RU2553624C1 - Method for predicting toxaemias of pregnancy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: predicting toxaemia of pregnancy is ensured by determining 24-hour urine placenta-like alkaline phosphatase and lactoferrin when the woman is 20-22 weeks pregnant, and then 2 weeks later, and the measured placenta-like alkaline phosphatase and lactoferrin of more than 16.0 ng/ml enable estimating potential toxaemia of pregnancy.

EFFECT: method enables predicting potential toxaemia of pregnancy, including the comprehensive assessment of protein risk factors taking into account the clinical presentation and significance of each factor in numeric equivalent.

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Description

The invention relates to medicine, namely to biochemistry for predicting the development of gestosis in pregnant women.

Gestosis is a multiple organ failure syndrome that develops as a result of pregnancy or worsens due to pregnancy. The classification of gestosis includes edema of pregnant women, proteinuria, arterial hypertension, preeclampsia and eclampsia. In recent years, pregnant women have seen a significant increase in OCG-gestosis. The frequency of gestosis, according to the literature, is 7-22% of the number of births. Gestosis remains the main cause of perinatal morbidity (64-68%) and mortality (18-30%). In the structure of causes of maternal mortality in the Russian Federation, gestosis steadily takes the third place and ranges from 11.8 to 14.8% (Repina M.A., 2010. Gridchik A.L., 2012, Ailamazyan E.K., 2013). The urgency of the problem is also due to the grave consequences of this disease. Gestosis leads to an increase in the frequency of perinatal complications in the mother, fetus and newborn, adversely affects the health status of children in subsequent years of life (Sidorova I.S., 2003; Savelyeva G.M., 2010; Vasilenko L.V. et al., 2012). In the pathogenesis of preeclampsia, preterm pregnancy, fetal growth retardation (PFR), dysfunction of the vascular endothelium plays a paramount role (Sukhikh G.T. et al., 2008).

It is known that in women with gestosis, disorders of many metabolic cycles are observed:

aerobic oxidation in the Krebs cycle, lipid peroxidation, antioxidant protection, endogenous synthesis of prostaglandins, lipid metabolism, immune reactions - all this contributes to the dysfunction of the vascular endothelium of the placenta, a change in the rheological properties of the blood, and thrombophilic conditions. Therefore, the development of an integrated approach to the prognosis and prevention of gestosis, severe gestosis in pregnant women is an urgent problem in modern biochemistry and obstetrics.

In the practice of biochemistry, methods for predicting the development of gestosis are known, based on biomicroscopy of the conjunctival vessels of the eye with a slit lamp with computer data processing using the computer program Adobe Photoshop CS in women in the first trimester of pregnancy. Conducted an analysis of the color of the pixels of the digital image of the vessels of the conjunctiva of the eye in case of microcirculation violation in comparison with the color of the pixels in the image of the vessels of the bulbar conjunctiva of healthy individuals. The assessment of microcirculation was determined in points: 7-8 points - normal, no red blood cell aggregation; 9-10 points - red blood cell aggregation increased; 11 points - mild red blood cell aggregation; 12 points - moderate red blood cell aggregation; 14 or more points - aggregation is pronounced, there is a sharp violation of microcirculation processes.

A blood test for homocysteine was performed in the first trimester of pregnancy by an enzyme immunoassay. For women, 4.6–12.4 μmol / L was considered conditionally normal indicators of homocysteine in the blood for a woman. The level of homocysteine in the blood in the first trimester of pregnancy is proportional to the severity of gestosis. With the development of mild gestosis, homocysteine indices amounted to 13.4 ± 0.3 μmol / L, with moderate severity - 15.9 ± 0.4 μmol / L, with severe severity - 31.4 ± 0.7 μmol / L (p <0.001) (Odnokozova O.S., Vasilenko L.V., Zryachkin N.I., Kolbenev O.I. Pregnancy, childbirth and the health status of newborns after preventive treatment of gestosis in pregnant women at risk // Saratov Scientific medical journal. - 2009. - V. 5. - No. 4. - S. 533-537). However, this prognostic model, based on a combined determination of the state of microcirculation and the level of homocysteine in the blood, has not proved to be effective for predicting gestosis as based on factors only remotely related to the pathogenesis of gestosis and placental insufficiency (Roach M., Lu J., Pilepich MV ., Asbell SO., Mohiuddin M., Terry R. et al .: Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials. Int. J. Radiat. Oncol. Biol. Phys . 2010, 1; 47: 609-615; Steuber T., Graefen M., Haese A. et al. Validation of a nomogram for prediction of side specific extracapsular extension at radical pr ostatectomy. J. Urol. 2006; 175: 939-14).

