Fetal and neonatal hypoxia

Fetal hypoxia is a condition characterized by decreased oxygen levels, causing fetal developmental impairment and increasing the risk of perinatal and infant mortality. [ 1 ] Indeed, fetal hypoxia accounts for 23% of neonatal deaths worldwide. [ 2 ] The most common risk factors causing fetal hypoxia are placental insufficiency, preeclampsia, umbilical cord injury, and maternal factors such as smoking, cardiac, renal, or pulmonary dysfunction. [ 3 ]

Prenatal hypoxia can be divided into three types: preplacental; uteroplacental and postplacental. Preplacental hypoxia affects both the fetus and the mother, unlike postplacental hypoxia, which only causes damage to the fetus. Instead, uteroplacental hypoxia is characterized by alterations in the uteroplacental circulation.

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Epidemiology of fetal hypoxia

The overall incidence of fetal hypoxia varies greatly across European hospitals, ranging from 0.06 to 2.8% ( Giannopoulou et al., 2018 ). Hypoxia and its consequences during pregnancy and childbirth are the leading causes of perinatal morbidity and mortality.

Against the background of a general decrease in perinatal mortality rates, the incidence of cerebral pathology has increased as a consequence of fetal hypoxia, often leading to severe childhood neurological disability.

In premature and newborn children with morphological and functional immaturity, hypoxia develops 10-15 times more often and has a less favorable course and outcome.

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Causes of fetal hypoxia

An extremely large number of complications during pregnancy and childbirth, as well as reasons unrelated to pregnancy, lead to oxygen deficiency in the fetus and newborn.

All causes of antenatal, intranatal and perinatal fetal hypoxia can be conditionally divided into five groups.

1. The first group of causes is associated with pathology of the placenta: abnormal development and attachment, placenta previa and detachment, trauma, hemorrhage, tumors, infectious lesions of the placenta.
2. The second group of reasons is associated with umbilical cord pathology: developmental anomaly, umbilical cord torsion, true umbilical cord knot.
3. The third group of causes is due to fetal pathology: Rh sensitization, intrauterine growth retardation, intrauterine infections, developmental defects, genetic diseases.
4. The fourth group of causes is related to complicated pregnancy and childbirth; the largest share in this group is gestosis and a long-term threat of termination of pregnancy. Other equally important causes include anemia of pregnancy, nephropathy, antiphospholipid syndrome, intrauterine infection, postmaturity, polyhydramnios and oligohydramnios, multiple pregnancy, premature birth, weakness of labor, discoordination of labor, protracted labor.
5. The fifth group of causes is caused by chronic pathology in the pregnant woman: cardiovascular (rheumatism, heart defects, neurocirculatory dystonia), endocrine (diabetes mellitus, thyroid pathology, obesity), chronic diseases of the kidneys, lungs, liver, blood, oncological diseases, drug addiction, alcoholism.

All of the above reasons lead to uteroplacental insufficiency, which is the main factor in the development of chronic hypoxia.

Chronic fetal hypoxia in some cases may be caused by the influence of so-called exogenous factors that arise under conditions of reduced partial pressure of oxygen in the inhaled air (highland areas, the Far North, etc.).

The causes of acute fetal hypoxia are situations that cause a rapid cessation of oxygen supply to the body: prolapse of the umbilical cord, tight entanglement of the umbilical cord around the neck, tight torsion of the umbilical cord, acute uterine bleeding, placenta previa and premature detachment during childbirth, abnormal presentation of the fetus, premature birth, etc.

Chronic intrauterine fetal hypoxia

In response to the impact of certain causes that cause oxygen deficiency, compensation mechanisms are launched to maintain adequate oxygenation. Such mechanisms include an increase in the rate of placental blood circulation, hyperplasia of the fetal part of the placenta, an increase in the capacity of the capillary bed and an increase in fetal blood flow, which leads to an increase in the heart rate. Increased fetal heart rate is the most important sign of incipient hypoxia. If the cause of hypoxia is not eliminated, fetoplacental insufficiency occurs - the basis for the development of chronic fetal hypoxia. Further, three links can be distinguished in the pathogenesis of chronic (intrauterine) hypoxia.

1. Oxygen deficiency causes activation of the fetal adrenal cortex, accompanied by increased production of catecholamines and their entry into the bloodstream, which causes a redistribution of blood aimed at increasing blood circulation in vital organs (heart, brain). As a result, blood pressure increases and there is a risk of hemorrhage.
2. Oxygen deficiency stimulates the process of hematopoiesis as a compensatory reaction of the fetus. This leads to the development of erythrocytosis, thrombocytosis in the vascular bed, blood viscosity increases, intravascular cell aggregation occurs, including platelets in the microcirculatory bed, which in turn leads to the formation of microthrombi. Microcirculation is disrupted, which can result in the development of ischemia of any organ. Along with the process of microthrombi formation, activation of the blood coagulation system can occur, an increase in the consumption of coagulation factors and blood cells (erythrocytes, platelets) around the thrombi, where a hypocoagulation zone is formed. This can provoke the development of DIC syndrome (hemorrhage and bleeding).
3. In response to oxygen starvation, metabolic changes occur, to which the fetal brain is particularly sensitive. First of all, tissue respiration increases, glycogenolysis and anaerobic glycolysis processes are activated, resulting in the formation of acidic metabolic products. Under conditions of pathological acidosis, the permeability of the vascular wall and cell membranes increases. Through the pores of the membranes of cells of the central nervous system, there is a loss of "excitatory" amino acids (glutamic, glycine, succinic, etc.), which can cause depression (inhibition) of the central nervous system.

