Method for predicting risk of perinatal complications in pregnant women with euthyroidism

Abstract

FIELD: obstetrics.SUBSTANCE: used to predict the risk of perinatal complications in pregnant women with euthyroidism. To implement the claimed method, risk factors of the current pregnancy are taken into account, including the platelet level at the first visit and the threat of spontaneous miscarriage, as well as the patient's anamnestic data - late spontaneous miscarriage and non-viable pregnancy. Next, the calculation is performed according to the stated mathematical formula. If the value is less than 0.5, a low risk of perinatal complications is predicted, and if the value is 0.5 or higher, a high risk is predicted.EFFECT: method is accurate and allows for increased efficiency in identifying perinatal complications.1 cl, 2 dwg, 1 tbl, 1 ex

Description

[0001] The proposed invention relates to medicine and can be used in obstetrics and perinatology to predict the risk of developing perinatal complications in pregnant women with iodine-deficiency diseases of the thyroid gland, depending on its functional state, through the development of prognostic models and elements of mathematical modeling.

[0002] The relevance of the proposed prediction method is due to the widespread prevalence of iodine deficiency (ID) worldwide, affecting approximately 40% of the world's population. Thyroid hormones and iodine are essential for increasing basal metabolic rate and regulating protein synthesis, long bone growth, and neuronal maturation. The development and functional development of the fetus depend on the mother's thyroid status during the most critical moments of embryogenesis. Consequently, thyroid dysfunction in a pregnant woman can lead to adverse pregnancy outcomes and primarily impact the child's psychoneurological health.

[0003] Thus, despite the well-established system for examination, observation, and correction of hypothyroidism in women with iodine deficiency diseases, the frequency of perinatal complications and their consequences remains one of the unresolved issues. Therefore, the development of informative methods for predicting perinatal complications is a key task in solving the problem of perinatal morbidity, and will influence the tactics of managing pregnant women and their newborns.

[0004] A method for predicting the risk of hypoxic ischemic encephalopathy in newborns born to women with different somatotypes is known. This method is based on determining the somatotype using R.N. Dorokhov's method. For this purpose, the woman's weight and length are measured before 10 weeks of pregnancy. The woman's fat and skeletal muscle mass are calculated. After 32 weeks of pregnancy, fetal cardiotocography is performed. The oscillation frequency per minute and oscillation amplitude are calculated. Based on Doppler ultrasound of the uteroplacental and fetoplacental blood flow, the severity of the blood flow disorder in the maternal-placental-fetal system is calculated. Then, using the developed mathematical formula, the probability of developing hypoxic ischemic encephalopathy in newborns born to women with different somatotypes is calculated as a percentage. Based on the obtained results, a high risk of developing hypoxic ischemic encephalopathy in newborns is predicted in 60%.The disadvantages of the prototype are that this method is aimed at women who registered for pregnancy early in pregnancy and cannot be applied to pregnant women whose appointments are made after 10 weeks of gestation. (K.G. Tomaeva, Z.V. Tedeeva, S.N. Gaidukov, et al. / / Patent for invention RU 2802667 C1 dated August 30, 2023).

[0005] A method exists for the individual prediction of perinatal complications in overweight or obese pregnant and postpartum women. The method consists of allele-specific amplification with DNA detection in overweight or obese pregnant and postpartum women associated with the rs9939609 T / A polymorphism of the FTO gene in the buccal epithelium. The allele (A) is isolated from the aforementioned genotypes at any stage of pregnancy or during labor.Then, the presence of factors influencing the course, outcome of pregnancy and childbirth is identified, and their prognostic coefficients are determined in points, designated by the sign "+" in the case of an aggressive nature of the factor and by the sign "-" in the case of their protective nature. With a sum of prognostic coefficients equal to "+13 or more" points, the development of perinatal complications is predicted, and with a sum of prognostic coefficients equal to "-13 or less" points, the absence of the development of perinatal complications associated with vascular endothelial dysfunction is predicted (patent RU 2673085 C1 dated 22.11.2018.). This method provides a high prognostic accuracy (95%), but requires special equipment for genetic analysis and is expensive.

