RU2761315C1 - Method for preventing complications of perinatal period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gynecology, and can be used for the prevention of complications of the perinatal period. In a woman planning a pregnancy, the magnesium content in the venous blood plasma is first determined and when the magnesium content is below 0.8 mmol/l, a magnesium preparation is used and the content of pyrilinx D and glycosaminoglycans in the urine is additionally determined. When the content of pyrilinx D is higher than 7.4 nmol/l and glycosaminoglycans are higher than 7.1 mg/mmol, drugs that improve collagen metabolism are additionally used, selected from the group: ascorbic acid, vitamin E, vitamin D2, calcium preparations. Monitoring of the content of magnesium in the venous blood plasma, pyrilinx D and glycosaminoglycans in the urine is carried out every three months of treatment. Pregnancy planning is recommended when the level of magnesium in the venous blood plasma is equal to or more than 0.8 mmol/l, the level of pirilinx D in the urine is equal to or less than 7.4 nmol/l, and the level of glycosaminoglycans in the urine is equal to or less than 7.1 mg/mol.

EFFECT: method provides an opportunity to improve perinatal outcomes in patients planning pregnancy by clarifying a differentiated approach to choosing optimal schemes for their examination and treatment due to the timely determination of magnesium deficiency, objective indicators of impaired collagen metabolism, which are criteria for the effectiveness of therapy, markers of a woman's preparation for pregnancy.

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Description

The invention relates to medicine, namely to gynecology, can be used when examining women before planning pregnancy. The method can be used in specialized gynecological institutions.

Magnesium is one of the most basic elements that is involved in providing important biochemical and physiological processes in the human body. Magnesium takes part in energy, plastic and electrolyte metabolism. Magnesium also stimulates many cellular processes. In Russia, according to various authors, the prevalence of magnesium deficiency among the population ranges from 16 to 42%. Magnesium deficiency has up to 10% of patients in the hospital, and in the emergency clinic - 30-70% of patients.

The lack of magnesium is combined with various complications from pregnancy and childbirth. So, for example, against the background of magnesium deficiency, there is an increase in the tone of the myometrium, possible premature birth, the development of preeclampsia and eclampsia, arterial hypertension, arrhythmias and muscle cramps in pregnant women, excessive weight gain, gestational diabetes and metabolic syndrome in the postpartum period [Gromova OA ., Torshin I.Yu. Connective tissue dysplasia, cell biology and molecular mechanisms of magnesium action. Russian medical journal. 2008. Volume 16. No4. S. 22-25; Ilyina I.Yu. Features of diagnosis, treatment, management of gynecological diseases in patients with connective tissue dysplasia. Abstract of thesis ... doct. honey. sciences. Moscow. 2013.S. 15-32; Wallace A., Lowry J., Smith S. M., Fahey T. The epidemiology of malpractice claims in primary care: a systematic review. BMJ Open. 2013. Vol.3, No. 7; Seagull B.K., Zheleznaya A.A., Luneva N.H. Management of complicated pregnancy in a pregnant woman with undifferentiated connective tissue dysplasia (clinical case). Medical and social problems of the family. 2019. Volume 24. No1. S. 104-111].

It is known that magnesium takes an active part in collagen synthesis, and quite often patients with connective tissue dysplasia have a deficiency of this macronutrient.

Considerable attention to the problem of connective tissue dysplasia is associated with the wide prevalence of its individual manifestations in the population, which ranges from 26 to 80% according to various authors [GI Nechaev, IA Viktorova. Connective tissue dysplasia: terminology, diagnostics, patient management tactics. Omsk. 2007. S. 11-47]. Undifferentiated connective tissue dysplasia (uCTD) is one of the most common connective tissue diseases. The high prevalence of this process in the population can provoke the development of a number of other diseases.

So, it is known that with pathology from the connective tissue, cases of preeclampsia are reliably more common - 51.7%, which ranks 2-3 in the structure of the causes of maternal mortality and is the main cause of perinatal mortality and morbidity. The course of labor in patients with UCTD is characterized by a large number of different complications. 12.5% -21.9% of women with UCTD have premature labor. In this category of patients, abnormalities of labor, untimely rupture of amniotic fluid are often observed. More often, the primary weakness of contractions develops, which indicates the presence of conditions for the occurrence of this pathology already by the beginning of labor.

Patients with premature rupture of amniotic fluid have a high risk of developing placental abruption, infectious complications [Klemenov AV, Alekseeva OP, Vostokova AA. and other Features of the course of pregnancy in women with undifferentiated connective tissue dysplasia. Reproduction problems. 2005. No. 3. S. 85-88; Manuck TA. The genomics of prematurity in an era of more precise clinical phenotyping: a review. Semin Fetal Neonatal Med. 2016.21: 2: 89-93; Ananth C.V., Getahun D., Peltier M.R. et al. Placental abruption in term and preterm gestations: evidence for heterogeneity in clinical pathways. - Obstet Gynecol. - 2006 Apr. - 107 (4): 785-92].

