Pregnancy during pregnancy

Gestosis is a complication of a physiologically occurring pregnancy, characterized by a profound disruption of the functions of vital organs and systems that occurs after 20 weeks of pregnancy and up to 48 hours after birth.

Clinically manifested by arterial hypertension, proteinuria, edema, symptoms of PON. In trophoblastic disease, gestosis can occur before the 20th week of pregnancy. HELLP-syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets) is a variant of severe gestosis, in which hemolysis, an increase in hepatic enzyme activity and thrombocytopenia occur. The diagnosis of eclampsia is established in the presence of convulsions.

In Ukraine and Russia, gestosis is diagnosed in 12-21% of pregnant women, severe form - in 8-10%. A severe gestosis as a cause of maternal mortality was recorded in 21% of cases. Perinatal mortality is 18-30% HELLP-syndrome occurs in 4-20% of pregnant women with preeclampsia. Maternal mortality with it reaches 24%, perinatal - from 8 to 60%.

Synonyms of gestosis

Gestosis, OPG-gestosis, late gestosis, toxemia of pregnant women, nephropathy, preeclampsia, preeclampsia / eclampsia.

ICD-10 code

Comparison of the names of diseases according to ICD-10 with the Russian classification of the Russian Association of Obstetricians and Gynecologists is presented in the table.

Correspondence of ICD-10 classification of gestosis of the Russian Association of Obstetricians and Gynecologists

ICD-10 code	ICD-10	RF
011	Existing hypertension with joined proteinuria	Gestosis *
012 2	Pregnancy-induced edema with proteinuria	Gestosis *
013	Pregnancy-induced hypertension without significant proteinuria
014 0	Preeclampsia (nephropathy) of moderate severity	Gestosis of moderate severity *
014 1	Severe preeclampsia	Gestosis of severe degree *
014 9	Preeclampsia (nephropathy), unspecified	Preeclampsia

* To assess the severity of gestosis use the Goke scale in the modification of GM Savelieva.

The Goka scale in the modification of GM Savelieva

Symptoms	Points
	1	2	3	4
Edema	No	On the tibia or abnormal weight gain	On the tibia, anterior abdominal wall	Generalized
Proteinuria, g / l	No	0.033-0.132	0.133-1.0	> 1.0
Systolic blood pressure, mmHg	<130	130-150	150-170	> 170
Diastolic blood pressure, mmHg	<85	85-90	90-110	> 110
The gestational age at which gestosis was first diagnosed	No	36-40	30-35	24-30
Chronic hypoxia, intrauterine growth retardation of fetus	No		Lagging for 1-2 weeks	Lagging for 3 or more weeks
Background diseases	No	Have appeared before pregnancy	During pregnancy	Outside and during pregnancy

The severity of gestosis corresponds to the received sum of points:

• 7 and less - gestosis of mild degree.
• 8-11 - moderate gestosis.
• 12 and more - severe gestosis.

Epidemiology

Epidemiology of gestosis

In recent years, the frequency of gestosis has increased and varies from 7 to 22%. Gestosis remains among the top three causes of maternal mortality in developed and developing countries. In the US, gestosis ranked second among causes of maternal mortality after various extragenital diseases and by the number of deaths are ahead of deaths from obstetric hemorrhages, infections and other complications of pregnancy. In the structure of the causes of maternal mortality in gestosis is consistently ranked 3rd and ranged from 11.8 to 14.8%. It remains the main cause of neonatal morbidity (640-780 ‰) and mortality (18-30 ‰). According to WHO, every fifth child born to a mother with a gestosis, to some extent violated the physical and psychoemotional development, significantly higher incidence in infancy and early childhood. Payment in social as well as in financial terms is very high.

[1], [2], [3], [4], [5], [6], [7], [8]

Causes of the gestosis

Causes of Gestosis

The causes of preeclampsia are not established. The connection with the fetus and placenta has been proved. The animals failed to model gestosis. Factors and the degree of risk of gestosis are listed in the table.

