Cerebral ischemia in newborns: symptoms, consequences, treatment

A disturbance of blood circulation in the vascular system of the child's brain immediately after birth, causing a lack of oxygen in the blood (hypoxemia), is defined as cerebral ischemia in newborns. ICD-10 code - P91.0.

Since ischemia, hypoxemia and hypoxia (oxygen starvation) are physiologically interconnected (while hypoxia can develop with normal cerebral blood flow), the critical state of oxygen deficiency for the brain of newborns is considered a clinical syndrome in neurology and is called neonatal hypoxic-ischemic encephalopathy, developing within 12-36 hours after birth.

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Epidemiology

In neonatal neurology and pediatrics, the epidemiology of clinical manifestations of cerebral ischemia in newborns is not recorded separately from hypoxic-ischemic encephalopathy syndrome, therefore, assessment of morbidity is problematic due to the lack of criteria for their differentiation.

The incidence of neonatal encephalopathy associated with decreased cerebral blood flow and cerebral hypoxia is estimated at 2.7-3.3% of cases per thousand live-born children. At the same time, 5% of children with infantile brain pathologies have suffered perinatal stroke (one case is diagnosed per 4.5-5 thousand infants with cerebral hemodynamic pathology).

The incidence of perinatal asphyxia is estimated at one to six cases per thousand full-term newborns and two to ten cases in premature babies. Global estimates vary widely: according to some data, neonatal asphyxia causes 840,000 or 23% of neonatal deaths worldwide each year, while according to WHO data, it causes at least 4 million, which is 38% of all deaths among children under five years of age.

Experts from the American Academy of Pediatrics have concluded that the best estimate of the incidence of neonatal brain pathology is population data: an average of three cases per thousand people. According to some Western neurophysiologists, some consequences of hypoxic-ischemic encephalopathy suffered at birth are observed in 30% of the population of developed countries and more than half of the inhabitants of developing countries.

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Causes of cerebral ischemia in newborns.

The brain requires a constant supply of blood that carries oxygen; in infants, the brain accounts for up to 10% of body weight, has a branched vascular system, and consumes one-fifth of the oxygen supplied by the blood to all tissues of the body. When cerebral perfusion and oxygenation are reduced, brain tissue loses the source of life support for its cells, and the causes of cerebral ischemia in newborns known to date are numerous. These may include:

• maternal hypoxemia due to insufficient ventilation of the lungs in cardiovascular diseases, chronic respiratory failure or pneumonia;
• decreased blood flow to the fetal brain and hypoxemia/hypoxia due to placental disorders including thrombosis, placental abruption and infection;
• prolonged clamping of the umbilical cord during childbirth, leading to severe metabolic acidosis of the umbilical cord blood, a systemic decrease in circulating blood volume (hypovolemia), a drop in blood pressure and impaired cerebral perfusion;
• acute cerebrovascular accident (perinatal or neonatal stroke), which occurs in the fetus from the 20th week of pregnancy, and in the newborn - within four weeks after birth;
• lack of automatic self-regulation of cerebral blood flow in premature infants;
• violation of intrauterine fetal circulation due to narrowing of the pulmonary artery or congenital cardiac anomalies (left-sided hypoplasia of the heart, patent ductus arteriosus, transposition of the great vessels, etc.).

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Risk factors

There are also numerous risk factors for the development of cerebral ischemia in newborns, among which neurologists and obstetricians note:

• first pregnancy at the age of over 35 or under 18;
• long-term infertility therapy;
• insufficient body weight of the newborn (less than 1.5-1.7 kg);
• premature birth (before 37 weeks of pregnancy) or post-term pregnancy (more than 42 weeks);
• spontaneous rupture of membranes;
• too long or too rapid labor;
• malpresentation of the fetus;
• vasa previa, most often observed in in vitro fertilization;
• trauma to the infant's skull during childbirth (as a result of obstetric errors);
• emergency caesarean section;
• heavy bleeding during childbirth;
• the presence of cardiovascular or autoimmune diseases, anemia, diabetes mellitus, functional disorders of the thyroid gland, blood clotting disorders (thrombophilia), antiphospholipid syndrome, infectious and inflammatory diseases of the pelvic organs in the pregnant woman;
• severe arterial hypotension during pregnancy and late gestosis.

Congenital blood pathologies associated with mutations in the genes of prothrombin, platelet coagulation factors V and VIII, plasma homocysteine, as well as DIC syndrome and polycythemia are also recognized as risk factors for cerebral ischemia in infants.

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Pathogenesis

Cerebral ischemia in newborns disrupts the metabolism of brain cells, which leads to irreversible destruction of the structure of nervous tissue and its dysfunction. First of all, the pathogenesis of the development of destructive processes is associated with a rapid drop in the level of adenosine triphosphate (ATP), the main supplier of energy for all biochemical processes.