Under conditions of anaerobic glycolysis, calcium accumulates in the axons of CNS cells, which can lead to the development of seizures.

And finally, the potassium-sodium exchange in the brain cells is disrupted. The loss of potassium by the cell causes sodium and water to enter the cells, resulting in edema (swelling) of the brain. The potassium content in the blood increases, and the sodium concentration decreases.

Thus, the consequences of chronic (intrauterine) fetal hypoxia can be:

• perinatal CNS damage;
• hemorrhages, bleeding, ischemia of internal organs (myocardium, lungs, kidneys, adrenal glands, intestines);
• intrauterine growth retardation;
• prematurity;
• fetal death.

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Acute intrauterine fetal hypoxia

The pathogenesis of acute fetal hypoxia is characterized by the rapid activation of reflex-adaptive reactions of the cardiovascular system of the fetus and newborn with minimal changes in metabolism.

Acute oxygen deficiency causes a rapid drop in its partial pressure in the fetus's blood, in response to which the adrenal system of the adrenal cortex is activated, catecholamines are released into the vascular bed, cardiac output increases, and tachycardia occurs, which ensures the flow of blood and oxygen to vital organs. At the same time, a compensatory spasm of the peripheral vessels develops, where acidic metabolic products are deposited without penetrating into the central bloodstream.

If the oxygen balance is not restored, the compensatory mechanisms fail: the function of the adrenal cortex is depleted, bradycardia develops, and arterial pressure in the central vessels drops. From the central bloodstream, blood flows into the peripheral bloodstream, and there is a sharp drop in oxygen perfusion in vital organs, which leads to their hypoxia, anoxia, and ischemia. In this case, the child may be born in a state of hypoxic shock or coma. Death of the fetus or newborn is possible.

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Classification of fetal hypoxia

Depending on the severity of the course, fetal hypoxia can be:

• moderate;
• heavy.

The severity of hypoxia is assessed using the Virginia Apgar scale. The scale for assessing the condition of a newborn in the first minutes of life was first presented at the XXVII Congress of Anesthesiologists in 1952. The scale represents a system of criteria (5 indicators) for assessing the condition of a newborn, including observation of:

• by the nature of breathing (no breathing; slow or irregular; good or screaming);
• reflexes - reaction to a catheter in the nose (no reaction; crying grimace; coughing, sneezing or crying);
• for muscle tone (weak; bending of arms and legs; active movements);
• by skin color (bluish, pale; body pink, limbs bluish; pink);
• for heartbeat (absent; heart rate less than 100 per minute; more than 100 per minute).

Each indicator is assessed on a three-point scale (0-1-2 points). The Apgar scale is assessed twice: in the first minute of life and five minutes after birth. A healthy newborn has a score of 8-10 points.

Most newborns receive a score of 7-8 points in the first minute of life due to cyanosis and decreased muscle tone. After five minutes, the score increases to 8-10 points, which indicates good adaptation of the child.

An Apgar score of 4-7 points indicates moderate hypoxia, while a score of 0-3 points characterizes severe hypoxia (asphyxia).

Classification of fetal hypoxia by severity is important for assessing the child’s condition in the first minutes after birth and deciding on the need for resuscitation measures and intensive care tactics.

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Classification of hypoxic CNS lesions in newborns

The successes achieved in perinatology over the past decades, the active introduction of new medical diagnostic technologies into the clinical practice of obstetrics and perinatology allow timely diagnosis of fetal hypoxia and its consequences, the most dangerous of which is damage to the central nervous system. For a long time, hypoxic damage to the central nervous system was designated by the terms "perinatal encephalopathy", "cerebrovascular accident", etc. The lack of clear terminology had a negative impact on the timely diagnosis of the consequences of perinatal damage to the nervous system, in particular the consequences of hypoxic damage to the central nervous system, on the implementation of timely and adequate therapy, which led to an increase in advanced cases and an increase in childhood psychoneurological disability.

The use of advanced technologies in perinatal practice has made it possible to clarify the etiology, pathogenetic mechanisms, clinical and morphological structures, typical localization of cerebral disorders for different gestational ages, to develop uniform approaches to terminology and to develop a new classification of perinatal lesions of the nervous system in newborns.

The classification was developed by the Russian Association of Perinatal Medicine Specialists and approved at the VI Congress of Russian Pediatricians in February 2000.