Methods are also known for determining other biochemical markers — for example, prostaglandins in combination with methods for determining vascular tone. In pregnant women in the 1st trimester, the averaged MMPI profile, the direction of vegetative regulation, the type of central hemodynamics and the level of prostaglandins in the blood serum are determined and with an increase in the averaged MMPI profile, increased sympathetic orientation of autonomic regulation, hypokinetic type of blood circulation and a decrease in the content of prostacyclins with an increase in thrombosis, prognosis Stolnikova I.I. Shpak L.V. METHOD FOR PREDICTING OCG HESTOSIS IN PREGNANT WOMEN WITH ESSENTIAL HYPERTENSION).

All described methods have disadvantages:

- the above methods are based on a combination of complex instrumental research methods (retinal vascular biomicroscopy, functional examination of the central nervous system and vascular tone), psychological tests (MMPI score) and complex biochemical analyzes for the determination of prostaglandins.

- lack of correlation of the level of prostaglandins with the MMPI profile;

- technical complexity of execution;

- the need for blood tests in the first 12 hours after collection due to the instability of prostaglandins.

- low accuracy of the study and the lack of clear limits for assessing the prognosis of gestosis.

Closest to the proposed method is a test to determine in blood serum and urine other preeclamps markers of Inhibin A and Activin A, the level of which in peripheral blood and urine correlates with an increased likelihood of developing gestosis. Particularly pronounced increase in the concentration of the proposed markers in the urine (more than 100 times). The authors propose considering levels of inhibin A and Activin A in the blood equal to and higher than 5.0 ng / ml, and levels of inhibin A and Activin A in the urine above 1.0 pcg / ml, as a border for assessing the likelihood of developing gestosis. (Muttukrishna S., Hyett J., Paine M., Moodley J., Groome N. and Rodeck C. Uterine vein and maternal urinary levels of activin A and inhibin A in pre-eclampsia patients Clinical Endocrinology - 2006 - v. 64 - p. 469-473).

However, the disadvantages of this method are:

- fuzzy distinction in assessing the prognosis of gestosis;

- lack of connection with the clinical signs of gestosis, except for hypertension;

- a narrow range of concentrations of inhibin A and Activin A, proposed by the authors to assess the development of gestosis;

- complex calculation for standardization and accounting of urine dilution;

- lack of data on the prognosis of gestosis (preeclampsia) in the 1st or early 2nd trimester of pregnancy.

The invention is aimed at predicting the development of gestosis on the basis of non-invasive dynamic immunochemical determination of placental alkaline phosphatase and lactoferrin in the daily urine of pregnant women, correlating with the subsequent development of gestosis. The specified technical result is achieved by the fact that to predict the development of gestosis, determine the concentration of placental alkaline phosphatase and lactoferrin, characterized in that determine the concentration of placental alkaline phosphatase and lactoferrin in the daily urine of pregnant women at 20-22 weeks of pregnancy and again after 2 weeks and the sum of the concentrations placental alkaline phosphatase and concentrations of lactoferrin above 16.0 ng / ml predict the development of gestosis.

The proposed method was successfully tested on 96 women in the period from 2009 to 2012, observed in the antenatal clinic of the Design Bureau No. 1 of Astrakhan from 15 to 36 weeks of gestation, with an observation interval of 2 weeks.

The method is illustrated by the following clinical examples of its implementation.

Clinical example 1

Patient A., 23 years old (medical history No. 14329). I applied on February 21, 2009. Daily urine for marker testing was taken at the 20th week of pregnancy 02/22/2009. The concentration of placental alkaline phosphatase was 0.9 ng / ml, lactoferrin 6.6 ng / ml, which amounted to 7.5 ng / ml At the 22nd week of pregnancy (March 6, 2009), urine was re-taken for the study of markers. The concentration of placental alkaline phosphatase was 1.8 ng / ml, lactoferrin 11.1 ng / ml, which in the total of two studies amounted to 20.4 ng / ml. Forecast - the likelihood of developing gestosis.

From 28 weeks of the course, pregnancy proceeded with transient proteinuria, periodic edema of the lower extremities. It was delivered on time, through the natural birth canal, by a living male fetus, weighing 3250 g with an Apgar score of 6-7 points.