Despite the high prevalence of uCTD among the population and the developed special diagnostic criteria for this pathology, based on clinical manifestations, the recognition of this pathological process is no more than 2.4%.

Determination of the level of pyrilinks D (DPID) in urine allows you to assess the state of resorption of type I collagen, which binds through pyridine ligaments: pyridinoline and dioxypyridinoline, which, due to resorption, is released into the bloodstream and excreted in the urine unchanged [TI Kadurina. Gorbunova V.N. Connective tissue dysplasia. 2009. SPb. S. 576-626].

The catabolism of the intercellular substance of the connective tissue can be judged by the magnitude of the excretion of glycosaminoglycans (GAGs) in daily urine. In patients with various clinical variants of connective tissue diseases, there is usually an increased excretion of GAG in the urine [OV Tarabanova, VA Krutova, AA Ordokova. et al. Laboratory and immunohistochemical predictors of recurrent genital prolapse. - Sechenov Bulletin. 2017. No. 4 (30). S. 42-50].

There are schemes of treatment and dispensary observation for patients with hereditary connective tissue diseases. Mandatory components of this observation are diet therapy, physiotherapy exercises, massage, physiotherapy, psychotherapy, taking vitamins, trace elements and metabolites [GI Nechaev, IA Viktorova. Connective tissue dysplasia: terminology, diagnostics, patient management tactics. Omsk. 2007. S. 11-47]. The main purpose of these therapeutic measures is to stimulate collagen formation and correct disorders in the synthesis and catabolism of GAG.

However, at the moment there are no objective criteria that determine the duration of therapy, allowing to predict the physiological course of pregnancy. Treatment and pregravid preparation that do not lead to the normalization of collagen metabolism may not lead to a decrease in the number of complications during pregnancy and childbirth.

We have set the task of developing a method of managing women planning pregnancy, which will improve perinatal outcomes due to reliable normalization of magnesium content and connective tissue metabolism in this category of women.

The technical result achieved by the implementation of the proposed method consists in improving perinatal outcomes in patients planning pregnancy, by clarifying the differentiated approach to the choice of optimal schemes for their examination and treatment by timely determination of magnesium deficiency, objective indicators of impaired collagen metabolism, which are criteria for the effectiveness of the therapy , markers of a woman's preparation for pregnancy.

We empirically established diagnostically significant objective indicators - criteria for assessing methods of preparation for planning pregnancy. The scheme of an integrated approach developed by us allows to improve perinatal outcomes: the incidence of the threat of termination of pregnancy, the likelihood of developing a high risk of perinatal losses, premature birth, untimely effusion of water, abnormalities of labor, and operative delivery decrease.

Our studies have shown that the level of magnesium in the venous blood plasma, the levels of DPID and GAG in the urine are reliable markers of the normalization of magnesium status and collagen metabolism in women, which made it possible to consider them as prognostic criteria in assessing perinatal outcomes.

The essence of the invention is as follows.

To prevent complications of the perinatal period in a woman planning a pregnancy, first determine the content of magnesium in the venous blood plasma and, if the content of magnesium is below 0.8 mmol / l, use a magnesium preparation and additionally determine the content of DPID and GAG in the urine, When the content of DPID is above 7.4 nmol / l and glycosaminoglycans above 7.1 mg / mmol, drugs that improve collagen metabolism are additionally used, selected from the group: ascorbic acid, vitamin E, vitamin D, calcium preparations. Monitoring of the content of magnesium in the plasma of venous blood, DPID and GAG in the urine is carried out every three months of treatment. Pregnancy planning is recommended when the level of magnesium in the venous blood plasma is equal to or more than 0.8 mmol / L, the level of DPID in the urine is equal to or less than 7.4 nmol / L, and the level of GAG in the urine is equal to or less than 7.1 mg / mol.

The method is carried out as follows.

Plasma magnesium levels should be measured for patients planning to become pregnant. If the magnesium level is below 0.8 mmol / l, a magnesium preparation is used in the dosage recommended in the instructions for the preparation, and the levels of DPID and GAG in the urine are determined.

DPID in urine was quantified using IMMULITE 2000 analyzers. The IMMULITE 2000 Pyrilincs-D (Deoxypyridinoline) test is based on a chemiluminescent enzyme-linked immunosorbent assay. DPID values are expressed in nmol / L.

