RU2492489C1 - Method of pre-clinic diagnostics of severity degree of respiratory distress-syndrome in case of intrauterine influenza a (h3n2) in premature infants - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: concentration of medium molecular peptides in supernatant part of biological fluid of nasopharyngeal aspirate is analysed. If concentration of medium molecular peptides equals 0.575-0.600 units of optic density, respiratory distress-syndrome of mild severity degree is diagnosed, if their concentration is 0.601-0.661 units of optic density, respiratory distress-syndrome of medium severity degree is diagnosed, and if their concentration is 0.662-0.722 units of optic density, development of distress-syndrome of severe degree is diagnosed.

EFFECT: possibility of pre-clinical diagnostics of severity degree of respiratory distress-syndrome in case of intrauterine influenza in premature infants.

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Description

The invention relates to medicine, namely to perinatology and neonatology.

It has been established that in the development of symptoms of respiratory distress syndrome in newborns at an early neonatal age, a pre-natal role is played by intrauterine respiratory viral infection, including influenza A (H3N2) [1, 6]. The development of a viral infection is accompanied by an increase in the concentration of medium molecular peptides represented by polypeptides with a molecular weight of 300 to 5000 daltons. With an increase in their plasma content in mothers with influenza A (H3N2) during pregnancy, their concentration in the nasopharyngeal aspirate in the fetus increases [3]. This increases the risk of developing respiratory distress syndrome in infants with intrauterine influenza A (H3N2).

A known method for the diagnosis of respiratory distress syndrome of various etiologies in newborns, which is based on the study of the concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate [3]. With values of the average molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate equal to 0.575-0.725 optical density units, in newborns with intrauterine influenza A (H3N2), respiratory distress syndrome is diagnosed 3-4 hours before the development of the clinical picture of the disease.

The disadvantages of this method [3] are:

1. The inability to preclinical assessment of the severity of respiratory distress syndrome with intrauterine influenza A (H3N2) in premature infants.

The objective of the proposed method is to provide preclinical diagnosis of the severity of respiratory distress syndrome with intrauterine influenza A (H3N2) in premature infants by examining the concentration of medium molecular peptides in the supernatant of the biological fluid of their nasopharyngeal aspirate.

The method contains the following techniques:

1. A soft probe made, for example, of polyvinyl chloride is attached to a sterile syringe [4].

2. The probe is carefully inserted into the nasal cavity of the newborn immediately after birth.

3. A syringe is slowly injected with 2.5-3 ml of biological fluid contained in the nasal passages and nasopharynx in newborns.

4. The resulting 2.5-3 ml of biological fluid of the nasopharyngeal aspirate is centrifuged in a centrifuge at 1500 rpm for 10 minutes to obtain its supernatant.

5. To determine the average molecular weight of the peptides using the express method, 1.0 ml of the supernatant of the biological fluid of the nasopharyngeal aspirate is poured into the centrifuge tube, 0.5 ml of 10% trichloroacetic acid is added. This mixture is shaken and centrifuged for 30 minutes at 3000 rpm. The detection of the supernatant of the biological fluid of the nasopharyngeal aspirate, freed from coarse proteins, is carried out after preliminary dilution, in which 4.5 ml of distilled water is added to 0.5 ml of the supernatant of the biological fluid of the nasopharyngeal aspirate. Measurements are carried out on a spectrophotometer, for example, SF-16 or HITACHI-557 (Japan), at a wavelength of 280 nm [2].

6. Preclinical diagnostics of the severity of respiratory distress syndrome with intrauterine influenza A (H3N2) in preterm infants is carried out: at a concentration of average molecular peptides of 0.575-0.600 units of optical density, mild respiratory distress syndrome is diagnosed; at a concentration of average molecular peptides of 0.601-0.661 units of optical density, a moderate respiratory distress syndrome is diagnosed; at a concentration of average molecular peptides of 0.662-0.722 units of optical density, a severe respiratory distress syndrome is diagnosed.

To establish differences between the concentration of medium-molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate with intrauterine influenza A (H3N2) in preterm infants with respiratory distress syndrome of varying severity (classification by NI Puzyreva et al., 1987) [5], we were examined 122 sick children from mothers with influenza A (H3N2) during pregnancy. The control was 32 healthy newborns from mothers with uncomplicated pregnancy. In newborns of this group, when studying blood serum in mother-child vapors using the hemagglutination inhibition reaction and complement fixation reaction, there was no 4-fold increase in titers of antibodies to respiratory group viruses (to influenza A, B, parainfluenza, PC- and adenovirus) [7] and symptoms of respiratory distress syndrome.

