RU2382361C1 - Method for prediction of intrauterine fetal infection - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to obstetrics and gynaecology. To predict intrauterine fetal infection, the blood of pregnant women is analysed for the level of placenta growth factor (PGF) and thermostable alkaline phosphatase (TAP) with following data analysis. Besides the blood is analysed for lymphocytes CD95 + count, interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNFα) concentrations. If values are as follows: PGF level (pcg/ml) - 157±10.9; TAP level (Un/l) - 86±7.3; lymphocytes CD95 + count (%) - 58.2±3.4; IL-1β concentration (pcg/ml) - 148±14.3; TNFα concentration (pcg/ml) - 1216±136.4, intrauterine fetal infection is predicted.

EFFECT: method is noninvasive, safe-health for the pregnant woman and foetus, accessible, improves accuracy of prediction of intrauterine fetal infection.

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Description

The risk of intrauterine infection of the fetus is significantly increased with a high activity of the infectious process in a pregnant woman, the presence of immunodeficiency, impaired immunobiological gestational tolerance, the development of placental insufficiency (Senchuk A.Ya., Dubossarskaya Z.M. Perinatal infections. M .: MIA, 2005. S .7-12).

The current level of obstetrics and perinatology currently excludes the possibility of reliable diagnosis of intrauterine infection in the fetus, even in the presence of infection in the pregnant woman (Orekhov N.V. Intrauterine infections and pathology of newborns. M: Medpraktika - M., 2002. P. 9-16 )

The diagnosis of intrauterine infection is made in the vast majority of cases retrospectively according to the results of clinical and laboratory and instrumental examination of newborns (Sidorova I.S., Makarov I.O., Matvienko N.A. Intrauterine infections. M .: MIA, 2006. P.4 -5).

In recent years, given the important role of the immune system in the regulation of homeostasis during infection, much attention has been paid to the search for immunological criteria for intrauterine infection of the fetus based on a study of the peripheral blood of pregnant women, since this excludes invasive intervention in the fetoplacental complex (Belokritskaya T.E., Vitkovsky Yu .A. Cytokines in the mother-fetus system with fetal growth retardation syndrome. Obstetrics and gynecology, 1999. - No. 5. - P.15-17).

The process of formation and functioning of the fetoplacental complex is controlled by processes unified in their biological essence and mutually opposite in biological effect: cell proliferation due to the action of growth factors, and apoptosis - programmed cell death due to the action of the so-called “death ligands” (Radzinsky V.E. , Orazmuradov A.A. Early pregnancy. M., 2005).

In recent years, a major role in the development of violations of the protective functions of the placenta has been attributed to the violation of immune relationships in the mother-placenta-fetus system (Chistyakova G.N., Gaziev I.A., Cherdantseva G.A. Expression of markers of activation of the immune system in early pregnancy. Immunology, 2004. - No. 6.- S. 377-378).

It is believed that one of the mechanisms that prevent unwanted immune reactions caused by infection, at the interface between the mother and the fetus, is trophoblast-induced lymphocyte apoptosis. Under experimental conditions, it was shown that trophoblast cells enriched with multinuclear fragments of syncytiotrophoblasts induce the most efficient lymphocyte apoptosis. Late placenta cytotrophoblast cells obtained from a woman with a physiological pregnancy induce a lesser increase in lymphocyte apoptosis. And finally, early placenta cytotrophoblast cells (I trimester of pregnancy) have almost no effect on lymphocyte apoptosis (Talayev V.Yu., Babaykina ON, Lomunova MA et al. Effect of human placenta cytotrophy and synthisotrophoblast on lymphocyte apoptosis Immunology, 2005. - No. 3. - S.132-138).

The early mechanisms of the regulation of reactions caused by the damaging effect of the infectious agent on the fetoplacental complex are associated with a change in the function of immunocompetent cells, realized through the action of pro-inflammatory and anti-inflammatory cytokines. Subsequently, with an increase in the alternative-exudative processes, a significant change in the ratio of immune factors occurs with an increase in the pro-inflammatory link with an imbalance of anti-inflammatory interleukins. To reduce the functional aggression of activated lymphocytes by trophoblast, apoptosis of immunocompetent cells is induced (Makatsaria AD, Bitsadze VO, Akinkina SV Syndrome of a systemic inflammatory response in obstetrics. M: MIA, 2006. P.305-346).

