RU2164079C1 - Method for predicting interruption in bearing child during pregnancy period - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves separating high and low frequency components in cardiac rhythm spectrum. Integral characteristic of vago-sympathetic balance is calculated using known method. The vago-sympathetic balance value being less than 0.35 or greater than 0.7, risk of pregnancy interruption is predicted. The value being between 0.35 and 0.7, intellectual and hyperventilation tests are additionally applied. Anomalous vago- sympathetic balance response being observed in these tests, unfavorable pregnancy outcome risk is predicted. EFFECT: high reliability of method; high accuracy of prognosis. 4 cl, 5 tbl

Description

 The invention relates to medicine, in particular to obstetrics.

 Miscarriage (NL) is currently one of the main causes of perinatal morbidity and mortality.

 The incidence of NB is 10–25% of all pregnancies, including 5–10% of preterm births. Premature infants account for over 50% of stillbirths, 70-80% of early neonatal mortality, 60-70% of infant mortality (Duda I.V., Duda V.I. Clinical obstetrics. - Minsk, 1997. - 107 pp.).

 The concept of NB refers to spontaneous abortion up to the 38th week and includes spontaneous abortions (early abortion up to 12 weeks, late abortion from 13 to 22 weeks), premature birth - from the 22nd to 38th weeks, as well as failed miscarriage and childbirth (the so-called "frozen" pregnancy).

 The medical and social significance of NB is determined by its slightly varying frequency, high perinatal mortality of premature babies, high labor and economic costs associated with their nursing, and also a significant share of these children among children with disabilities and patients with chronic pathology. (Frolova O.G., Tokova Z.Z., Volgina V.F. and others // Akush. And gin. - 1996. - N 4. - S. 7-11).

 The pathogenesis of NB in the early (up to 22 weeks) and late pregnancy (after 28 weeks) is different.

 Spontaneous abortion up to 22 weeks of pregnancy is associated with hormonal and neurovegetative factors. Violation of autonomic regulation in the mother's body towards a sharp predominance of vagal (cholinergic) innervation tone causes a risk of abortion. This is because the uterus, being a muscular organ, experiences a tonic effect from the autonomic ganglia, which are stimulated exclusively by cholinergic innervation. The predominance of the latter causes a tonic contraction of the smooth muscle fibers of the uterus. As a result, the blood supply to the fetal egg and the normal development of syncytium are disrupted, its detachment sets in, followed by a possible abortion.

 Preterm birth after 28 weeks of pregnancy is primarily associated with a primary violation of the uteroplacental circulation, causing chronic placental insufficiency (CRF). With a long-term threat of abortion, CRF occurs in 100% of cases (Murashko L.E., Badoeva F.S., Asymbekova G.U. et al. // Akush. And gyn. - 1996. - N 4. - P. 43 -45). The decrease in utero-placental blood flow, in turn, is due to a violation of autonomic regulation in the mother's body towards a sharp predominance of the tone of sympathetic innervation. It is known that the uterine vessels respond with spasm and increased resistance to blood flow during sympathetic stimulation of alpha-adrenergic receptors included in the muscle layer of the arterial vascular system of the uterus. As a result of this, the diastolic blood flow in the mentioned system decreases and the insufficiency of the placental complex occurs, which subsequently leads to a delay in the fetal development of the fetus and possible premature birth.

 Therefore, NB is pathogenetically associated with both the pronounced predominance of the vagal and, conversely, the dominance of the sympathetic innervation of the uterus and its vascular system.

 In the first case, there is a risk of spontaneous abortion, and in the second case, premature birth.

 In pregnancy from 22 to 28 weeks, both of the above forms of vegetative innervation disturbance may be significant.

 Severe medical consequences of NB and its social significance prompt researchers to search for more advanced ways to predict this pregnancy complication.

 A known method of ultrasound examination of the utero-fetoplacental complex. It allows you to visually assess the level of contractile activity by changing the echo density of the uterine tissue. Thus, a conclusion is made that there is a threat of NB due to the increased tone of the smooth muscle layer of the uterus (Demidov V.N., Stygar A.M. // Akush. And gin. - 1985. - N 10. - C 63-67.).

 This method is harmless and can be used from 4-6 weeks of pregnancy.

 Its disadvantage is the lack of information about the causes of increased uterine tone and, therefore, the possibility of effective prognosis of NB.

 There is another method for predicting NB, based on an ultrasound Dopplerometric study of the uteroplacental blood flow (Ignatko I.V., Strizhakov A.N. / Akush. And gin., 1997. - N 1. - P. 23-26).

