, a high-pitched cry, spasmodic torticollis, opisthotonus, setting sun sign, fever, seizures, and even death. If the bilirubin is not rapidly reduced, ABE quickly progresses to chronic bilirubin encepalopathy.

CBE is a chronic state of severe bilirubin-induced neurological lesions. Reduction of bilirubin in this state will not reverse the sequelae. Clinically, manifestations of CBE include:

1. movement disorders - athetoid cerebral palsy and or dystonia, 60% have severe motor disability(unable to walk).

2. auditory dysfunction - auditory neuropathy (ANSD)

3. oculomotor impairments (nystagmus, strabismus, Impaired upward or downward gaze, and/or cortical visual impairment),

4. dental enamel hypoplasia/dysplasia of the deciduous teeth,

5. Gastroesophageal reflux,

6. impaired digestive function.

Intellectual disability occur in 25% of cases. But they are often look like intellectually disabled because their severe motor handicaps.

Epilepsy occur in 20% of cases.

These impairments are associated with lesions in the basal ganglia, auditory nuclei of the brain stem, and oculomotor nuclei of the brain stem. Cortex and white matter are mildly involved. Cerebellum may be involved.

Neonatal Stroke, similar to a stroke which occurs in adults, is defined as a disturbance to the blood supply of the developing brain in the first 28 days of life. This description includes both ischemic events, which results from a blockage of vessels, and hypoxic events, which results from a lack of oxygen to the brain tissue, as well as some combination of the two. A neonatal stroke occurs in approximately 1 in 4000 births, but is likely much higher due to the lack of noticeable symptoms. One treatment with some proven benefits is hypothermia, but may be most beneficial in conjunction with pharmacological agents. Neonatal strokes may lead to cerebral palsy, learning difficulties, or other disabilities. Well-designed clinical trials for stroke treatment in neonates are lacking, but some current studies involve the transplantation of neural stem cells and umbilical cord stem cells; it is not yet known if this therapy is likely to be successful.

A neonatal stroke is one that occurs in the first 28 days of life, though a late presentation is not uncommon (as contrasted with perinatal stroke, which occurs from 28 weeks gestation through the first 7 days of life). 80% of neonatal strokes are ischemic, and their presentation is varied, making diagnosis very difficult. The most common manifestation of neonatal strokes are seizures, but other manifestations include lethargy, hypotonia, apnoea, and hemiparesis. Seizures can be focal or generalized in nature. Stroke accounts for about 10% of seizures in term neonates.

Details of the mechanism of damage from cerebral hypoxia, along with anoxic depolarization, can be found here: Mechanism of anoxic depolarization in the brain

Hypoxic-anoxic events may affect the fetus at various stages of fetal development, during labor and delivery and in the postnatal period. Problems during pregnancy may include preeclampsia, maternal diabetes with vascular disease, congenital fetal infections, drug/alcohol abuse, severe fetal anemia, cardiac disease, lung malformations, or problems with blood flow to the placenta.

Problems during labor and delivery can include umbilical cord occlusion, torsion or prolapse, rupture of the placenta or uterus, excessive bleeding from the placenta, abnormal fetal position such as the breech position, prolonged late stages of labor, or very low blood pressure in the mother. Problems after delivery can include severe prematurity, severe lung or heart disease, serious infections, trauma to the brain or skull, congenital malformations of the brain or very low blood pressure in the baby and due to suffocation in cases of Münchausen syndrome by proxy.

The severity of a neonatal hypoxic-ischaemic brain injury may be assessed using Sarnat staging, which is based on clinical presentation and EEG findings, and also using MRI.

Patients with intraparenchymal bleeds have symptoms that correspond to the functions controlled by the area of the brain that is damaged by the bleed. Other symptoms include those that indicate a rise in intracranial pressure caused by a large mass putting pressure on the brain.

