Placental insufficiency: diagnosis

The diagnosis of placental insufficiency with a pronounced delay in fetal development of the fetus is not difficult to establish, it is much more difficult to reveal its initial manifestations, when placental insufficiency is realized at the level of metabolic reactions in the mother and fetus. That is why the diagnosis should be established on the basis of a comprehensive survey of pregnant women, carefully collected history, taking into account the conditions of life and work, bad habits, extragenital diseases, the features of the course and outcomes of previous pregnancies, as well as the results of laboratory research methods.

A comprehensive examination of the fetoplacental complex should include:

• Evaluate the growth and development of the fetus by carefully measuring the height of the uterine fundus, taking into account the circumference of the abdomen and the body weight of the pregnant woman.
• Ultrasonic fetal biometry.
• Evaluation of the fetus by studying its motor activity and cardiac activity (cardiotocography, echocardiography, determination of the biophysical profile of the fetus, in some cases - cordocentesis).
• Ultrasonic evaluation of the placenta state (localization, thickness, area, volume of the maternal surface, degree of maturity, presence of cysts, calcification).

Anamnesis and physical examination

Currently, various methods are used to diagnose placental insufficiency. Clinical methods include the detection of anamnestic risk factors, an objective examination of the pregnant and fetus by measuring the circumference of the abdomen and the height of the standing of the uterine fundus, determining the tone of the myometrium, the position of the fetus, and calculating its estimated weight. It is known that the lag of the height of the standing of the uterus bottom by 2 cm or more in comparison with the proper value for a specific gestation period or the absence of an increase within 2-3 weeks indicates the probability of the development of the FGR. Clinical evaluation of the state of his cardiovascular system is carried out by auscultation. For female counseling, a ballistic system for determining the risk of placental insufficiency, developed by O.G. Frolova and E.N. Nikolaeva (1976, 1980).

Important information in childbirth about the functional reserves of the fetus is the evaluation of the quality of amniotic fluid. At present, prognostic criteria for a severe complication of placental insufficiency are found - meconial aspiration of fetus and newborn (by the nature of amniotic fluid in combination with data on its cardiac activity and respiratory activity). A scoring scale is created that takes into account the color of the water, the consistency of meconium, the duration of pregnancy and the presence of signs of hypoxia according to the evaluation of cardiac activity of the fetus. At 12 points the probability of meconial aspiration in a fetus is 50%, 15 and more - 100%. However, the individual variability of the size of the abdomen and uterus of a pregnant woman, depending on the anthropometric features, the severity of the subcutaneous fat layer, the amount of amniotic fluid, the position and the number of fruits, are considered to be a significant limitation of clinical diagnostic methods. Changes in the auscultatory pattern occur only in the late stages of fetal suffering and are more often manifested in childbirth. Assessment of the condition of amniotic fluid in practice is possible only after their outflow, since amnioscopy is poorly informative, and amniocentesis is referred to as invasive methods, having a number of limitations and requiring special conditions. Almost 60% of pregnant women have no clinical signs of placental insufficiency. On the other hand, only in each of the three pregnant women with suspected FFS, sent to ultrasound, the clinical diagnosis is confirmed.

Laboratory and instrumental research

Among the laboratory methods in recent years, the determination of the hormonal and protein-synthesizing function of the fetoplacental complex (placental lactogen, progesterone, estriol, cortisol, a-fetoprotein, SP1, PP12, etc.) has been used in recent years, a biochemical study of its enzymatic activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and etc.). Laboratory diagnosis of placental insufficiency, based on the determination of hormone concentration, has its own characteristic signs, which outstrip the clinical manifestations of placental insufficiency for 2-3 weeks. Placental insufficiency in the early stages of pregnancy mainly depends on the insufficient hormonal activity of the yellow body and is accompanied by a low content of progesterone and hCG. Later, in the second and third trimesters of pregnancy, the development of placental insufficiency is accompanied by morphological disorders, which gradually causes the development of insufficiency of the hormone-producing function of the placenta.

