Method for predicting gestosis in pregnant women with the risk for miscarriage of infectious genesis

FIELD: medicine, obstetrics, gynecology.

SUBSTANCE: in the first trimester of pregnancy one should study the content of CD8+CD11b lymphocytes and at their values being either equal or above 2% it is possible to predict gestosis. The present innovation enables to choose correct tactics of treating pregnant women that, in its turn, leads to decreased frequency of this complication of pregnancy and the risk for the development of fetal and neonatal pathology.

EFFECT: higher accuracy of prediction.

3 ex, 1 tbl

 

The invention relates to medicine, namely to obstetrics and gynecology, and can be used to predict the development of preeclampsia in women with threatened miscarriage of infectious Genesis in the first trimester.

Miscarriage remains one of the main problems of modern obstetrics. The frequency of miscarriage ranges from 10 to 25%, and in the first trimester is 50% of spontaneous abortions (5). Among the causes of miscarriage are one of the leading places occupied by urogenital infection, 29,3-43.1% of cases, causing a threat of miscarriage (11, 12, 14). In women with threatened miscarriage of infectious Genesis most often is a complication of pregnancy like preeclampsia (12, 13, 15). The frequency of preeclampsia remains high and is according to different authors from 3.5 to 20% (5, 6, 8). Preeclampsia is a risk factor maternal (11,4%) and perinatal mortality (44%) (5). Prediction of complication of pregnancy, especially its pre-clinical and early pregnancy represents a difficult clinical problem.

There is a method of prediction of preeclampsia by determining the level of lipids and phospholipids in the urine during pregnancy and 20-24 8-12 weeks (3). When the levels of lipids 513,1+65,8 and 706,4+84,7 optical unit p is h and phospholipids 5,74+1,7 and 16.5+6,1 mg/l predicted preeclampsia.

The accuracy of the method and 64.5%.

The method has drawbacks:

- the need for a dual examination of the pregnant woman in 8-12 20-24 weeks of pregnancy;

- bad choice of substrate studies, since the advent of the lipids and phospholipids in the urine is characteristic for chronic diseases of the urinary system nephritis and pyelonephritis) and other somatic pathology;

- low accuracy.

The closest technical solution is a method for predicting preeclampsia by determining the relative content of T-suppressor cells in peripheral venous blood and the rate of 18% or less predicted the development of this complication of pregnancy (4).

This method is chosen as the closest analogue (prototype).

The disadvantages of the prototype method are;

- do not specify the duration of pregnancy, which is recommended to conduct a survey;

- currently there is no such thing as a "population of T-suppressors, and the population of T-lymphocytes, previously designated by this term, is called cytotoxic T-lymphocytes (or CD8+), the function of which is different from the function pool suppressor lymphocytes, which worked authors (10);

when preeclampsia content CD8+ T cells, most accurately reflects the number of cytotoxic T-lymphocytes, the practice is Cesky does not change (9);

- the level of cytotoxic lymphocytes decreases in infectious and autoimmune diseases (viral hepatitis a and b, chronic otitis, uveitis, pneumonia in acute, chronic bronchitis, rheumatism, rheumatoid arthritis, systemic lupus erythematosus, exacerbation of chronic glomerulonephritis) and some somatic diseases, including pyelonephritis and myocarditis (7).

- do not specify the accuracy of the method.

These drawbacks can be eliminated in the proposed method.

The claimed technical result is achieved that in the first trimester of pregnancy (6-13 weeks) in peripheral venous blood of pregnant women with threatened miscarriage of infectious Genesis determine the relative content of CD8+D11b+lymphocytes and the values of this index is equal to or more than 2%, predict the development of preeclampsia with precision 83,33%, sensitivity 84,00% and specificity 80,00%.

The novelty of the proposed method lies in the fact that for the first time proposed to predict preeclampsia, by definition, the relative content of CD8+CD11b+cells in peripheral venous blood of pregnant women with threatened miscarriage of infectious Genesis in the first trimester of pregnancy.

Earlier studies of the level of CD8+CD11b+cells in pregnant women in order to predict preeclampsia was not conducted.

But what was shown what in the peripheral blood of pregnant women with severe preeclampsia at 32-40 weeks of gestation significantly increased the content of total population of CD11b+lymphocytes (9).

We assume that the gain on early pregnancy in the expression of CD11b molecules promotes migration of activated CD8+CD11b+) cytotoxic lymphocytes from the vasculature into the tissue with the subsequent development of pathological reactions both at the system and at the placental level.