Intracerebral hemorrhages are often misdiagnosed as subarachnoid hemorrhages due to the similarity in symptoms and signs. A severe headache followed by vomiting is one of the more common symptoms of intracerebral hemorrhage. Another common symptom is a patient can collapse. Some people may experience continuous bleeding from the ear. Some patients may also go into a coma before the bleed is noticed.

White softening is another form of cerebral softening. This type of softening occurs in areas that continue to be poorly perfused, with little to no blood flow. These are known as "pale" or "anemic infarcts" and are areas that contain dead neuronal tissue, which result in a softening of the cerebrum.

Red softening is one of the three types of cerebral softening. As its name suggests, certain regions of cerebral softening result in a red color. This is due to a hemorrhagic infarct, in which blood flow is restored to an area of the brain that was previously restricted by an embolism. This is termed a "red infarct" or also known as red softening.

Upon autopsy of several subjects, Dr. Cornelio Fazio found that the most common areas of this type of softening occurred where there was a hemorrhage of the middle cerebral artery or the superior or deep branches to it. The subjects' softened area was not always near the arteries but where the capillaries perfused the brain tissue. The symptoms were similar to that of a stroke.

The risk of death from an intraparenchymal bleed in traumatic brain injury is especially high when the injury occurs in the brain stem. Intraparenchymal bleeds within the medulla oblongata are almost always fatal, because they cause damage to cranial nerve X, the vagus nerve, which plays an important role in blood circulation and breathing. This kind of hemorrhage can also occur in the cortex or subcortical areas, usually in the frontal or temporal lobes when due to head injury, and sometimes in the cerebellum.

For spontaneous ICH seen on CT scan, the death rate (mortality) is 34–50% by 30 days after the insult, and half of the deaths occur in the first 2 days. Even though the majority of deaths occurs in the first days after ICH, survivors have a long term excess mortality of 27% compared to the general population.

The primary symptom is yellowish discoloration of the white part of the eyes and skin in a newborn baby. Other symptoms may include excess sleepiness or poor feeding.

A bilirubin level more than 34 μmol/l (2 mg/dL) may be visible. For the feet to be affected level generally must be over 255 μmol/l (15 mg/dL).

Perinatal asphyxia, neonatal asphyxia or birth asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Hypoxic damage can occur to most of the infant's organs (heart, lungs, liver, gut, kidneys), but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity.

It results most commonly from a drop in maternal blood pressure or some other substantial interference with blood flow to the infant's brain during delivery. This can occur due to inadequate circulation or perfusion, impaired respiratory effort, or inadequate ventilation. Perinatal asphyxia happens in 2 to 10 per 1000 newborns that are born at term, and more for those that are born prematurely. WHO estimates that 4 million neonatal deaths occur yearly due to birth asphyxia, representing 38% of deaths of children under 5 years of age.

Perinatal asphyxia can be the cause of hypoxic ischemic encephalopathy or intraventricular hemorrhage, especially in preterm births. An infant suffering severe perinatal asphyxia usually has poor color (cyanosis), perfusion, responsiveness, muscle tone, and respiratory effort, as reflected in a low 5 minute Apgar score. Extreme degrees of asphyxia can cause cardiac arrest and death. If resuscitation is successful, the infant is usually transferred to a neonatal intensive care unit.

There has long been a scientific debate over whether newborn infants with asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.

There is considerable controversy over the diagnosis of birth asphyxia due to medicolegal reasons. Because of its lack of precision, the term is eschewed in modern obstetrics.

Coagulopathy is another cardinal feature of ALF. The liver has the central role in the synthesis of almost all coagulation factors and some inhibitors of coagulation and fibrinolysis. Hepatocellular necrosis leads to impaired synthesis of many coagulation factors and their inhibitors. The former produces a prolongation in prothrombin time which is widely used to monitor the severity of hepatic injury. There is significant platelet dysfunction (with both quantitative and qualitative platelet defects). Progressive thrombocytopenia with the loss of larger and more active platelets is almost universal. Thrombocytopenia with or without DIC increases risk of intracerebral bleeding.