Risk factors for gestosis

Factor	Degree of risk
Chronic kidney disease	20: 1
Homozygosity for the T235 gene (angiotensinogen)	20: 1
Heterozygosity by gene T235	4: 1
Chronic hypertension	10: 1
Antiphospholipid syndrome	10: 1
Hereditary anamnesis of preeclampsia	5: 1
Primipara	3: 1
Multiple Fertility	4: 1
Disturbance of fat metabolism	3: 1
Age> 35	3: 1
Diabetes	2: 1
African-American origin	1.5: 1

Low socio-economic level and young age as a risk factor for gestosis is not recognized by all.

[9], [10], [11], [12], [13], [14], [15], [16], [17]

Pathogenesis

Pathogenesis of gestosis

Currently, there are various theories of the pathogenesis of gestosis. Recent research has made it possible to put forward the theory of SSRM with the formation of PON and the development of endothelial dysfunction, generalized vasospasm, hypovolemia, disturbance of rheological and coagulation properties of blood, microcirculation, water-salt metabolism.

The most important role in the development of SSRM is a typical pathophysiological process - ischemia-reperfusion, which initially develops in the placenta, and then in vital organs. Many researchers note the predominantly immune genesis of placental ischemia associated with factors of immunological aggression from the fetus and a violation of immunological tolerance in the mother. The vascular system of the placenta is the primary link for immunological aggression. The activation of the complement system, the production of cytokines, in particular, TNF, the release of endotoxin, the activation of platelets, which lead to generalized damage to the vascular endothelium, their spasm and ischemia of vital organs, are recorded. Endothelial dysfunction causes an increase in the permeability of histohematic barriers, a decrease in tissue perfusion and the development of the PON syndrome.

Pathogenetic disorders in the central nervous system

In the central nervous system, ischemia is observed, due to cerebral artery vasospasm or cerebral edema, which causes visual disturbances in the form of photophobia, diplopia, scotoma, amaurosis or "veils before the eyes." When carrying out EEG, as a rule, stretched, delayed rhythms (in the form of θ- or σ-waves), or sometimes including slowly varying focal activity or paroxysmal adhesions.

Headache can occur in 40% of patients with preeclampsia and in 80% - with the subsequent development of eclampsia. It can be accompanied by nausea, irritability, a sense of fear and a visual impairment.

Pathogenetic disorders in the cardiovascular system

Hypertension, which may be a consequence of vasospasm, is an early precursor of pre-eclampsia. At the first stage of the development of the disease, blood pressure does not differ in stability at rest, and depending on fluctuations in blood pressure, the circadian rhythm changes around the 24-hour period. Initially, there is no reduction in blood pressure at night, and subsequently observe an inverse relationship when the pressure begins to rise during sleep. The sensitivity of the vessels to the circulating adrenaline and norepinephrine, angiotensin II increases.

In patients with severe gestosis, the volume of plasma decreases, the level of protein in it decreases due to its excretion in the urine and losses through the porous wall of the capillaries. There is a decrease in oncotic pressure - indices at the level of 20 and 15 mm Hg with medium and severe forms of the disease, respectively.

Pathogenetic disorders in the respiratory system

The most severe complication, more often of iatrogenic nature, is AL. The reasons for its development:

• low oncotic pressure with simultaneous increase in intravascular hydrostatic pressure,
• increased capillary permeability.

Pathogenetic disorders in the excretory system

In most pregnant women with gestosis, a decrease in renal perfusion and CF is observed along with a corresponding increase in the serum creatinine concentration. The reason for the decrease in CF is the swelling of the glomeruli, the narrowing of the lumen of glomerular capillaries, and the deposition of fibrin in endothelial cells (glomerular capillary endotheliosis). Increased permeability promotes a proportional increase in the concentration in the urine of proteins with a large molecular weight, for example, transferrin and globulins. Despite the prevalence of oliguria (those diuresis less than 20-30 ml / h for 2 h), the development of renal failure is relatively rare. Acute tubular necrosis is often the cause of reversible renal failure, which has a very favorable prognosis. As a rule, premature detachment of the placenta, ICE and hypovolemia precedes the development of renal failure.