The first experimental group consisted of 42 premature infants with mild respiratory distress syndrome and a 4-fold increase in the titer of antibodies to influenza A virus (H3N2) [7]. The second experimental group included 40 preterm infants with moderate respiratory distress syndrome and a 4-fold increase in the titer of antibodies to influenza A virus (H3N2) [7]. The third experimental group included 40 premature infants with severe respiratory distress syndrome and a 4-fold increase in the titer of antibodies to influenza A virus (H3N2) [7]. Premature infants in the first, second and third experimental groups 3-4 hours after birth developed respiratory distress syndrome.

The concentration of medium-molecular peptides in the supernatant

Table 1 Differences in the concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate in newborns of the control and experimental groups Statistical indicators The concentration of medium molecular peptides (units of optical density) Control Group (n = 32) The first experimental group (n = 42) The second experimental group (n = 40) The third experimental group (n = 40) M 0.330 0.585 0.631 0.692 m 0.01 0.001 0.001 0.001 σ 0,037 0.01 0.02 0.02 M ± 1.5δ 0.275-0.385 0.570-0.600 0.601-0.661 0.662-0.722 R p <0.001 p <0.001 p <0.001 P ₁ <0.001 p ₂ <0.001 Note: p - level of significance of differences between indicators in the control and main groups; p ₁ - level of significance of differences between indicators in the first and second experimental groups; p ₂ - level of significance of differences between indicators in the second and third experimental groups.

parts of the biological fluid of the nasopharyngeal aspirate in healthy newborns (control group), in premature infants with mild respiratory distress syndrome with intrauterine influenza A (H3N2) (the first experimental group), in premature infants with moderate respiratory distress syndrome with intrauterine influenza A (H3N2) (second experimental group) and in premature infants with severe respiratory distress syndrome and intrauterine influenza A (H3N2) (third experimental group) Lena in Table 1. As seen from Table 1, the concentration of middle molecules in the supernatant portion of the biological fluid nasopharyngeal aspirate of preterm infants with respiratory distress syndrome, mild severity was significantly different from that of the infants in the control group (p <0,001). At the same time, it is noteworthy that there are significant differences between the indicators of concentration of average molecular peptides in the control group (0.275-0.385 units of optical density) and in the first experimental group (0.570-0.600 units of optical density) due to pronounced endogenous intoxication with intrauterine influenza A (H3N2). In the interval between the concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate from 0.386 to 0.569 units of optical density, respiratory distress syndrome of non-infectious etiology is diagnosed in newborns, for example, from mothers with late gestosis [3].

When comparing the concentrations of medium molecular peptides in the supernatant of the nasopharyngeal aspirate in the newborns of the first experimental, second experimental, highly reliable differences were recorded in the third experimental group (p <0.001).

Given the statistical significance of the differences in the indicators reflecting the differences in the concentration of medium-molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate in premature infants at the preclinical stage of the development of respiratory distress syndrome, we propose using these indicators as criteria for the preclinical diagnosis of respiratory distress syndrome of varying severity with intrauterine influenza A (H3N2). At a concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate equal to 0.575-0.600 units of optical density, a mild respiratory distress syndrome is diagnosed, at a concentration of medium molecular peptides equal to 0.601-0.661 units of optical density, a moderate respiratory distress syndrome is diagnosed and at a concentration of average molecular peptides equal to 0.662-0.722 units of optical density, respiratory distress syndrome of severe Yeni gravity.

To illustrate the effectiveness of the proposed method for preclinical diagnosis of respiratory distress syndrome of varying severity in preterm infants with intrauterine influenza A (H3N2), clinical examples are given.

Example 1

Newborn S. Born from the first pregnancy. The mother during the first trimester up to 9 weeks showed signs of mild early gestosis. Blood type A (II), Rhesus positive. The antenatal clinic was observed regularly from 7 weeks of gestation. At week 22, she had influenza A (H3N2) with an increase in body temperature up to 38.4 °, headache, runny nose, cough with a moderate amount of sputum mucosa (antibody titer to influenza A virus (H3N2) 1: 4-1: 16). The birth is first, premature at 35 weeks of gestation, through the natural birth canal. Amniotic fluid slightly stained with meconium.

