Placental insufficiency: treatment

Objectives of treatment of placental insufficiency and intrauterine growth retardation

Therapy should be aimed at improving uteroplacental and placental blood flow, intensification of gas exchange, correction of rheological and coagulation properties of blood, elimination of hypovolemia and hypoproteinemia, normalization of vascular tone and contractile activity of the uterus, enhanced antioxidant protection, and optimization of metabolic and metabolic processes.

Indications for hospitalization for placental insufficiency and intrauterine growth retardation

Subcompensated and decompensated placental insufficiency, a combination of placental insufficiency and FGRS with extragenital pathology, gestosis, threatening premature birth.

Drug treatment for placental insufficiency and intrauterine growth retardation

Given that among the causes of placental insufficiency, the damaging effect of chemical agents, unbalanced nutrition, extragenital and infectious diseases, gestosis, the prolonged threat of termination of pregnancy and other complications of pregnancy are of great importance, it is methodologically correct to begin treatment with the elimination of the adverse effect of these etiological factors. Normalization of the food ration in the group of pregnant women with a low level of quality of life due to an increase in the protein and basic minerals content with a decrease in the proportion of fats and carbohydrates to a balanced content makes it possible to reduce the frequency of development of the FFS by 19%.

Great importance in the treatment of placental insufficiency is given to the normalization of the tone of the uterus, as its increase contributes to the violation of blood circulation in the intervillous space due to the reduction of venous outflow. For this purpose, antispasmodic and tocolytic drugs (fenoterol and hexoprenaline) are used. As shown by our studies, with adequate treatment of placental insufficiency against the background of the threat of termination of pregnancy in 90% of the observations it is possible to obtain a positive effect. The effectiveness of therapy compensated and subcompensated forms of placental insufficiency against anemia of pregnant women is close to 100%. It is also quite effective to treat placental insufficiency with the use of antibacterial drugs for intrauterine infection (a positive effect in 71.4% of observations). However, in pregnant women with gestosis, the treatment of placental insufficiency is effective only in 28.1% with initial circulatory disturbances in the mother-placenta-fetus system, which is probably associated with morphological disturbances in the process of placenta formation.

The most common medications for the treatment of placental insufficiency include antiplatelet agents and anticoagulants. Of this group of drugs usually used acetylsalicylic acid, dipyridamole (curantyl), pentoxifylline (trental), nikospan, xanthinal nicotinate, heparin sodium. Reduction in the manifestations of placental insufficiency in the treatment of antiplatelet agents and anticoagulants is due to increased activity of the peripheral cytotrophoblast, a decrease in the volume of intervillar fibrinoid, glued villi, intervillar hemorrhages, and placenta infarcts. The use of antiplatelet agents is most effective when excessive activation of the vascular-platelet link of the hemostasis system; with more severe disorders, including also pathological increase of the plasma link, it is advisable to supplement the treatment with heparin. This drug has an antihypoxic effect, is involved in the regulation of tissue hemostasis and enzyme processes. Heparin does not penetrate the placental barrier and does not have a damaging effect on the fetus. In recent years, in the treatment of placental insufficiency, low molecular weight heparins are used that have more pronounced antithrombotic activity and give fewer side effects (calcium supraparin, dalteparin sodium).

Given the relationship of uteroplacental blood flow and blood enzyme activity in pregnant women with a high risk of perinatal pathology, it is advisable to conduct metabolic therapy using ATP, inosine, cocarboxylase, vitamins and antioxidants, as well as hyperbaric oxygenation for the prevention and treatment of fetal hypoxia. Metabolic therapy is considered an obligatory component in the treatment of placental insufficiency. To reduce the intensity of lipid peroxidation, stabilize the structural and functional properties of cell membranes, improve fetal trophicity, use membrane stabilizers - vitamin E and phospholipids + multivitamins (Essentiale). Currently, metabolic therapy of placental insufficiency both in outpatient and inpatient settings includes the use of actovegin (highly purified hemoderivat from calf blood with low molecular weight peptides and nucleic acid derivatives). The basis of pharmacological action of actovegin is the influence on the processes of intracellular metabolism, improvement of glucose transport and oxygen uptake in tissues. Inclusion of a large amount of oxygen into the cell leads to activation of the processes of aerobic glycolysis, an increase in the energy potential of the cell. In the treatment of PN, actovegin activates cellular metabolism by increasing transport, accumulating and enhancing intracellular utilization of glucose and oxygen. These processes lead to an acceleration of the metabolism of ATP and an increase in the energy resources of the cell. Also actovegin increases blood supply. The basis of the anti-ischemic action of actovegin is also considered to be the antioxidant effect (activation of the superoxide dismutase enzyme). Actovegin is used in the form of intravenous infusions of 80-200 mg (2-5 ml) in 200 ml of a 5% solution of dextrose (No. 10) or in a dragee (1 dragee 3 times a day for 3 weeks). The neuroprotective effect of actovegin on the brain of the fetus under hypoxic conditions is proved. It also has an anabolic effect, which plays a positive role in FGR.