Pathogenetic disorders in the blood clotting system

Thrombocytopenia less than 100x109 / l is noted in 15% of patients with severe gestosis. This is due to increased consumption of platelets, which is due to a violation of the equilibrium between prostacyclin and thromboxane. An increased concentration of fibrinopeptide, level of von Willebrand factor, high activity of Ville factor and a low content of antithrombin III indicate the activation of a coagulation cascade. The phenomenon of hemolysis can be observed in violation of liver function, with HELLP-syndrome. The formation of chronic DIC syndrome occurs in 7% of patients with severe gestosis.

Pathogenetic disorders in the liver

The cause of liver dysfunction is not clear. Changes can occur due to periportal liver necrosis, subcapsular hemorrhages, or the deposition of fibrin in the sinusoids of the liver. Violation of liver function in severe gestosis can have a negative effect on the removal of the body of drugs in the metabolism of which the liver is involved. Spontaneous rupture of the liver occurs very rarely and in 60% of cases leads to death.

Gestosis - Causes and pathogenesis

Forms

Classification of gestosis

The complexity of the problem of gestosis is evidenced by the lack of a single classification throughout the world. There are many different recommendations regarding terminology for referring to hypertensive conditions found during pregnancy. Along with the term "gestosis" abroad, the following are used: preeclampsia and eclampsia, pregnancy-induced hypertension, and OPG-gestosis (O-edema, P-proteinuria, D-hypertension).

At present the following classifications are accepted in the world:

• The International Society for the Study of Hypertension in Pregnancy;
• Organization of gestosis;
• American Association of Obstetricians and Gynecologists;
• Japanese Society for the Study of "Toxemia of Pregnant Women".

The clinical classification of gestosis is used.

1. Edema.
2. Gestosis:
   1. light degree;
   2. middle degree;
   3. severe degree.
3. Preeclampsia.
4. Eclampsia.

Gestosis is also divided into pure and combined, i.e. It occurs against the background of pre-existing chronic diseases. The frequency of combined gestosis, the course of which depends on previous diseases, is about 70%. For combined gestosis is characterized by an early clinical manifestation and a more severe course, usually with a predominance of symptoms of the disease, against which gestosis developed.

Currently, the diagnosis of gestosis in Russia is verified on the basis of the International Statistical Classification of Diseases and Health Problems, X Revision (1998), adopted by the 43rd World Health Assembly. II block of obstetrics division is called "Edema, proteinuria and hypertensive disorders during pregnancy, childbirth and the postpartum period."

The use of statistical and clinical classification of gestosis for the assessment of morbidity leads to a different interpretation of statistical indicators and assessment of the severity of this disease.

[18], [19], [20], [21]

Diagnostics of the gestosis

Severity Criteria

Criteria for severe gestosis

• Systolic blood pressure more than 160 mm Hg or diastolic blood pressure more than 110 mm Hg in two dimensions for 6 hours.
• Proteinuria is more than 5 g / day.
• Oliguria.
• Interstitial or alveolar AL (more often iatrogenic origin).
• Hepatocellular dysfunction (increased activity of AJIT and ACT).
• Thrombocytopenia, hemolysis, DIC-syndrome.
• Intrauterine growth retardation Criteria for pre-eclampsia.
• Cerebral disorders headache, hyperreflexia, clonus, visual impairment.
• Pain in epigastrium or right hypochondrium, nausea, vomiting (HELLP-syndrome).

[22], [23], [24], [25], [26], [27], [28]

Diagnosis of gestosis

Diagnosis of gestosis is not difficult and is based on the clinical picture and data of laboratory and instrumental studies. The gestation period, when hypertension or proteinuria were first documented, helps in setting the right diagnosis. The onset of hypertension or proteinuria before conception or until 20 weeks. Pregnancy is typical for chronic hypertension (essential or secondary) or renal pathology. High blood pressure, established in the middle of pregnancy (20-28 weeks) may be associated with either early onset of gestosis, or with unrecognized chronic hypertension. In the latter case, BP usually decreases in the first trimester, and this "physiological" decrease can be even more pronounced in patients with essential hypertension, masking the diagnosis during pregnancy.

