RU (11) 2193864 (13) C2 (51) 7 A61B8/06  (12) DESCRIPTION OF THE INVENTION TO THE PATENT OF THE RUSSIAN FEDERATION  Status: as of 07/09/2007 - terminated  -------------- -------------------------------------------------- ---------------- (14) Publication date: 2002.12.10  (21) Application registration number: 2000124051/14  (22) Application filing date: 2000.09.19  (24) Start date patent term countdown: 2000.09.19  (45) Published: 2002.12.10  (56) Analogues of the invention: Dopplerography in obstetrics / Ed. M.V. MEDVEDEVA and others - M.: Vidar, 1999. RU 2149592 C1, 05/27/2000. RU 2148256 C1, 04/27/2000. SAVELIEVA G.M. and others. Placental insufficiency. - M.: Medicine, 1991, pp. 171-176.  (71) Name of the applicant: Kursk State Medical University  (72) Name of the inventor: Gazazyan M.G.; Ponomareva N.A.; Ivanova O.Yu.  (73) Name of the patent holder: Gazazyan Marina Grigorievna  (98) Address for correspondence: 305033, Kursk, st. K. Marksa, 3, KSMU, patent department  (54) METHOD FOR EARLY DIAGNOSIS OF SECONDARY PLACENTAL INSUFFICIENCY  The invention can be used in medicine, namely in obstetrics. All cases of primary placental insufficiency at 30-31 weeks of pregnancy are preliminarily excluded. A Doppler study is carried out at 34-35 weeks of pregnancy to determine the average value of the resistance index in the two uterine arteries and the resistance index in the umbilical artery and calculate the ratio of the resistance index of the uterine arteries to the resistance index in the umbilical artery. With unchanged blood flow in the utero-placental-fetal complex, the speed of blood flow in the vessels of the uterus exceeds the speed of blood flow in the umbilical cord artery. With the development of secondary placental insufficiency, peripheral resistance in the small spiral and radial vessels of the uterus increases, which affects the decrease in the intensity of blood flow in the uterine arteries and leads to an increase in the digital values ​​of the uterine artery resistance index. On Dopplerograms this is manifested by a decrease in the numerical values ​​of the resistance index. The changes that occur are reflected in the ratio of the resistance index of the uterine arteries to the umbilical cord artery, the digital values ​​of which become greater than or equal to one. The method improves diagnostic accuracy.  DESCRIPTION OF THE INVENTION The invention relates to medicine, namely to obstetrics, and can be used in the third trimester of pregnancy to diagnose the initial manifestations of secondary placental insufficiency of the hemodynamic type. Perinatal morbidity and health of newborn children largely depend on the duration and severity of placental insufficiency. Currently, placental dysfunction is mainly diagnosed based on indirect signs of fetal hypoxia. All diagnostic methods indicate an existing pathology and require emergency management tactics. A more promising and pathogenetically substantiated method should be considered a direct method for diagnosing placental dysfunction by studying blood flow velocity curves in the utero-placental and placental-fetal circulation using Doppler and color Doppler mapping. The closest to the claimed method is the existing classification of disorders of the uteroplacental-fetal blood flow (A.N. Strizhakov, A.T. Bunin, M.V. Medvedev, G.A. Grigoryan, 1989). Based on the assessment of blood flow velocity curves in the uterine arteries and the umbilical cord artery, a classification of disorders of the uteroplacental-fetal blood flow has been developed. The authors developed on a large material average values ​​of the resistance index according to the gestational age and fluctuations in the values ​​of the resistance index from the 5th to the 95th percentile. Finding the resistance index values ​​within these limits is considered by the authors as corresponding to the norm, and exceeding the resistance index values ​​above the 95th percentile is considered pathological. According to this classification, three degrees of hemodynamic disorders are distinguished: IA degree: disturbances of uteroplacental blood flow with preserved fetal-placental blood flow; IB degree: disturbances of fetal-placental blood flow with preserved uteroplacental blood flow; II degree: simultaneous disturbance of the uteroplacental and placental-fetal blood flow, which does not reach critical changes (end-diastolic blood flow is preserved); III degree: critical disturbances of fetal-placental blood flow (absence or reverse diastolic blood flow) with preserved or impaired uteroplacental blood flow. A directly proportional relationship with a high correlation coefficient was noted between the degree of hemodynamic disturbances and clinical manifestations of decompensated placental insufficiency in the form of intrauterine growth retardation, fetal hypoxia, antenatal fetal distress with high perinatal losses (Dopplerography in obstetrics / Edited by MB Medvedev, A. Kuryak, E .V. Yudina, 1999). In the first degree of disturbances of uteroplacental-fetal hemodynamics, an isolated disturbance is observed in only one (uteroplacental or fetal-placental) component of the blood flow. If we consider that uteroplacental and fetal-placental hemodynamics are two links of one uteroplacental-fetal blood flow, it is difficult to imagine that pathological changes in the first link do not affect the second. Isolated disturbances of placental-fetal blood flow are most often associated with anatomical malformations, disturbances in the structure of the placenta, malformations of the uterus, and malformations of the fetal heart and its cardiovascular system. In the third degree of disturbance of the uteroplacental