RU2420737C1 - Differential diagnostic technique for foetal maturity degree - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: simultaneously, urine of pregnant women in their 37-42 weeks of pregnancy is analysed for daily excretion levels of pregnandiol, allopregnandiol, 16-hydroxyandrosterone by capillary gas chromatography to calculate a design coefficient K by formula: K=4.0313-(0.0115A+0.0007-B+0.077C), where A is daily excretion of pregnandiol; B is excretion of allopregnandiol; C is daily excretion of 16-hydroxyandrosterone, in mcmol/24 hour, and if observing K less than 1.5, a mature foetus is diagnosed, the K value 1.5 to 2.5 enables to diagnose an immature foetus, while K exceeding 2.5 shows an overmature foetus. ^ EFFECT: use of the method allows determining an optimal delivery date, reducing a number of children born with morphofunctional immaturity and overmaturity signs. ^ 3 ex

Description

The invention relates to medicine, namely to obstetrics, and is intended for differential diagnosis of the degree of maturity of the fetus (FFP) in pregnant women in the period 37-42 weeks.

The most important characteristic of the condition of the newborn is the functional maturity of its organs and systems from the moment of birth and in the early neonatal period. Only sufficient maturity of the vital organs of the fetus provides a full physiological adaptation after birth and the survival of the newborn. If the fetal ripening of the fetus is disturbed after birth, frustration of functional adaptation to extrauterine existence often occurs, which leads to increased postnatal morbidity and mortality in the early neonatal period (Laricheva I.P., Pankratova T.S., Salyaeva M.V. according to indicators of α-fetoprotein and β2-microglobulin in the early neonatal period // Motherhood and childhood. - 1992. - T.37. - No. 1. - S.10-13).

When pregnancy is delayed, the fetus develops a symptom complex of “overriding”. The main pathogenetic mechanism in this case is the progressive aging of the placenta, the development of placental insufficiency, oligohydramnios, fetal hypoxia. These processes lead to the untimely occurrence of respiratory movements in the ante- and intrapartum period, which can result in amniotic fluid aspiration and fetal asphyxiation (I.P. Laricheva. Determining the degree of fetal maturity and predicting the risk of aspiration syndrome and respiratory failure in a newborn. - Obstetrics problems and gynecology in the research MONIIAG. - M .: Academia. - 1995. - S.135-139).

Therefore, a method for accurately assessing FFP in the last weeks before birth can determine the optimal time of delivery and the condition of the baby at birth.

A known method for the diagnosis of FFP by determining the level of estriol in amniotic fluid in the last weeks of pregnancy. A level of less than 100 mg / l indicates an immaturity of the fetus or a violation of its condition (Arutyunyan A.V., Pavlova N.G., Konstantinova I.N. Study of biochemical markers of intrauterine hypoxia of a human fetus in an amniotic fluid. Abstract of the 2nd Congress Biochemical Society. - 1997. - Part 2. - S.401-402).

The disadvantage of this method is the low reliability of the results in the presence of amniotic fluid in the amniotic fluid and meconium, with a lot of or low water. For this test, amniotic fluid is obtained by amniocentesis, which can be the cause of trauma, bleeding, the onset of labor, infection, which is the main disadvantage of this method.

A known method for the diagnosis of FFP using ultrasound technique by assessing the intensity of sound imaging during ultrasound examination of the lungs and liver of the fetus in the last trimester of pregnancy, the size of the nucleus of ossification of the fetal knee, the biparietal size of the fetal head, the degree of maturity of the placenta (Moodley S., Liu JH, Herkis RC et al. // Int. J. Gynec. Obstet. - 1983. - Vol.21. - No. 3. - P.199-203).

The disadvantage of this method is that the ultrasound assessment is based on morphological signs of maturity, which does not allow to identify early functional changes, as well as the lack of clear diagnostic criteria for FFP.

A known method for the diagnosis of FFP by determining the level of alpha-fetoprotein (AFP) in the blood serum of a pregnant woman 3-8 days before childbirth. The results of AFP concentration are expressed as a percentage of the average level for a given gestation period. If the level of AFP before childbirth is increased and is 200% or more, then this indicates a functional immaturity of the fetus, which prognostically threatens the development of respiratory failure in newborns after childbirth. If the AFP level before childbirth is reduced and is 50% or less, the functional “overripeness” of the fetus is diagnosed and the threat of aspiration of amniotic fluid is predicted (Laricheva I.P. Determining the degree of fetal maturity and predicting the risk of developing aspiration syndrome and respiratory failure in the newborn. - Obstetrics problems and gynecology in the research MONIIAG. - M .: Academia. - 1995. - S.135-139).