The catabolism of the intercellular substance of the connective tissue is judged by the amount of GAG excretion in daily urine. In patients with various clinical variants of connective tissue diseases, there is usually an increased excretion of GAG in the urine. GAGs are determined spectrophotometrically.

As a magnesium preparation, one of the following preparations can be used in therapeutic dosages: magnesium salt of orotic acid 2 t × 3 times a day or magnesium citrate 2 t × 3 times a day.

With an increase in the level of DPID above 7.4 nmol / l and GAG above 7.1 mg / mmol in urine, drugs are additionally prescribed that improve collagen metabolism, selected from the group: ascorbic acid 500 mg / day, vitamin Ε 400 mg / day, vitamin D 2 thousand units / day, calcium preparations 500 mg / day.

Then, every 3 months, the level of magnesium in the blood plasma, DPID and GAG in the urine is re-determined until the determined values are within 0.8 mmol / L and above, 7.4 nmol / L and below, and 7, 1 mg / mmol and below, respectively. Upon reaching the indicated values, pregnancy planning is recommended.

The possibility of realizing the declared purpose and achieving the specified technical result is confirmed by the following data.

Clinical examples.

Example 1.

Patient D., 26 years old, consulted a gynecologist regarding pregnancy planning.

At the time of treatment, the patient was taking folic acid preparations 400 mg per day and 250 μg of iodine per day.

History: childbearing function: first pregnancy 2 years ago, which was accompanied by the threat of termination of pregnancy, which required repeated inpatient treatment, premature birth at 34 weeks.

Concomitant pathology: nephroptosis on the right, hernia repair in childhood for inguinal hernia on the right, scoliosis of the cervical spine, mitral valve prolapse without significant regurgitation, not accompanied by hemodynamic disturbances.

On examination, an asthenic body type is noted, height 164 cm, weight 49 kg, BMI 18.2 kg / cm ² . According to the classification of the severity of UCTD - 14 points, which indicates the moderate severity of UCTD.

Clinical, laboratory and instrumental examination was carried out: magnesium in venous blood 0.62 mmol / l, DPID in urine 7.8 nmol / l, GAG in urine 8.9 mg / mmol.

Diagnosis: Undifferentiated CTD of moderate severity. Mitral valve prolapse without regurgitation. Magnesium deficiency.

Recommended: continue taking folic acid preparations 400 mg per day and 250 mcg of iodine per day. Additionally, magnesium preparation 400 mg per day, ascorbic acid 500 mg per day, vitamin D 2 thousand units per day.

After 3 months, the results of clinical and laboratory studies were as follows: magnesium 0.7 mmol / l, DPID in urine 7.9 nmol / l, GAG in urine 8.5 mg / mmol.

Recommended: continue taking folic acid preparations 400 mg per day and 250 μg of iodine per day, magnesium preparation 400 mg per day, ascorbic acid 500 mg per day, vitamin D 2 thousand units per day.

After 6 months, the results of clinical and laboratory studies were as follows: magnesium 0.72 mmol / l, DPID in urine 7.6 nmol / l, GAG in urine 8.2 mg / mmol.

Recommended: continue taking folic acid preparations 400 mg per day and 250 μg of iodine per day, magnesium preparation 400 mg per day, ascorbic acid 500 mg per day, vitamin D 2 thousand units per day.

Despite the recommendations to continue therapy aimed at replenishing the magnesium deficiency and normalizing collagen metabolism, the patient became pregnant.

Pregnancy was complicated by the threat of termination of pregnancy, which required two inpatient treatment, the patient at 37 weeks had an untimely rupture of amniotic fluid, in childbirth there was a weakness of labor. At 37 weeks, a premature girl of 2740 grams was born.

Thus, the presence of magnesium deficiency, elevated levels of markers of collagen breakdown, determines the course of pregnancy.

In the postpartum period, the patient is advised to continue taking medications aimed at replenishing the magnesium deficiency, normalizing collagen synthesis under the control of determining the level of magnesium in the blood plasma, DPID and GAG in the urine. Planning for a subsequent pregnancy is recommended when the magnesium deficiency is fully replenished.

Example 2.

Patient S., 31 years old, consulted a gynecologist regarding pregnancy planning.

At the time of treatment, the patient was taking folic acid preparations 400 g per day and 250 μg of iodine per day.

History: fertility: first pregnancy 3 years ago, which was accompanied by the threat of termination of pregnancy, treatment was carried out on an outpatient basis, operative delivery at 39 weeks for preeclampsia, fetal weight at birth 3010 grams.

Concomitant pathology: chronic hemorrhoids, hernia repair in childhood for umbilical hernia, mitral valve prolapse without significant regurgitation, not accompanied by hemodynamic disturbances.