An early preclinical sign of placental insufficiency is a decrease in the synthesis of all hormones in the fetoplacental system (estrogens, progesterone, placental lactogen). The greatest practical significance was acquired by the determination of the concentration of estriol, as a method of monitoring the fetus during pregnancy. In case of complicated pregnancy, a decrease in the concentration of estriol is an early diagnostic sign of impaired fetal development. A decrease in the excretion of estriol with urine to 12 mg / day or less indicates a marked deterioration in the fetus and fetoplacental system. However, significant fluctuations of this index in normal and with fetal hypotrophy make it necessary to conduct research in dynamics. A sign of placental insufficiency is a decrease in the concentration of estriol in the amniotic fluid. For diagnosis, the estriol index is determined - the ratio of the amount of the hormone in the blood and urine. As the progression of insufficiency progresses, the index value decreases. One of the most common reasons for the low content of estriol in the blood of pregnant women is considered to be fetal growth retardation. A sharp decrease in estriol (less than 2 mg / day) is observed in fetal anencephaly, hypoplasia of its adrenal gland, Down's syndrome, intrauterine infection (toxoplasmosis, rubella, cytomegalovirus infection). A high content of estriol is observed with multiple pregnancies or with a large fetus. In addition to the fetal condition, there are a number of exogenous and endogenous factors that affect the biosynthesis, metabolism and excretion of estriol. Thus, treatment with a pregnant glucocorticoid causes a temporary suppression of adrenal function of the fetus, which leads to a decrease in the concentration of estriol. When treating pregnant with betamethasone or antibiotics, the synthesis of estriol is also reduced. Severe liver diseases in the mother can lead to a violation of the conjugation of estrogens and the excretion of them with bile. The change in kidney function in a pregnant woman leads to a decrease in the clearance of estriol, as a result of which the content of the hormone in the urine decreases, its concentration in the blood increases inadequately to the state of the fetus. In more rare cases, congenital enzymatic defects of the placenta arise, which are the cause of extremely low estriol values, while the fetal condition will not be disturbed. Similar patterns are observed when determining the content of estriol in the blood of pregnant women. Of particular interest is the study of the content of neuron-specific enolase in the mother's blood and the isoenzyme of creatine kinase in the amniotic fluid as antenatal markers of brain development disorder, whose concentration increases with fetal hypoxia. However, it should be borne in mind that most hormonal and biochemical tests have wide boundaries of individual oscillations and low specificity, in order to obtain reliable data, it is necessary to determine the content of the hormone or enzyme in dynamics. The general drawback of these tests is the lack of the possibility of interpreting the result at the time of the fetal examination.

In the early stages of pregnancy, the most informative indicator is the concentration of the chorionic gonadotropin, the reduction of which, as a rule, is accompanied by a delay or stopping the development of the embryo. This test is used when examining pregnant women in case of suspicion of an undeveloped pregnancy and the threat of its interruption. There is a significant decrease in the level of chorionic gonadotropin and its beta-subunit, which, as a rule, is combined with a decrease in the concentration of progesterone in the blood.

In the first trimester of pregnancy with the development of placental insufficiency, the level of placental lactogen can also be significantly reduced. Extremely low values of placental lactogen in the blood are detected in pregnant women on the eve of the death of the embryo or fetus and 1-3 days before the spontaneous abortion. The greatest informative value in predicting the emerging placental insufficiency in the first trimester of pregnancy has a decrease in the level of placental lactogen by 50% or more in comparison with the physiological level.

The state of the fetoplacental system also reflects the concentration of estriol (E3), since when the fetus suffers from placental insufficiency, the production of this hormone decreases with the fetus's liver.

However, unlike placental insufficiency, a decrease in the level of E3 by 40-50% is most informative in the prognosis of placental insufficiency after 17-20 weeks of pregnancy.

Cortisol also refers to the hormones of the fetoplacental system, produced with the participation of the fetus. Despite the fact that its content in the serum of a pregnant woman is subject to great fluctuations, with placental insufficiency, low concentration and a steady tendency to decrease in its production are determined when the fetus is hypotrophic.