fetal blood flow, when a zero or reverse diastolic component of blood flow is recorded, the fetus develops such severe metabolic changes in vital organs that even emergency delivery does not save the life of the newborn. Disturbances in blood flow in the small vessels of the villous tree lead to changes in two links of the fetoplacental complex and, as a rule, the intensity of blood flow in the uteroplacental link primarily decreases. To maintain the vital functions of the fetus, compensatory changes occur secondarily in the placental-fetal link in the form of an increase in the intensity of blood flow. The umbilical cord blood flow resistance index decreases, but its absolute values ​​do not go beyond the 5-95 percentile. Here it is more important to determine not the absolute values ​​of the resistance index, but to evaluate their ratio. In a physiologically developing pregnancy without placental insufficiency, the intensity of blood flow increases until the end of pregnancy in both the uteroplacental and placental-fetal links. The ratio of the uterine artery resistance index to the umbilical artery resistance index during the third trimester is less than one relative unit (0.7-0.95 units). With the development of secondary placental insufficiency, the intensity of uterine blood flow decreases, the resistance index of the uterine arteries increases, and the speed of blood flow in the umbilical cord artery compensatory increases, which is expressed by a decrease in the numerical values ​​of the resistance index. In this case, the ratio of the resistance index of the uterine arteries to the resistance index in the umbilical cord artery becomes greater than or equal to one. With ineffective treatment and progression of secondary placental insufficiency, the speed of blood flow in the uterine arteries continues to decrease, the compensatory activity of the placental-fetal blood flow is depleted, and decompensation occurs, which is manifested by a decrease in the intensity of blood flow in the umbilical cord artery. These changes lead to pathological values ​​of blood flow indicators in the uteroplacental and placental-fetal link, which do not go beyond the 5-95th percentile and are considered as grades 1 and 2 of disorders of the uteroplacental-fetal blood flow (according to the classification of M. V. Medvedev). Pathological deviations of the resistance index above the 95th percentile occur, as a rule, with a long course of placental insufficiency, when decompensation of placental function occurs, which is confirmed by clinical manifestations of placental insufficiency in the form of intrauterine growth retardation, fetal hypoxia with adverse perinatal outcomes. The main disadvantages of the method under consideration should be considered the late diagnosis of the decompensated stage of placental insufficiency, without taking into account the pathogenetic nature of the processes occurring (possible primary placental insufficiency, malformations of the fetus and placenta) and without taking into account the mutually occurring processes in the two links of the utero-placental-fetal complex. The objective of the invention is to improve the accuracy of diagnosis of the initial manifestations of secondary placental insufficiency of the hemodynamic type. The task is achieved by preliminarily excluding cases of primary placental insufficiency during pregnancy 30-31 weeks, and if the ratio of the uterine artery resistance index to the umbilical cord artery resistance index corresponds to 0.7-0.95 relative units, the absence of secondary placental insufficiency is diagnosed, if the ratio of the resistance index of the uterine artery to the resistance index of the umbilical artery is greater than or equal to 1, hemodynamic disorders in the utero-placental-fetal complex are diagnosed, characterizing the initial manifestations of secondary placental insufficiency. It is known that placental-fetal blood flow is completely established by 30 weeks of pregnancy (Medvedev MB et al., 1992). Characteristic features of blood flow velocity curves are their biphasic nature, a high systolic curve and a flat diastolic curve located above the isoline. If the uterine artery resistance index is between the 5th and 95th percentile for a given stage of pregnancy, we assess the blood flow to be “within normal limits,” i.e. exclude primary placental insufficiency. Then we calculate the “indicator” (P) P = IRMA/IRAP. Normally, this indicator is in the range of 0.7-0.9 relative units. This is explained by the fact that during the physiological course of pregnancy, the intensity of blood flow in the uteroplacental link is much greater than in the placental-fetal blood flow, while the resistance index of the uterine artery always has lower digital values ​​than the resistance index in the umbilical cord vessels. At the same time, we identify a group of pregnant women without pronounced primary disorders of placental insufficiency, and then we conduct a dynamic study of them in order to identify the initial manifestations of placental insufficiency in the form of disturbances of placental-fetal hemodynamics. With the development of secondary placental insufficiency in the placenta, dystrophic processes begin to prevail over regenerative ones, blood clots form in the small vessels of the terminal villi, and then in larger arteries, blood flow stops in them, infarctions and petrification are formed (G. K. Stepankovskaya et al., 1994). Morphological changes in the placenta are manifested by a significant increase in peripheral vascular resistance of the fetal part of the placenta and are expressed at the final stage in an increase in vascular resistance indices