The disadvantages of this method are: significant variations in normative indicators, depending on the type of immunological method used, significantly reduce the reliability of the determination; the range of available, especially in modern Russia, sets of reagents necessary for use with the maximum effectiveness of this method is insufficient. In addition, the high cost and limited storage time of the sets imposes additional restrictions on their practical use in the clinical setting; finally, a blood test, not being a non-invasive diagnostic method, always creates some chance of accidental infection of a patient and a laboratory doctor by human immunodeficiency viruses, hepatitis B, C, etc.

The above diagnostic methods for FFP are mainly based on the quantitative and qualitative characteristics of the composition of the amniotic fluid and blood, as well as the morphometry of the fetus and placenta, their results allow only indirectly to judge the functional state of the fetus, its readiness for extrauterine existence.

The closest analogue of the diagnostic method for FFP is to determine the level of daily excretion of pregnanediol, 16α-hydroxyandrosterone, 16α-hydroxyethiocholanolone and 16α-hydroxydehydroepiandrosterone in pregnant women urine during pregnancy 37-41 weeks by capillary gas chromatography, in micromol / 24 hours. If the level of pregnanediol is 154.5 ± 2.6 μmol / 24 hours, 16α-hydroxyandrosterone 7.3 ± 0.7 μmol / 24 hours, 16α-hydroxyethiocholanolone 8.6 ± 0.9 μmol / 24 hours, 16α- hydroxydehydroepiandrosterone - 17.5 ± 1.1 μmol / 24 hours, this indicates the functional maturity of the fetus. If the level of pregnanediol is 89.7 ± 2.1 μmol / 24 hours, 16α-hydroxyandrosterone is 5.5 ± 0.5 μmol / 24 hours, 16α-hydroxyethiocholanolone is 6.2 ± 0.8 μmol / 24 hours, 16α- hydroxydehydroepiandrosterone - 9.4 ± 0.8 μmol / 24 hours, this indicates a functional immaturity of the fetus. If the level of pregnanediol is 353.7 ± 2.7 μmol / 24 hours, 16α-hydroxyandrosterone 4.9 ± 0.4 μmol / 24 hours, 16α-hydroxyethiocholanolone 5.2 ± 0.6 μmol / 24 hours, 16α- hydroxydehydroepiandrosterone - 8.2 ± 0.5 μmol / 24 hours, the functional “overripeness” of the fetus is diagnosed (Salikhova I.R. Diagnostic capabilities of the steroid profile of urine in assessing the functional maturity of the fetus and predicting the condition of the newborn // Medical business. Periodical educational publication of Russian State Medical University. - 2009. - Special edition dedicated to the III International Conference of Young Scientists “Modern issues of obstetrics and gynecology.” - P.41-43).

The disadvantages of this method are the need to study a large number of indicators and insufficient diagnostic accuracy due to large fluctuations in their values during the quantitative determination of these indicators.

The present invention is the development of a simpler and more accurate method for the differential diagnosis of FFP in pregnant women in the period 37-42 weeks to determine the optimal delivery time and improve perinatal outcomes.

The technical result of the invention is to optimize the differential diagnosis of FFP, reduce the number of children born with signs of morphofunctional immaturity and overripeness, and therefore, determine the optimal delivery time, improve perinatal outcomes in pregnant women in the period 37-42 weeks by improving the accuracy of diagnosis of FFP with simplification and cheaper diagnostics.

The technical result is achieved by the fact that in the method of differential diagnosis of FFP, including the study of biological fluid, according to the invention, during pregnancy 37-42 weeks, the level of daily excretion of the following steroids is simultaneously determined: pregnanediol, allopregnandiol, 16α-hydroxyandrosterone in pregnant women’s urine by capillary gas chromatography and determine the calculated coefficient K by the following formula:

K = 4.0313- (0.0115 · A + 0.0007 · B + 0.077 · C),

where A is the daily excretion of pregnanediol; B - daily excretion of allopregnandiol; C - daily excretion of 16α-hydroxyandrosterone, in μmol / 24 hours,

and with a K value of less than 1.5, fetal maturity is diagnosed, with a K value of 1.5 to 2.5, fetal immaturity is diagnosed, and with a K value of more than 2.5, fetal overripe is diagnosed.

We have selected the indicated parameters empirically.

The method is as follows.