Trophoblastic beta-globulin (TBG) is considered a specific marker of the fetal part of the placenta and is synthesized by cells of the cyto- and syncytiotrophoblast. In the dynamics of physiological pregnancy, its content progressively increases in terms of 5-8 to 37 weeks. The most unfavorable for the prognosis of the development of placental insufficiency and perinatal pathology in the case of miscarriage are low levels of secretion of TBG (5-10 times or more in comparison with the norm) from the first trimester of pregnancy and have no pronounced tendency to increase in the II and III trimesters. Most often, a decrease in the level of TBG from the first trimester of pregnancy is determined in cases of low placentation (according to ultrasound) or phenomena of chorion detachment, when pregnancy occurs with the threat of interruption, which has a recurrent nature.

Placenta-specific alpha-microglobulin (PAMG) is secreted by the decidual membrane and is a marker of the maternal part of the placenta, in contrast to TBG. In case of physiological pregnancy, the level of PAMG in the blood does not exceed 30 g / l. However, as with the initially formed placental insufficiency, the concentration of this protein is initially high and does not tend to decrease with the development of the gestational process. The results of the determination of PAMG in the II and III trimesters have the highest prognostic and diagnostic value, and a sharp increase in its level (up to 200 g / L) allows predicting perinatal pathology up to antenatal fetal death with high reliability (up to 95%).

• Assessment of the state of metabolism and hemostasis in the pregnant body (CBS, CPO, enzymes aspartate aminotransferase (ACT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), alpha hydroxybutyrate dehydrogenase (a-GBH), creatine phosphokinase (CKF) , y-glutamintranspeptidase (y-GTP), bulk oxygen transport, hemostasiogram parameters). At the heart of placental insufficiency of any etiology lie placental circulatory disorders, including microcirculation and metabolic processes, which are interrelated and often interdependent. They are accompanied by changes in blood flow not only in the placenta, but also in the body of the mother and fetus. Particularly pronounced violations of the rheological and coagulation properties of blood are observed with a delay in intrauterine development of the fetus in the presence of autoimmune causes of miscarriage. However, it is possible to detect signs of microcirculation disturbance at the early stages of placental insufficiency formation by analyzing the parameters of the hemostasiogram (pronounced hypercoagulation, decrease in the number of platelets, increase in their aggregation, development of chronic DVS-syndrome).

In the diagnosis of fetal abnormalities in placental insufficiency, the determination of the concentration of a-fetoprotein (AFP), which is clearly correlated with the gestation period and the fetal body mass, is of great value. Changes in the physiological level of AFP in the course of pregnancy, both in the direction of its increase, and in the direction of lowering indicate not only the developmental defects, incl. And genetic, but also on the expressed disturbances of metabolic reactions in the fetus.

The indicated disadvantages are deprived methods of echography and functional evaluation of the fetus condition (cardiotocography, cardiointervalography, Doppler examination of blood flow), which are currently leading in the diagnosis of placental insufficiency. The main significance of the echography for the diagnosis of placental insufficiency lies in the identification of the FGR and its shape and severity. Ultrasound diagnosis of the NWFP is based on comparing the fetometric parameters obtained as a result of the study with the normative indices for a given period of pregnancy. The greatest distribution in the diagnosis of intrauterine growth retardation of the fetus was measured by the biparietal size of the head, the mean diameters of the chest and abdomen, the circumferences and areas of their cross section, and the length of the thigh. For the purpose of monitoring the development of the fetus, the percentile approach is used, which makes it possible to determine exactly the correspondence of fetal dimensions to gestational age in each specific period of pregnancy, as well as the degree of their deviation from the normative values. The diagnosis of FERD is set if the fetal size is below 10 percentile or more than 2 standard deviations below the mean for this term of pregnancy. Proceeding from the results of ultrasound, it is possible to determine the shape of the NWFP (symmetrical, asymmetric), characterized by different ratios of fetometry parameters (femur length / abdominal circumference, thigh length / head circumference). It is possible to form a "mixed" form of intrauterine growth retardation, characterized by a disproportionate lagging behind all indicators of fetometry with the most pronounced lag in the dimensions of the abdomen. Based on the data of fetometry, it is possible to determine the severity of fetal growth retardation. At the I stage, the difference between the indicators of fetometry and normative ones is noted, and their compliance with indicators characteristic of pregnancy for 2 weeks less (34.2%), at grade II - 3-4 weeks less (56.6%), with III - more than for 4 weeks less (9.2%). The severity of intrauterine growth retardation correlates with the severity of fetoplacental insufficiency and adverse perinatal outcomes.