above standard values. Dynamic observation of changes in blood flow in the uteroplacental and placental-fetal units during the third trimester of pregnancy showed that these processes occur in two stages. During the initial stages of the formation of placental insufficiency, a compensatory increase in blood flow occurs, activation of blood flow both in the uteroplacental and in the fetal-placental complex. However, more significant compensatory changes still occur in the fetal-placental link; they are aimed at maintaining fetal homeostasis. As a rule, the digital values ​​of the resistance index in the uterine artery and umbilical cord artery are within the normative values, i.e. they do not exceed the 95th percentile of normal resistance index values. However, the ratio of the resistance index in the analyzed vessels changes and approaches unity or exceeds unity. This is mainly due to an increase in the speed of blood flow in the umbilical cord artery due to a relative decrease in blood flow in the uterine artery. At the second stage, the compensatory capabilities of hemodynamic processes are exhausted and their decompensation develops. At this stage, we note that the numerical values ​​of the umbilical artery resistance index approach or exceed the 95th percentile of normal resistance index values, and the ratio of the uterine artery resistance index to the umbilical artery resistance index becomes greater than or equal to one. The method is carried out as follows. All cases of primary placental insufficiency are preliminarily excluded. At 30-31 weeks of pregnancy, Doplerometry is performed to calculate the average resistance index in the two uterine arteries and the umbilical cord artery. In the absence of primary placental insufficiency and severe extragenital pathology, this indicator is in the range of 0.7-0.9 relative units. We carry out a repeat Doppler study at 34-35 weeks of pregnancy with the determination of the previously listed indicators: the average value of the resistance index in the two uterine arteries and the resistance index in the umbilical artery and calculate the ratio of the resistance index of the uterine arteries to the resistance index in the umbilical artery. With unchanged blood flow in the utero-placental-fetal complex, the speed of blood flow in the vessels of the uterus exceeds the speed of blood flow in the umbilical cord artery. With the development of secondary placental insufficiency, peripheral resistance in the small spiral and radial vessels of the uterus increases, which affects the decrease in the intensity of blood flow in the uterine arteries and leads to an increase in the digital values ​​of the uterine artery resistance index. Considering that in response to hemodynamic disturbances in the utero-placental link, to maintain homeostasis, blood flow in the placental-fetal link is activated by increasing the fetal heart rate and increasing the speed of blood flow in the umbilical cord artery. On Dopplerograms this is manifested by a decrease in the numerical values ​​of the resistance index. The changes that occur are reflected in the ratio of the resistance index of the uterine arteries to the umbilical cord artery, the digital values ​​of which become greater than or equal to one. The invention is illustrated by the following practical examples. Example 1. Pregnant F. Birth history 3245. She was under dynamic observation at the antenatal clinic No. 2 in Kursk. A standard obstetric examination was carried out with triple ultrasound examination and Doppler examination at 31 and 35 weeks of pregnancy. Ultrasound examination revealed the physiological course of pregnancy in the cephalic presentation of the fetus. A Doppler study at 31 weeks revealed the following indicators of the resistance index in the uterine arteries and the umbilical cord artery: IRMA = 0.553, IRAP = 0.639. The ratio of the uterine artery resistance index value to the umbilical cord artery resistance index value is 0.8. At 35 weeks of pregnancy, an ultrasound examination also did not reveal any abnormalities during pregnancy; resistance indicators in the uterine arteries were 0.533 and in the umbilical cord artery 0.649. The ratio of the uterine artery resistance index value to the umbilical cord artery resistance index value is 0.5. The birth ended on time, through the natural birth canal with a male fetus, weighing 3400 g, with an Apgar score of 8-9 points. The period of adaptation of the newborn passed without pathological deviations. The child and mother were discharged home on the sixth day. Observation by a pediatrician during the first three months did not reveal any pathological abnormalities in the child. Histological examination of the placenta revealed the following: no visible changes in the maternal and fetal surfaces were detected. Vascularization of the villi is uniform; there is a slight lymphocytic infiltration of the decidual tissue. There are small areas of fibrinoid mass deposition. Example 2. Pregnant N. Birth history 3218. Pregnant N. underwent a routine ultrasound and Doppler examination at 30 weeks. Ultrasound examination revealed no pathology. The resistance index of the uterine artery is 0.475, the resistance index of the umbilical artery is 0.633. The ratio of the uterine artery resistance index value to the umbilical cord artery resistance index value is 0.62. At 35 weeks, the pregnant woman consulted a gastrointestinal doctor with complaints of pain in the lower abdomen. After a clinical and ultrasound examination, the following diagnosis was made: 35 weeks. Threat of miscarriage of moderate severity. Chronic placental insufficiency, stage of compensation. When performing