[0006] A more cost-effective method for predicting neonatal encephalopathy is to determine the activity of NADPH oxidase to reduce 2,6-dichlorophenylindophenol in the presence of NADPH (I.I. Krukier / / Patent for invention RU 2254573 C1 dated 06 / 20 / 2005). To implement the method, placental tissue is examined, from which a 10% homogenate is prepared, and the activity of NADPH oxidase to reduce 2,6-dichlorophenylindophenol in the presence of NADPH is determined. The reaction results are recorded spectrophotometrically at a wavelength of 600 nm. If the NADPH oxidase activity is equal to 13.5 units of optical density and higher, the development of encephalopathy in the newborn is predicted. This method is non-traumatic and allows for a high degree of accuracy in predicting the development of neonatal encephalopathy. However, it does not allow for the prediction of complications from the early stages of pregnancy, but only after labor, and therefore does not allow for the implementation of preventive measures from the early stages of pregnancy.

[0007] The closest method in technical essence and achievable positive results is a method for predicting perinatal morbidity by determining the presence of anamnestic factors: socio-biological risk factors, obstetric and gynecological history, extragenital diseases of the mother, as well as pregnancy factors (pregnancy complications, fetal assessment). The identified factors are assigned a point value. The identified points are then summed up, and a total of up to 15 points predicts a low risk of perinatal morbidity, a total of 15 to 25 points predicts a moderate risk, and a total of over 25 points predicts a high risk.

[0008] This method allows for the timely classification of a pregnant woman as a risk group and the implementation of timely preventive and therapeutic measures, as well as the selection of the most appropriate methods and timing of delivery. A disadvantage of this method is its labor-intensive nature; the calculation involves over 90 different factors, which is inconvenient and requires manual calculation of the total score (patent RU 2 369 331 C1 dated October 10, 2009).

[0009] Currently, there is no method for predicting perinatal complications in pregnant women with iodine deficiency thyroid disease based on a personalized assessment of a set of clinical, anamnestic data and laboratory parameters.

[0010] The authors propose a method for predicting the degree of risk of perinatal complications based on an assessment of anamnestic data (obstetric history, course of the current pregnancy), as well as some laboratory parameters (platelet level at the first visit).

[0011] The technical result of the invention is to increase the efficiency of predicting the degree of risk of perinatal complications.

[0012] This result is achieved by using the following indicators in predicting the risk of developing perinatal complications in pregnant women with iodine deficiency thyroid disease and euthyroidism, namely:

[0013] X1 - history of late spontaneous miscarriage (yes - 1, no - 0)

[0014] X2 - history of non-viable pregnancy (yes - 1, no - 0)

[0015] X3 - threatened spontaneous miscarriage during the current pregnancy (yes - 1, no - 0)

[0016] X4– platelet level at the first visit (indicator value).

[0017] In developing the proposed method, a group of patients (n=94) with iodine deficiency disorders diagnosed before or during pregnancy were examined. This group was divided depending on the functional state of the thyroid gland: women with thyroid dysfunction in the form of hypothyroidism (n=53) and women with iodine deficiency disorder but without thyroid dysfunction (n=41). Patients with hypothyroidism were subsequently excluded. The control group consisted of pregnant women (n=58) with no diagnosed iodine deficiency disorder before or during pregnancy. Based on anamnestic data analysis, the most significant risk factors for perinatal complications were identified and used as indicators to calculate the risk of developing these complications.

[0018] By evaluating the coefficients, the established signs were ranked according to the degree of their influence on the risk of developing perinatal complications for a group of patients with iodine deficiency diseases identified before or during pregnancy.

[0019] The discriminant function was constructed using the logistic regression method:

[0020]

[0021] where -constant,

[0022] - regression coefficients

[0023] X1,…X р - indicators.

[0024] The values ​​were calculated based on the data collected in the practical part of the study, including 41 patients in the main group and 58 in the control group.