 Detection using this method of reduced parameters of blood flow in the uteroplacental arteries at 16-26 weeks of pregnancy is a reliable prognostic sign of the development of NB in the third trimester. This method is highly informative in relation to forecasting NB. Its disadvantage is the need for a large investment of time for the examination procedure and evaluation of the results.

 Meanwhile, modern forecasting methods must meet the requirements of not only high reliability, but also simplicity and low time spent on their implementation (Shekhtman M.M., Elokhina TB // Akush. And gin. - 1996. - N 3. - S. 3-6).

 Closest to the claimed is a method of mathematical spectral analysis of the variability of the mother’s cardiorhythm to predict the course of pregnancy and the development of its complications, including NB (Fleishman A.N. Slow hemodynamic fluctuations: Theory, practical application in clinical medicine and prevention. - Novosibirsk, 1999. -215 FROM.).

 The essence of this method is to highlight the spectral-frequency peaks in the high-frequency (HF, high frequency) and ultra-low-frequency (VLF, very low frequency) spectral range of the mother’s cardiorhythm.

 As a result of numerous studies, it was found that the spectral power in the HF region reflects the activity of vagal innervation, while the spectral power in the VLF region is a marker of sympathetic innervation in the body (Heart Rate Variability: Standards of Measurement, Physiological Interpretation and Clinical Use // Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. - Circulation. - 1996. - V. 93. - P. 1043-1065).

 Based on this, the peaks in the spectral regions of HE and VLF are extracted and calculated in real time using a personal computer when registering the patient's electrocardiographic signal. Thus, the method allows to evaluate the vagal and sympathetic activity of autonomic regulation and, therefore, to formulate a diagnostic and prognostic conclusion about the risk of NB.

 The disadvantage of this method is the lack of an integrated assessment of the vago-sympathetic balance using a single indicator that takes into account the ratio of the tone of the vagal and sympathetic departments of autonomic regulation and their reactivity.

 Meanwhile, the presence of such an indicator would make it possible to monitor the condition of patients in order to effectively determine the risk of NB.

 The objective of the invention is to increase the accuracy and reliability of forecasting NB taking into account the disadvantages of the above analogues.

 The task is achieved in that the patient determines the integral indicator of the vago-sympathetic balance of the body (AFI), including the high-frequency and ultra-low-frequency components of the spectrum of the mother’s cardiorhythm, and if the value of the IRI is less than 0.35 or more than 0.70, the risk of miscarriage is determined, and with normal the background value of the AFI at rest within the range of (0.35-0.70) the patient is presented with mental and hyperventilation stress tests and, with inadequate reactivity of the AFI to these tests, the risk of adverse effects is also determined iyatnogo pregnancy outcome in a miscarriage; inadequate AXI reactivity to a mental stress test is established when the BC-index decreases by more than 20% of its background value, recorded in a state of calm wakefulness; inadequate reactivity of the VSI is established by the absence of its changes to the hyperventilation stress test or by increasing the VS-index by less than 20% of its background value; inadequate reactivity of the VSI is established when its changes are opposite in comparison with the normal direction, consisting in an increase in mental and a decrease in case of hyperventilation load.

The novelty of the method:
1. The definition of the integral indicator of vago-sympathetic balance (VSI) as a prognostic criterion for miscarriage.

 2. Conducting stress tests (mental and hyperventilation), providing a more accurate prognosis of miscarriage by identifying latent insufficiency of the vagal and (or) sympathetic innervation in the body of pregnant women.

 3. The digital indicators of the AFI within the boundaries of (0.35-0.70) are reliable. They were obtained as a result of studying changes in the BC index in a sample of 986 pregnant women.

 The method is as follows.

The patient is examined in the morning, in a sitting position, in a calmly awake state, after preliminary adaptation to the setting and examination procedure. By a standard method, the patient's ECG signal is recorded, which is automatically processed in real time on a PC. The output data in the form of maximum values of the amplitude of the power spectral density (PSD) in the frequency ranges HF and VLF are processed with the calculation of the vagosympathetic balance index
VSI = log HF / log VLF.

 The last relation is the desired vago-sympathetic index (VSI). The logarithm procedure is necessary to bring the variable values of the AFI to the function of the normal (Gaussian) statistical distribution. Our research on a sample of about 1000 pregnant women showed that the VSI changes in this population according to the multiplicative law. In other words, the distribution of VSI is log-normal in nature. This property of the vago-sympathetic index is of great practical value, since it makes it possible to use exact parametric methods of variation statistics in processing the obtained data.