A known method for predicting intrauterine infection by morphological examination of the placenta (Radzinsky V.E., Milovanov A.P. Extraembryonic and amniotic structures in normal and complicated pregnancy. M: MIA, 2004. S.229-253).

In the known method for predicting intrauterine infection, morphological signs of inflammation of the placenta and membranes are revealed: leukocyte and lymphocytic infiltration; Hofbauer-Kashchenko cell activation; the presence of large cells with basophilic inclusions in the nucleus, surrounded by a rim of enlightenment; basal deciduitis; in vessels, the identification of giant cells with large structureless nuclei, degenerative and destructive changes in tissues, etc. If they are present, they judge the possible transmission of the infection from the mother to the fetus.

The disadvantage of this method is the late identification of a possible intrauterine infection, which does not allow timely treatment and preventive measures in pregnant women.

A known method for predicting intrauterine infection of the fetus by using an ultrasound examination of the placenta and amniotic fluid (Boznoshenko GB, Dolgikh TI, Krivchik GV Intrauterine infections (diagnostic and medical tactics). M: MedKniga; N.- Novgorod: Publishing house NGMA, 2006. S.9-15).

In the known method for predicting intrauterine infection of the fetus by ultrasound examination of the placenta, fetus and amniotic fluid, ultrasonic infection criteria are identified: multi- and oligohydramnios, hyperechoic suspension in amniotic fluid, amniotic strands, chorionic villus hypoplasia, placental edema and thickening, placenta thickening, different or doubling the contour of the basal plate, premature aging of the placenta. If available, they judge the possible transmission of infection from the mother to the fetus.

The disadvantage of this method is the low accuracy of prediction of antenatal infection due to the low credibility of ultrasound criteria, the lack of their specificity, the possibility of their registration for other pregnancy complications and fetal diseases (preeclampsia, placental insufficiency, hemolytic disease of the newborn, malformations, etc.)

Closest to the claimed is a method for predicting intrauterine infection of the fetus by recording the relative contents of subpopulations of lymphocytes and interferon levels in the blood of pregnant women by immunoluminescent and enzyme immunoassay methods (Tyutyunnik V.L., Burlev V.A., Zaydieva Z.S. Morphofunctional state of the mother - placenta - a fetus with placental insufficiency and infection. Obstetrics and gynecology, 2003, No. 6. - S.11-16.).

In this method for predicting intrauterine infection of the fetus in the diagnosis of placental insufficiency (by the level of placenta growth factor and thermostable alkaline phosphatase) in the blood of infected pregnant women, the relative contents of T-helper cells (CD4 +), B-cells (CD19 +), T-suppressors (CD8 +) were determined by calculating the immunoregulatory index (CD4 + / CD8 +), the level of α- and γ-interferons, and by their deviations from the norm, a possible infection of the fetus is judged.

The disadvantage of this closest to the claimed method is the low accuracy of predicting intrauterine infection of the fetus due to lack of information (only 53.2% of cases of intrauterine infection) due to a possible change in the cluster composition of lymphocytes with various somatic and obstetric pathologies, as well as the fact that interferon status is a non-specific defense factor and is more dependent on the production of interferons by immunocytes. This method does not take into account the levels of lymphocytes induced to apoptosis, there is no comparison with the results of postnatal verification of the diagnosis of intrauterine infection in newborns.

The problem solved by the invention is to predict intrauterine infection of the fetus. The technical result is to increase the accuracy of forecasting. The specified technical result is achieved by the fact that in the method for predicting intrauterine infection of the fetus by determining the placenta growth factor (FRF) and thermostable alkaline phosphatase (THF) in the blood of infected pregnant women (for the diagnosis of placental insufficiency, since it occurs in 100% of cases with intrauterine infection of the fetus) additionally determine the content of the apoptosis marker - SD95 + lymphocytes and the concentration of proinflammatory cytokines - interleukin one beta (IL-1β) and non-factor Rose tumor alpha (TNFa) and a change of these parameters compared to normal predicted fetal intrauterine infection.

A method for predicting intrauterine infection of the fetus is as follows.

