Neonatal encephalopathy | |
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Other names | Hypoxic and ischemic brain injury in the newborn, perinatal asphyxia, neonatal hypoxic and ischemic brain injury |
Specialty | Pediatrics |
Neonatal encephalopathy (NE), previously known as neonatal hypoxic-ischemic encephalopathy (neonatal HIE or NHIE), is defined as a encephalopathy syndrome with signs and symptoms of abnormal neurological function, in the first few days of life in an infant born after 35 weeks of gestation. [1] [2] In this condition there is difficulty initiating and maintaining respirations, a subnormal level of consciousness, and associated depression of tone, reflexes, and possibly seizures. [3] Hypoxia refers to deficiency of oxygen, Ischemia refers to restriction in blood flow to the brain. The result is “encephalopathy” which refers to damaged brain cells. Encephalopathy is a nonspecific response of the brain to injury which may occur via multiple methods, but is commonly caused by birth asphyxia, leading to cerebral hypoxia. [2] [3]
In neonates born at or beyond 35 weeks, neonatal encephalopathy may present itself as the following symptoms: [4] [5]
Cord blood gas analysis can be used to determine if there is perinatal hypoxia/asphyxia, which are potential causes of hypoxic-ischemic encephalopathy or cerebral palsy, and give insight into causes of intrapartum fetal distress. [7] Cord blood gas analysis is indicated for high-risk pregnancies, in cases where C-sections occurred due to fetal compromise, if there were abnormal fetal heart rate patterns, Apgar scores of 3 or lower, intrapartum fever, or multifetal gestation. [8]
Evidence of brain injury related to the hypoxic-ischemic events that cause neonatal encephalopathy can be seen with brain MRIs, CTs, magnetic resonance spectroscopy imaging or ultrasounds. [9] [10] Neonatal encephalopathy may be assessed using Sarnat staging. [11] Brain MRI is usually performed within eight days of life. [12] Features that can be seen on MRI brain are: periventricular leukomalacia, basal ganglia and thalamus lesions, and multicystic encephalopathy. [13] Besides that, diffusion MRI would show low apparent diffusion coefficient (ADC) values in the first seven days of life. This is followed by pseudonormalisation of ADC values (normalisation of ADC values despite having persistent underlying brain injuries) which can persists up to two weeks. [14]
In the past, treatment options were limited to supportive medical therapy. [15] Currently, neonatal encephalopathy is treated using hypothermia therapy. [16] This has been shown to reduce brain damage, reduce future disability, and improve survival. [17] Hypothermia therapy is also sometimes termed hypothermic neural rescue therapy. Clinical trials are taking place to investigate the effectiveness of stem cell-based interventions, which are thought to have the potential to reduce mortality and improve the long-term development of newborn infants with neonatal encephalopathy. [18]
HIE is a major predictor of neurodevelopmental disability in term infants. 25 percent have permanent neurological deficits. [19]
Overall, the relative incidence of neonatal encephalopathy is estimated to be between 2 and 9 per 1000 term births. [6] 40% to 60% of affected infants die by 2 years old or have severe disabilities. [15] In 2013 it was estimated to have resulted in 644,000 deaths down from 874,000 deaths in 1990. [20]
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.
Intrauterine growth restriction (IUGR), or fetal growth restriction, is the poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.
The Apgar score is a quick way for health professionals to evaluate the health of all newborns at 1 and 5 minutes after birth and in response to resuscitation. It was originally developed in 1952 by an anesthesiologist at Columbia University, Virginia Apgar, to address the need for a standardized way to evaluate infants shortly after birth.
Perinatal 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. It remains a serious condition which causes significant mortality and morbidity. It is also the inability to establish and sustain adequate or spontaneous respiration upon delivery of the newborn, an emergency condition that requires adequate and quick resuscitation measures. Perinatal asphyxia is also an oxygen deficit from the 28th week of gestation to the first seven days following delivery. It is also an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs and may be associated with a lack of ventilation. In accordance with WHO, perinatal asphyxia is characterised by: profound metabolic acidosis, with a pH less than 7.20 on umbilical cord arterial blood sample, persistence of an Apgar score of 3 at the 5th minute, clinical neurologic sequelae in the immediate neonatal period, or evidence of multiorgan system dysfunction in the immediate neonatal period. Hypoxic damage can occur to most of the infant's organs, 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.
Cerebral hypoxia is a form of hypoxia, specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.
Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis of white matter near the lateral ventricles. It can affect newborns and fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. The white matter in preterm born children is particularly vulnerable during the third trimester of pregnancy when white matter developing takes place and the myelination process starts around 30 weeks of gestational age.
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, maternal diabetes and maternal smoking. Intrauterine growth restriction may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system. 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, attention deficit hyperactivity disorder, eating disorders and cerebral palsy.
Intraventricular hemorrhage (IVH), also known as intraventricular bleeding, is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through towards the subarachnoid space. It can result from physical trauma or from hemorrhagic stroke.
Targeted temperature management (TTM) previously known as therapeutic hypothermia or protective hypothermia is an active treatment that tries to achieve and maintain a specific body temperature in a person for a specific duration of time in an effort to improve health outcomes during recovery after a period of stopped blood flow to the brain. This is done in an attempt to reduce the risk of tissue injury following lack of blood flow. Periods of poor blood flow may be due to cardiac arrest or the blockage of an artery by a clot as in the case of a stroke.
