RU2577759C1 - Method for prediction of clinical outcome of pregnancy in women with thrombophilia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to obstetrics, and can be used for prediction of risk of pathology of is embryo and extra-embryo structures in pregnant women with thrombophilia. In the first trimester the Doppler examination of blood circulation in trophoblast vessels is made. Duplex scanning is performed in the mode of colour Doppler Imaging. At annular, intermittent types and single loci of blood flow the additionally triplex scanning is made. Control volume is placed in a projection of trophoblast vessels and resistance index (IR) of trophoblast vessels is determined. When IR is less than 0.5 adequate blood flow is identified and a favorable outcome of pregnancy is predicted. When IR exceeds 0.5, or in the absence of blood flow in vessels of the trophoblast the inadequate blood flow and a high risk of adverse pregnancy outcome are predicted during duplex scanning process.

EFFECT: method enables more reliable prediction of risk of developing complications in the embryo and extra-embryo structures in pregnant women with thrombophilia, forming a risk group at the stage of ultrasonic examination in the first trimester.

1 cl, 4 ex

Description

The present invention relates to medicine, namely to obstetrics, and can be used to predict the risk of developing pathology of the embryo and extraembryonic structures in pregnant women with thrombophilia caused by a mutation of the MTHFR gene in the first trimester.

A significant role in preserving and strengthening the health of the population belongs to the protection of motherhood and childhood as a system of state, medical and public events aimed at protecting the health of mothers and children, as well as ensuring the fulfillment of the most important social function of a woman - the birth and upbringing of a child. (S.I. Vedischev, E.M. Osmanov, E.V. Zhernakov, A.S. Pyshkina, U.V. Zhabina. Medical and social aspects of miscarriage UDC 618.39-06-082).

Miscarriage (NL) is an urgent problem of modern obstetrics, as it is often the result of a complex of pathological factors, the identification of which requires not only a high qualification of a specialist, but also high-tech examination methods. Despite the numerous and effective methods of diagnosis and treatment developed in recent years, the frequency of NB according to the World Health Organization over several years is 20% of all desired pregnancies (15% - spontaneous miscarriages and 5% - premature births) and has no tendency to decrease. (Modern methods for diagnosing early pregnancy miscarriage. Yu.V. Kukharchik, LV Gutikova EE "Grodno State Medical University", Grodno, Belarus, Journal of Grodno State Medical University, 2012, No. 4.). In addition, the statistics do not include a large number of abortions in a very early period. (EA Kornyushina, MS Zainulina. Hemostatic system disorders, methods for their correction and pregnancy outcomes in patients with miscarriage and thrombophilia. Obstetrics and Women's Diseases Journal, vol. LVII, issue 4/2008). Women with a predisposition to thrombophilia represent a risk group not only for obstetric pathology, but also constitute, in general, a huge prognostically unfavorable part of patients with a threat of thrombotic complications, especially since the onset of pregnancy can aggravate existing coagulation disorders. (Z.S. Alekberova et al. Institute of Rheumatology, Center for Obstetrics, Gynecology and Perinatology, RAMS, Habitual miscarriage during primary antiphospholipid syndrome (Case Description). Scientific and Practical Rheumatology, 2000, No. 1).

The most common form among genetically determined thrombophilia is a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (G.K. Rapilbekova. Genetic polymorphism of methylenetetrahydrofolate reductase, hyperhomocysteinemia and folate deficiency as risk factors for the development of obstetrics, obstetrics and obstetrics, obstetrics and obstetrics, perinatology, Almaty, Kazakhstan, volume LVI, issue 3/2007).

A known method for predicting miscarriage with myometrial hypertonicity in B-mode and determining IR in the uterine arteries with hypertonicity. (Dopplerographic criteria for diagnosing the threat of termination in the first trimester of pregnancy. Balabanova TS. Abstracts of the 1st Congress of Physicians of Ultrasound Diagnostics of the Ural Federal District (Ekaterinburg, March 22-24, 2006), edited by I.G. Fedotov).

The essence of the method is the assessment of Doppler parameters in the uterine arteries and vessels of the umbilical cord in the first trimester of pregnancy as an additional diagnostic criterion for myometrial hypertonicity, recorded during the first ultrasound screening at 11-14 weeks of pregnancy.

Disadvantages: late research, myometrial hypertonicity may appear directly during an ultrasound examination, which reduces the reliability of the results.

For the closest analogue, a method has been adopted for determining the threat of miscarriage by echographic and Doppler criteria for corpus luteum failure. (Echographic criteria for functional failure of the corpus luteum with the threat of miscarriage. Ageeva MI, Baysangurova Z. Kh., Abstracts of the 5th Congress of the Russian Association of Ultrasound Diagnostic Specialists. 2007, No. 4,).

The essence of the method lies in the fact that they form a risk group for the threat of miscarriage during functional insufficiency of the corpus luteum in pregnant women using ultrasound and evaluation of Dopplerometry parameters, with CDK and measuring the value of IR in the vessels of the corpus luteum. The disadvantage of this method is that not always insufficient blood flow in the corpus luteum leads to a violation of blood flow in the uterine arteries and vessels of the trophoblast. The method is unreliable.