A pregnant woman is examined for the presence of infection (chlamydial, herpetic, etc.) using the methods of polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). When an infection is detected, a pregnant woman is considered to be at high risk for intrauterine infection of the fetus. Next, the woman is examined taking into account the revealed significant differences in the studied parameters for the physiological course of gestation, for pregnancy in infected patients with placental insufficiency in the absence of intrauterine infection of the fetus and pregnancy in infected patients with placental insufficiency and with a verified diagnosis of intrauterine infection (according to the examination of newborn babies born by cesarean section, which excluded the infection factor in childbirth, when passing through the birth canal). All laboratory parameters are determined in the peripheral blood of a pregnant woman, taken once on an empty stomach.

The survey is carried out by determining:

- the level of placental growth factor;

- level of thermostable alkaline phosphatase;

- the content of lymphocytes CD95 +;

- concentrations of interleukin one beta;

- Concentration of tumor necrosis factor alpha.

The above data were obtained when determining the level of FRP and the concentration of IL-1β, TNFα in the blood serum by enzyme-linked immunosorbent assay using a set of reagents "P&D systems" (Great Britain) and Protein circuit LLP (St. Petersburg), TSPF on a biochemical analyzer “Ultra” using reagents of the company “KONE” (Finland), the identification of the lymphocyte phenotype (CD95 +) was carried out by the standard method of immunofluorescence analysis using monoclonal antibodies to the surface antigen CD95 + of human lymphocytes and labeled with FITC Fab - fragments of anti-mouse immunoglobulins produced by NPF MedBioSpektr (Russia).

Laboratory parameters are presented, respectively, for different options for the course of pregnancy, depending on the presence of intrauterine infection in the newborn.

In the third trimester of physiological pregnancy, the above parameters had the following quantitative characteristics:

- placental growth factor (PCG / ml) - 388 ± 16.2 (range of values 352-430);

- thermostable alkaline phosphatase (U / L) - 152 ± 14.3 (120-170);

- CD95 + lymphocytes (%) - 21.7 ± 2.1 (17-25);

- interleukin one beta (pkg / ml) - 9 ± 2.5 (5-14);

- tumor necrosis factor alpha (PCG / ml) - 88 ± 11.3 (50-115).

For pregnancy in infected women, ending without intrauterine infection of the fetus, the following indicators are characteristic:

- placental growth factor (PCG / ml) - 282 ± 22.5 (range of values 241-315);

- thermostable alkaline phosphatase (U / L) - 203 ± 18.5 (182-233);

- CD95 + lymphocytes (%) - 34.1 ± 2.6 (29-38);

- interleukin one beta (PCG / ml) - 36 ± 4.9 (30-45);

- tumor necrosis factor alpha (PCG / ml) - 262 ± 24.3 (220-300).

For pregnancy in infected women, ending in fetal infection of the fetus, the following indicators are characteristic:

- placental growth factor (PCG / ml) - 157 ± 10.9 (range of values 126-184);

- thermostable alkaline phosphatase (U / L) - 86 ± 7.3 (75-103);

- CD95 + lymphocytes (%) - 58.2 ± 3.4 (47-74);

- interleukin one beta (PCG / ml) - 148 ± 14.3 (125-170);

- tumor necrosis factor alpha (PCG / ml) - 1216 ± 13 6.4 (1022-1574).

Example 1. Pregnant M., 28 years old, registered at the place of residence in the women's consultation of the city clinic with a diagnosis of pregnancy I, 9-10 weeks. Chronic salpingo-oophoritis in remission. Pseudo-erosion of the cervix.

Of the past diseases, SARS, appendectomy at age 18, mumps and chickenpox in childhood are noted. Tuberculosis, syphilis, viral hepatitis denies. Extragenital diseases are absent. Menstrual function without features. Gynecological diseases - suffered acute salpingoophoritis at 22 years old, ectopia of the cervix from 22 years old, was treated conservatively with a partial effect. Parity - the first pregnancy. Contraception - a condom, interrupted sexual intercourse. The husband is healthy. At the local obstetrician-gynecologist was observed regularly. At 11-12 weeks - ultrasound screening - pathology was not detected. In the second trimester of pregnancy (22 weeks), prenatal screening was performed - no pathology from the fetoplacental complex was detected. She took the Vitrum Prenatal vitamin and mineral complex. At 27 weeks of pregnancy, clinical and instrumental signs of the threat of termination of pregnancy, about which she was hospitalized in the maternity ward of MMU GKB No. 2 named after N.A.Semashko. Examination data (ultrasound fetometry, ultrasound dopplerography (Doppler ultrasound), cardiotocography (CTG) of the mother and fetus, ophthalmoscopy, examination for the presence of antiphospholipid antibodies - negative, uterine fundus dynamics in dynamics, general analysis of blood, urine, smears for purity, culture from cervical channel for chlamydia, ureaplasma - negative, biochemical blood tests, including TGF - 145 U / l, FRP level - 392 pcg / ml, coagulogram) before discharge corresponded to the "pregnancy rate". When examined by PCR in the epithelium of the cervical canal, a positive reaction was revealed - DNA of the herpes simplex virus was detected. To assess the clinical course of herpetic infection, ELISA was performed: IgM - negative, IgG 1: 800.