 As a result of studying changes in AFI in a large group of pregnant women, we found that during physiologically ongoing pregnancy, the value of AFI in a calm awake state is on average 0.51 ± 0.17 (M ± s), i.e. it ranges from (0.35-0.70).

 Values of VSI greater than 0.70 (M ± s) reflect the pronounced predominance of vagal innervation and, therefore, conditions in the body that contribute to an increase in uterine tone. Values of AFI of less than 0.35 (M-s) reflect the marked predominance of sympathetic innervation and, therefore, the conditions for the development of spasm of the uterine arteries and a decrease in uteroplacental blood flow. Both situations are associated with NB risk, as described above.

 However, normal background values of VSI (within the range of 0.35-0.70) can occur with stress of homeostatic regulation and excessive energy expenditure in the body of pregnant women. In such conditions, the risk of miscarriage is associated with latent insufficiency of autonomic regulation.

 Identification of latent insufficiency is carried out during standard stress tests: mental (counting in the mind (500-7)) and hyperventilation (deep diaphragmatic breathing).

 Mental load serves to identify latent insufficiency of sympathetic innervation, since this test normally causes sympathetic activation.

 Hyperventilation load is specific for stimulation of the vagal nerve and serves to identify latent insufficiency of vagal innervation.

 Thus, at normal values of VSI in the range of (0.35-0.70), the load test reveals the latent insufficiency of one of the two departments of autonomic regulation: vagal or sympathetic.

 When the background values of the IRI are more than 0.70 or less than 0.35, the load test clarifies the prognostic conclusion, revealing the reserves of vegetative regulation.

 Standard stress tests are performed regardless of the background values of the BC index. However, these tests are by far the most necessary and informative with normal background values of the AFR in the range of (0.35-0.70).

 In a physiologically occurring pregnancy, the response of the AFI to mental stress consists in a slight decrease in the index by no more than 20% from its initial value, recorded in a calm state of the patient. In the recovery period, the VSI returns to its initial level.

 The reaction to hyperventilation consists in a significant increase in the AFR by more than 50% of its initial value, with subsequent return to it in the recovery period.

 In pathological situations, inadequate reactivity of the BC-index is recorded upon presentation of standard load samples to the patient.

Inadequate reactivity of the VSI at any of its background values is as follows:
1. Excessive reactivity of the AFI to mental stress in the form of a sharp decrease in the index by more than 20% of its background value.

This symptom indicates a risk of NB due to the increased reactivity of the sympathetic innervation and the presence of conditions for spasm of the uterine arteries with the subsequent development of placental insufficiency;
2. Lack of reactivity of the AFR to hyperventilation load or a slight reaction to the latter in the form of an increase in the index by less than 20% of its initial value in a calm awake state.

This symptom indicates a vagal insufficiency and (or) a latent predominance of sympathetic innervation, as a result of which there is a risk of developing NB by the same mechanism as in the previous situation (see paragraph 1);
3. The perverse reactivity of the AFI to test loads.

 This means that changes in the index occur in the opposite direction to those observed in the norm: an increase in the ASI in response to mental stress instead of a normal decrease and (or) a decrease in the ASI during hyperventilation instead of its increase observed under normal conditions.

So, the application of this method for predicting NB is divided into two stages:
Stage 1. Registration of the background value of the BC-index in a calm awake state of the patient;
2 stage. Registration of the BC-index upon presentation of functional stress tests to the patient: counting in the mind (500-7) and hyperventilation.

 As a result, at the 1st stage, the deviation of the background AFI above 0.70 or below 0.35 (a positive test result) is taken into account. Next, at the 2nd stage, the nature of the reactivity of the AFR to test loads is taken into account in accordance with the rules described above. With excessive, absent (lowered) or perverted reactivity of the index, a positive test result is ascertained.

 The presence of at least one positive test result during a patient examination means a risk of developing NB.

 Our statistical studies of the information content of the proposed method on a sample of 398 pregnant women with various forms of miscarriage gave the following results.

 The predictive reliability (i.e., information content) of the method, defined as the percentage of cases of miscarriage among all patients with a positive test result, was 83%.

 False negative results were 28%. The specificity of the method (the percentage of negative test results among patients without this pregnancy complication) was 78%.

