RU2749107C2 - Method for early prediction of fetoplacental insufficiency in the beginning of the second trimester of pregnancy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to obstetrics and gynecology, and can be used for early detection of risk of developing fetoplacental insufficiency. Three groups of early predictable factors of fetoplacental insufficiency are determined: real pregnancy, obstetric anamnesis and somatic pathology, wherein an increase in the pulsation index PI of any of the uterine arteries in real pregnancy over 2.5 is estimated as 4 points. More than 2 MoM (multiple of median) increase of PAPP-A (pregnancy-associated plasma protein A) is estimated as 1 point, and a less than 0.8 MoM decrease of PAPP-A as 3 points. More than 2 MoM increase of HCG (human chorionic gonadotropin) is estimated as 1 point, and a less than 0.8 MoM decrease of HCG as 2 points. More than 2 but less than 4.3 increase of TSH (thyroid stimulating hormone) is estimated as 1 point, and more than 4.3 increase of TSH as 2 points. 1 point each is assigned if any of the following factors is present: number of nocturnal urination (nocturia) more than 1, early toxicosis of moderate and severe degrees, a more than 4 increase in fibrinogen, less than 110 hemoglobin, 5 or more bloody discharge and sugar, acute infection and exacerbation of chronic infection in I trimester. In an obstetric anamnesis, moderate preeclampsia is estimated as 2 points and severe as 4 points, missed miscarriages or miscarriages before 9 weeks as 1 point each and after 9 weeks as 2 points each, the first pregnancy as 1 point, stillbirth or early neonatal mortality as 3 points, premature birth, fetal growth retardation at the weight of any of the children at birth of 2800 grams or less, the weight of the woman herself at birth of 2800 grams or less as 2 points. In somatic factors each chronic disease is estimated, such as: gastritis, cholecystitis, pyelonephritis, tonsillitis, bronchitis, arterial hypertension, diabetes mellitus, diseases of lower extremity veins and vulva and smoking as 2 points, body mass index, BMI, of more than 30 and less than 40 as 1 point, and BMI over 40 as 2 points, age over 40 as 1 point. At a total score of up to 4, low risk of FPI is predicted. At a total score of 5 to 9, an average degree, at a total score of more than 10, a high degree is predicted.

EFFECT: method allows increasing accuracy and objectivity of predicting FPI, attributing a pregnant woman to a risk group on time and performing activities aimed at improving perinatal outcomes in time in the beginning of the second trimester.

1 cl, 2 ex, 1 tbl

Description

The invention relates to medicine, namely to obstetrics and gynecology, and can be used for early detection of the risk of developing placental insufficiency (FPI) and associated pregnancy complications, such as growth retardation and intrauterine fetal hypoxia.

FPN is a clinical syndrome caused by morphological and functional changes in the placenta and manifested by impaired growth and development of the fetus, its hypoxia, which arise as a result of the combined reaction of the fetus and the placenta to various disorders of the state of the pregnant woman (Makatsaria A. Davidovich., Bitsadze V.O. , Khizroeva D.Kh., Hamani NM Placental insufficiency in complicated pregnancy and the possibility of using dipyridamole. Obstetrics, gynecology and reproduction, 016, t 12, No. 4, pp. 72-82).

This syndrome is based on pathological changes in the fetal and / or uterine-placental complexes with impaired compensatory-adaptive mechanisms at the molecular, cellular and tissue levels. At the same time, the functions of the placenta are disrupted, which underlie the occurrence of pathology in the fetus and newborn (Arzhanova O.N., Paikacheva Yu.M., Kapustin R.V., Ruleva A.V., Nichiporuk N.G. Causes of obstetric complications in patients after assisted reproductive technologies. Journal of Obstetrics and Women's Diseases. - 2017. - T. 66. - No. 3. - P. 25-33. doi: 10.17816 / JOWD66325-33).

The causes of placental dysfunction can be the transferred infections during pregnancy; vascular disorders, antiphospholipid syndrome (APS), complications of the course of pregnancy (preeclampsia, threat of interruption, prolonged pregnancy), extragenital pathology (chronic venous diseases, endocrine, hematological disorders, diseases of the cardiovascular and genitourinary systems, intoxication). Rybalka A.N., Egorov Ya.A. Placental dysfunction and perinatal loss. Crimean Journal of Experimental and Clinical Medicine. 2012, volume 2, no. 3-4 (7-8), p. 50-54).