In newborns, jaundice tends to develop because of two factors—the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the relatively immature metabolic pathways of the liver, which are unable to conjugate and so excrete bilirubin as quickly as an adult. This causes an accumulation of bilirubin in the blood (hyperbilirubinemia), leading to the symptoms of jaundice.

If the neonatal jaundice does not clear up with simple phototherapy, other causes such as biliary atresia, Progressive familial intrahepatic cholestasis, bile duct paucity, Alagille syndrome, alpha 1-antitrypsin deficiency, and other pediatric liver diseases should be considered. The evaluation for these will include blood work and a variety of diagnostic tests. Prolonged neonatal jaundice is serious and should be followed up promptly.

Severe neonatal jaundice may indicate the presence of other conditions contributing to the elevated bilirubin levels, of which there are a large variety of possibilities (see below). These should be detected or excluded as part of the differential diagnosis to prevent the development of complications. They can be grouped into the following categories:

Symptoms are dependent on the type of TBI (diffuse or focal) and the part of the brain that is affected. Unconsciousness tends to last longer for people with injuries on the left side of the brain than for those with injuries on the right. Symptoms are also dependent on the injury's severity. With mild TBI, the patient may remain conscious or may lose consciousness for a few seconds or minutes. Other symptoms of mild TBI include headache, vomiting, nausea, lack of motor coordination, dizziness, difficulty balancing, lightheadedness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue or lethargy, and changes in sleep patterns. Cognitive and emotional symptoms include behavioral or mood changes, confusion, and trouble with memory, concentration, attention, or thinking. Mild TBI symptoms may also be present in moderate and severe injuries.

A person with a moderate or severe TBI may have a headache that does not go away, repeated vomiting or nausea, convulsions, an inability to awaken, dilation of one or both pupils, slurred speech, aphasia (word-finding difficulties), dysarthria (muscle weakness that causes disordered speech), weakness or numbness in the limbs, loss of coordination, confusion, restlessness, or agitation. Common long-term symptoms of moderate to severe TBI are changes in appropriate social behavior, deficits in social judgment, and cognitive changes, especially problems with sustained attention, processing speed, and executive functioning. Alexithymia, a deficiency in identifying, understanding, processing, and describing emotions occurs in 60.9% of individuals with TBI. Cognitive and social deficits have long-term consequences for the daily lives of people with moderate to severe TBI, but can be improved with appropriate rehabilitation.

When the pressure within the skull (intracranial pressure, abbreviated ICP) rises too high, it can be deadly. Signs of increased ICP include decreasing level of consciousness, paralysis or weakness on one side of the body, and a blown pupil, one that fails to constrict in response to light or is slow to do so. Cushing's triad, a slow heart rate with high blood pressure and respiratory depression is a classic manifestation of significantly raised ICP. Anisocoria, unequal pupil size, is another sign of serious TBI. Abnormal posturing, a characteristic positioning of the limbs caused by severe diffuse injury or high ICP, is an ominous sign.

Small children with moderate to severe TBI may have some of these symptoms but have difficulty communicating them. Other signs seen in young children include persistent crying, inability to be consoled, listlessness, refusal to nurse or eat, and irritability.

In ALF, hepatic encephalopathy leads to cerebral edema, coma, brain herniation, and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle deficit in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV). Patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral oedema and grade IV encephalopathy. The pathogenesis remains unclear, but is likely to be a consequence of several phenomena. There is a buildup of toxic substances like ammonia, mercaptan, benzodiazepines, serotonin and tryptophan in the brain. This affects neurotransmitter level and neuroreceptor activation. Autoregulation of cerebral blood flow is impaired, and is associated with anaerobic glycolysis and oxidative stress. Neuronal cell astrocytes are susceptible to these changes, and they swell up, resulting in increased intracranial pressure. Inflammatory mediators also play important role.