Recently, echographic research has also been used to assess the state of the umbilical cord as a criterion for intrauterine fetal suffering. When the umbilical cord diameter is 28-41 weeks in pregnancy, no more than 15 mm (skinny umbilical cord), and the diameters of the vein and arteries are 8 and 4 mm, respectively, in 66% of the cases there are signs of fetal hypoxia and 48% - FGR. The authors consider the hyperbarity of the umbilical cord to be an additional criterion of intrauterine fetal suffering and a prognostic sign of a newborn's distress.

Important information about the condition of the fetus is his motor and respiratory activity. The presence of regularly repeated respiratory movements of the fetus in the presence of meconium in the amniotic fluid is considered a risk factor for the development of the aspiration syndrome. A particularly unfavorable prognostic factor is the long period of movement of the "gasping" type (choking).

In the last decade, three-dimensional ultrasound has been used to conduct fetometry, including placental insufficiency and FGRS. This technique has more accuracy in measuring the biparietal diameter, the circumference of the head and the circumference of the fetal abdomen, the length of the femur in comparison with the two-dimensional ultrasound, especially in case of malnutrition or abnormal fetal position in the uterus. This gives a much smaller error in calculating the estimated body weight of the fetus (6.2-6.7% vs. 20.8% with two-dimensional ultrasound).

In the diagnosis of placental insufficiency, an important role is played by ultrasound placentography, which, in addition to determining the localization of the placenta, assess its structure and magnitude. The appearance of stage II up to 32 weeks, and the third stage of maturity of the placenta to 36 weeks gestation indicates its premature maturation. In some cases, ultrasound is observed cystic changes in the placenta. Cysts of the placenta are defined as echo-negative formations of various shapes and sizes. They occur more often on the fetal side of the placenta and are formed due to hemorrhages, softening, heart attacks and other degenerative changes. Depending on the pathology of pregnancy, the failure of the placenta functions is manifested by a decrease or increase in the thickness of the placenta. So, a characteristic sign for gestosis, the threat of termination of pregnancy, FGRS is considered a "thin" placenta (up to 20 mm in the third trimester of pregnancy), hemolytic disease and diabetes mellitus is indicated by placental thick placenta (up to 50 mm and more). One of the most widely used methods of functional evaluation of the fetal condition is cardiotocography. Along with the indicators of cardiac activity of the fetus, this method allows you to register the motor activity of the fetus and the contractile activity of the uterus. The most widely used non-stress test, assessing the nature of the fetal heart activity in vivo. Less often study the reaction of the fetus to certain "external" effects (sound, uterine contractions under the influence of exogenous oxytocin, etc.). In the presence of FWRN, a nonstress test in 12% of cases reveals tachycardia of the fetus, in 28% - a decrease in basal rhythm variability, in 28% - variable decelerations, in 13% - late decelerations. At the same time, it should be borne in mind that, in connection with the timing of the formation of the myocardial reflex (by 32 weeks gestation), a visual evaluation of cardiotocograms is possible only in the III trimester of pregnancy. In addition, as the results of expert assessments show, the frequency of discrepancies in the visual assessment of cardiocograms by several specialists can reach 37-78%. The nature of the cardiotocographic curve depends not only on the gestational age, but also on the sex of the fetus, the weight of the body, the characteristics of the management of labor (anesthesia, induction, and rhodostimulation). In recent years, the definition of echographic investigation of the so-called biophysical profile of the fetus has become very popular. This test includes a complex score (scale from 0 to 2 points) of the amount of amniotic fluid, motor activity and muscle tone of the fetus, respiratory movements, as well as the results of a non-stress cardiotocography test.