 Correctional therapy in the case of positive test results was carried out mainly on the basis of a day-time in-patient clinic. In more persistent and difficult to correct cases, patients were hospitalized in the department of pregnancy pathology. The traditional medical and non-medical methods were used (Duda I.V., Duda V.I. Clinical obstetrics. - Minsk, 1997. - 122 p.). The difference was the possibility of constant monitoring of the autonomic balance against the background of the therapy. This made it possible to significantly reduce the percentage of adverse pregnancy outcomes in comparison with indicators recorded in the same obstetric institutions before the introduction of the spectral diagnostic method.

 So, perinatal mortality according to the data of antenatal clinic No. 1, where the method for predicting NB developed by us was used, in 1998 decreased to 3.1% (compared with 15.9% of the previous year). No cases of bleeding and clinically significant symptoms of detachment of a normally located placenta were observed in 1998, although in previous years the number of these cases was 3-4%.

 Example 1

 Patient Peninsula, 22 years old, first pregnant. The gestation period is 28 weeks. Complaints of intermittent and slight nausea in early pregnancy. For the period of the examination no complaints. Heart rate 101 beats / min; HELL = 110/70 mm RT. Art.

 The spectrogram data are given in table. 1.

 In this example, the spectral data correspond to the clinical state of the norm and the absence of any indications of abnormalities in the development of pregnancy.

 Example 2

 Patient K., 23 years old, pre-pregnant, gestational age 28 weeks. Complaints of pain in the lower abdomen, especially with moderate physical exertion. Takes partusisten 1/4 t. 2-3 times / day, iron preparations, vitamin E, L-thyroxine. The history of hypothyroidism, nephroptosis P Art. on right. Heart rate 94 beats / min, BP = 100/60 mm Hg. Art.

 The spectrogram data are given in table. 2.

 In this example, lower values of the AFR in the background and in the dynamics of stress tests correspond to complaints indicating the risk of miscarriage. At the same time, the relatively satisfactory dynamics of AFI during hyperventilation, which consisted of an increase in its level by 67% relative to the background, made it possible to determine in this case a favorable prognosis of pregnancy. When re-examining the same patient at 34 weeks, the spectrogram data are shown in table. 3.

 There is a lack of complaints, despite the abolition of medications.

 Therefore, in the analyzed example, the forecast based on spectrographic data was adequate to the subsequent course of pregnancy. The repeated spectrogram corresponds to the idea of the normal level and reactivity of the AFR.

 Example 3. Patient F-va, 31 years old, first pregnant, gestational period of 13 weeks. Complaints of moderate pastosity of the face and legs, general malaise, sometimes headaches. Suffers from obesity II tbsp. (growth-weight coefficient 0.74). Heart rate 80 beats / min, BP = 150/100.

 The spectrogram is given in table. 4.

 Based on spectrography data, the risk of NB in combination with the clinical signs of pregestosis was determined; unfavorable prognosis. The patient was hospitalized for corrective therapy.

 When re-examination of 22 weeks: blood pressure = 130/90 mm Hg

 The spectrogram is given in table. 5.

 The spectrogram data had a positive trend. The forecast is favorable. Pregnancy outcome: delivery on time, newborn weight 3.5 kg, Apgar 8 points.

 The most unfavorable prognostic sign is the lack of reactivity of the AFI under standard stress tests or even a distortion of the reaction, i.e., its opposite to normal. In this case, the background values of the AFR can be close to normal, as in the example below.

 Example 4

Pregnant U., 21 years old, 33 weeks gestation, gestosis, VVD, pyelonephritis, chronic renal failure. Was in the hospital examination and treatment. Clinically, the possibility of a sudden fetal death was not recognized. Spectrograms were recorded 5 and 2 days before the death of the fetus (see table. 6)
In this example, the first and repeated spectrograms were characterized by either a decrease or a slight increase in the IRR in response to a sample with hyperventilation, while the normal reaction is a significant increase in the IRR to 0.80-2.0. In addition, in the first registration from 10.25.93, one can see a sharp decrease in AFI with a mental load of 54% i.e. twice instead of 10-20% under normal conditions (see above). When re-recording from 10.28.93, there was a perverted dynamics of AFI on mental stress in the form of an increase of 122%, i.e. more than double compared to its background value. Meanwhile, the normal reactivity of the VSI consists, on the contrary, in a moderate decrease in this indicator under stress load, which in this case simulates a countdown in the mind.

 Such a dynamics of VSI with its stability in repeated registrations corresponds to an extremely unfavorable prognosis in terms of the risk of NB, up to the antenatal death of the fetus.