Unfortunately, signs of elevated intracranial pressure, such as papilledema and loss of pupillary reflexes, are not reliable, and occur late in the disease process. CT imaging of the brain is also unhelpful in detecting early cerebral oedema, but is often performed to rule out intra-cerebral bleeding. Invasive intracranial pressure monitoring via subdural route is often recommended; however, the risk of complications must be weighed against the possible benefit (1% fatal haemorrhage). The aim is to maintain intracranial pressures below 25 mm Hg, and cerebral perfusion pressures above 50 mm Hg.

Reperfusion injury or reperfusion insult, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ("" + "perfusion") after a period of ischemia or lack of oxygen (anoxia or hypoxia). The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than (or along with) restoration of normal function.

Birth trauma (BT) refers to damage of the tissues and organs of a newly delivered child, often as a result of physical pressure or trauma during childbirth. The term also encompasses the long term consequences, often of a cognitive nature, of damage to the brain or cranium. Medical study of birth trauma dates to the 16th century, and the morphological consequences of mishandled delivery are described in Renaissance-era medical literature. Birth injury occupies a unique area of concern and study in the medical canon. In ICD-10 "birth trauma" occupied 49 individual codes (P10-Р15).

However, there are often clear distinctions to be made between brain damage caused by birth trauma and that induced by intrauterine asphyxia. It is also crucial to distinguish between "birth trauma" and "birth injury". Birth injuries encompass any systemic damages incurred during delivery (hypoxic, toxic, biochemical, infection factors, etc.), but "birth trauma" focuses largely on mechanical damage. Caput succedaneum, subcutaneous hemorrhages, small subperiostal hemorrhages, hemorrhages along the displacements of cranial bones, intradural bleedings, subcapsular haematomas of liver, are among the more commonly reported birth injuries. Birth trauma, on the other hand, encompasses the enduring side effects of physical birth injuries, including the ensuing compensatory and adaptive mechanisms and the development of pathological processes (pathogenesis) after the damage.

Systems also exist to classify TBI by its pathological features. Lesions can be extra-axial, (occurring within the skull but outside of the brain) or intra-axial (occurring within the brain tissue). Damage from TBI can be focal or diffuse, confined to specific areas or distributed in a more general manner, respectively. However, it is common for both types of injury to exist in a given case.

Diffuse injury manifests with little apparent damage in neuroimaging studies, but lesions can be seen with microscopy techniques post-mortem, and in the early 2000s, researchers discovered that diffusion tensor imaging (DTI), a way of processing MRI images that shows white matter tracts, was an effective tool for displaying the extent of diffuse axonal injury. Types of injuries considered diffuse include edema (swelling) and diffuse axonal injury, which is widespread damage to axons including white matter tracts and projections to the cortex. Types of injuries considered diffuse include concussion and diffuse axonal injury, widespread damage to axons in areas including white matter and the cerebral hemispheres.

Focal injuries often produce symptoms related to the functions of the damaged area. Research shows that the most common areas to have focal lesions in non-penetrating traumatic brain injury are the orbitofrontal cortex (the lower surface of the frontal lobes) and the anterior temporal lobes, areas that are involved in social behavior, emotion regulation, olfaction, and decision-making, hence the common social/emotional and judgment deficits following moderate-severe TBI. Symptoms such as hemiparesis or aphasia can also occur when less commonly affected areas such as motor or language areas are, respectively, damaged.

One type of focal injury, cerebral laceration, occurs when the tissue is cut or torn. Such tearing is common in orbitofrontal cortex in particular, because of bony protrusions on the interior skull ridge above the eyes. In a similar injury, cerebral contusion (bruising of brain tissue), blood is mixed among tissue. In contrast, intracranial hemorrhage involves bleeding that is not mixed with tissue.