According to this classification, neurological disorders, depending on the leading mechanism of damage, are divided into four groups:

• I - hypoxic;
• II - traumatic;
• III - toxic-metabolic;
• IV - infectious.

Each of these groups has a distinct nosological form, severity, and main neurological symptoms and syndromes.

A fundamentally new feature in the classification is the division of hypoxic brain damage into cerebral ischemia and intracranial hemorrhage.

Cerebral ischemia (hypoxic-ischemic encephalopathy, perinatal hypoxic brain damage)

According to severity, three nosological forms are distinguished.

1. Cerebral ischemia of the first degree (mild) is characterized by excitation and/or depression of the central nervous system (no more than 5-7 days).
2. Cerebral ischemia of the second degree (moderate severity) is characterized by depression and/or excitation of the central nervous system (more than 7 days), development of seizures, intracranial hypertension, and vegetative-visceral disorders.
3. Cerebral ischemia of the third degree (severe) is characterized by progressive loss of cerebral activity (over 10 days), depression developing into coma, or depression developing into excitation and convulsions, or depression developing into convulsions and coma. Convulsions are typical, and status epilepticus may occur. Dysfunction of the brainstem, decortication, decerebration, vegetative-visceral disorders, and progressive intracranial hypertension occur.

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Intracranial hemorrhages of hypoxic genesis

There are five nosological forms.

1. Intraventricular hemorrhage grade I (subependymal) - typical for premature babies. There are no specific neurological symptoms.
2. Intraventricular hemorrhage grade II (subependymal + intraventricular) - typical for premature babies. Clinical symptoms: shock, apnea, depression progressing to coma; seizures, intracranial hypertension (rapidly or slowly progressing).
3. Intraventricular hemorrhage grade III (subependymal + intraventricular + periventricular) - typical for premature infants. Clinical symptoms: shock, apnea, deep depression progressing to coma, seizures (usually tonic), intracranial hypertension (rapidly or slowly progressing with dysfunction of the caudal parts of the brainstem).
4. Primary subarachnoid hemorrhage - more common in premature infants. Characteristic clinical syndromes: CNS hyperexcitability, hyperesthesia, partial (focal) clonic seizures, intracranial hypertension (acute hydrocephalus).
5. Hemorrhage into the brain substance (parenchymatous) - more common in premature babies. The clinical picture depends on the location and volume of hemorrhage: hyperexcitability, turning into seizures, deep depression, turning into coma, partial (focal) seizures, intracranial hypertension. Asymptomatic course is possible.

Combined ischemic and hemorrhagic lesions of the central nervous system (non-traumatic)

The clinical picture and severity of the condition depend on the leading type of lesion and localization.

In the first days of life, nosological diagnostics of CNS lesions is often difficult, since clinical neurological manifestations in various pathological conditions are similar, and additional information is lacking. For this reason, a syndromological diagnosis is acceptable (for example, hyperexcitability syndrome, depression syndrome, etc.), which should be further clarified upon receipt of anamnestic, clinical and laboratory research data.

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Criteria for the diagnosis of hypoxic lesions of the central nervous system

The principles of constructing a diagnosis of perinatal CNS lesions in newborns should be based on the following data:

• anamnesis;
• clinical symptoms and syndromes;
• results of additional examinations.

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Cerebral ischemia

Cerebral ischemia grade I (mild), or hypoxic-ischemic CNS damage grade I.

• History: intranatal fetal hypoxia, mild asphyxia at birth.
• Clinical syndromes: CNS excitation (more common in full-term infants), CNS depression (in premature infants) lasting no more than 5-7 days.
• Results of examinations.
  • Metabolic disorders (moderate hypoxemia, hypercapnia, acidosis).
  • NSG, CT, MRI - no pathological abnormalities.
  • DEG is a compensatory increase in blood flow velocity in the main arteries of the brain.

Cerebral ischemia of the second degree (moderate severity), or hypoxic-ischemic damage to the central nervous system of the second degree.

• History: intrauterine fetal hypoxia, moderate asphyxia at birth.
• Clinical symptoms:
  • CNS depression, excitation or change of phases of cerebral activity (lasting more than 7 days); convulsions: in premature infants - tonic or atypical (apnea, oral automatism, eyelid fluttering, myoclonus of the eyeballs, "rowing" movements of the arms, "pedaling" of the legs); in full-term infants - clonic (short-term, single, less often repeated);
  • intracranial hypertension (transient, more common in full-term infants);
  • vegetative-visceral disorders.
• Results of examinations.
  • Metabolic disorders (hypoxemia, hypercapnia, acidosis) are more pronounced and persistent.
  • NSG: local hyperechoic foci in the brain tissue (in premature infants, more often in the periventricular region; in full-term infants, subcortically). MRI: focal lesions in the brain parenchyma.
  • CT scan of the brain: local foci of low density in the brain tissue (in premature infants, more often in the periventricular region; in full-term infants, subcortically and/or cortically).
  • FDEG: signs of hypoperfusion in the middle cerebral artery in full-term infants and the anterior cerebral artery in premature infants. Increased diastolic component of blood flow velocity, decreased resistance index.