A score of 8-10 points indicates a normal fetal condition. Repeated examination should be performed only in pregnant women at high risk after 1-2 weeks. When assessing 4-6 points, obstetric tactics are determined taking into account the signs of the maturity of the fetus and the preparedness of the birth canal. In cases of insufficient maturity of the fetus and the lack of readiness of the birth canal, the test is repeated after 24 hours. When receiving a repeated adverse result, glucocorticoid therapy with subsequent delivery is necessary no earlier than 48 hours. If there are signs of maturity of the fetus, delivery is indicated. Score 0-2 points - an indication for urgent and careful delivery. In the absence of signs of maturity of the fetus, delivery should be performed after 48 hours of preparation of the pregnant glucocorticoids.

The method of dopplerometric blood flow research in the fetoplacental system, which has been intensively developing in recent years, is considered safe, relatively simple and at the same time highly informative for evaluating its functional reserves. In the early period, dopplerometry provides information not only on the formation of uteroplacental and placental-placental blood circulation, but also reveals hemodynamic markers of chromosomal pathology. Intraplacental blood circulation (blood flow in the spiral arteries and terminal branches of the umbilical artery) in uncomplicated pregnancy is characterized by a progressive decrease in vascular resistance, reflecting the main stages of placenta morphogenesis. The most pronounced decrease in vascular resistance in spiral arteries in terms of 13-15 weeks, and in the terminal branches of the cord artery - in 24-26 weeks, which is 3-4 weeks ahead of the peak reduction in vascular resistance in the uterine arteries and terminal branches of the cord artery. When examining the blood flow in the uterine arteries, the umbilical artery and the intraplacental blood circulation is fundamentally important for predicting the development of gestosis and placental insufficiency starting from 14-16 weeks of pregnancy, the fact that violations of intraplacental blood flow reveal 3-4 weeks earlier in the backbone links.

The most important study of utero-placental and fetoplacental blood circulation in order to predict the development and early diagnosis of gestosis and placental insufficiency is in the second trimester of pregnancy. In addition to increasing the indices of vascular resistance in the uterine arteries, a dicrotic excision may occur in the phase of early diastole. When the pathological parameters of hemodynamics are revealed in the mother-placenta-fetus system, the patient is referred to the high-risk group for the development of gestosis and PN, and she needs a differentiated medical correction for the detected hemodynamic disorders. With violations in the utero-placental blood circulation, drugs of choice - agents that improve the rheological properties of blood (acetylsalicylic acid, pentoxifylline), in cases of disorders in the fetus-placental link, it is advisable to use actovegin. In the vast majority of observations of complicated pregnancy and extragenital diseases, the initial stage in the development of the pathological process is a violation of uteroplacental blood flow with a gradual involvement in the pathological process of the placenta blood circulation and cardiovascular system of the fetus. This sequence of pathogenetic mechanisms of development of hemodynamic disorders is presented in the developed by A.N. Strizhakov et al. (1986) classification of blood flow disorders in the mother-placenta-fetus system.

• IA degree - a violation of uteroplacental blood flow with preserved fruit-placental.
• IB degree - a violation of the placental blood flow with a preserved utero-placental.
• II degree - simultaneous disturbance of uteroplacental and fetus-placental blood flow, not reaching critical values (preservation of a positively directed diastolic blood flow in the artery of the umbilical cord).
• III degree - a critical violation of the placental blood flow (absence or retrograde direction of the end-diastolic blood flow) with the uteroplacental blood flow preserved or disturbed.

Reduction of blood flow velocities in the artery of the umbilical cord to the diastole to zero or the appearance of retrograde blood flow indicates a significant increase in vascular resistance in the placenta, which is usually combined with a critically high content of lactate accumulation, hypercapnia, hypoxemia and fetal acidemia.