[29], [30], [31], [32], [33], [34], [35]

Laboratory research

Laboratory tests recommended for the diagnosis and treatment of hypertension in pregnancy, serve primarily for the differentiation of gestosis from chronic or transient hypertension and kidney disease. They also help assess the severity of gestosis. Attempts to find the perfect screening test have not been successful until now. It was shown that indicators such as the measurement of blood pressure in the middle of pregnancy, outpatient monitoring of blood pressure, serum β-hCG, sensitivity to angiotensin II, urinary excretion of urine, urine kallikrein, uterine artery doppler, can be used as early markers of this pathology, fibronectin plasma and platelet activation. However, their practical value for individual patients is not proven.

Studies proposed for screening gestosis

Test	Justification
Hematocrit	Hemoconcentration confirms the diagnosis of gestosis (hematocrit more than 37%) and acts as an indicator of severity of pathology. Values may be low if gestosis accompanies hemolysis
Platelet count	Thrombocytopenia less than 100 thousand in ml confirms severe gestosis
Protein content in urine	Hypertension in combination with proteinuria> 300 mg / day indicates severe gestosis
Concentration of serum creatinine	Increase in the concentration of creatinine, especially in combination with oliguria, involves severe gestosis
Concentration of uric acid in blood serum	Increase in serum uric acid concentration suggests
Activity of transaminases in serum	Increased activity of transaminases in serum presupposes severe gestosis with liver involvement
Concentration of albumin in serum	Decrease in albumin concentration indicates the degree of damage (permeability) of the endothelium

Criteria for diagnosis of NELP-syroid

• Pain in epigastrium or right hypochondrium.
• Icery sclera and skin.
• Hemolysis hemolyzed blood, hyperbilirubinemia, LDH> 600 units.
• Increase in activity of hepatic enzymes AST> 70 units.
• Thrombocytopenia the number of platelets is less than 100x10 ⁹ / l.

Gestosis - Diagnosis

Treatment of the gestosis

Treatment of Gestosis

Indications for delivery are severe gestosis and preeclampsia. Pregnancy is prolonged as long as the adequate state of the intrauterine environment is maintained to maintain the growth and development of the fetus without endangering the health of the mother. Treatment should be conducted with the simultaneous involvement of an obstetrician-gynecologist and an anesthesiologist-resuscitator, preferably in a specialized intensive care unit.

Gestosis - Treatment

Treatment of severe gestosis includes the prevention of convulsive syndrome, antihypertensive and infusion-transfusion therapy (ITT).

Prevention of convulsive syroid

Magnesium sulfate

In pregnant women with severe gestosis and pre-eclampsia, magnesium sulfate is used to prevent eclampsic seizures. The initial dose of 4 g is given within 10-15 minutes, and then a supporting infusion is performed at a rate of 1-2 g / h. After that, the blood is reached and within 4 hours the therapeutic concentration of magnesium sulfate is maintained, equal to 4-6 mmol / l. Against the background of the introduction of magnesium sulfate should be monitored knee reflex and diuresis. The disappearance of the knee reflex is a sign of hypermagnesia. In this case, the infusion of magnesium sulfate should be stopped until the knee reflex appears. Magnesium ions circulate in the blood in a free and plasma-bound form. Excreted by the kidneys. The half-life in healthy people is about 4 hours. Disorders of kidney function (diuresis less than 35 ml / h) can cause hypermagnesemia, and therefore the dose of magnesium sulfate should be reduced.

In the therapeutic concentration, magnesium sulfate inhibits neuromuscular transmission and CNS by affecting glutamic acid receptors. In high doses, it can cause conduction disorders in the heart and bradycardia. The most dangerous, life-threatening effect of magnesium sulphate is respiratory depression due to the slowing down of neuromuscular transmission. In case of an overdose, 1 g of calcium gluconate or 300 mg of calcium chloride is injected intravenously.

Effects of magnesium sulphate

Effects	Concentration of magnesium ions in blood plasma, mmol / l
Normal level in plasma	1.5-2.0
Therapeutic range	4.0-8.0
Electrocardiographic changes (prolongation of the PQ interval, expansion of the QRS complex)	5.0-10.0
Loss of deep tendon reflexes	10.0
Depression of breathing	12.0-15.0
Respiratory arrest, sinoatrial and AV blockade	15.0
Heart failure	20.0-25.0

Anticonvulsant therapy is performed within 24 hours after birth.