On examination, an asthenic body type is noted, height 160 m, weight 48 g, BMI 18.75 kg / cm ² . According to the classification of the severity of UCTD - 10 points, which indicates an average severity of UCTD. The severity of perinatal risks is 12 points, which indicates high risks.

Clinical, laboratory and instrumental examination was carried out: magnesium 0.78 mmol / l, DPID in urine 7.7 nmol / l, GAG in urine 8.4 mg / mol.

Diagnosis: Undifferentiated CTD of moderate severity. Mitral valve prolapse without regurgitation. Chronic hemorrhoids. Magnesium deficiency.

Recommended: continue taking folic acid preparations 400 mg per day and 250 mcg of iodine per day. Additionally, magnesium preparation 400 mg per day, calcium preparation 500 mg, vitamin D 2 thousand units per day.

After 3 months, the results of clinical and laboratory studies were as follows: magnesium 0.82 mmol / l, DPID in urine 7.4 nmol / l, GAG in urine 7.8 mg / mmol.

Recommended: despite the normal level of magnesium in blood plasma and DPID in urine, the level of GAG remains above normal, and therefore it is recommended to continue treatment: taking folic acid preparations 400 mg per day and 250 mcg iodine per day, magnesium preparation 400 mg per day , calcium preparation 500 mg, ascorbic acid 500 mg per day, vitamin D 2 thousand units per day.

After 6 months, the results of clinical and laboratory studies were as follows: magnesium 0.8 mmol / l, DPID in urine 7.4 nmol / l, GAG 7.1 mg / mmol.

Recommended: continue taking folic acid preparations 400 mg per day and 250 μg of iodine per day, magnesium preparation 400 mg per day, vitamin D 2 thousand units per day. Planning a pregnancy.

After 2 months, the patient became pregnant, proceeded without complications. At 39-40 weeks, a planned cesarean section (for a scar on the uterus). A full-term girl, 3270 grams, was born.

Thus, normalization of magnesium levels, markers of collagen breakdown, determines the normal course of pregnancy.

According to the proposed method, 155 patients were prepared for pregnancy, of which 97 patients (62.6%) were found to be deficient in magnesium, and there was no metabolic disorder of the connective tissue. In 58 patients (37.4%) magnesium deficiency was detected, and the levels of DPID and GAG in urine were also increased. All patients received magnesium supplements. Patients with increased levels of DPID and GAG in the urine received additional drugs that improve collagen metabolism. During the study, after 3 and 6 months, the level of magnesium in the blood plasma, biochemical markers of collagen breakdown (DPID, GAG in urine) were determined. When normal levels of magnesium in blood plasma and DPID and GAG in urine were reached, pregnancy was planned. At the onset of pregnancy, every 3 months, the indicators of magnesium in the blood plasma and DPID and GAG in the urine, hemostasis indicators were monitored, fetal ultrasound and Doppler measurements of the uteroplacental-fetal blood flow were performed, and the incidence of complications of pregnancy and childbirth was assessed. In patients with diagnosed magnesium deficiency (97 patients) and concomitant disorders of connective tissue metabolism (58 patients) before pregnancy, who were recommended pregnancy after normalization of these indicators in accordance with the proposed method, complications of pregnancy and childbirth, characteristic of patients with magnesium deficiency and impaired collagen metabolism (premature birth, untimely rupture of amniotic fluid, abnormalities of labor, preeclampsia, birth trauma) were absent.

Also, the proposed method of managing women before planning pregnancy, which assumes a differentiated approach to the treatment of this contingent of patients, improves perinatal outcomes 2.4 times compared with patients who received therapy aimed at normalizing collagen metabolism for 2-3 months without taking into account indicators of magnesium status and collagen metabolism.

Claims (1)

A method for preventing complications of the perinatal period, in which the content of magnesium in the venous blood plasma is first determined in a woman planning pregnancy, and when the content of magnesium is below 0.8 mmol / l, a magnesium preparation is used and additionally the content of pyrilinx D and glycosaminoglycans in urine is determined; when the content of pyrilinka D is above 7.4 nmol / l and glycosaminoglycans above 7.1 mg / mmol, drugs that improve collagen metabolism are additionally used, selected from the group: ascorbic acid, vitamin E, vitamin D2, calcium preparations; monitoring of the content of magnesium in the plasma of venous blood, pyrillinx D and glycosaminoglycans in the urine is carried out every three months of treatment, and pregnancy planning is recommended when the level of magnesium in the plasma of venous blood is equal to or more than 0.8 mmol / l, the level of pyrillinx D in urine, equal to or less than 7.4 nmol / l, and the level of glycosaminoglycans in urine equal to or less than 7.1 mg / mol.