Pregnant women in the period of 37-42 weeks determine the daily excretion of pregnanediol, allopregnanediol, 16α-hydroxyandrosterone by capillary gas chromatography. The methodology for determining these steroids is described, for example, in the following source of information (Orlov E.N. Capillary gas chromatography: analysis of urine steroids // Abstracts of the 5th Russian Congress of Laboratory Diagnostics, Moscow, May 24-26, 1995. - Part 2. - S.212). Using the following formula, we determine the calculated coefficient K:

K = 4.0313- (0.0115 · A + 0.0007 · B + 0.077 · C),

where A is the daily excretion of pregnanediol; B - daily excretion of allopregnandiol; C - daily excretion of 16α-hydroxyandrosterone, in μmol / 24 hours,

and with a K value of less than 1.5, fetal maturity is diagnosed, with a K value of 1.5 to 2.5, fetal immaturity is diagnosed, and with a K value of more than 2.5, fetal overripe is diagnosed.

In total, the proposed method was used in 100 pregnant women in the period 37-42 weeks. In all cases, the diagnosis made using the proposed method was confirmed after the birth of the baby.

The method is simple, it required the use of only three indicators.

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

Example 1

Pregnant C, 27 years old with a diagnosis of I timely delivery. The patient was registered with the antenatal clinic from 7 weeks of pregnancy. Height 166, weight 75 kg (before pregnancy 62 kg). Somatic history is not burdened. Menstrual function without features. The first pregnancy was uneventful. In 40-41 weeks she was admitted to the department of pregnancy pathology of the hospital in the direction of a doctor of antenatal care. Clinical diagnosis: Pregnancy 40-41 weeks. Head presentation. Upon admission to the hospital for the diagnosis of FFP, a study was made of the daily excretion of pregnanediol, allopregnanediol, 16α-hydroxyandrosterone by capillary gas chromatography. The following indicators of daily excretion were obtained (μmol / 24 hours): pregnanediol - 213.4; allopregnandiol - 20; 16α-hydroxyandrosterone - 6.2.

K = 4.0313- (0.0115 · 213.4 + 0.0007 · 20 + 0.077 · 6.2)

Given that K is 1.09, the patient was diagnosed with fetal maturity. The diagnosis was confirmed at birth.

Clan activities developed independently, childbirth proceeded without complications. During childbirth, promedol was anesthetized intramuscularly. The total duration of labor is 7 hours. Anhydrous interval of 4 hours 20 minutes. The waters are bright. The baby was born lively, full-term, female gender, weight 3700, height 51 cm. Apgar score in the first minute 9 points, in the fifth minute 9 points. The postpartum period was uneventful. Mother was discharged home with her child for 4 days.

Thus, the study of the daily excretion of pregnanediol, allopregnanediol, 16α-hydroxyandrosterone in the period of 37-42 weeks allows us to diagnose FFP and predict the birth of a mature child.

Example 2

Pregnant Z., 26 years old with a diagnosis of I timely delivery. Fetal growth retardation syndrome, Art. A burdened obstetric and gynecological history.

The patient was registered with the antenatal clinic from 10 weeks of pregnancy. Pregnancy proceeded with toxicosis in the first trimester, in the second trimester - twice inpatient treatment due to the threat of termination of pregnancy. In the third trimester, swelling of the legs was noted. Somatic history is not burdened. Menstrual function is not impaired. Of the gynecological diseases, an ectopia of the cervix is noted, no treatment has been carried out, chronic adnexitis. This pregnancy is the first. Height 155, weight 67 kg (before pregnancy 52 kg). At 37-38 weeks she was admitted to the department of pregnancy pathology of the hospital in the direction of a doctor of antenatal care. Clinical diagnosis: Pregnancy 37-38 weeks. Head presentation. Gestational edema. A burdened obstetric and gynecological history.

Upon admission to the hospital for the diagnosis of FFP, a study was made of the daily excretion of pregnanediol, allopregnanediol, 16α-hydroxyandrosterone by capillary gas chromatography. The following indicators of daily excretion were obtained (μmol / 24 hours): pregnanediol - 128.8; allopregnanediol - 9.8; 16α-hydroxyandrosterone - 6.8.

K = 4.0313- (0.0115 · 128.8 + 0.0007 · 9.8 + 0.077 · 6.8)

Given that K is 2.02, the patient was diagnosed with fetal immaturity. The diagnosis was confirmed at birth.