Risk factors for the development of placental insufficiency also include: the mother's age over 40 years, nutritional disorders, bad habits (smoking, alcohol, drugs), unfavorable social conditions, the harmful effects of physical or chemical factors in the early stages of the gestational period, the presence of foci of latent infection, burdened obstetric and gynecological history. More than half of pregnant women with placental dysfunction have various autoimmune disorders - hyperandrogenism, thyroid pathology, diabetes mellitus (Zakharova I.V., Chabanova E.B., Fedorenko O.A., Toropkina E.L., Belova N.G. The risk of developing placental insufficiency in pregnancy complicated by miscarriage. Siberian medical journal, 2010. T. 25. No. 4-2. S. 130-132).

The physiological course of pregnancy is possible only in healthy women, when the placenta is formed without somatic and infectious pathology, without a deficiency of vitamins and microelements. In practice, women often enter pregnancy with a burdened history and / or extragenital diseases leading to the development of placental insufficiency and unfavorable pregnancy outcomes.

Some risk factors for FPD development can be identified before pregnancy, while others - during real pregnancy. Risk factors are summed up, creating the prerequisites for a complicated course of gestation. At the same time, it is extremely important to calculate the risk factors for the formation of FPI during pregnancy, when the prevention of this complication is still possible and effective. Isolation of women with a high risk of FPI will allow organizing intensive monitoring of fetal development from the beginning of pregnancy according to a plan drawn up individually for each woman (Tezikov Yu.V., Lipatov I.S., Risk factors for decompensation of placental insufficiency. Kazan Medical Journal, 2011 ., Volume 92, No. 3. P. 372-375), V.E. Radzinsky. Obstetric risk. Maximum information - minimum danger for mother and baby. Moscow: Eksmo, 2009 .-- 288 p.).

In connection with the above, early prognosis and prevention of FPI is a promising and optimal strategy for pregnancy management.

It is known that predicting the risk of FPI development was carried out earlier, for example, using the L.S. Persianinov modified by O.G. Frolova and E.I. Nikolaeva. Over time, a number of previously existing scales have lost their meaning or have become less significant. New, more reliable scales for assessing the risk of developing FPI have appeared, in particular, the scale of V.E. Radzinsky. - Kostina IN, which has become widespread in obstetric practice (Radzinsky VE Obstetric risk. Maximum information - minimum danger for mother and baby. Moscow: Eksmo, 2009. - 288 p.). There are freely available FMF calculators for calculating the risk of fetal growth retardation.

Noteworthy are the scales proposed by N. Kibardina (N. Kibardina, Modern possibilities for predicting perinatal morbidity \\ Abstract of the thesis ... Candidate of Medical Sciences, Moscow, 2009, p. 19). Fayzullin A.Sh., (Fayzullin A.Sh. Suverneva A.A. Differentiated approach in predicting unfavorable perinatal outcomes // International Journal of Applied and Fundamental Research. - 2013. - No. 11-1. - P. 69-71).

Most of the proposed scales require special methods of examining pregnant women, which are inaccessible to most medical institutions, or they offer an assessment of risk factors at the end of pregnancy, which is optimal for the correct routing and choice of delivery tactics, but is not suitable for preventing the development of FPN. Therefore, the scoring of the risk of developing placental insufficiency in the second trimester of pregnancy for the prevention of this complication is an extremely important task.

As a prototype, a method for assessing the degree of risk of pregnancy complications based on the results of mass monitoring of pregnant women at the regional level (RU 2.497437 C1, 2012) (Gorbunov A.V., Zvezdochetov M.F., Merkushin I.L., Bychkovsky A.A., Faizullin A.Sh., 2013).

The proposed method includes a threefold calculation of prenatal risk factors in a pregnant woman: when registering a pregnant woman at an antenatal clinic, at 20-24 and at 30-34 weeks of pregnancy. Each prenatal risk factor is scored in accordance with the developed table. The points obtained are summed up.