Doppler measurements, the resistance index of the uterine artery was 0.471, the resistance index in the umbilical artery was 0.507. The ratio of the uterine artery resistance index value to the umbilical cord artery resistance index value is 0.94. The patient was hospitalized in a hospital, where conservation therapy and treatment of placental insufficiency were carried out. The baby was preserved, the birth occurred at 39 weeks, a female fetus, weighing 3250, with an Angar score of 8-9 points. The adaptation period proceeded without complications. The woman was discharged home on the 5th day along with the child. Histological examination of the placenta revealed the following: pronounced lobulation of the placenta is noted. There are areas of calcification and fibrosis. The phenomena of hypervascularization of villi, sclerosis and fibrinoid swelling of the stroma. Example 3. Pregnant M. Birth history 2415. Pregnant M, 35 years old, came to the hospital at 30 weeks with complaints of swelling of the legs. A clinical examination revealed the following: blood pressure 150/110 mm Hg, proteinuria 0.132 g/l. An ultrasound examination revealed grade 1-2 IUGR, placental maturity degree III. When performing Doppler measurements, the resistance index of the uterine artery was 0.989, the resistance index in the umbilical artery was 0.786. The ratio of the uterine artery resistance index value to the umbilical cord artery resistance index value is 1.1. Based on the examination, a diagnosis was made: 30 weeks. Moderate gestosis. Chronic placental insufficiency, subcompensation stage. Intrauterine growth retardation, grade 1-2. The woman was hospitalized in a hospital, where gestosis and chronic placental insufficiency were treated. Despite the treatment, the woman continued to have symptoms of gestosis and signs of fetal distress. When performing Doppler measurements, the resistance index of the uterine artery was 0.759, the resistance index in the umbilical artery was 0.629. The ratio of the uterine artery resistance index value to the umbilical cord artery resistance index value is 1.2. The diagnosis was made: 34 weeks. Preeclampsia of severe severity (by duration). Chronic placental insufficiency, stage of decompensation of IUGR, 2nd degree. Early delivery was performed. As a result of the cesarean section, a live male fetus was born, weighing 2200 g, with an Apgar score of 4-5 points. After birth, the child was in the neonatal intensive care unit with a diagnosis of severe fetal hypoxia. Respiratory distress syndrome. Intrauterine fetal hypotrophy. On the tenth day, the woman was discharged along with the child for the second stage of rehabilitation. Histological examination of the placenta revealed the following: significant areas of calcification and pronounced lobulation are noted. There are disturbances in the maturation of the villous chorion, narrowing of the intervillous space. More than 25% of the volume is occupied by infarctions, intravascular and intervillous thrombi. Thus, the goal was achieved by taking into account the pathogenetic nature of the processes occurring in the mother-placenta-fetus system by excluding all cases of primary placental insufficiency based on normal indicators of the resistance index in the uterine arteries and umbilical cord artery; conducting dynamic monitoring of changes in blood flow indicators in the uteroplacental and placental-fetal circulation in order to identify the initial manifestations of placental insufficiency in the form of disturbances in uteroplacental and placental-fetal hemodynamics; studies of the compensatory capabilities of placental-fetal blood flow. With the initial manifestations of placental insufficiency, both the uteroplacental and fetal-placental blood flow are activated, but more significant compensatory changes develop in the placental-fetal link, aimed at maintaining the compensatory link of fetal homeostasis. These processes lead to an increase in the speed of blood flow in the umbilical artery due to a relative decrease in blood flow in the uterine artery. When performing Doplerometry, this change in hemodynamic state leads to an increase in the numerical values ​​of the resistance index in the uterine artery and a decrease in the numerical values ​​of the resistance index in the umbilical artery. The ratio of the resistance index in the analyzed vessels approaches one or exceeds one. Further deterioration of blood circulation leads to depletion of the compensatory capabilities of hemodynamic processes, the development of their decompensation, the ratio of the numerical values ​​of the uterine artery resistance index to the numerical value of the umbilical cord artery resistance index becomes greater than or equal to one.  FORMULA OF THE INVENTION A method for diagnosing secondary placental insufficiency by simultaneous Doppler measurement at 34-35 weeks of pregnancy of the resistance index in the uterine arteries and umbilical cord artery with subsequent calculation of the ratio of the uterine artery resistance index to the umbilical cord artery resistance index, characterized in that cases of primary placental insufficiency are first excluded at a gestational age of 30-31 weeks and, if the ratio of the uterine artery resistance index to the umbilical cord artery resistance index corresponds to 0.7-0.95 relative units, the absence of secondary placental insufficiency is diagnosed if the ratio of the uterine artery resistance index to the umbilical cord artery resistance index is greater than or equal to 1 - hemodynamic disorders in the utero-placental-fetal complex are diagnosed, characterizing the initial manifestations of secondary placental insufficiency.