RU2180113C1 - Method for diagnosing developing placental insufficiency at early stage - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves making biochemical analysis of blood to determine malonic dialdehyde (MDA) concentration, general blood plasma antioxidation activity (AOA) and evaluating organism antioxidation protection (OAP). Venous blood sample is taken once from pregnant woman in the period from the sixth to the twelfth week of pregnancy period. The analysis results are used for additionally determining catalase activity and lipid hydroxides concentration and evaluating organism antioxidation protection using depression coefficient of antioxidation potential K(K_DAC), calculating from formula

where A $\genfrac{}{}{0ex}{}{\text{om}}{\text{AOA}}$ , A $\genfrac{}{}{0ex}{}{\text{om}}{\text{CAT}}$ , C $\genfrac{}{}{0ex}{}{\text{om}}{\text{HP}}$ , C $\genfrac{}{}{0ex}{}{\text{om}}{\text{MDA}}$ - are general antioxidation activity, catalase activity, lipid hydroxides concentration and malonic dialdehyde concentration determined from woman patient under study to normal state reference mean statistic values determined on healthy women during the first pregnancy trimester, respectively. Developing placental insufficiency diagnosis is set when K_DAC ≤ 0,75. EFFECT: enhanced effectiveness and reliability of diagnosis method.

Description

 The invention relates to medicine, in particular to obstetrics and gynecology. It can be used to diagnose emerging placental insufficiency in the first trimester of pregnancy, which is extremely important for choosing effective preventive and treatment measures in early pregnancy.

 A known method for predicting the course of pregnancy (AS USSR 1770906 from 10.19.89, IPC 6 G 01 N 33/48, BI 39, 1992) [1], according to which by examining the blood and determining the content of pyruvic acid in its red blood cells they predict a threat of abortion, and when the concentration of pyruvic acid decreases to 0.39-0.37 μmol / g, gestosis of the second half of pregnancy is predicted, and with a value of 0.36 μmol / g and lower, a threat of pregnancy termination is predicted. The disadvantage of this method is the high probability of obtaining false-positive results when conducting analysis according to the specified method with the addition of trichloroacetic acid, due to the ease of conversion of pyruvic acid into lactic acid.

 A known method for predicting placental insufficiency (AS USSR 1807001 from 07.04.93, IPC 6 G 01 N 33/48, BI 13, 1993) [2] by biochemical examination of urine with determination of the content of malondialdehyde (MDA) before and after the addition of dibunol, and with an increase in the content of MDA by more than 4.2 μmol / L, placental insufficiency is predicted. However, a significant drawback of this method is its rather low reliability, because the biochemical composition of urine (in this case, the content of MDA in the urine) does not accurately reflect the true picture, being less stable compared to blood, depends on the functional state of the kidneys, and accordingly changes when pathology, which is quite common during pregnancy.

A known method for the early diagnosis of placental insufficiency by determining the proteins of the pregnancy zone (Mamedalieva N.M., Sidelnikova V.M. The value of determining trophoblastic β ₁ -glycoprotein (TBH) for early diagnosis and prediction of placental insufficiency in pregnant women with habitual miscarriage // Obstetrics and Gynecology. - 1991. - 11.) [3]. However, the method for determining TBH is a lengthy and costly one; far from all laboratories for antenatal clinics and municipal clinics have the ability to work with hormones.