Clinical example 2

Patient S., 24 years old (medical history No. 23124). Turned on November 1, 2010. Daily urine for the study of markers was taken at 21 weeks of gestation (November 2, 2010). The concentration of placental alkaline phosphatase was 0.1 ng / ml, lactoferrin 2.5 ng / ml, which amounted to 2.6 ng / ml in total. 11.16.2010 urine for the study of markers was taken again at 23 weeks of gestation. The concentration of placental alkaline phosphatase was 4.7 ng / ml, lactoferrin 4.3 ng / ml, which in the total of two studies amounted to 11.6 ng / ml. Forecast - there is no likelihood of developing gestosis. During pregnancy, blood pressure correction was performed, a diet with a low salt content was recommended. Pregnancy was uneventful. It was delivered on time, through the natural birth canal with a full-term girl weighing 3100 g with an Apgar rating of 7-8 points.

Clinical example 3

Patient S., 26 years old (medical history No. 10217), was received on 04/02/2011. Daily urine for the study of markers was taken at 22 weeks of gestation (04/03/2010). The concentration of placental alkaline phosphatase was 10.1 ng / ml, lactoferrin 14.5 ng / ml, which amounted to 24.6 ng / ml. 04/16/2010 urine for the study of markers was taken again at 24 weeks of pregnancy. The values of the concentration of placental alkaline phosphatase were 13.0 ng / ml, lactoferrin 10.3 ng / ml, which in the sum of two studies was 47.8 ng / ml. Forecast - the likelihood of developing gestosis. Pregnancy proceeded with transient proteinuria, periodic edema of the lower extremities. From 30 weeks, the course of pregnancy was complicated by severe late gestosis with eclampsia. It was delivered in the period of 39-40 weeks of pregnancy by Caesarean section with a live male fetus, weighing 2950 g with an Apgar rating of 6-7 points.

The invention was based on a survey of 96 pregnant women. The average age of patients was 23.5 ± 0.4 years (from 21 to 24 years) (Table 1).

The diagnosis of gestosis was made on the basis of clinical (complaints, the presence of latent and overt edema, arterial hypertension, the presence of concomitant extragenital pathology, the degree of violation of the uteroplacental and fetal-placental blood flow, fetal IUGR, signs of fetal hypoxia), laboratory data (OAK, OAM, biochemical blood test, coagulogram, urinalysis according to Zimnitsky, Reberg, Nechiporenko. Study of daily proteinuria), instrumental examination data (ultrasound, dopplerometry, CTG, fundus examination, monitor ing blood pressure) were assessed for severity of preeclampsia scale GM Savelyeva.

The conducted studies allowed a comprehensive assessment of risk factors taking into account the informative significance of each factor. The results of the study are presented in table 1. Positive = 12; false positive = 8; false negative = 4. Sensitivity of the method: True Positive / True Positive + False negative = 75.0%.

Specificity: True negative / true negative + false positive = 89.7%.

Thus, this means: in 75.0% of pregnant women with a total level of PSC and lactoferrin above 16.0 ng / ml, the prognosis of developing gestosis is correct. The specificity is 89.7%, therefore, in 89.7% of patients with a clearly negative prognosis, the test results are negative. A negative difference of 14.7% between a reliably positive prognosis and a reliably negative prognosis is a factor of uncertainty and in this case opens up the possibility of introducing new prognostic signs to increase sensitivity.

The proposed method has the following advantages:

- increasing the accuracy of the prognosis of development of gestosis on the basis of determining the total concentration of placental alkaline phosphatase and lactoferrin with a high probability of prediction of 75.0% (r = 0.7; P <0.00001).

- It has general accessibility and economic feasibility, as it is based on the assessment of only laboratory methods that have been introduced into widespread practice and does not require the use of expensive laboratory equipment.

- has simplicity, as it is based on a non-invasive study

- is an open predictive system, because allows you to easily enter additional laboratory parameters to increase sensitivity and reduce the number of false positive results, i.e. increase specificity.

METHOD FOR PREDICTING GESTOSIS IN PREGNANT WOMEN

Claims (1)

A method for predicting gestosis of pregnant women, consisting of a biochemical study of biological fluids, characterized in that the concentrations of placental alkaline phosphatase and lactoferrin in the daily urine of pregnant women are determined at 20-22 weeks of gestation and again after 2 weeks and by the sum of the concentrations of placental alkaline phosphatase and concentrations of lactoferrin above 16 , 0 ng / ml predict the development of gestosis.