Socio-biological factors, somatic indicators, genetic factors, obstetric and gynecological history, complications of pregnancy and childbirth in history, extragenital diseases before and during pregnancy, the period of taking under the supervision of antenatal clinics, especially the course of pregnancy are taken into account. In order to increase the practical benefits, each prenatal risk factor on the basis of its organizational criterion of significance, taking into account regional characteristics, is assigned to one of the levels of health care facilities, where: 1 level is the central district hospital; Level 2 - interdistrict perinatal center; Level 3 - Republican Perinatal Center.

According to the developed outcome assessment system, each of them belongs to one of the postnatal risk groups:

- low risk (in the sum of 49 or less points and not a single factor from the groups of medium, high and emergency risk, its achievement means a favorable pregnancy outcome). Further observation and delivery is carried out in obstetric facilities of the Central District or City Hospital

- medium risk (in the sum of 50-169 points or any factor from the group of medium risk, and not a single factor from the groups of high and emergency risk, its achievement means a dubious outcome). The tactics of further management of pregnancy and delivery are determined in the Interdistrict Perinatal Center or the City Maternity Hospital

- high risk (in the sum of 170-249 points or any factor from the high-risk group, and not a single factor from the urgent risk group, its achievement means an unfavorable outcome). The tactics of further management of pregnancy and delivery are determined in the Republican Perinatal Center or the Regional or Regional Maternity Hospital.

- emergency risk (in the amount of 250 points or more, or any factor from the group of emergency risk, its achievement means that there is a direct threat to life or the fact of death of the mother and / or newborn). Emergency hospitalization.

The disadvantages of this invention include the complexity of using data without special software, the impossibility of using it in routine daily practice. In addition, risk assessment is carried out in late pregnancy (end of the second trimester), when preventive measures are ineffective.

The aim of the invention is to simplify the determination of the risk of developing FPN and associated complications of gestation. This is achieved by additional counting of available risk factors at the beginning of the second trimester of pregnancy and prescribing drug prophylaxis depending on the sum of risk factors.

Prediction of FPI was carried out by calculating the sum of statistically significant risk factors available for assessment.

The essence of the invention lies in the fact that the determination of the risk of FPN is carried out at the beginning of the second trimester of pregnancy, followed by the appointment of drug and non-drug prophylaxis in the 2nd trimester in high-risk groups.

The proposed method for early forecasting of FNP is carried out as follows. The following pregnancy factors are taken into account in three groups: examination data and the course of this pregnancy, obstetric history and somatic factors such as gastritis, cholecystitis, pyelonephritis, tonsillitis, bronchitis, arterial hypertension, diabetes mellitus, vein disease of the lower extremities and vulva and are evaluated in points in accordance with table 1.

If the PI value (pulsation index) of any of the uterine arteries is more than 2.5, 4 points are awarded, with an increase in PAPP-A (Pregnancy-associated Plasma Protein-A), more than 2 MoM (multiple of median times the median ) - coefficient showing the degree of deviation of the indicator from the average value for the gestational age) is awarded 1 point, with a decrease of less than 0.8 MoM - 3 points, with an increase in hCG (human chorionic gonadropin) more than 2 MoM, 1 point is awarded, with a decrease of less than 0, 8 MoM - 2 points. 1 point is awarded if each of the following factors is present: hemoglobin less than 110, TSH (thyroid stimulating hormone) above 2 but less than 4.3, increased fibrinogen more than 4, sugar more than 5, spotting in the 1st trimester, more than 1 urination per night (nocturia more than 1), moderate or severe early toxicosis, acute infection or exacerbation of chronic in the 1st trimester. In the presence of anamnestic factors, such as a history of miscarriages and missed pregnancies before 9 weeks of pregnancy, body mass index BMI more than 30, but less than 40, age over 40 years is awarded 1 point. With a history of moderate preeclampsia, fetal growth retardation (fetal growth retardation) takes into account the birth weight of any of the previous children 2800 or less), premature birth, the weight of the pregnant woman at birth less than 2800, smoking women, the presence of each chronic somatic disease such as gastritis, cholecystitis, pyelonephritis, tonsillitis, bronchitis, arterial hypertension, diabetes mellitus, disease of the veins of the lower extremities and vulva, BMI more than 40, as well as an increase in TSH above 4.3 for each factor, 2 points were awarded, if there was a history of stillbirth or early neonatal mortality - 3 points, severe preeclampsia - 4 points. In the case of the first pregnancy, the patient is awarded 1 point, given the lack of information on anamnestic factors in relation to previous pregnancies.