The balance between the intracellular and extracellular concentrations of ions migrating across their membranes is also important for normal neuronal function. When the brain is deprived of oxygen, the transmembrane gradient of potassium (K+) and sodium (Na+) ions in neurons is disrupted, and the extracellular concentration of K+ increases, leading to progressive anoxidative depolarization. At the same time, the influx of calcium ions (Ca2+) increases, initiating the release of the neurotransmitter glutamate, which acts on the brain's NMDA receptors; their excessive stimulation (excitotoxicity) leads to morphological and structural changes in the brain.

The activity of hydrolytic enzymes, which break down nucleic acids of cells and cause their autolysis, also increases. In this case, the base of nucleic acids, hypoxanthine, is transformed into uric acid, accelerating the formation of free radicals (active forms of oxygen and nitrogen oxide) and other compounds toxic to the brain. The antioxidant protective mechanisms of the brain of newborns are not yet fully developed, and the combination of the listed processes has an extremely negative effect on its cells: neuronal gliosis, atrophy of glial cells and oligodendrocytes of the white matter occur.

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Symptoms of cerebral ischemia in newborns.

Clinical symptoms of cerebral ischemia in newborns and the intensity of their manifestation are determined by its type, severity and localization of neuronal necrosis zones.

Types of ischemia include focal or topographically limited damage to brain tissue, as well as global damage that extends to many cerebrovascular structures.

The first signs of cerebral ischemia at birth can be detected by checking the reflexes of congenital spinal automatism. But the assessment of their deviations from the norm depends on the degree of cerebral perfusion disorder and the physiological maturity of the newborn.

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Stages

Thus, cerebral ischemia of the 1st degree in a newborn (a mild form of hypoxic-ischemic encephalopathy) manifests itself in a full-term infant by a moderate increase in muscle tone and tendon reflexes (grasping, Moro, etc.). Symptoms also include excessive anxiety with frequent movements of the limbs, post-hypoxic myoclonus (twitching of individual muscles against the background of muscle rigidity), problems with attachment to the breast, spontaneous crying, and intermittent sleep.

If the child was born prematurely, then, in addition to a decrease in unconditioned reflexes (motor and sucking), a weakening of the general muscle tone is observed during the first few days after birth. As a rule, these are temporary anomalies, and if the state of the infant's central nervous system stabilizes within a few days, then ischemia practically does not give neurological complications. But everything depends on the endogenous regenerative activity of the developing brain of a particular child, as well as on the production of cerebral neurotrophins and growth factors - epidermal and insulin-like.

Cerebral ischemia of the 2nd degree in a newborn (causing a moderately severe form of hypoxic-ischemic encephalopathy) adds to the list of already mentioned symptoms epileptic seizures; decreased arterial and increased cerebral pressure (an enlargement and noticeable pulsation of the fontanelle is observed); lethargy during feeding and frequent regurgitation; intestinal problems; periods of abnormal heart rhythms and apnea (stopping breathing during sleep); labile cyanosis and the effect of "marbled skin" (due to vegetative-vascular disorders). The acute period lasts for about ten days. In addition, neonatologists note the possibility of complications in the form of hydrocephalus, eye movement disorders - nystagmus, and misalignment of the eyes (strabismus).

If there is grade 3 cerebral ischemia in a newborn, then neonatal reflexes (sucking, swallowing, grasping) are absent, and seizures are frequent and prolonged (within 24-48 hours after birth). Then the seizures decrease, giving way to a progressive decrease in muscle tone, a state of stupor, and an increase in brain tissue edema.

Depending on the location of the main foci of cerebral ischemia, there may be respiratory dysfunction (the infant often requires mechanical respiratory support); changes in heart rate; dilated pupils (poorly responsive to light) and lack of oculomotor conjugation (“doll eyes”).

These manifestations are increasing, indicating the development of severe hypoxic-ischemic encephalopathy, which, due to cardiorespiratory failure, can be fatal.

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Complications and consequences

The development of cerebral ischemia in newborns causes oxygen deficiency-induced damage to its cells and leads to very serious, often irreversible neurological consequences and complications that correlate with the topography of the lesions.

As studies have shown, pyramidal cells of the hippocampus, Purkinje cells in the cerebellum, reticular neurons of the peri-rolandic region of the cerebral cortex and ventrolateral part of the thalamus, cells of the basal ganglia, nerve fibers of the corticospinal tract, nuclei of the midbrain, as well as neurons of the neocortex and brainstem are more susceptible to cerebral ischemia in newborns.

In full-term newborns, the cerebral cortex and deep nuclei are primarily affected; in premature infants, diffuse destruction of white matter cells in the hemispheres is observed, which causes chronic disability in surviving children.

And with global ischemia of the cells of the brain stem (where the centers of regulation of respiration and heart function are concentrated), their total death and almost inevitable death occur.