Mild total body hypothermia, induced by cooling a baby to 33-34°C for three days after birth, is nowadays a standardized treatment after moderate to severe hypoxic ischemic encephalopathy in full-term and near to fullterm neonates. It has recently been proven to be the only medical intervention which reduces brain damage, and improves an infant's chance of survival and reduced disability.
Athetoid cerebral palsy, or dyskinetic cerebral palsy, is a type of cerebral palsy primarily associated with damage, like other forms of CP, to the basal ganglia in the form of lesions that occur during brain development due to bilirubin encephalopathy and hypoxic–ischemic brain injury. Unlike spastic or ataxic cerebral palsies, ADCP is characterized by both hypertonia and hypotonia, due to the affected individual's inability to control muscle tone. Clinical diagnosis of ADCP typically occurs within 18 months of birth and is primarily based upon motor function and neuroimaging techniques. While there are no cures for ADCP, some drug therapies as well as speech, occupational therapy, and physical therapy have shown capacity for treating the symptoms.
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. One treatment with some proven benefits is hypothermia, but may be most beneficial in conjunction with pharmacological agents. 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 hypothermia cap is a therapeutic device used to cool the human scalp. Its most prominent medical applications are in preventing or reducing alopecia in chemotherapy, and for preventing cerebral palsy in babies born with neonatal encephalopathy caused by hypoxic-ischemic encephalopathy (HIE). It can also be used to provide neuroprotection after cardiac arrest, to inhibit stroke paralysis, and as cryotherapy for migraine headaches.
Ulegyria is a diagnosis used to describe a specific type of cortical scarring in the deep regions of the sulcus that leads to distortion of the gyri. Ulegyria is identified by its characteristic "mushroom-shaped" gyri, in which scarring causes shrinkage and atrophy in the deep sulcal regions while the surface gyri are spared. This condition is most often caused by hypoxic-ischemic brain injury in the perinatal period. The effects of ulegyria can range in severity, although it is most commonly associated with cerebral palsy, mental retardation and epilepsy. N.C. Bresler was the first to view ulegyria in 1899 and described this abnormal morphology in the brain as “mushroom-gyri." Although ulegyria was first identified in 1899, there is still limited information known or reported about the condition.
Sarnat staging, Sarnat Classification or the Sarnat Grading Scale is a classification scale for hypoxic-ischaemic encephalopathy of the newborn (HIE), a syndrome caused by a lack of adequate oxygenation around the time of birth which manifests as altered consciousness, altered muscle tone, and seizures. HIE is graded based on the infant's clinical presentation, examination findings, the presence of seizures and the duration of illness. Sarnat staging is used alongside electroencephalogram findings to provide information about the prognosis for the infant. Mild HIE, according to the scale, usually has a normal outcome, whereas in severe HIE the mortality rate is 75%, and 80% of survivors have neurological sequelae.
A neonatal seizure is a seizure in a baby younger than age 4-weeks that is identifiable by an electrical recording of the brain. It is an occurrence of abnormal, paroxysmal, and persistent ictal rhythm with an amplitude of 2 microvolts in the electroencephalogram,. These may be manifested in form of stiffening or jerking of limbs or trunk. Sometimes random eye movements, cycling movements of legs, tonic eyeball movements, and lip-smacking movements may be observed. Alteration in heart rate, blood pressure, respiration, salivation, pupillary dilation, and other associated paroxysmal changes in the autonomic nervous system of infants may be caused due to these seizures. Often these changes are observed along with the observance of other clinical symptoms. A neonatal seizure may or may not be epileptic. Some of them may be provoked. Most neonatal seizures are due to secondary causes. With hypoxic ischemic encephalopathy being the most common cause in full term infants and intraventricular hemorrhage as the most common cause in preterm infants.
Neonatal resuscitation, also known as newborn resuscitation, is an emergency procedure focused on supporting approximately 10% of newborn children who do not readily begin breathing, putting them at risk of irreversible organ injury and death. Many of the infants who require this support to start breathing well on their own after assistance. Through positive airway pressure, and in severe cases chest compressions, medical personnel certified in neonatal resuscitation can often stimulate neonates to begin breathing on their own, with attendant normalization of heart rate.
Perinatal stroke is a disease where an infant has a stroke between the 140th day of the gestation period and the 28th postpartum day, affecting up to 1 in 2300 live births. This disease is further divided into three subgroups, namely neonatal arterial ischemic stroke, neonatal cerebral sinovenous ischemic stroke, and presumed perinatal stroke. Several risk factors contribute to perinatal stroke including birth trauma, placental abruption, infections, and the mother's health.
Anthony David EdwardsMBE is a British Paediatrician and Neuroscientist. He is Professor of Paediatrics and Neonatal Medicine, and the Director of the Centre for the Developing Brain, at King's College London and Consultant Neonatologist at Guy's and St Thomas' NHS Foundation Trust.
Andrew G. L. Whitelaw is a British neonatologist and academic, known for his work on treating conditions affecting newborn babies. He holds the position of Emeritus Professor at Bristol Medical School, associated with Bristol Neuroscience.