Cerebral ischemia grade III (severe), or hypoxic-ischemic CNS damage grade III.

• History: intrauterine fetal hypoxia and/or severe perinatal asphyxia, persistent brain hypoxia.
• Clinical symptoms:
  • progressive loss of cerebral activity (over 10 days);
  • repeated seizures (possible epileptic status);
  • dysfunction of the brain stem (disturbances in breathing rhythm, pupillary reactions, oculomotor disorders);
  • decortication and decerebration posture (depending on the extent of the lesion);
  • pronounced vegetative-visceral disorders;
  • progressive intracranial hypertension.
• Results of examinations.
  • Persistent metabolic disorders.
  • NSG: diffuse increase in echogenicity of the brain parenchyma (in full-term infants), periventricular structures (in premature infants). Narrowing of the lateral ventricles. Formation of cystic periventricular cavities (in premature infants). Appearance of signs of atrophy of the cerebral hemispheres with passive expansion of the spaces of cerebrospinal fluid circulation.
  • CT: decreased density of the brain parenchyma, narrowing of the spaces of cerebrospinal fluid circulation, multifocal cortical and subcortical foci of low density, changes in the density of the basal ganglia and thalamus (in full-term infants), periventricular cystic cavities in premature infants (should be clarified with a radiologist).
  • MRI: brain parenchyma lesion.
  • DEG: paralysis of the main arteries with transition to persistent cerebral hypoperfusion. Decreased diastolic blood flow velocity, change in the nature of the curve. Increased resistance index.

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Intracranial hemorrhages (hypoxic, non-traumatic)

Intraventricular hemorrhage grade I (subependymal).

• History: ante- and intranatal fetal hypoxia, mild asphyxia at birth, repeated attacks of apnea, jet injection of hyperosmolar solutions.
• Clinical symptoms: develops mainly in premature or immature newborns. The course is asymptomatic, there are no specific neurological disorders.
• Results of examinations.
  • Transient metabolic disorders.
  • NSG: hyperechoic areas of unilateral or bilateral localization in the thalamocaudal notch or in the region of the head of the caudate nucleus. The time of transformation of the subependymal hematoma into a cyst is 10-14 days or more.
  • CT and MRI have no diagnostic advantages over neurosonography.
  • DEG - without pathology.

Intraventricular hemorrhage grade II (subependymal, intraventricular) develops mainly in premature babies.

History: intrauterine fetal hypoxia, moderate asphyxia at birth, defects in primary resuscitation, arterial hypertension or fluctuations in systemic blood pressure due to SDR, iatrogenic factors (inadequate mechanical ventilation modes, rapid administration of large volumes or hyperosmolar solutions, functioning fetal communications, pneumothorax, etc.), coagulopathy.

Clinical symptoms: there are 2 main types of progression - gradual (wave-like) and catastrophic.

Catastrophic course: short-term motor excitation is suddenly replaced by progressive depression of cerebral activity with transition to coma, deep apnea, increasing cyanosis and “marbling” of the skin, tonic convulsions, oculomotor disorders, bradyarrhythmia, thermoregulation disorders, indicating increasing intraventricular hypertension.

• Gradual progression: periodic changes in phases of cerebral activity, attacks of repeated apnea, muscle hypotonia, atypical seizures.
• Results of examinations.
  • Decrease in systemic blood pressure.
  • A drop in hematocrit and hemoglobin concentration.
  • Metabolic disorders: hypoxemia, hypercapnia, acidosis, hypocalcemia, fluctuations in plasma glucose levels.
  • CSF with blood admixture, reactive pleocytosis, increased protein concentration, decreased glucose content.
  • NSG: at the initial stages - hyperechoic zones, then - ventriculomegaly, echo-positive formations (thrombi) in the ventricular lumens. Blockage of the cerebrospinal fluid outflow pathways with the development of acute hydrocephalus is possible.
  • CT, MRI, PET have no diagnostic advantages over NSG in newborns.
  • DEG: fluctuations in blood flow in the main arteries of the brain up to the development of intraventricular hemorrhage, stabilization after hemorrhage. With the progression of ventriculomegaly (after 10-12 days) - increasing hypoperfusion.

Intraventricular hemorrhage grade III (subependymal + intraventricular + periventricular).

History: the same as with stage II IVH.

Clinical symptoms:

• most often occurs in premature babies with extremely low birth weight;
• typically catastrophic course: rapid suppression of cerebral activity with the development of coma, progressive disorder of vital functions (bradycardia, arrhythmia, apnea, pathology of rhythm, breathing), tonic convulsions, oculomotor disorders, high frequency of fatal outcomes in the first days of life.

Results of examinations.