Antihypertensive therapy

Antihypertensive treatment is recommended if blood pressure exceeds 140/90 mmHg. Arterial diastolic pressure should not be reduced dramatically, as its reduction can cause a decrease in the blood supply of the placenta. It is advisable to determine the parameters of central hemodynamics (echocardiography, rheovasography), daily monitoring of blood pressure Diuretics are indicated only for the treatment of AL.

Antihypertensive therapy

A drug	Class	Therapy of pre-eclampsia	Therapy of severe gestosis	Side effects
Clonidine	α-Adrenomimetic	100-300 mcg iv	Up to 300 mcg / day in / m or enterally	Sedation Syndrome cancellation
Gidralazine	Peripheral Vasodilator	5-10 mg iv, can be re-introduced after 15-30 min	20-40 mg	Reflex tachycardia
Nifedipine	The blocker of slow calcium channels	10 mg per os every 15-20 minutes until the effect is achieved Parenterally slowly 6-10 μg / kg and then using an infusomat 6-14.2 μg / kg per minute	10-30 mg orally	Headache Reflex tachycardia
Labetalol	α-, β-Adreno-blocker	5-10 mg iv, you can re-double the dose in 15 minutes to a maximum dose of 300 mg	100-400 mg orally after 8 hours	Bradycardia in fetus and mother
Propranolol	Non - selective β-adrenergic blocker	10-20 mg orally	10-20 mg orally	Bradycardia of the mother

Preparations of the first row can be considered nifedipine, clonidine, anaprilin. The use of nitroglycerin and sodium nitroprusside has serious complications and is not recommended. The use of atenolol is associated with intrauterine growth retardation of the fetus. The results of several randomized studies show that antihypertensive therapy in women with preeclampsia or preeclampsia does not improve perinatal outcomes.

[36], [37], [38], [39], [40], [41], [42], [43]

Infusion-transfusion therapy

Due to vasospasm, patients with preeclampsia have a reduced vascular volume and are sensitive to fluid loading. It is necessary to refrain from the introduction of large volumes of liquid, since hyperhydration and AL are possible. At the same time, it is impossible to completely abandon the introduction of infusion solutions.

Moderate dehydration is better than hyperhydration. The volume of ITT is approximately 1-1.2 l / day. Preference is given to crystalloids. The infusion rate is not more than 40-45 ml / h (maximum - 80) or 1 ml / (kgh). In the first 2-3 days diuresis should be positive (negative fluid balance). The optimum CVP is 3-4 cm of water. Art. Diuretics are used only with OL. Transfusion of albumin is possible only with hypoalbuminemia (less than 25 g / l), better after delivery.

Infusion load is necessary for epidural anesthesia, parenteral antihypertensive therapy, intravenous administration of magnesium sulfate, for oliguria or signs of central dehydration (with low CVP).

Therapy of the NELP-syroid

• Priority is the exclusion of liver rupture and bleeding.
• Hemolysis and thrombocytopenia are indications for carrying out plasmapheresis in the plasma exchange regime with additional injection of FFP.
• It is necessary to abstain from transfusion of platelets if there is no active bleeding.
• The appointment of glucocorticoids (according to different data, from 10 mg of dexamethasone intravenously every 12 hours).

Anesthesia allowance

During caesarean section, epidural anesthesia is more preferable compared to the general (exclusion of eclampsia). Recent studies have shown that spinal and combined spinal-epidural anesthesia is as safe as epidural. Advantages of regional anesthesia - control of blood pressure, increased renal and uteroplacental blood flow, prevention of convulsive syndrome. The dangers of general anesthesia are hemodynamic instability during induction, intubation and extubation of the trachea. Hypertension and tachycardia can be the cause of increased intracranial pressure (ICP). The risk of regional anesthesia is usually associated with the development of epi- and subdural hematoma.

During labor, through natural birth canal, epidural anesthesia is performed. Despite thrombocytopenia, the formation of epidural and subdural hematomas is extremely rare in obstetrics. Nevertheless, usually the level of prohibition of regional anesthesia (the number of platelets is 70-80x10 ³ / mm ³ ).

[44], [45], [46]