[0025] Indicators and their constants of perinatal complications for a group of patients with iodine deficiency diseases, identified before or during pregnancy, depending on the functional state of the thyroid gland, with euthyroidism:

[0026] Index (Xp) b History of non-viable pregnancy 20,336 History of late spontaneous miscarriage 0,635 Threatened spontaneous miscarriage during the current pregnancy 20,928 Platelet count at first visit 0,082 Constant -31,737

[0027] Classification Table

[0028] Observed Predicted Perinatal complications Percentage correct 0,00 1,00 Step 1 Perinatal complications 0,00 14 1 93,3 1,00 2 7 77,8 Overall percentage 87,5 The dividing value is 0.500.

[0029] This function, after inserting the values ​​of the patient's parameters listed above, yields an estimate of the probability of developing perinatal complications. The closer the resulting value is to 1, the higher the risk. Values ​​of 0 indicate virtually no risk.

[0030] Following the accepted forecasting methodology in logistic regression problems, if the function value is less than 0.5, perinatal complications are not predicted; if the value is 0.5 or higher, they are predicted.

[0031] Based on this prognostic function, a “Calculation Tool” was created in the Excel program, which assesses the chances of developing perinatal complications.

[0032] Thus, for any patient, using the anamnesis data presented in the “Calculation Tool” as 0 (absence of the indicator) or 1 (presence of the indicator), as well as the data of laboratory research methods (blood platelets in thousands / μl of blood), it is possible to assess the risk of developing perinatal complications without using labor-intensive and materially expensive research methods, since the provided laboratory indicators of a comprehensive blood test are included in the standard study during the physiological course of pregnancy.

[0033] Advantages of the claimed method:

[0034] 1. Good reproducibility of the method;

[0035] 2. Simplicity and accessibility of the technique;

[0036] 3. Easy to interpret the examination results;

[0037] 4. Does not require large material costs (examination under the compulsory medical insurance).

[0038] The effectiveness of the claimed method is confirmed by the following clinical example.

[0039] Clinical example 1.

[0040] Patient Ch, 32 years old. Admitted to the pregnancy pathology department for antenatal hospitalization. Somatic pathology: diffuse goiter stage 1 (WHO), euthyroidism. B 238x10*9 / L. According to the hormone profile (to confirm euthyroidism): TSH - 0.41 mIU / ml; T4 - 16.2 pmol / L.

[0041] 6th pregnancy, desired.

[0042] I - Urgent spontaneous labor

[0043] II - Spontaneous miscarriage at 8 weeks.

[0044] III - Urgent abdominal delivery on a planned basis

[0045] IV - Medical Abortion

[0046] V - Medical Abortion

[0047] VI - Real pregnancy.

[0048] At 10-11 weeks of pregnancy, inpatient treatment due to the threat of termination of pregnancy.

[0049] Clinical and anamnestic data have been added to the "Calculation Tool" for predicting perinatal complications in iodine deficiency disease without thyroid dysfunction:

[0050] History of non-viable pregnancy 0 History of late spontaneous miscarriage 0 Threatened spontaneous miscarriage during the current pregnancy 1 Platelet count at first visit 238

[0051] The prognosis is 0.99 – high risk of perinatal complications.

[0052] The pregnancy ended in childbirth at 37.6 weeks of gestation. The fetus weighed 3270g and was 52cm long. The Apgar score was 5 / 6. The child's diagnosis at discharge was: unspecified neonatal jaundice. Acute cerebral ischemia, moderate muscular hypotonia syndrome. Grade 1 intraventricular hemorrhage in the fetus and newborn. Respiratory distress syndrome in the newborn. Grade 2 respiratory failure. Moderate asphyxia at birth.

[0053] The forecast for the claimed method was confirmed.

[0054] Calculation of the sensitivity and specificity of the risk scale in relation to prognosis showed that the sensitivity of the method is 77.78%. The specificity of the prognostic scale is 96.1%. (Fig. 1).

[0055] When using this method, the percentage of correct predictions is 87.5% of cases, therefore the 0.5 boundary is chosen correctly, and no other research is required, once again confirming the correctness of the calculations and choice of boundaries.

[0056] Thus, the claimed method for predicting perinatal complications, which has a high prognostic value due to the study of anamnestic and laboratory parameters, will find wide application in practical healthcare in outpatient and inpatient institutions to justify the scope of examinations, treatment and preventive measures in patients with a high risk of perinatal complications.

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