• Severe, difficult to correct metabolic disorders (hypoxemia, hypercapnia, acidosis, electrolyte disturbances), DIC syndrome.
• Critical drop in hematocrit and hemoglobin concentration.
• Progressive decrease in systemic blood pressure and cardiac arrhythmia.
• CSF: significant blood admixture, reactive pleocytosis, increased protein concentration, increased cerebrospinal fluid pressure. Spinal puncture is performed according to strict indications and with extreme caution due to the high risk of wedging of the brainstem into the foramen magnum.
• NSG: extensive hyperechoic area of periventricular localization (hemorrhagic infarction more often in the frontal-parietal region). Later - ventriculomegaly and deformation of the lateral ventricle as a result of the formation of a cystic cavity. Often in the lumen of the ventricles - thrombi. In most cases, occlusive hydrocephalus is formed.
• CT, MRI, PET have no diagnostic advantages in the neonatal period over NSG.
• DEG: at the initial stages - a decrease in systolic-diastolic blood flow velocity, an increase in the resistance index. Then - a decrease in diastolic blood flow velocity, a decrease in the resistance index.

Primary subarachnoid hemorrhage (non-traumatic) - predominantly in premature and immature infants.

History: intranatal fetal hypoxia, birth asphyxia, short gestation period, immaturity, coagulopathy.

Variants of clinical course:

• asymptomatic;
• agitation syndrome with hyperesthesia and acute intracranial hypertension (tension and bulging of the large fontanelle, suture divergence, profuse regurgitation, inconstant Graefe's symptom);
• convulsions that suddenly occur on the 2nd-3rd day of life (clonic - in full-term babies, atypical - in premature babies).

Results of examinations.

• Metabolic disturbances are not typical.
• NSG is uninformative. There may be widening of the interhemispheric fissure.
• CT and MRI: accumulation of blood in various parts of the subarachnoid space, but more often in the temporal regions.
• DEG is uninformative (primary and secondary vasospasm).
• CSF: increased pressure, increased red blood cell count, increased protein concentration, neutrophilic pleocytosis.

Hemorrhage into the brain substance (non-traumatic) parenchymatous (rarely - hemorrhage into the cerebellum and posterior cranial fossa).

History: intrauterine fetal hypoxia, severe or moderate birth asphyxia, coagulopathy, prematurity, vascular malformations.

The clinical picture depends on the location and volume of the hemorrhagic infarction:

• in case of scattered petechial hemorrhages of subcortical localization, an asymptomatic course is possible;
• in case of extensive petechial hematomas of hemispheric localization, the clinical course is similar to IVH grade III. Progressive loss of cerebral activity with transition to stupor or coma, focal neurological symptoms contralateral to the lesion (asymmetry of muscle tone, seizures, oculomotor disorders, etc.), increasing intracranial hypertension;
• Hemorrhages into the posterior cranial fossa and cerebellum are characterized by increasing signs of intracranial hypertension and brainstem disorders (respiratory, cardiovascular disorders, oculomotor disorders, bulbar syndrome).

Results of examinations.

• Severe, difficult-to-correct metabolic disorders, DIC syndrome (accompanied by massive hematomas).
• Decreased hematocrit and hemoglobin concentration.
• The progressive increase in systemic blood pressure is subsequently followed by a decrease.
• Heart rhythm disturbance.
• CSF: increased pressure, increased erythrocyte content, increased protein concentration, neutrophilic pleocytosis (except in cases of small focal parenchymal hemorrhages).
• NSG is of little information in case of pinpoint hemorrhages. Massive hemorrhagic infarctions are projected as asymmetric hyperechoic foci in the brain parenchyma. After 2-3 weeks, pseudocysts and leukomalacia are formed in their place.
• CT: foci of increased density in the brain parenchyma, deformation of the spaces of cerebrospinal fluid circulation.
• MRI: changes in the MR signal from foci of hemorrhage in the non-acute stage.
• DEG: asymmetric hypoperfusion in the cerebral arteries on the affected side.

Combined ischemic and hemorrhagic lesions of the central nervous system

Combined ischemic and hemorrhagic lesions of the central nervous system (non-traumatic) occur significantly more frequently than all isolated forms of CNS damage (occur mainly in premature infants).

History: intrauterine hypoxia and birth asphyxia, premature babies with low body weight (1000-1500 g), defects in providing primary resuscitation care, arterial hypotension, hypertension or fluctuations in systemic blood pressure, coagulopathy, DIC syndrome.

The clinical picture depends on the leading type of CNS damage (ischemia or hemorrhage), its severity and localization. These types of damage are the most severe.

Results of examinations.

• Metabolic disorders that are difficult to correct.
• CSF: pressure is increased, morphological characteristics depend on the degree of hemorrhage into the spaces of cerebrospinal fluid circulation.
• NSG, CT, MRI: various variants of deformation of the cerebrospinal fluid outflow system, foci of altered density of varying intensity, mainly periventricular localization.
• DEG: fluctuations in cerebral blood flow, paralysis of the main arteries of the brain, decreased blood flow.
• The diagnosis is formulated as follows: combined (non-traumatic) ischemic-hemorrhagic lesion of the central nervous system. In cases of diagnosis of specific structural changes in the brain, this is reflected in the diagnosis.