The results of the examination to predict intrauterine infection of the fetus: the content of CD95 + lymphocytes in the peripheral blood - 19.9%, the concentration in the blood serum of TNF-α - 91 pkg / ml, IL-1β - 11 pkg / ml. The indicators were in line with the norm.

Discharged with a diagnosis of pregnancy I, 29 weeks. Head presentation of the fetus. Herpetic infection, latent course. Pseudo-erosion of the cervix. Burdened obstetric history.

At 34 weeks of pregnancy in a short-term inpatient hospital GKB number 2 named. N.A.Semashko performed obstetric screening (ultrasound fetometry, ultrasound placentometry, ultrasound of uterine and fetal blood flow, ELISA for antibodies to herpes: IgM - negative, IgG 1: 800).

The results of the examination for predicting intrauterine infection of the fetus: the level of PDF - 301 pcg / ml, TSPF - 223 U / l, the content of lymphocytes CD95 + - 23.5%, the concentration of TNFα - 89 pkg / ml, IL-1β - 10 pkg / ml) .

Clinical diagnosis: pregnancy I, 34 weeks. Head presentation of the fetus. Herpetic infection, latent course. Chronic placental insufficiency. Pseudo-erosion of the cervix. A burdened gynecological history.

Given the development of placental insufficiency, complicated by the threat of termination during a real pregnancy, the high risk of intrauterine infection of the fetus (herpetic infection, chronic salpingoophoritis, pseudo-erosion of the cervix), it was decided to hospitalize the pregnant woman in the pathology department of the Moscow Clinical Hospital No. 2 named after N.A.Semashko for complex treatment. Within 2 weeks, therapy was carried out aimed at the treatment of chronic placental insufficiency - antioxidants, adrenomimetics, actovegin, trental, magnesium B 6.

Follow-up examination at 37 weeks: ultrasound fetometry, ultrasound placentometry, ultrasound of the uterine and fetal blood flow without features, ELISA for antibodies to herpes: IgM - negative, IgG 1: 800.

The results of the examination for predicting intrauterine infection of the fetus: the level of FRP - 265 pg / ml, TSPF - 196 U / l, the content of lymphocytes CD95 + - 20.8%, the concentration of TNF-a - 92 pkg / ml, IL-1β - 11 pkg / ml) .

Given the positive dynamics of the survey results, the adequate clinical course of pregnancy, it was decided to write out under the supervision of a local obstetrician-gynecologist with continued treatment of chronic placental insufficiency in an outpatient setting. Treatment of herpes infection is not indicated in connection with a latent course.

Spontaneous birth through the natural birth canal occurred at 39-40 weeks, proceeded without complications. A lively mature female fetus was born, with a body weight of 3100 g, a length of 51 cm, with an Apgar score of 1 minute - 8 points, 5 minutes - 8 points. The period of early adaptation was uneventful. PCR for herpes simplex virus in the newborn is negative. The postpartum period was uneventful. Discharged on the 5th day in satisfactory condition. The results of a histological examination of the placenta: compensated placental insufficiency.

Conclusion: in this clinical example, despite the development of chronic placental insufficiency from 34 weeks of gestation (FRP - 301 pcg / l, TSPF - 223 U / l) in a woman with herpes infection, which is classified as a high risk for intrauterine infection of the fetus, the implementation of intrauterine fetal infection did not occur. The CD95 + lymphocyte counts, the concentration of pro-inflammatory cytokines TNFα and IL-1β in pregnancy dynamics (34 weeks: FRP level - 301 pcg / ml, TSPF - 223 U / L, CD95 + lymphocyte content - 23.5%, TNFα concentration - 89 pcg / ml, IL-β - 10 pkg / ml, 37 weeks: the level of FRP - 265 pg / ml, TSPF - 196 U / l, the lymphocyte count of CD95 + - 20.8%, the concentration of TNFα - 92 pkg / ml, IL-1β - 11 PCG / ml) remained within the limits according to the recommended forecasting method, not typical for predicting antenatal transmission of the infection from mother to child.