To confirm the effectiveness of this method, the course and outcomes of pregnancy were analyzed in 180 pregnant women who did not receive FPN prophylaxis in the first half of pregnancy. Women were divided into 2 groups: group 1 of 60 - pregnant women with manifestations of FPI, such as preeclampsia, IGR (fetal growth retardation), FPI according to ultrasound data in combination with proteinuria or gestational hypertension, signs of antenatal fetal hypoxia according to examination data. Group 2 - 120 pregnant women with the physiological course of pregnancy and childbirth, full-term fetuses weighing more than 3000 g, an APGAR score of 8 points or more at 1 minute after childbirth. Among these 180 women, a variety of risk factors were analyzed that are easily available for assessment in 1-2 trimesters of pregnancy, such as the presence of dissociation of serum markers, an increase in PI (pulsation index), uterine arteries, the value of serum markers (PAPP-A and hCG) at 11 -13 weeks, complications of the 1st trimester of pregnancy, aggravation of obstetric history, somatic pathology, age of the pregnant woman and the child's father, blood type, marital status, height, parity, hyperthyroidism. The value of fibrinogen, total blood protein, hemoglobin, sugar, TSH, reduced number of platelets, erythrocytes and lymphocytes in the 1st trimester).

As an indicator of risk for each parameter, the calculation of the relative risk (RR) was carried out simultaneously with the calculation of the sensitivity and specificity.

After analyzing the influence of the parameters of the anamnesis and the course of the 1st trimester on the likelihood of an unfavorable perinatal outcome and the development of FPI, a scale of the sum of risk factors was compiled. The proposed scale included factors with an RR of more than 1.2 with a confidence CI of 95% (p <0.05), provided that the upper and lower limits of the confidence interval did not include 1 and in the case when their sensitivity and specificity were 40% and more. The rest of the studied parameters were excluded from the scale. With an RR of 1.2 to 2 in combination with a sensitivity above 40%, the parameter was assigned 1 point, from 2 to 3 - 2 points, from 3 to 4 - 3 points, above 4 - 4 points.

In a retrospective analysis of the sum of risk factors for the development of FPI, it turned out that in 53 (88%) patients of group 1 (with developed FPI) the sum of risk factors ranged from 5 to 15 points. Whereas in the physiological course of pregnancy and the normal state of the fetus and newborn, the sum of risk factors in 101 (85% of cases) did not exceed 4 points, and in 15% it was 5-7 points.

With a score of up to 4, a low risk of FPI is predicted, with a score of 5 to 9 - an average degree, with a score of more than 10 - a high degree.

The main idea of the invention is to improve the accuracy of predicting FPI at the beginning of the second trimester, when, on the one hand, the maximum of necessary information has already been accumulated to identify risk groups, on the other hand, there are still opportunities for the effect of preventive measures.

Clinical example 1

Pregnant R-a. L.D., 26 years old, primary pregnant, somatically burdened with metabolic syndrome (BMI 34). She did not undergo pregravid training. She was registered for pregnancy for a period of 9 weeks. In the GI, the pregnant woman was assigned to the group of low risk of obstetric complications. During pregnancy, she received folic acid, courses of vitamin complexes.

Retrospectively, the sum of risk factors was calculated according to the proposed scale for a period of 13 weeks after undergoing ultrasound and biochemical screening. Revealed: Increase in PI on one side more than 2.5-4 points, Decrease in PAPP-a less than 0.8 MoM - 3 points, increase in TSH more than 2-1 points, Number of nocturnal urinations> 1 - 1 point, Sugar 5.4 c 1 trimester - 1 point, First pregnancy - 1 point, BMI (mass index) more than 30 - 1 point.

Thus, the score was -12, which corresponds to a high risk of FPI development.