The method is performed by a standard method as follows (1):

1. the selection of lymphocytes from peripheral venous blood;

2. 100 μl of lymphocytes in a concentration of 1×106cells/ml are incubated with 20 μl of monoclonal anti-CD8, FITC labeled with 20 μl of monoclonal anti-CD11b, labeled D, for 30 minutes at room temperature in the dark, after which the cells washed 1 time with 1 ml of saline by centrifugation at 1500 rpm for 2 minutes. Cells resuspended in 500 μl of saline. The reaction accounting is performed on a flow cytometer, determining the content of CD8+CD11b+cells in the lymphocyte gate. The result is read in percent (%).

Significant differences of the claimed method are:

- proposed a new prognostic parameter in the relative content of CD8+CD11b+cells in peripheral venous blood from jensens threat of miscarriage of infectious Genesis in the first trimester of pregnancy - equal to or more than 2%, is to predict the development of preeclampsia.

The essence of the proposed method is illustrated by the following examples.

Example 1: a Pregnant W., 24 years. This second pregnancy. The first pregnancy ended in miscarriage in the period of 8 weeks. In the period of 6-7 weeks was admitted to the hospital complaining of nagging pain in the lower abdomen, spotting from the genital tract. According to ultrasound - pregnancy 7 weeks, hypertonicity of the uterus, echoprint detachment of the ovum. Diagnosis: Pregnancy 7 weeks. Burdened obstetric history. Threatening miscarriage. According to the survey on urogenital infection detected antigens of chlamydia in the cervical canal and IgM antibodies to chlamydia in the peripheral blood. During the examination of the inventive method: the relative content of CD8+D11b+lymphocyte - 3.9%, which is above the forecast level for the development of preeclampsia, it is predicted the development of preeclampsia. After saving therapy she was discharged from the hospital with progressive pregnancy in the period of 10 weeks. When surveyed in 34 weeks pregnancy pregnant III. the observed increase in the blood pressure to 140/90 mm Hg, edema of the legs, the presence of pathological weight gain per week 600 g, the total weight gain was 12 kg, proteinuria of 0.066 g/L. Basemanagedentity in the hospital with a diagnosis of Pregnancy 34 weeks. Burdened obstetric history. Preeclampsia (nephropathy first degree). The pregnancy ended in timely delivery and birth of full-term newborn weighing 3200 g, 52 cm tall, with rating on a scale of Apgar 8/9 points. Conclusion: the prognosis of the claimed method was confirmed.

Example 2: a Pregnant E., 25 years. This second pregnancy. The first pregnancy ended in timely delivery and birth of full-term newborn weighing 3000 grams and height of 50 cm, with rating on a scale of Apgar 8/9 points. In the period of 12 weeks was admitted to the hospital with complaints dragging pain in the abdomen, according to ultrasound - pregnancy 12 weeks, hypertonicity of the uterus. Diagnosis: Pregnancy 12 weeks. Threatening miscarriage. According to the survey on urogenital infection identified antigens of chlamydia and Ureaplasma in the cervical canal. During the examination of the inventive method: the relative content of CD8+D11b+lymphocyte - 0.2%, which is below the forecast level for the development of preeclampsia, the development of preeclampsia is not expected. After saving therapy she was discharged from the hospital with progressive pregnancy in the period 14-15 weeks. When surveyed in 37 weeks signs of preeclampsia is not revealed. The pregnancy ended in timely delivery and birth of full-term newborn weighing 3000 g, the height of 51 cm, with an estimate of the scale And the Gare 8/9 points. Conclusion: the prognosis of the claimed method was confirmed.

Example 3: a Pregnant K., 22 years. This first pregnancy. Admitted to the hospital complaining of nagging pain in the lower abdomen, Danna m ultrasound pregnancy 10 weeks, the increase in uterine tone. Diagnosis: Pregnancy 10 weeks. Threatening miscarriage. According to the survey on urogenital infection detected in the blood of antibodies of class IgG antibodies to herpes simplex virus type 2 and trichomonads. During the examination of the inventive method: the relative content of CD8+D11b+Limpopo - 2%, which is predictive in the development of preeclampsia, it is predicted the development of preeclampsia. After saving therapy she was discharged from the hospital with progressive pregnancy in the period of 13 weeks. When surveyed in 36 weeks of pregnancy in pregnant K. revealed swelling of the legs, abnormal weight gain per week 550 g, the total gain weight 13 kg diagnosis: Pregnancy 36 weeks. Preeclampsia (dropsy of the first degree). The pregnancy ended in timely delivery and birth of full-term newborn weighing 3500 g, height of 54 cm, with rating on a scale of Apgar 8/9 points. Conclusion: the prognosis of the claimed method was confirmed.