Example 2. Pregnant N., 32 years old, registered at the place of residence in the women's consultation of the city clinic with a diagnosis of pregnancy I, 16 weeks. Nulliparous older. Chronic genital herpetic infection. A burdened gynecological history.

Of the past illnesses, acute respiratory viral infections, chickenpox in childhood. Tuberculosis, syphilis, viral hepatitis denies. Extragenital diseases are absent. An allergic history without features. 2 years before this pregnancy, according to the results of clinical (the appearance of burning and itching in the genital area, vesicle rashes) and laboratory examinations (positive PCR in the study of cervical epithelium, negative PCR in blood tests, in ELISA IgM - 1: 400, IgG - negative ) was diagnosed with primary genital herpes, for which a woman received treatment. In the control analyzes conducted after 6–9 months, positive dynamics was noted: after 6 months, IgM - 1: 200, IgG - 1: 800, PCR negative in the study of blood and cervical canal epithelium; after 9 months, only IgG class titers of 1: 600 remained elevated. Menstrual function without features - menstruation regular, after 28 days, 5 days, moderate. Gynecological diseases - chronic salpingoophoritis. Obstetric history is not burdened. Unmarried. When registering from the anamnesis, it was revealed that at the 2nd week of pregnancy the woman had clinical manifestations of herpes, about which she was not examined, was treated independently. A PCR test was performed for genital infection: chlamydia, ureaplasma - negative, herpetic infection - positive. To assess the activity of herpetic infection, ELISA was performed: IgM - negatively, IgG 1: 600.

Diagnosis: pregnancy I, 16 weeks. Nulliparous older. Chronic herpetic infection, latent course. A burdened gynecological history.

Taking into account the diagnosis, the pregnant woman is assigned to a high risk group for developing placental insufficiency, miscarriage and intrauterine infection of the fetus. At the local obstetrician-gynecologist was observed regularly. Treatment of herpetic infection taking into account the latent course was not carried out. A complex of preventive measures was prescribed (herbal medicine, vitamin and mineral complex, magnesium B6). According to the results of prenatal screening at 22 weeks of gestation, no pathology was detected.

At 34 weeks of pregnancy, a comprehensive examination was conducted in the conditions of a short-term inpatient hospital GKB No. 2 named after N.A.Semashko. Examination results: total weight gain during pregnancy - 5 kg, fetometric data correspond to gestational age; Doppler ultrasound of uterine and fetal blood flow within the gestational norm; eukinetic type of hemodynamics, CTG - without features; fundus without pathology; conjunctival biomicroscopy data - no microcirculation disturbance; general analysis of blood and urine, biochemical blood tests without pathology, ELISA for antibodies to herpes: IgM - negative, IgG 1: 1200.

The results of the examination for predicting intrauterine infection of the fetus: the level of FRP - 196 pkg / ml, TSPF - 184 U / l, the content of lymphocytes CD95 + - 56.2%, the concentration of TNF-α - 1124 pkg / ml, IL-1β - 142 pkg / ml) .

Clinical diagnosis: 34 weeks pregnancy. Head presentation of the fetus. Nulliparous older. Chronic placental insufficiency. Chronic genital herpetic infection, latent course. A burdened gynecological history.

Considering the results of the examination - the development of chronic placental insufficiency in primiparas, the high risk of antenatal lesions of the fetus with herpes infection (according to laboratory tests taking into account the developed forecasting method), the pregnant woman was offered hospitalization, which she refused due to family circumstances.

She received treatment for chronic placental insufficiency (Actovegin, Trental, Vitamin E) as an outpatient; she refused antiviral treatment.

At 39 weeks she was admitted to antenatal hospitalization in the maternity ward of MMU GKB No. 2 named after N.A.Semashko. The results of the examination according to the recommended method for predicting intrauterine infection of the fetus: FRP level - 296 pcg / ml, TSPF - 221 U / l, lymphocyte count CD95 + - 60.9%, TNF-α concentration - 1341 pcg / ml, IL-1β - 159 pcg / ml )

According to the survey, despite the latent course of chronic herpetic infection in the mother, there remains a high risk of intrauterine infection of the fetus.