With subcompensated and decompensated forms of placental insufficiency, combined use of actovegin and hexobenzidine + etamivin + etofillina (instenone), a combined drug combining nootropic, vascular and neurotonic components, is also possible.

A sufficient supply of fetal oxygen plays an important role in its life-support. In this regard, with placental insufficiency, oxygen therapy is indicated.

However, the development of protective reactions should be considered when inhaling excess 100% oxygen. Therefore, 30-60-minute inhalations of a gas mixture with an oxygen concentration of not more than 50% are used.

An important component of the treatment of placental insufficiency on the background of extragenital pathology and complications of pregnancy is infusion therapy. One of the most important components of a complex of therapeutic measures for placental insufficiency is the provision of energy needs of the fetus by introducing dextrose in the form of intravenous infusions in combination with an adequate amount of insulin.

The infusion of a glucose-novocaine mixture as a means of reducing vascular spasm, improving microcirculation and blood flow in the arterial vessels of the placenta has not lost its therapeutic value. Intravenous introduction of ozonized isotonic sodium chloride solution promotes normalization of fetal status in the presence of laboratory-instrumental signs of hypoxia.

In order to correct hypovolemia, improve the rheological properties of blood and microcirculation in the placenta, it is effective to administer dextran [cf. Mol. Weight 30 000-40 000] and solutions based on hydroxyethyl starch. Infusion of a 10% solution of hydroxyethyl starch in the treatment of placental insufficiency against gestosis makes it possible to achieve a significant reduction in vascular resistance in the uterine arteries, and perinatal mortality decreases from 14 to 4 ‰. When detecting hypoproteinemia in pregnant women, as well as the presence of disturbances in the plasma link of the hemostasis system, infusions of fresh frozen plasma in the amount of 100-200 ml 2-3 times per week are performed. With protein deficiency, severe loss or increased need for proteins, in particular with FGR, it is possible to use infusion therapy with preparations containing a solution of amino acids (aminosol, aminostearyl KE 10% non-carbohydrate, infezole 40). However, it should be borne in mind that an increase in the concentration of amino acids in the mother's blood does not always lead to an increase in their content in the fetus.

Non-pharmacological treatment of placental insufficiency and intrauterine growth retardation

In the treatment of placental insufficiency, physical methods of action (electrorelaxation of the uterus, magnesium electrophoresis, the appointment of thermal procedures to the perineal region), relaxing myometrium and leading to vasodilation are of great importance.

A new method in treating pregnant women with placental insufficiency is conducting sessions of therapeutic plasmapheresis. The use of discrete plasmapheresis in the absence of effect from the treatment of placental insufficiency by medicinal preparations makes it possible to improve the metabolic, hormone-producing functions of the placenta and contributes to the normalization of feto utero-placental blood flow.

Treatment of placental insufficiency is effective if the first course begins before 26 weeks of pregnancy, and repeated in 32-34 weeks. Treatment at a later date improves the fetus and increases resistance to hypoxia, but it does not allow to normalize its condition and provide adequate growth. The high frequency of unfavorable perinatal outcomes in FWR is largely due to the need for early delivery in a time when the newborn is poorly adapted to the external environment (an average of 31-33 weeks). When addressing the issue of preterm delivery in the preparation for delivery include glucocorticoids for the prevention of complications in the neonatal period [44]. These drugs not only accelerate the process of ripening of the fetal lungs, but also reduce the incidence of certain complications. According to the American National Institutes of Health (1995), the incidence of intraventricular hemorrhage and enterocolitis in newborns with NWFP is lower in observations of prenatal glucocorticoid use. Dexamethasone is administered internally at a dose of 8-12-16 mg for 3 days or intramuscularly at 4 mg every 12 hours 4 times.