 Example 5

 Patient A-on, 20 years old, first pregnancy, gestational period 21 weeks. Under the supervision of 16 weeks. The condition is satisfactory. No complaints. The abdomen is soft, painless. HELL = 120/70 mm RT. Art., body weight 75.8 kg.

 The spectrogram data are given in table. 7.

 In the first recording of the spectrogram from 11/13/96 there was a marked depression of AFI in the background and during exercise tests, the lack of response to the mental test and hyperventilation.

 Active correctional therapy was recommended in the conditions of a day-time in-patient clinic because of the threat of miscarriage according to the spectral analysis of the pregnant woman’s cardiorhythm.

 Riboxin and cocarboxylase, an intravenous glucose solution with vitamin C, potassium orotate, multivitamins, kelp, and sedatives were administered intramuscularly.

 In the re-registration from 11/27/96 there is a positive trend in the form of an increase in the background value of the AFR to 1.18. However, the combination of an excessively increased AFI in the background and its decrease during hyperventilation (a perverse reaction) indicated that the risk of NB remains unchanged, despite active therapy.

 Medical correction was supplemented by oral administration of no-shpa, however, in the subsequent registration of 01.01.97 (gestational period of 28 weeks), the responsiveness of the AFI to hyperventilation remained inadequate, although its background value corresponded to the norm.

 Hospitalization of the patient and the continuation of corrective therapy in a hospital were recommended due to the continuing threat of NB.

 Subsequent recording of the spectrogram at 36 weeks (03.03.97) testified to the normalization of not only the background level of the AFR, but also its reactivity to the presentation of load samples.

 Self-delivery at 38.5 weeks, body weight of the newborn 2.8 kg, Apgar 7 points.

 Therefore, in the last example, spectrographic information in the form of dynamics of the BC-index made it possible to achieve a relatively favorable outcome of pregnancy, despite the stubborn and difficultly corrected risk of miscarriage.

 In general, the above examples show the high reliability of the method, its ability to predict NB and adequate pregnancy management based on information about the state of the autonomic balance in the body of pregnant women.

 Thus, the proposed method for predicting miscarriage, based on an integrated assessment of vegetative status through spectral analysis of the mother’s cardiac rhythm, has a number of significant advantages. Having a sufficiently high reliability with respect to identifying the risk of NB, the method is relatively simple, safe, affordable for outpatient obstetric institutions, bloodless, requiring little time (about 3 minutes), suitable for monitoring the condition of patients, starting from the very first weeks pregnancy.

 The use of this method in obstetric practice on the basis of antenatal clinics allowed us to achieve good results in the form of a decrease in the percentage of early and late forms of miscarriage, a decrease in perinatal mortality with timely and adequate correction of the vegetative balance of the patient’s body. Note that the "sighted" approach in choosing medical tactics for conducting pregnancy on an outpatient basis is extremely important for increasing the antihypoxic resistance of the fetus and preparing it for the critical phase of childbirth. The regularities found by us in the dynamics of the vago-sympathetic balance during a normal pregnancy allow us to reasonably use pharmacotherapy in the amount of correction that is objectively necessary and sufficient.

Claims (4)

 1. A method for predicting miscarriage based on a spectral analysis of cardiac rhythm variability, characterized in that the patient determines the integral indicator of vago-sympathetic balance of the body (AFI) according to the formula VSI = log HF / log VLF, where HF is the high-frequency and VLF-ultralow-frequency components of the spectrum the cardiac rhythm of the mother, and with an AFI value of less than 0.35 or more than 0.70, the risk of miscarriage is determined, and with a normal background value of the AFI at rest between 0.35 and 0.70, the patient is presented with mental and hypervenous tilation stress tests, and with inadequate reactivity of the AFR to these tests also determine the risk of an unfavorable pregnancy outcome in the form of miscarriage.  2. The method according to claim 1, characterized in that the inadequate reactivity of the AFI for a mental stress test is established when the BC index is reduced by more than 20% of its background value, recorded in a state of calm wakefulness.  3. The method according to claim 1, characterized in that the inadequate reactivity of the VSI is established by the absence of its changes to the hyperventilation stress test or by increasing the VS index by less than 20% of its background value.  4. The method according to claim 1, characterized in that the inadequate reactivity of the AFI is established when its changes are opposite in comparison with the normal direction, consisting in an increase in mental and decrease in case of hyperventilation load.

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