Given the high degree of perinatal risk in primogenous older children with chronic placental insufficiency from 34 weeks of pregnancy, the high degree of intrauterine infection of the fetus, it was decided to deliver the pregnant woman through cesarean section in a planned manner. The operation went without features. A lively mature male fetus was born with a body weight of 3250 g and a length of 53 cm, with an Apgar score of 1 minute - 8 points, 5 minutes - 8 points.

The period of early adaptation was uneventful. The postpartum period was uneventful. In a newborn in the early neonatal period, a positive result for herpetic infection was obtained by PCR. On the 8th day with the results of the examination, a woman with a newborn was discharged home under the supervision of a local obstetrician-gynecologist and pediatrician.

Conclusion: in this clinical example, in a pregnant woman with a latent course of genital herpetic infection against a background of chronic placental insufficiency (FRP - 198 pkg / L, TSPF - 184 U / L), the fetal antenatal infection occurred. Indicators of CD95 + lymphocyte counts, concentration of pro-inflammatory cytokines TNFα and IL-1β in pregnancy dynamics (34 weeks: FRP level - 198 pcg / ml, TSPF - 184 U / L, CD95 + lymphocyte content - 56.2%, TNFα concentration - 124 pcg / ml, IL-1β - 142 pkg / ml, 39 weeks: the level of PDF - 296 pg / ml, TSPF - 221 U / l, the lymphocyte count of CD95 + - 60.9%, the concentration of TNF-α - 1341 pg / ml, IL-1β - 159 pcg / ml) corresponded according to the recommended method for predicting intrauterine infection, data characteristic for predicting intrauterine infection of the fetus.

Example 3. Pregnant K., 24 years old, registered at the place of residence in the antenatal clinic of the city clinic with a diagnosis of Pregnancy II, 30 weeks. Head presentation of the fetus. Burdened obstetric history.

From the anamnesis: suffered ARVI, as a child, suffered from scarlet fever, whooping cough. Tuberculosis, syphilis, viral hepatitis denies. Extragenital and gynecological diseases are absent. An allergic history without features. Parity: the first pregnancy at age 20 ended in medical abortion with a period of 8-9 weeks, without complications. The husband is healthy. Contraception - combined oral contraceptives (marvelon). Real pregnancy proceeded without complications. Examination by PCR revealed a chlamydial infection (Chlamidiae trachomatis). ELISA results: IgA - 1:10, IgM - 1:10, IgG - 1:40. Survey data for placental insufficiency, apoptosis markers and pro-inflammatory cytokines: FRP level - 188 pcg / ml, TSPF - 126 U / l, CD95 + lymphocyte content - 59.7%, TNFα concentration - 1338 pcg / ml, IL-1β - 134 PCG / ml.

In addition to the clinical diagnosis: chlamydial infection, chronic course in the acute stage. Chronic placental insufficiency.

A pregnant woman is classified as a high-risk fetus. Due to the high risk of intrauterine infection of the fetus, confirmed by laboratory data on the background of placental insufficiency, the pregnant woman was treated with chlamydial infection with vilprafen (yosamycin) 3 ml units 3 times a day for 10 days and placental insufficiency: actovegin, hofitol, vitamin E, magnesium B6, vitamin and mineral complex.

Control examination for chlamydial infection after 4 weeks: PCR - negative, in ELISA IgA - negative, IgM - negative, IgG 1: 5. The results of the examination for predicting intrauterine infection of the fetus: the level of FRP - 374 pcg / ml, TSPF - 164 U / l, the content of lymphocytes CD95 + - 35.9%, the concentration of TNFα - 95 pcg / ml, IL-1β-11.3 pcg / ml).

Clinical diagnosis: 34 weeks pregnancy. Head presentation of the fetus. Nulliparous older. Chronic placental insufficiency. Chlamydial infection, chronic course without exacerbation. A burdened gynecological history.

The management plan for the pregnant woman provides for delivery through the natural birth canal.