Patient education

Be sure to explain to a woman about the need to maintain a rational diet, sleep and rest during pregnancy. The patient should be trained to control the body weight, arterial pressure. To diagnose hypoxia, you should teach the woman how to move the fetus throughout the day and discuss the situations in which she should immediately seek medical help.

Further management of placental insufficiency and intrauterine growth retardation

For compensated placental insufficiency, favorable perinatal outcomes are characteristic. Spontaneous birth through natural birth canal occurs in 75.82% of cases, without complications - at 69.57%. Most often, the course of the birth act with compensated placental insufficiency is complicated by a pathological preliminar period, the progression of chronic intrauterine fetal hypoxia, untimely outflow of amniotic fluid, weakness and discoordination of labor. The occurrence of these complications of pregnancy is an indication for emergency delivery by surgery in 38.1% of cases. Indications for a planned cesarean operation in most cases: an obstructed gynecological anamnesis (including a cervical scar after a previous cesarean section operation, infertility, pregnancy loss syndrome) in combination with compensated placental insufficiency, as well as a complicated course of pregnancy, and the presence signs of fetal impairment (grade I, IH, hemodynamic disorders in the mother-placenta-IA or Istrong system, initial signs of fetal hypoxia) in older women th group if there is a miscarriage of pregnancy. As the degree of severity of placental insufficiency worsens, the frequency of a favorable outcome of spontaneous delivery decreases, and in this connection, with a subcompensated placental insufficiency, the planned delivery is considered by the cesarean section at a time close to term.

Subcompensated placental insufficiency

Indications for planned delivery by cesarean section:

• moderately severe fetal hypoxia (decrease in variability of basal rhythm, number of accelerations, their amplitude and duration);
• hemodynamic disorders in the mother-placenta-fetus system of the 2nd degree in the presence of bilateral changes and dicrotic excavations in the uterine arteries;
• combination with other obstetric pathology;
• FGRS in combination with gestosis or pregnancy retention. Criteria for prolonging pregnancy:
  • IZD I-II degree with adequate growth of fetometric parameters in control ultrasound at intervals of 7 days;
  • FGRS of the III degree without increasing the lag of the fetometric indicators against the background of non-progressive violations of the placental blood circulation and / or initial signs of centralization of the blood flow (SDO in the fetal aorta more than 8.0 with the SDO value in the AGR 2.8-9.0 at 33-37 weeks );
  • absence of pronounced disorders of uteroplacental blood flow (unilateral, without disturbance of the blood flow spectrum in the uterine arteries, SDO more than 2,4) with gestosis of moderate severity;
  • absence of clinical progression of combined gestosis;
  • initial signs of hypoxia according to cardiotocography in the absence or initial centralization of arterial fetal blood circulation, normal indices of organ (renal) fetal blood flow (SDR not more than 5.2 in a period of up to 32 weeks, and not more than 4.5 in a period of 33-37 weeks);
  • eukinetic and hyperkinetic type of fetal central hemodynamics in the absence of intracardiac hemodynamic disturbances. A comprehensive study of the fetal hemodynamics and analysis of perinatal outcomes in placental insufficiency made it possible to develop indications for urgent delivery by cesarean section in this pathology. They include:
• cardiotocographic signs of severe fetal hypoxia (spontaneous declerations against a background of monotonous rhythm and low variability, late decelerations in the oxytocin test);
• critical condition of the placenta blood flow at the term of pregnancy more than 34 weeks;
• marked disturbances of blood flow in the venous duct and inferior vena cava.

Indications for emergency delivery - the onset of labor in pregnant women with subcompensated placental insufficiency, as well as premature discharge of amniotic fluid. Indications for the transfer of a newborn to the intensive care unit are prematurity, hypoxic-ischemic lesions of the central nervous system of varying severity.

Decompensated placental insufficiency

Indications for urgent delivery by cesarean section:

• FGRS of severe degree with signs of pronounced centralization of fetal arterial blood flow with intracardiac blood flow disturbances and with signs of moderate fetal hypoxia according to CTG data;
• progression of gestosis on the background of complex therapy with pronounced disorders of uteroplacental blood flow (bilateral disturbances with dicrotic excavation in the spectrum);
• term of pregnancy in the presence of signs of decompensated placental insufficiency of more than 36 weeks.