The negative consequences and complications of perinatal and neonatal cerebral ischemia of the 2-3 degree in young children are manifested by epilepsy, unilateral loss of vision, delayed psychomotor development, motor and cognitive impairments, including cerebral palsy. In many cases, their severity can be fully assessed by the age of three.

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Diagnostics of cerebral ischemia in newborns.

Initial diagnostics of cerebral ischemia in newborns is performed immediately after birth during a standard examination of the child and determination of the so-called neurological status (according to the Apgar scale) – by checking the degree of reflex excitability and the presence of certain congenital reflexes (some of which were mentioned when describing the symptoms of this pathology). Heart rate and blood pressure indicators are necessarily recorded.

Instrumental diagnostics, especially neurovisualization, allows identifying areas of cerebral ischemia. For this purpose, the following are used:

• computed tomography of cerebral vessels (CT angiography);
• magnetic resonance imaging (MRI) of the brain;
• craniocerebral ultrasound examination (ultrasound);
• electroencephalography (EEG);
• echocardiography (ECG).

Laboratory tests include a complete blood count, as well as blood tests for electrolyte levels, prothrombin time and fibrinogen levels, hematocrit, arterial blood gas levels, and a cord or venous blood pH test (to detect acidosis). Urine is also tested for its chemical composition and osmolality.

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Differential diagnosis

To exclude the presence of perinatal meningoencephalitis, brain tumor, tyrosinemia, homocystinuria, congenital Zellweger syndrome, pyruvate metabolism disorder, as well as genetically determined mitochondrial neuropathies, methylmalonic or propionic acidemia in the infant, differential diagnostics are carried out.

Treatment of cerebral ischemia in newborns.

In many cases, in the early stages, treatment of cerebral ischemia in newborns requires cardiopulmonary resuscitation in newborns with artificial ventilation of the lungs and all measures to restore the hemodynamics of the vascular system of the brain, maintain hemostasis, and prevent hyperthermia, hypo and hyperglycemia.

Controlled hypothermia significantly reduces the degree of moderate and severe ischemic damage to brain cells in infants: cooling the body to +33-33.5ºC for 72 hours, followed by gradual temperature increase to physiological norm. This treatment is not used for premature babies born before 35 weeks.

Drug therapy is symptomatic, for example, for tonic-clonic seizures, the most commonly used anticonvulsant drugs are Diphenin (Phenytoin), Trimethin (Trimethadione) - twice a day, 0.05 g (with systematic monitoring of blood composition).

To reduce muscle hypertonicity after three months, the muscle relaxant Tolperisone (Mydocalm) can be administered intramuscularly - 5-10 mg per kilogram of body weight (up to three times a day). The drug can cause side effects in the form of nausea and vomiting, skin rashes and itching, muscle weakness, suffocation and anaphylactic shock.

Improvement of cerebral perfusion is facilitated by intravenous drip administration of Vinpocetine (dosage is calculated based on body weight).

To activate brain functions, it is customary to use neuroprotective drugs and nootropics: Piracetam (Nootropil, Noocephal, Pyrroxil, Dinacel) - 30-50 mg per day. Ceraxon syrup is prescribed 0.5 ml twice a day. It should be borne in mind that this drug is contraindicated in case of muscle hypertonicity, and its side effects include allergic urticaria, decreased blood pressure and heart rhythm disturbances.

When the functions of the central nervous system are suppressed, Glutan (glutamic acid, Acidulin) is used - three times a day, 0.1 g (with blood composition monitoring). And nootropic drugs of hopantenic acid (Pantogam syrup) improve oxygenation of brain tissue and exhibit neuroprotective properties.

Vitamins B6 (pyridoxine hydrochloride) and B12 (cyanocobalamin) are used parenterally with glucose solution.

Physiotherapy treatment

In case of mild cerebral ischemia in a newborn child, physiotherapy treatment is mandatory, in particular therapeutic massage, which helps to reduce muscle hypertonicity. However, in the presence of epileptic syndrome, massage is not used.

Improve the condition of newborns with cerebral ischemia with water treatments in the form of a bath with a decoction of chamomile flowers, peppermint or lemon mint. Herbal treatment - see Sedatives for children

Prevention

Neurologists believe that prevention of neonatal hypoxic-ischemic encephalopathy syndrome in newborns is problematic. Here we can only talk about proper obstetric support of pregnancy and timely detection of risk factors: cardiovascular pathologies in the expectant mother, endocrine disorders, blood clotting problems, etc. It is possible to prevent the effects of anemia, high or low blood pressure or infectious and inflammatory diseases with timely treatment. However, many problems today cannot be solved by available means.

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Forecast

Unfortunately, a favorable prognosis regarding the consequences that cerebral ischemia in newborns leads to is observed only in its mild degree.

Neonatal encephalopathies are a cause of high mortality and long-term neurological pathologies in infants worldwide.

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