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Consequences of hypoxic lesions of the central nervous system

Perinatal CNS lesions, in particular those of hypoxic genesis, are not limited to the neonatal period. Their consequences are of particular importance in the first year of life. Timely and adequate therapy during this period can lead to more favorable outcomes and reduce the risk of developing persistent neurological disorders.

In this regard, the Russian Association of Perinatal Medicine Specialists proposed a project “Classification of the consequences of perinatal lesions of the nervous system in children of the first year of life.”

The classification is based on the following principles.

• Etiology and pathogenetic basis of lesions of the nervous system in the perinatal period.
• Variants of the clinical course: transient and persistent (organic) neurological disorders.
• Main clinical syndromes.
• Outcomes (complete compensation, functional impairment or persistent neurological deficit by the first year of life). Hypoxic CNS lesions have the following consequences.
• Consequences of cerebral ischemia-hypoxia of I-II degree - perinatal transient post-hypoxic-ischemic encephalopathy.
• The consequences of hypoxic intracranial hemorrhages of grades I-II are perinatal transient posthemorrhagic encephalopathy.
• The consequences of cerebral ischemia-hypoxia and/or intracranial hemorrhage of grade II-III are perinatal persistent (organic) post-hypoxic and post-hemorrhagic damage to the central nervous system.

Clinical syndromes of the above-mentioned first two variants of encephalopathy:

• hydrocephalus (unspecified);
• autonomic nervous system disorder (unspecified);
• hyperactive behavior, hyperexcitability;
• violation (delay) of motor development;
• combined forms of developmental delay;
• symptomatic seizures and situationally determined paroxysmal disorders (curable epileptic syndromes).

Outcomes:

• complete compensation of neurological abnormalities in the first year of life;
• minor functional impairments may persist.

Clinical syndromes of the third type of encephalopathy:

• various forms of hydrocephalus;
• severe organic forms of mental development disorders;
• severe forms of motor development disorders (CP);
• symptomatic epilepsies and epileptic syndromes of early childhood;
• cranial nerve damage.

Outcomes:

• neurological abnormalities are not compensated by the end of the first year of life;
• total or partial neurological deficit persists.

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Criteria for the diagnosis of fetal hypoxia

The following are criteria for the diagnosis of hypoxia.

• Low water content.
• Meconium in amniotic fluid.
• Changes in feto- and placentometry parameters (oligohydramnios, structural changes in the placenta, condition of the fetal membranes and umbilical cord).
• Changes in Doppler ultrasound parameters (pathological values of blood flow parameters in the uterine artery, umbilical cord vessels, middle cerebral artery of the fetus, pathological blood flow in the venous duct of the fetus in the second half of pregnancy).
• Changes in cardiac monitoring parameters (fetal bradycardia less than 120 beats per minute, monotony of the heart rhythm, periodic decelerations, areactive non-stress test).
• Changes in the characteristics of amniotic fluid (the presence of meconium) during amnioscopy (if the maturity of the cervix reaches 6~8 points on the Bishop scale, when the cervical canal is passable for one finger) or amniocentesis (if there are no conditions for amnioscopy).

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Differential diagnostics of hypoxic lesions of the central nervous system

• The most relevant issue is differential diagnostics between intracranial hemorrhages of hypoxic genesis and intracranial birth trauma.
• Epidural, subdural, supratentorial, and subtentorial hemorrhages are characteristic exclusively of birth trauma and do not occur with hypoxia.
• Intraventricular, parenchymatous and subarachnoid hemorrhages develop both with fetal hypoxia and with birth trauma. The main criteria for differential diagnosis are:
  • anamnesis data;
  • features of the clinical picture;
  • examination results.

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In case of intraventricular traumatic hemorrhage

• History: fact of birth trauma (rapid rotation of the head, forced extraction of the fetus).
• Clinically: often, but not always, the clinical picture manifests itself on the 1st-2nd day of life or later, and not at birth.

Results of examinations.

• There are no specific metabolic disorders.
• NSG: deformation of the contours of the vascular plexuses.
• CSF: blood admixture is detected only in cases of blood penetration into the subarachnoid space.

In traumatic parenchymal hemorrhages (hemorrhagic infarction)

History: complicated births (mismatch between the birth canal and the size of the fetal head, pathological fetal presentation, etc.).

It is more common in full-term babies with large birth weight (more than 4000 g) and post-term babies.

Results of examinations.

• Metabolic changes are not typical.
• CT, MRI, DEG are not very informative.

In subarachnoid traumatic hemorrhage

History: birth anomalies (mismatch of birth canal to fetal head size, abnormal presentation, instrumental delivery). In 1/4 of cases, combined with skull fractures.