Indications for emergency delivery:

• disorders of venous blood flow of the fetus (retrograde blood flow in the venous duct, increase of the reverse flow of blood in the inferior vena cava of the fetus), presence of pulsations in the umbilical vein;
• preeclampsia and eclampsia.

In case of premature pregnancy (32-36 weeks) and absence of zero and retrograde values of blood flow in the venous duct during atrial systole and pulse index up to 0.74, with the percentage of reverse blood flow in the inferior vena cava up to 43.2% within 32 weeks and up to 34.1% in the period of 32-37 weeks) pregnancy should be prolonged. Simultaneously, complex treatment of placental insufficiency with obligatory intravenous injection of a solution of hexobendin + etamivin + etofillin is carried out at daily dopplerometric and cardiotocographic control. The complex treatment includes glucocorticoids to accelerate the maturation of the fetus.

The delivery is performed by a caesarean section if there is evidence of progression of venous blood flow disorders or the appearance of spontaneous decelerations, a hypokinetic type of hemodynamics, and an "adult" type of pericardial fetal blood flow. The duration of the prolongation of pregnancy was from 4 (in a period of 35-36 weeks) to 16 days (in a period of 32-34 weeks).

Forecast

Timely diagnosis of placental insufficiency and FGRS, correct and competent management of pregnant women allow prolonging pregnancy before the term of a viable fetus with a favorable perinatal outcome. The choice of the term of delivery should be based on a set of diagnostic tests. In case of early delivery, it is necessary to take into account the availability of conditions for intensive care and intensive care for newborns.

Children with low birth weight in the future have a high risk of physical, neuropsychological and high somatic diseases. Most often the newborn is noted:

• disorders of cardiopulmonary adaptation with perinatal asphyxia, meconial aspiration or persistent pulmonary hypertension;
• when FVRP is combined with prematurity - high risk of neonatal death, necrotizing enterocolitis, respiratory distress syndrome, intraventricular hemorrhages;
• thermoregulation disorders due to increased heat transfer (due to a decrease in the subcutaneous fat layer) or a decrease in heat production (depletion of catecholamines and reduced delivery of nutrients);
• hypoglycemia (in 19.1% of newborns);
• polycythemia and hypercoagulation (diagnosed in 9.5% at the I degree of FGR and in 41.5% at grade III);
• decreased immunoreactivity (in 50% of newborns with grade III FGRS neutropenia is detected, in 55% - nosocomial infections).

Disorders of physical development

Newborns with low birth weight have different options for physical development, depending on the etiology and severity of intrauterine growth retardation. With moderate severity of FEV, within 6-12 months after birth, high growth rates are noted, during which children reach normal mass-growth relationships. However, according to some reports, newborns reach normal body weight for 6 months after birth, but maintain a growth deficit of 0.75 standard deviations during the first 47 months of life compared with children who have a normal birth weight. In the case of severe FGR, the lag in mass and growth is below the 10th percentile not only in childhood, but also in the adolescent period. Thus, the average height at the age of 17 years with a severe delay in intrauterine growth is 169 cm in boys and 159 cm in girls versus 175 cm and 163 cm at normal birth weight, respectively.

Violations of the neuropsychological development

Many researchers with a severe degree of FGRS (birth weight less than 3 percent), especially with premature pregnancy, note a decrease in IQ and significant learning difficulties. So, at the age of up to 5 years, 2.4 times more often than with normal body weight at birth, children have small brain dysfunctions, motor disorders, cerebral palsy and poor cognitive abilities; 16% of children at the age of 9 years need correctional training; 32% of adolescents with severe respiratory distress syndrome have significant learning disabilities that prevent them from completing the full course of secondary school. In a study conducted by LM McCowan (2002), 44% of newborns with FHNP due to hypertension of pregnant women have a low mental development index. Disorders of psychomotor development are more often noted in newborns who have not been breastfed for at least 3 first months of life, who have been in the hospital for a long time, who required artificial ventilation.

Adults born with low body weight have a higher risk of coronary artery disease, hypertension, cerebral circulatory disorders, diabetes, hypercholesterolemia. Thus, among men, mortality from cardiovascular diseases was 119 ‰ at a mass of 2495 g at birth versus 74 ‰ at a weight of 3856 g. Animal studies have shown that disruption of trophic function of the placenta leads to structural and functional adaptation that ensures the survival of the newborn. In the future, the transferred adaptive stress leads to the development of the above diseases.

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