Spontaneous delivery at 40 weeks was uneventful. The total duration of labor is 11 hours 40 minutes. Anhydrous period - 4 hours. A lively mature male fetus was born with a body weight of 3500 g and a length of 54 cm, with an Apgar score of 1 minute - 8 points, 5 minutes - 8 points. The period of early adaptation was uneventful. The postpartum period was uneventful. The result of the examination of the newborn for infection with chlamydial infection according to the PCR method is negative. On the 5th day, a woman with a child was discharged home.

Conclusion: in this clinical example, given the high clinical and laboratory risk of intrauterine infection of the fetus (at 30 weeks of gestation, the pregnant woman has a positive result of PCR, ELISA on Chlamidiae trachomatis; the lymphocyte count of CD95 + is 59.7%, the concentration of TNFα is 1338 pg / ml, IL-1β - 134 pg / ml), the woman received etiotropic treatment, after which, against the background of negative PCR results and specific antibodies of the IgA and IgM class and a residual level of IgG antibodies of 1: 5, normalization of indicators characterizing the possibility of transplantation ary transmission from mother to child (content lymphocytes CD95 + - 35,9%, the concentration of TNF - 95 pg / ml, IL-1β - 11,3 pg / ml), indicating a possible in favor of the absence of fetal infection. After giving birth in a newborn, when examined by PCR, a negative result for infection with a chlamydial infection is negative.

Thus, the use of a marker of apoptosis — lymphocytes with the CD95 + phenotype activated by infection of immunocompetent cells — as well as determining the concentration of proinflammatory cytokines IL-1β, TNFα (TNFα can initiate apoptosis) along with markers of placental insufficiency along with markers of placental insufficiency to predict fetal infection of the fetus FRP and TGF, significantly expands the prognostic capabilities of the method, allows you to timely record changes in the early stages of fetal infection and conduct adec atnoe prophylactic treatment with the etiologic agent.

The reduced accuracy of predicting intrauterine infection of the fetus only by the presence of placental insufficiency markers (FRF, TGF) is due to the fact that placental insufficiency in itself, although it is necessary, is not the only factor in the transmission of infection from mother to child.

Changes in indicators proposed for predicting intrauterine infection of the fetus (CD95 +, IL-1β, TNFα lymphocytes), makes it possible to judge deep damage to the protective placental barrier, can be used to monitor the effectiveness of treatment for infection in a pregnant woman, and can also serve as a basis for choosing method of delivery.

Based on the results of verification of the diagnosis of intrauterine infection of the fetus (confirmed by the presence of infection in the newborn) from the perspective of evidence-based medicine, the sensitivity, specificity, accuracy, prognostic value of the positive and negative results of this method for predicting intrauterine infection of the fetus during pregnancy, which are respectively 91.4%, 93 , 2%, 95%, 89.1%, 88.4%, which indicates a high information content and reliability of the proposed forecasting method.

The positive effect of the proposed method for predicting intrauterine infection of the fetus gives, in principle, new opportunities to predict intrauterine infection of the fetus with high efficiency due to the assessment of previously unused parameters. The method is non-invasive, safe for the health of the pregnant woman and the fetus, widely available for modern obstetric institutions.

On the filing date, the applicant did not find a diagnostic method with the claimed combination of features, as a result of which we conclude that the claimed technical solution meets the criteria of the invention of “novelty”.

According to the results of the comparative analysis, the totality of the features of the proposed diagnostic method provides it with new properties in the form of increasing the accuracy of forecasting, that is, according to the applicant, ensures that the proposed method meets the criterion of "inventive step".

The criterion of the invention "industrial applicability" is confirmed by the fact that the inventive diagnostic method can be successfully applied in mass examinations of pregnant women as screening with the identification of accurate and early signs of intrauterine infection of the fetus.

Claims (1)

A method for predicting intrauterine infection of the fetus, including determining the level of placental growth factor (FRF) and thermostable alkaline phosphatase (TSPF) in the blood of pregnant women, followed by data analysis, characterized in that they additionally determine the content of CD95 + lymphocytes and the concentration of interleukin one beta (IL-β ), tumor necrosis factor alpha (TNFα), and with a value of indicators: the level of FRP (PCG / ml) 157 ± 10.9; the level of TSPF (U / L) 86 ± 7.3; the content of CD95 + lymphocytes (%) 58.2 ± 3.4; the concentration of IL-1β (PCG / ml) 148 ± 14.3; TNFα concentration (PCG / ml) 1216 ± 136.4 predict intrauterine infection of the fetus.