In a complex study of the arterial blood circulation of the fetus with placental insufficiency, the following changes are noted:

• increase indices of vascular resistance in the artery of the umbilical cord (SDO> 3.0);
• increased indices of vascular resistance in the aorta of the fetus (SDO> 8.0);
• decrease in indices of vascular resistance in the middle cerebral artery (SDO <2.8);
• reduction of blood flow in the renal arteries;
• violation of intracardiac hemodynamics (appearance of reverse blood flow through the tricuspid valve).

In fetoplacental insufficiency, there are disturbances of intracardiac fetal hemodynamics, which involve a change in the ratio of maximum flow rates through valves to the left heart, and the presence of regurgitation flow through the tricuspid valve. In the critical condition of the fetus, the following changes in fetal hemodynamics are revealed:

• zero or negative blood flow in the artery of the umbilical cord;
• regurgitation through the tricuspid valve;
• absence of diastolic component of blood flow in the aorta of the fetus;
• an increase in the diastolic component of the blood flow in the middle cerebral artery;
• violation of blood flow in the venous duct and inferior vena cava. In this case, the Dopplerometric criterion for the disturbance of blood flow in the venous duct is a decrease in the rate of blood flow to the phase of late diastole, down to zero or negative values. In the critical state of the fetus, the pulsation index in the venous duct exceeds 0.7. Dopplerometric criteria for blood flow disorders in the inferior vena cava include: an increase in the rate of reverse blood flow greater than 27.5-29% and the appearance of zero / reverse blood flow between systolic and early diastolic flow.

[1], [2], [3]

Differential diagnosis of placental insufficiency and intrauterine growth retardation syndrome

A number of criteria are proposed that allow differential diagnosis between FWRP and a constitutionally small fetus ("fetus, small for the period of pregnancy"). Some of the criteria are:

1. The use of a set of indicators (diagnosis of the estimated fetal weight, estimation of the number of amniotic fluid, the presence of arterial hypertension in the mother) in diagnosis of the NWFP allows to increase the accuracy of the diagnosis of FGRS to 85%.
2. Dopplerometric study of blood flow in the artery of umbilical cord and uterine arteries.
3. Calculation of the podderal index [body mass (g) x 100 / length (cm) ³ ].
4. Increase in the number of nuclear forms of erythrocytes in fetal blood obtained during cordocentesis (due to hypoxia in the presence of PN and NWFP).
5. Features of weight gain after birth (25% of newborns with severe (III) degree of FGRS up to 24 months of life retain a lag of mass-growth rates below 3 percentiles).

[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]

Screening of placental insufficiency and intrauterine growth retardation

Routine prenatal screening for diagnosis of placental insufficiency and its associated FERD include:

• identification of pregnant high risk groups of placental insufficiency and FGR;
• assessment of the height of the standing of the uterus during pregnancy;
• biochemical screening (double and triple tests);
• Ultrasound in the period of 10-14 weeks, 20-24 weeks, 30-34 weeks gestation with assessment of fetal anatomy, detection of markers of chromosomal abnormalities, intrauterine infection, malformations of the fetus;
• ultrasonic fetometry in the specified terms with diagnostics of NWFP of symmetric and asymmetric form, evaluation of the degree of severity of the syndrome;
• assessment of the number of amniotic fluid;
• assessment of the degree of maturity of the placenta;
• dopplerometry of blood flow in the uterine, spiral arteries, the umbilical artery and its terminal branches in 16-19 weeks, 24-28 weeks and 32-36 weeks of gestation;
• assessment of hemodynamics of the fetus (middle cerebral artery, aorta, renal arteries, venous duct, inferior vena cava);
• cardiotocography (with a period of more than 28 weeks gestation).

In addition, according to indications, it is possible to use invasive methods of investigation (amniocentesis, chorionic villus sampling, placentocentesis, cordocentesis) followed by karyotyping at a high risk of having chromosomal abnormalities and gene defects in the fetus.

Thus, the diagnosis of placental insufficiency is established on the basis of a dynamic, complex examination, including clinical and laboratory data, studies of hormonal, transport, protein-synthesizing function of the placenta, evaluation of the fetal status according to functional methods.