Clinical symptoms:

• occurs rarely, mainly in full-term babies.
• CNS depression or hyperexcitability and convulsions develop within 12 hours, vascular shock is possible (in the first hours), subsequently replaced by arterial hypertension; development of posthemorrhagic anemia.

Results of examinations.

• Metabolic changes are not typical.
• NSG: increased echo density of the subcortical white matter on the side of the hemorrhage, progressive expansion of the subarachnoid space.
• CT: increased density of the subarachnoid space with subsequent expansion.

Intracranial birth trauma is characterized by rupture of intracranial tissue and hemorrhage due to birth trauma.

Hypoxic CNS lesions can also be differentiated in some cases from neuroinfections and brain tumors. In these cases, it is necessary to use information obtained from CT, MRI, and CSF examination.

Treatment of fetal hypoxia and its consequences

Treatment in the acute period depends on the severity of fetal hypoxia (asphyxia).

The tactics for managing newborns with hypoxia in the delivery room are as follows.

• Clearing the upper respiratory tract (suctioning the contents from the upper respiratory tract).
• Restoration of external respiration.
• Warming.
• Monitoring of vital functions and symptomatic therapy as indicated.

If the Apgar score of a newborn, who was given primary resuscitation measures in the delivery room for vital indications, does not reach 7 points 5 minutes after birth, he or she must be urgently transferred to the intensive care unit (ward).

After completion of resuscitation in the delivery room, a newborn with severe hypoxia is transferred to the intensive care unit.

The goal of intensive care is to prevent or minimize functional and organic disorders caused by the action of unfavorable perinatal factors.

The main goal of intensive care is rapid primary (or early) stabilization of the condition of sick newborns.

The complex of treatment and diagnostic measures for primary stabilization of the condition includes the following measures:

• Monitoring (dynamic assessment) of vital functions.
• Maintaining adequate oxygenation (oxygen masks, oxygen tents). In the absence of spontaneous breathing or its ineffectiveness, respiratory support is provided (forced or assisted forced ventilation of the lungs). The partial pressure of oxygen in the inhaled mixture in full-term infants should be within 60-80 mm Hg, in premature infants - 50-60 mm Hg. Hyperoxygenation can lead to the formation of free radicals and the development of fibrotic changes in the lung tissue.
• Maintaining adequate body temperature.
• Correction of cardiovascular function.

Drugs used to correct the function of the cardiovascular system

Preparation	Doses	Route of administration	Action
Albumen	5% solution 10-20 ml/kg/day)	Intravenous drip	Replenishment of BCC
Glucose	5-10% solution, 10 ml/kg/day)	Intravenous drip
Infucol	6% solution 10 ml/kg/day)	Intravenous drip
Dopamine	2-10 mcg/kg x min)	Intravenous drip	Vasopro tectors

• Replenishment of circulating blood volume (CBV): 5-10% glucose solution 10 ml/kg, 5% albumin solution 10-20 ml/kg, 6% hydroxyethyl starch solution (Infucol HES) 10 ml/kg intravenously by drip. When performing infusion therapy, it is necessary to strictly monitor the volume and rate of fluid administration. An increase in the volume or rate of administration may lead to arterial hypertension.
• Administration of vascular drugs: dopamine 2-10 mcg/kg x min) intravenously by drip.
• Syndromic treatment.

Drugs for syndromic therapy

Preparation	Doses	Route of administration	Indications
Furosemide	1 mg/kg/day)	Intravenously	Cerebral edema
		Intramuscularly
Dopamine	2-10 mcg/kg x min)	Intravenously
Dexamethasone	0.5-1 mg/kg/day)	Intravenously
		Intramuscularly
Magnesium sulfate	25% solution 0.1 - 0.2 ml/kg/day)	Intravenously	Intracranial hypertension
Phenobarbital	10-20 mg/kg/day)	Intravenously	Cramps
	5 mg/kg/day) - maintenance dose	Inside
Diazepam	0.1 mg/kg - single dose	Intravenously
Sodium oxybate	20% solution 100-150 mg/kg	Intravenously
Anti-edema therapy:		Diuretics	(furosemide

Dehydration therapy. In case of development of intracranial hypertension, it is recommended to prescribe 25% solution of magnesium sulfate (0.1-0.2 ml/kg/day) intravenously.

Anticonvulsant therapy is prescribed only if seizures develop: phenobarbital 10-20 mg/kg intravenously [maintenance dose - 5 mg/kg x day]], 20% sodium oxybate solution 100-150 mg/kg intravenously, diazepam (Relanium) 0.1 mg/kg.

Hemostatic therapy: 1% solution of vicasol 1.0-1.5 mg/kg x day), 12.5% solution of etamsylate (dicynone) 10-15 mg/kg x day (in 2-3 administrations).

From the 2nd day of life, the dynamics of body weight, electrolyte composition of the blood, concentration of ionized calcium in the blood plasma, concentration of protein, bilirubin, urea, creatinine, glucose in the blood are additionally taken into account.