Hematomas, also focal lesions, are collections of blood in or around the brain that can result from hemorrhage. Intracerebral hemorrhage, with bleeding in the brain tissue itself, is an intra-axial lesion. Extra-axial lesions include epidural hematoma, subdural hematoma, subarachnoid hemorrhage, and intraventricular hemorrhage. Epidural hematoma involves bleeding into the area between the skull and the dura mater, the outermost of the three membranes surrounding the brain. In subdural hematoma, bleeding occurs between the dura and the arachnoid mater. Subarachnoid hemorrhage involves bleeding into the space between the arachnoid membrane and the pia mater. Intraventricular hemorrhage occurs when there is bleeding in the ventricles.

Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction and maternal smoking. Intrauterine growth restriction (IUGR) may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, ADHD, eating disorders and cerebral palsy.

Neonatal cholestasis defines persisting conjugated hyperbilirubinemia in the newborn with conjugated bilirubin levels exceeding 15% (5.0 mg/dL) of total bilirubin level. The disease is either due to defects in bile excretion from hepatocytes or impaired bile flow.

General presentations in neonates include abdominal pain and general GI upset. Physical examination may show palpable liver and enlarged spleen. Differential diagnosis typically presents with a host of possibilities, many of them not treatable. Histopathology shows dilated bile duct system at all levels and bile duct proliferation in response to back pressure. The incidence has been found to be about 1:2,500 live births.

There are various causes for intrauterine hypoxia (IH). The most preventable cause is maternal smoking. Cigarette smoking by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. Among the negative effects are carbon monoxide induced tissue hypoxia and placental insufficiency which causes a reduction in blood flow from the uterus to the placenta thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a causal effect in the development of pre-eclampsia. While some previous studies have suggested that carbon monoxide from cigarette smoke may have a protective effect against preeclampsia, a recent study conducted by the Genetics of Pre-Eclampsia Consortium (GOPEC) in the United Kingdom found that smokers were five times more likely to develop pre-eclampsia.

Nicotine alone has been shown to be a teratogen which affects the autonomic nervous system, leading to increased susceptibility to hypoxia-induced brain damage.

Maternal anemia in which smoking has also been implicated is another factor associated with IH/BA. Smoking by expectant mothers causes a decrease in maternal nucleated red blood cells (NRBC), thereby reducing the amount of red blood cells available for oxygen transport.

The perinatal brain injury occurring as a result of birth asphyxia, manifesting within 48 hours of birth, is a form of hypoxic ischemic encephalopathy.

Subcutaneous fat necrosis of the newborn (SCFN or SFN) is a rare form of lobular panniculitis occurring in newborns that is usually self-remitting and non-recurring. Proposed causes include perinatal stress, local trauma, hypoxia and hypothermia, though the exact cause is unknown. It has been suggested that the brown fat seen in newborns is more sensitive to hypoxic injury than fat seen in adults, and that such hypoxia, usually in the context of a complicated birth, leads to the fat necrosis. Complications can include hypercalcemia, hyperlipidemia and thrombocytopenia, and can present months after the onset of SCFN symptoms.

Asphyxia or asphyxiation is a condition of severely deficient supply of oxygen to the body that arises from abnormal breathing. An example of asphyxia is choking. Asphyxia causes generalized hypoxia, which affects primarily the tissues and organs. There are many circumstances that can induce asphyxia, all of which are characterized by an inability of an individual to acquire sufficient oxygen through breathing for an extended period of time. Asphyxia can cause coma or death.

In 2015 about 9.8 million cases of unintentional suffocation occurred which resulted in 35,600 deaths. The word asphyxia is from Ancient Greek "without" and , "squeeze" (throb of heart).

While any number of injuries may occur during the birthing process. A number of specific conditions are well described. Brachial plexus palsy occurs in 0.4 to 5.1 infants per 1000 live birth. Head trauma and brain damage during delivery can lead to a number of conditions include: caput succedaneum, cephalohematoma, subgaleal hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, and intraventricular hemorrhage.

The most common fracture during delivery is that of the clavicle (0.5%).