On the third day of hospitalization, complaints of worsening fetal movement. According to cardiotocography and dopplerometry, the condition of the fetus is satisfactory. During a joint examination, an amniotomy was performed, 100 ml of clear water was poured out. Clan activities developed independently, childbirth proceeded without complications. The total duration of labor is 7 hours 35 minutes. Anhydrous period of 8 hours 35 minutes. The baby was born alive, full-term, female gender, weight 2680 grams, height 52 cm. Apgar score in the first minute 7 points, in the fifth minute 8 points. The condition at birth is moderate, the cry is quiet, the muscle tone is reduced, it moans. The skin is pink, clean, pasty tissue, generous generic lubrication, the skin on the feet and palms is smoothed, little outlined. Inhibition of the central nervous system. Intrauterine malnutrition I Art. Morphofunctional immaturity. The early period of adaptation was complicated by conjugated jaundice. Mother was discharged home with her child on the 6th day.

Thus, the study of daily excretion of pregnanediol, allopregnanediol, 16α-hydroxyandrosterone in the period of 37-42 weeks allows us to diagnose FFP and predict the birth of a child with signs of morphofunctional immaturity.

Example 3

Pregnant N., 30 years old with a diagnosis of IV delayed birth at 41 weeks of gestation. Early outflow of water. A burdened obstetric and gynecological history. Unexamined.

The patient was not registered with the antenatal clinic; she does not speak Russian well. Height 173, weight 80 kg (before pregnancy 67 kg). According to the words, somatically not burdened, she denies gynecological diseases. Menstrual function is not impaired. This pregnancy is the third. I pregnancy in 2001, urgent delivery, a boy was born, weighing 3300 g, height 50 cm, the child died on the 14th day of life, he does not know the reason. II pregnancy in 2002, urgent delivery, a girl was born weighing 3300 g, height 51 cm. Discharged on the 4th day, without complications. The child is alive and well. III pregnancy - real, proceeded without complications. In 40-41 weeks she was admitted to the maternity ward of the maternity hospital with complaints of mucus plug passage. During the observation process, she did not complain and was transferred to the Department of Pregnancy Pathology, where for the diagnosis of FFP, the daily excretion of pregnandiol, allopregnandiol, 16α-hydroxyandrosterone was determined. The following indicators of daily excretion were obtained (μmol / 24 hours): pregnanediol - 71.4; allopregnanediol 5.3; 16α-hydroxyandrosterone - 3.8.

K = 4.0313- (0.0115 · 71.4 + 0.0007 · 5.3 + 0.077 · 3.8)

Given that K is 2.91, the patient was diagnosed with overripe fetus. The diagnosis was confirmed at birth.

Labor activity developed against the background of labor stimulation by enzaprost, childbirth proceeded without complications. The total duration of labor is 4.5 hours. Anhydrous interval of 1.5 hours. Meconial waters. The child was born alive, born, male gender, weight 3800, height 55 cm. Apgar score in the first minute 7 points, in the fifth minute 8 points. The state of moderate severity, a cry painful, moaning. Muscle tone is reduced, lamellar peeling of the feet, “bath” palms. Central nervous system depression syndrome. Mother was discharged home with her child on the 7th day.

Thus, the study of daily excretion of pregnanediol, allopregnanediol, 16α-hydroxyandrosterone in the period of 37-42 weeks allows us to diagnose FFP and predict the birth of an overripe child.

The inventive method for the diagnosis of FFP in the period 37-42 weeks has several advantages over the chosen one as the closest analogue.

1. The method requires the use of only three indicators, which simplifies and cheapens the diagnosis of FFP, and therefore can be widely used in obstetric hospitals.

2. The high reliability and accuracy of the differential diagnosis of FFP makes it possible to determine the optimal delivery time, which is an active prevention of perinatal morbidity and mortality.

Thus, the proposed method optimizes the differential diagnosis of FFP during pregnancy 37-42 weeks, reducing the number of children born with signs of morphofunctional immaturity and overriding, and thereby improves perinatal outcomes.

Claims (1)

A method for differential diagnosis of the degree of fetal maturity, including determining the level of daily excretion of pregnanediol, the level of daily excretion of 16α-hydroxyandrosterone in the urine of pregnant women during pregnancy 37-42 weeks by capillary gas chromatography, characterized in that they additionally examine the level of daily excretion of allo-pregnanediol in the urine of pregnant women during pregnancy 37-42 weeks by capillary gas chromatography and determine the calculated coefficient K by the following formula:
K = 4.0313- (0.0115 · A + 0.0007 · B + 0.077 · C),
where A is the daily excretion of pregnanediol; B - daily excretion of allo-pregnanediol; C - daily excretion of 16α-hydroxyandrosterone, in μmol / 24 h,
and with a K value of less than 1.5, fetal maturity is diagnosed, with a K value of 1.5 to 2.5, fetal immaturity is diagnosed, and with a K value of more than 2.5, fetal overriding is diagnosed.