 Closest to the claimed method, a method for the diagnosis of fetal hypoxia was selected (AS USSR 1752185 from 01/18/91, A 61 B 10/00, BI 28, 1992) [4], carried out by blood with the determination of malondialdehyde (MDA) , antioxidant activity (AOA) and antioxidant protection of the body (AOD) as the ratio of AOA / MDA in red blood cells and with a decrease in AOD to 1.90-0.82, fetal hypoxia is diagnosed. However, this method cannot be used to diagnose emerging placental insufficiency, because at the initial stages of gestation to assess the state of the antioxidant system of blood, which is one of the markers of the body's adaptive capabilities (syntoxic, catatoxic adaptation programs, disadaptation), and, consequently, placental insufficiency during gestation as a manifestation of disadaptation of the body. It is not enough to determine only the concentration of MDA and AOA. For an objective analysis, it is necessary to take into account the concentration of lipid hydroperoxides (GPL) and the activity of catalase (AK). Catalase activity and plasma antioxidant activity together reflect the state of the antioxidant system of the blood (syntoxic adaptation programs), but with pathology they vary to different degrees, therefore, to obtain a more reliable result, it is necessary to analyze both indicators. The concentration of malondialdehyde and lipid hydroperoxides in the aggregate reflect how intensively the oxidative processes (catatoxic adaptation programs) take place in the body, and, in addition, with pathology, these indicators vary to different degrees, therefore, to obtain a more reliable result, it is necessary to analyze both indicators. The methodology for determining MDA and AOA, referred to by the authors in the prototype, is not correct, and therefore reliable.

 The present invention solves the problem of increasing the reliability of early diagnosis of emerging placental insufficiency in the first trimester of pregnancy, the possibility on the basis of this timely treatment, the technical simplicity of the diagnosis and the absolute harmlessness of the method for mother and fetus.

где относительные величины A_ОАО ^оm - общая антиокислительная активность плазмы, A_КАТ ^оm - активность каталазы, С_ГП ^оm - концентрация гидроперекисей, С_МДА ^оm - концентрация малонового диальдегида, рассчитанные как отношение активностей или концентраций соответствующих параметров крови обследуемой беременной к нормальным идентичным среднестатистическим показателям здоровых женщин в первом триместре беременности.The problem is solved in that during the period from the 6th to the 12th week of pregnancy, a woman’s venous blood is sampled once, antioxidant blood parameters are determined (catalase activity, plasma antioxidant activity) and blood parameters reflecting the intensity of oxidative processes in the body associated with with lipid peroxidation, generation of free radicals, lipid hydroperoxides, and by their ratio value calculated depressed blood antioxidant system _(DAS K), which reflects step Hb inclusion sintoksicheskih adaptation programs, dominant in the first trimester of pregnancy and empathy aimed at the mother's body and fetus. This coefficient is calculated according to

where the relative values of A _OJSC ^OM are the total antioxidant activity of the plasma, A _CAT ^OM is the activity of catalase, With _GP ^OM is the concentration of hydroperoxides, and _MDA ^OM is the concentration of malondialdehyde, calculated as the ratio of the activities or concentrations of the corresponding blood parameters of the examined pregnant woman to normal identical average statistics healthy women in the first trimester of pregnancy.

In the article "The role of placental proteins in maintaining physiological functions during normal and pathologically ongoing pregnancy" authors Yu.K. Gusak, Yu. V. Lazarev, V.N. Morozov et al. // Bulletin of new medical technologies.-1999. -T. VI, 2 - S.91-95.) 151 shows the average statistical data obtained by clinical observation of 30 pregnant women with a normal pregnancy (total antioxidant plasma activity 35.0 ± 0.82%, catalase activity 9.2 ± 0 , 16 μat / L, the concentration of malondialdehyde 4.07 ± 0.12 μmol / L, the concentration of lipid hydroperoxides 1.21 ± 0.06 OU / ml). With numerical values of K _DAS ≤0.75, the emerging placental insufficiency is diagnosed.

 The inventive method is as follows: in a woman in the first trimester of pregnancy (usually from the 6th to the 12th week of pregnancy), blood is taken once from the ulnar vein in an amount of 5 ml, the total antioxidant activity of the plasma, the activity of catalase are determined, the concentration of malondialdehyde and lipid hydroperoxides by conventional methods.