In this way were examined 30 women at 6-13 weeks of gestation. The research results are summarized in table 1.

Table 1
IndexThe number of the examined
Total female30
true-positive result21
false-positive result1
a true-negative result4
a false-negative result4
Total: the accuracy of the proposed method - 83,33%, the sensitivity of the proposed method is 84%, specificity of the proposed method - 80%

The advantages of the proposed method:

1. The study of peripheral venous blood of the woman is in early pregnancy (6-13 weeks), that allows to clinical manifestations of the disease to predict preeclampsia and timely measures.

2. Set the relative content of CD8+CD11b+cells in peripheral venous blood in women in the first trimester of pregnancy, is equal to or more than 2%, which predicted the development of preeclampsia.

3. High precision 83,33%, a sensitivity of 84% and specificity of 80% of the way.

Thus, the claimed method is simple to perform and allows high accuracy to predict the development of preeclampsia in women with the threat of Nevins the of pregnancy infectious Genesis in the examination in the first trimester of pregnancy, that will allow you to choose the right tactics for the management of women at risk of developing preeclampsia and will help reduce the frequency of this complication of pregnancy, the risk of developing pathology of the fetus and newborn and reduce the economic cost of treatment.

References:

1. Boyum A. Isolation of mononuclear cell and granulocytes from human blood and bone marrow // Scand.J.Clin.Lab.Invest. - 1968. -V.21. No. 97. - R.

2. Cetlinski S.A., Kalinin NM Immunology for clinicians //s-Pb. - 1998. - S.

3. Muratova P.M., V. Krasnopolsky, St. George E.A., N.V. Alexeeva, exaltation Y.S. a Method for predicting a late toxicosis of pregnant women. Copyright certificate №1572534.

4. Chernova BECAUSE, the great) DU a Method for predicting a late toxicosis of pregnant women. Copyright certificate №1748066

5. Serov V.N., The summary A.N., Markin, S.A. Manual of practical obstetrics. M: LLC "Medical information Agency, 1997

6. Sidorov, I.S. pharmacological prevention of late gestosis//Herald of the Russian Association of obstetricians and gynecologists. - 1994. No. 1. - Pp.33-38.7.

7. Clinical immunology: a Textbook for medical students/edited Averella. - M: Medical information Agency, 1999. - 604 S.

8. Panova I.A. the Role of specific and nonspecific protein of human reproductive system in the Genesis of preeclampsia. - Abstract. dis... Kida. the honey. Sciences. - M., 1995. - 23 S.

9. And is trough NV Features of the phenotype and cytokine profile of the decidual lymphoid cells in preeclampsia. - Abstract. dis... Kida. the honey. Sciences. - M., 2002. - 23C.

10. The Yarylo AA "fundamentals of immunology": Tutorial. - M.: Medicine. - 1999. - str.

11. Tereshina, L.P. Tract infections in women with recurrent miscarriages// Journal of obstetrics and female diseases. Spec. release. - 1998. - P.46.

12. Simakova MG, Smirnov, V.S., A. Durov Clinic, diagnostics and treatment of intrauterine infection// Obstetrics and gynecology. - 1995. No. 4. - P.7-9.

13. ECCO L.A. Modern medical technologies for the early diagnosis and treatment of intrauterine infection and placental insufficiency// health Protection of mother and child. The book of abstracts. The role of infection in the pathology of the reproductive system in women, the fetus and newborn. - Moscow. - MORAG EXPO. - 2000. - P.119-121.

14. Oboskalova T.A. the Role of STI in the development of complications of pregnancy, Journal of obstetrics and female diseases. Spec. release. -1998. - P.44.

15. Kosheleva N.G. Urogenital infection and miscarriage//World of Medicine. - 1999. - №3-4.

A method for predicting preeclampsia in women with threatened miscarriage of infectious Genesis through study of peripheral venous blood, characterized in that in the 1st trimester of pregnancy examine the content of CD8+lymphocytes and CD11b if the values are equal, or Bo is 2%, predict preeclampsia.



 

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