Tasks:

1. Provide a prognosis of pregnancy outcome in patients with thrombophilia caused by a mutation of the MTHFR gene at an earlier date.

2. To increase the reliability of the method.

The inventive Doppler study of blood flow in the vessels of trophoblast is carried out in the first trimester, performing duplex scanning in the color Doppler mapping mode, and with annular, intermittent types and single loci of blood flow, additional triplex scanning is carried out, placing the control volume in the projection of the trophoblast vessels, the resistance index is determined ( IR) of trophoblast vessels, with IR less than 0.5, adequate blood flow is detected and a favorable pregnancy outcome is predicted; with IR greater than 0.5, as well as in the absence of blood flow in the vessels of the trophoblast, when performing duplex scanning, an inadequate type of blood flow is determined and a high risk of an adverse pregnancy outcome is predicted.

The method allows:

- to predict more reliably the risk of complications in the embryo and extraembryonic structures in pregnant women with thrombophilia caused by a mutation of the MTHFR gene in the first trimester;

- at the stage of ultrasound in the first trimester to form risk groups;

- reliable identification of risk groups;

- apply the method as an additional Doppler study when conducting a standard ultrasound examination in the first trimester of pregnancy in pregnant women with thrombophilia.

The achievement of a more effective diagnostic result is due to the fact that the Doppler study of blood flow in the vessels of the trophoblast is carried out in the first trimester, performing duplex scanning in the color Doppler mapping mode, and in the case of annular, intermittent types and single blood flow loci, additional triplex scanning is carried out, placing the control volume in the vascular projection trophoblast, determine the index of resistance (IR) of the vessels of the trophoblast, with IR less than 0.5, adequate blood flow is detected predict a favorable outcome of pregnancy; with IR greater than 0.5, as well as in the absence of blood flow in the vessels of the trophoblast, when performing duplex scanning, an inadequate type of blood flow is determined and a high risk of an adverse pregnancy outcome is predicted. The method was tested in 80 (100%) pregnant women in the first trimester of pregnancy with a diagnosis of thrombophilia caused by a mutation in the MTHFR gene. In the study of 80 pregnant women, 40 (50%) pregnant women - group I - underwent an echographic study of the embryo and extraembryonic structures, and 40 (50%) pregnant women - group II underwent an additional Dopplerometric study of blood flow in the vessels of the trophoblast. When conducting a study in group I, echo-signs were determined in 4 (10%) pregnant women, which allowed them to be attributed to the risk group for spontaneous miscarriage and undeveloped pregnancy (reduction of the amniotic cavity in 3 pregnant women and 1 pregnant identified chorion fragmentation). During an additional Doppler study in pregnant women in the second group, the types of trophoblastic blood flow were distinguished: in 17 (42.5%) - ring-shaped; 7 (17.5%) - intermittent, 6 (15%) - single loci, 10 - (25%) lack of blood flow. Moreover, in 10 (25%), the absence of blood flow in the vessels of the trophoblast was determined and, therefore, this group has a high degree of risk of developing spontaneous miscarriage and non-developing pregnancy, and in the case of ring-shaped, intermittent, single loci of blood types, additional triplex scanning is carried out, placing the control volume in the projection trophoblast vessels, fix the curve of the Doppler spectrum, on this curve I place the cursors at the maximum systolic and final diastolic speeds and calculate resistance dex (a quantitative indicator in this Doppler spectrum curve): in 19 (47.5%) the resistance index is less than 0.5 and, thus, an adequate blood flow and prognosis of a favorable pregnancy outcome are revealed, and in 11 (27.5%) more 0.5 - inadequate type of blood flow and a high degree of risk of adverse pregnancy outcome. Thus, 21 (52.5%) pregnant women from the second group entered the risk group for developing spontaneous miscarriage and non-developing pregnancy. All pregnant women who were at risk were referred to a hematologist for advice and were prescribed anticoagulant therapy, after which 6 (17.5%) pregnant women did not have blood flow loci, and with other types of trophoblastic blood flow, a resistance index of more than 0.5 was determined in 5 (12.5%) pregnant. Consequently, the number of pregnant women who were at risk of developing spontaneous miscarriage and non-developing pregnancy after prescribing anticoagulant therapy decreased and amounted to only 11 (27.5%).

The outcomes of all pregnancies were evaluated: 18 (45%) of the pregnant women from group I had a miscarriage and an undeveloped pregnancy, and 27 (55%) of the pregnancies ended in delivery on time. In group II, 5 (12.5%) pregnancies ended in spontaneous miscarriages and an undeveloped pregnancy, and 35 (87.5%) pregnancies ended in delivery on time.

From the above it can be concluded that the reliability of the research method that was used in group I is lower compared to the reliability of the method that was used in group II. Thus, the proposed method using additional Dopplerometric studies in the vessels of the trophoblast can be used to determine the risk of developing spontaneous miscarriage and non-developing pregnancy and reduce the frequency of spontaneous miscarriages and non-developing pregnancy by more than 3 times.