где A_ОАО ^оm, A_КАТ ^оm, С_ГП ^оm, С_МДА ^оm соответственно отношения общей антиокислительной активности, активности каталазы, концентрации гидроперекисей липидов и концентрации малонового диальдегида, полученные при анализе крови диагностируемых женщин, к нормальным идентичным среднестатистическим показателям здоровых беременных женщин, и при К_ДАС≤0,75 диагностируют формирование плацентарной недостаточности.Then, according to the results of the analysis of the indicated blood sampling, the coefficient of depression of the antioxidant blood system (K _DAS ) is calculated according

where A _OJSC ^OM , A _CAT ^OM , With _GP ^OM , With _MDA ^OM, respectively, the ratios of total antioxidant activity, catalase activity, concentration of lipid hydroperoxides and concentration of malondialdehyde obtained in the analysis of blood of diagnosed women, to normal identical average statistics of healthy pregnant women, and with K _DAS ≤0.75, the formation of placental insufficiency is diagnosed.

The method allows to evaluate the nature of the adaptive capabilities of the body of a pregnant woman by the value of the coefficient of depression of antioxidant blood mechanisms (K _DAS ) in the early stages of gestation, because it reflects the degree of inclusion of syntactic adaptation programs in pregnant women in the first trimester of pregnancy. This allows you to timely diagnose emerging placental insufficiency and conduct treatment.

Example 1. Patient A., 23 years old, turned to a antenatal clinic for a delay of menstruation for 2.5 months. She noted slight nausea. From the anamnesis: suffered salpingoophoritis, colpitis. On examination, the uterus is enlarged to 10-11 weeks of pregnancy, painful on palpation. Appendages on palpation are painful, not enlarged. The diagnosis was made: first pregnancy, 10-11 weeks, burdened gynecological history. According to the results of determining K _DAS = 0.66, the presence of emerging placental insufficiency was diagnosed, treatment was prescribed and carried out, the pregnancy was full-term, delivery on time.

Example 1. Pregnant G., 26 years old. Was admitted to the hospital with symptoms of early gestosis of moderate severity. Complaints of nausea, vomiting up to 3-4 times a day, headache, weight loss over the past week amounted to 2 kg, lack of appetite. Pregnancy is 11-12 weeks, the value of K _DAS at admission is 0.54, indicating a clear formation of placental insufficiency. Was treated, pregnancy is full-term, delivery on time.

Example 3. Patient T., 25 years old, was admitted to the hospital with complaints of moderate intensity pain in the lower abdomen and lower back. Last menstruation 9 weeks ago. From the anamnesis: was treated for infertility over the past three years. Married, first marriage. Objectively: with a vaginal examination, the uterus is enlarged to 7 weeks of pregnancy, excitable by palpation. Diagnosis: first pregnancy, 7 weeks, threatened abortion, burdened gynecological history. When examining K _DAS = 0.47, which indicates a very unfavorable situation that develops during the formation of the fetoplacental complex. Despite the treatment, after 2 weeks the pregnancy froze.

 The proposed method allows for early diagnosis of emerging placental insufficiency with high reliability (98.9%), which is very important at the initial stages of gestation for timely treatment and a favorable pregnancy outcome in the future. In addition, this method is absolutely harmless to the mother and the fetus, technically simple, has no contraindications for use.

Claims (1)

A method for early diagnosis of emerging placental insufficiency, including a biochemical blood test to determine the concentration of malondialdehyde (MDA), the total antioxidant activity of the plasma (AOA) and the subsequent assessment of the antioxidant protection of the body (AOD), characterized in that from the 6th to the 12th the fifth week of pregnancy, a woman’s venous blood is sampled once, according to the results of which, along with the above indicators, the activity of catalase and the concentration of hydroperoxides lipids, evaluate the antioxidant protection of the body by the coefficient of depression of the antioxidant potential of the blood (K _DAS ), calculated by the dependence

where A _AOA ^om , A _CAT ^om , With _GP ^om , With _MDA ^om are the ratios of total antioxidant activity, catalase activity, concentration of lipid hydroperoxides and concentration of malondialdehyde obtained in the blood test of the diagnosed woman to normal identical average statistical values of healthy women in the first trimester of pregnancy
and the formation of placental insufficiency is diagnosed with values of K _DAS ≤0.75.