Hemostatic drugs

Preparation	Doses	Route of administration
Vikasol	1% solution 1.0-1.5 mg/kg/day) 2-3 times a day	Intravenous, intramuscular
Dicynone	12.5% solution 10-15 mg/kg/day)	Intramuscular, intravenous

Treatment during the recovery period

A course of treatment with drugs that improve cerebral circulation and metabolic processes in the brain:

• restoration of cerebral hemodynamics: 0.5% solution of vinpocetine (cavinton) 1 mg/kg x day, vincamine 1 mg/kg x day);

Drugs that improve cerebral circulation (selective cerebrovascular action)

Preparation	Doses	Route of administration
Vinpocetine	0.5% solution 1 mg/kg/day)	Intravenous drip
	1 mg/kg 3 times a day	Inside
Vincamine	0.5% solution 1 mg/kg/day)	Intramuscularly
	1 mg/kg 3 times a day	Inside

• correction of metabolic disorders of the brain: hopantenic acid (pantogam) 0.25-0.5 g/day, piracetam (nootropil) 30-50 mg/kg/day orally, cerebrolysin 1 ml per 10 kg/day.

The treatment includes therapy with psychotropic (neurotropic) drugs: acetylaminosuccinic acid (cogitum) 0.5-1 ml orally, gamma-aminobutyric acid (aminalon) 0.1-0.25 g 2-3 times a day, pyriginol (encephabol) 0.05 g 1-2 times a day, glutamic acid 0.1 g 2-3 times a day, glycine 0.3 g (1/2 tablet), 0.6 g (1 tablet) 2 times a day.

• According to indications, antiplatelet (anticoagulant) therapy is carried out: pentoxifylline (Trental) 2-3 mg/kg x day, piracetam 20% solution 30-50 mg/kg 1-2 times a day.
• If necessary, syndrome-based therapy is carried out (sedative, anticonvulsant, dehydration, etc.).

Metabolic therapy drugs (nootropic drugs)

Preparation	Doses	Route of administration
Pantogam	0.25-0.5 g/day	Inside
Piracetam	30-50 mg/kg/day)	Intravenously
	50-150 mg/kg three times daily	Inside
Cerebrolysin	1 ml/10 (kg x day) once a day or every other day	Intramuscularly
Cogitum	0.5-1.0 ml	Inside
Aminalon	0.1-0.25 g 2-3 times a day	Inside
Pyritinol	0.05 g (1/2 teaspoon) 1-3 times a day	Inside
Glutamic acid	0.1 g 2-3 times a day	Inside
Glycine	0.3 g ('/2 tablets) 2 times a day	Inside

Antiplatelet drugs

Preparation	Doses	Route of administration
Pentoxifylline	2-3 mg/kg/day)	Intravenous drip
Piracetam	20% solution 30-50 mg/kg 1-2 times a day	Intravenous, intramuscular

• Correct focal disorders (massage, gymnastics, special positions).
• They carry out possible correction of impaired functions (visual and hearing impairments), speech disorders, orthopedic disorders, and psychological problems.
• They are deciding on the possibility of surgical treatment for progressive hydrocephalus.
• Outpatient observation at the clinic

A child who has suffered hypoxia should be observed by a pediatrician, neurologist, orthopedist, ophthalmologist, otolaryngologist, speech therapist, psychologist and, in some cases, a sociologist.

Prevention of fetal hypoxia

• Prenatal diagnosis of utero-fetal-placental insufficiency (MFPI) in pregnant women.
• Prevention of MPPP in pregnant women at risk.
• Timely and adequate treatment of MPN in pregnant women.
• Treatment of pregnancy complications leading to the development of hypoxia.
• Optimization of delivery methods in case of pathology, which is the main cause of the development of MPPP.
• Diagnosis of MPN during pregnancy is carried out using the following methods:
  • Ultrasound fetometry and placentometry;
  • Doppler ultrasound of blood flow in the vessels of the uteroplacental complex;
  • fetal heart rate monitoring;
  • amnioscopy;
  • amniocentesis.
• Prevention of MPPP in pregnant women at risk is carried out using preparations containing vitamin E, glutamic acid and Essentiale.
• Therapy for MPN includes:
  • normalization of uteroplacental blood flow by restoring vascular tone, rheological and coagulation properties of the blood;
  • improving placental metabolism;
  • increasing the immunological reactivity of the pregnant woman's body;
  • normalization of structural and functional properties of cell membranes;
  • oxygen therapy.
• Treatment of pregnancy complications leading to the development of hypoxia: correction of anemia, OPG gestosis, threatened miscarriage, antiphospholipid syndrome, diabetes mellitus, etc.
• The decision on timely delivery and the choice of delivery method (operative delivery or through the natural birth canal).
• If signs of hypoxia increase during pregnancy, early surgical delivery (caesarean section) is recommended.
• If acute fetal hypoxia is detected during labor, the issue of emergency operative delivery is decided.
• In case of post-term pregnancy (at gestation periods of 41 weeks or more), active tactics of pregnancy management should be followed (labor induction, amniotomy).