Childbirth - at 37 weeks by an emergency caesarean section due to an increase in the severity of preeclampsia. A live male fetus was born weighing 2690, height 51 cm, Apgar score 6-7 points. The newborn was transferred to the neonatal pathology department on the 3rd day.

Clinical example 2

Pregnant P-va A.I., 33 years old, forthcoming labor II. The first birth 8 years ago ended in antenatal fetal death at 35 weeks, weighing 1900. The marriage was repeated. Pregravid preparation - self-administered folic acid 400 mg for 2 months before conception. Examined for sexually transmitted infections (STIs) - no infection was detected. When registered for a period of 6-7 weeks, it was classified as a high-risk group for FPI.

During this pregnancy, she received folic acid, basic vitamin complexes in courses.

Retrospectively, the sum of risk factors was calculated according to the proposed scale for a period of 13 weeks after the results of ultrasound and biochemical screening. Revealed - the PI values of the uterine arteries and serum markers within the reference values, TSH, hemoglobin, fibrinogen, sugar values are normal. During the 1st trimester without complications, nocturia - no more than 1. Somatic history is not burdened - 0 points. BMI - 24-0 points. Anamnestic factors - 2 points of IGR, 2 points - premature birth.

The sum of risk factors on a scale of risk factors for FNP development at the beginning of the second trimester was 4 points (low risk).

Ultrasound screening was performed three times, no signs of placental insufficiency and FGR were detected. CTG monitoring - no peculiarities.

Was admitted to the maternity ward with a diagnosis of Pregnancy 38 weeks. End of period 1 of 2 urgent labor. OAA. She was born as a girl m = 3280 g, height 51 cm, with an Apgar score of 8-9 points. The adaptation period was uneventful, she was discharged home on the 3rd day under the supervision of a local pediatrician. Postpartum period without complications.

The method is aimed at improving the accuracy and objectivity of predicting FPI, allows a pregnant woman to be assigned to a risk group in time and timely at the beginning of the second trimester (the period of a window of preventive opportunities) to take measures aimed at improving perinatal outcomes.

Claims (1)

A method for early prediction of placental insufficiency at the beginning of the second trimester of pregnancy, including an assessment in points of factors for the development of complications of pregnancy or, in the absence of a factor, equating its score to 0, characterized in that three groups of early predictable factors of fetoplacental insufficiency are determined: real pregnancy, obstetric history and somatic pathology, while in this pregnancy, an increase in the pulsation index of PI of any of the uterine arteries more than 2.5 is estimated as 4 points, an increase in PAPP-A (protein A associated with pregnancy) more than 2 MoM (multiple of median - a multiple of the median) as 1 point, and a decrease in PAPP-A is less than 0.8 MoM as 3 points, an increase in hCG (human chorionic gonadotropin) is more than 2 MoM as 1 point, and a decrease in hCG is less than 0.8 MoM as 2 points, an increase in TSH (thyroid stimulating hormone) is more than 2, but less than 4.3 as 1 point, and an increase in TSH of more than 4.3 as 2 points, assign 1 point if each of the following f actors: the number of nocturnal urination (nocturia) more than 1, early toxicosis of moderate and severe degrees, increased fibrinogen more than 4, hemoglobin less than 110, bleeding, sugar 5 or more, acute infection and exacerbation of chronic in the first trimester; with an obstetric history, moderate preeclampsia is assessed as 2 points, and severe as 4 points, missed pregnancies or miscarriages before 9 weeks each as 1 point, and after 9 weeks each as 2 points, the first pregnancy as 1 point, stillbirth or early neonatal mortality as 3 points, premature birth, IGR with the weight of any of the children at birth 2800 grams or less, the weight of the woman herself at birth 2800 grams or less as 2 points: for somatic factors, each chronic disease is assessed, such as: gastritis, cholecystitis, pyelonephritis, tonsillitis, bronchitis, arterial hypertension, diabetes mellitus, disease of the veins of the lower extremities and vulva and smoking, as 2 points, body mass index BMI more than 30 less than 40 as 1 point, and BMI more than 40 as 2 points, age over 40 years as 1 point, and with a score of up to 4, a low degree of risk of FPI is predicted, with a score of 5 to 9 - an average degree, with a score of more than 10 - a high degree.