Example 1 (see photo 1,2: photo 1 - B and flow modes are presented, with Color Doppler Mapping (CDM) - an adequate ring-shaped type of blood flow, photo 2 shows a triplex scan with a quantitative indicator of blood flow, IR less than 0, 5).

A pregnant woman born in 1980 applied for an ultrasound scan. Third pregnancy, third birth, obstetric history is not burdened. Before pregnancy, a comprehensive examination was carried out and the results revealed a genetic predisposition to hereditary thrombophilia caused by a mutation in the MTHFR gene, but at the time of this pregnancy, changes in the rheological properties of the blood were not detected. At the time of the examination, the gestational age was 8–9 weeks. When determining trophoblastic blood flow with CDK, there is an adequate annular blood flow, with a triplex scan of IR = 0.46, so the woman did not fall into the risk group. All subsequent echographic and dopplerometric studies were within normal limits and at 39 weeks of gestation a girl was born weighing 3560 g, body length 56 cm, with no apparent pathology.

Example 2 (see photo 3.4: photo 3 - B and flow modes are presented, with CDC - intermittent type of blood flow, photo 4 shows a triplex scan with a quantitative determination of blood flow, IR more than 0.5)

To conduct an ultrasound examination, a pregnant woman was born in 1976. Second pregnancy, first birth, obstetric history was burdened (in 2010 there was an undeveloped pregnancy of 5 weeks), the patient was diagnosed with thrombophilia caused by a mutation in the MTHFR gene. At the time of the examination, the gestational age was 8–9 weeks. When determining trophoblastic blood flow in CDC, there is an intermittent type of blood flow, when conducting a triplex scan, IR = 0.53, so the woman is at risk. The patient was referred to a hematologist and anticoagulant therapy was prescribed, after which the study of trophoblastic blood flow was carried out again and against the background of anticoagulant therapy, IR was 0.49. However, subsequent echographic and dopplerometric studies were after 16 weeks with periodic impaired hemodynamics IA. At 37 weeks of gestation, a girl was born weighing 2670 g, body length 49 cm, with no apparent pathology.

Example 3 (see photo 5.6: photo 5 - B and flow modes are presented, with CDK - single blood flow loci along the chorionic basement membrane, photo 6 shows a triplex scan with a quantitative determination of blood flow, IR more than 0.5) .

A pregnant woman born in 1986 applied for an ultrasound examination. Third pregnancy, first birth, obstetric history was burdened (in 2011 and 2012 there were undeveloped pregnancies at 5 and 7 weeks), the patient was diagnosed with thrombophilia caused by a mutation in the MTHFR gene. At the time of the examination, the gestational age was 9 weeks. When determining trophoblastic blood flow in CDC, there are single blood flow loci; when conducting a triplex scan, IR = 0.56, thus, a woman is at risk. The patient was referred to a hematologist and anticoagulant therapy was prescribed, after which the study of trophoblastic blood flow was carried out again and against the background of anticoagulant therapy, IR was 0.53. Subsequent Doppler studies were with impaired blood flow, first in the vessels of the trophoblast, then after 16 weeks with impaired hemodynamics of the II degree. At week 26, antenatal fetal death was recorded.

Example 4 (see photo 7; photo 7 - B and flow modes are presented, with CDK the absence of blood flow loci in the chorion).

A pregnant woman born in 1970 applied for an ultrasound examination. Fifth pregnancy, second birth, obstetric history was burdened (in 1995 there was an abortion for a period of 6 weeks, then for 8 years it was treated for infertility and in 2004 there was a pregnancy that stopped developing for a period of 15 weeks, then in 2006 there was a pregnancy and a boy was born at 37 weeks, weighing 2850 g and 52 cm, all of this pregnancy had a violation of hemodynamics IA, periodically turning into grade 2. In 2011, there was an undeveloped pregnancy of 5 weeks, the patient was diagnosed with thrombophilia caused by a mutation in the MTHFR gene. and the time of examination, the gestational age was 5-6 weeks. When determining trophoblastic blood flow with CDC - the absence of blood flow loci, so the woman is at risk. The patient was referred to a hematologist and anticoagulant therapy was prescribed, after which the trophoblastic study was conducted blood flow and against the background of anticoagulant therapy, an improvement in blood flow in the vessels of the trophoblast was not observed. This pregnancy stopped developing at a period of 9 weeks.

Claims (1)

A method for predicting the outcome of pregnancy in women with thrombophilia, including a Doppler study, characterized in that the Doppler study of blood flow in the vessels of the trophoblast is carried out in the first trimester, performing duplex scanning in the color Doppler mapping mode, and in the case of ring-shaped, intermittent types and single blood flow loci, additionally triplex scanning, placing the control volume in the projection of the vessels of the trophoblast, determine the resistance index (IR) of satisfactory, with IR less than 0.5, adequate blood flow is detected and a favorable pregnancy outcome is predicted; with IR greater than 0.5, as well as in the absence of blood flow in the vessels of the trophoblast, when performing duplex scanning, an inadequate type of blood flow is determined and a high risk of an adverse pregnancy outcome is predicted.

Images