Clinical diagnosis of the mother: Delivery first, premature at 35 weeks of gestation. Chronic intrauterine hypoxia of the fetus. Overweight pregnancy (influenza A (H3N2). Episiotomy. Episioraphy.

A girl was born with a mass of 2480 g, a length of 45 cm, a head circumference of 32 cm and a breast of 30 cm. In the maternity room, an Apgar score of 5/7 points. Blood type A (II), Rhesus positive. The condition of the child is satisfactory. When examining a child, signs of immaturity are determined. Activity and muscle tone are normal. Tendon and physiological reflexes are clear. Breathing and heart activity are normal. A serological blood test using the hemagglutination inhibition reaction showed an increase in the titer of antibodies to the influenza virus (1: 16-1: 64) in the child compared with that in the mother. At birth, the number of leukocytes in a child was: 9 * 10 ⁹ / l, s / I - 65%, s / I - 2%, lymph. - 24%, mon - one%. The concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate was 0.585 units. opt. density.

After 3.5 hours, the condition of the newborn is moderate. Cyanosis of the nasolabial triangle was observed. Activity and muscle tone are reduced. Tendon and physiological reflexes are not distinct. Heart sounds are muffled, rhythmic up to 134 beats in 1 minute. Respiratory rate 48 in 1 minute. Limited pulmonary breathing was detected in the lungs. After 3.5 hours, the child developed acrocyanosis. Heart sounds are muffled to 152 in 1 minute. Difficulty breathing through the nose and tension of the wings of the nose were noted. The intercostal space was drawn in by inspiration in the lower chest. Respiratory rate increased to 62 in 1 minute. Synchronized breathing with a hard tint.

Diagnosis of the newborn: Intrauterine influenza A (H3N2) (antibody titer 1: 16-1: 64). Mild respiratory distress syndrome. Premature 1 degree.

Example 2

Newborn E. Born from the first pregnancy, which lasted up to 8 weeks against the background of early gestosis with clinical symptoms of nausea and single vomiting. At 30 weeks, the patient suffered influenza A (H3N2) (titers of antiviral antibodies 1: 4-1: 16) with an increase in temperature to 37.8 °, which was recorded for 3 days. The duration of intoxication symptoms was 7 days. Catarrhal phenomena were noted: serous discharge from the nose for 2-3 days, mucopurulent discharge for 4-5 days, sore throat and cough with a slight amount of sputum for 8 days. Signs of chronic intrauterine hypoxia were noted. Mother's age is 24 years old, serving. In childhood, up to 7 years old, she suffered from tonsillitis with exacerbations up to 2 times a year. Blood type 0 (I), rhesus positive. The antenatal clinic was observed regularly from 5 weeks of pregnancy. The birth is first, premature with a period of 35 weeks of pregnancy, through the natural birth canal. Amniotic fluid green. In the mother's birth, prenatal discharge of amniotic fluid was noted.

Clinical diagnosis of the mother: Delivery first, premature at 35 weeks of gestation. Prenatal discharge of amniotic fluid. Chronic intrauterine hypoxia. Episiotomy Episioraphy.

A boy was born with a mass of 2450 g, a length of 48 cm, a head circumference of 31 cm and a chest circumference of 30 cm. The Apgar assessment of the child’s health status in the delivery room was 5/7 points. Blood type 0 (I), rhesus positive. The condition is satisfactory. Active. Muscle tone saved. Tendon and physiological reflexes are distinct. Changes in the respiratory and cardiovascular systems are absent. A serological blood test using the hemagglutination inhibition reaction showed an increase in the titer of antibodies to the influenza A (H3N2) virus 1: 16-1: 64 in the child compared with that in the mother. In the blood of a child at birth, the number of leukocytes was 8.2 * 10 ⁹ / l, e - 4%, s / I - 4%, s / I - 56%, lymph. - 36%. The concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate was 0.610 optical density units.

After 4 hours, the condition of the newborn is serious. Acrocyanosis was noted. The scream is weak. Activity reduced. Muscle tone is reduced, and tendon reflexes are not clear. Physiological reflexes are weakened. Heart sounds are muffled, rhythmic up to 134 beats in 1 minute. Respiratory rate 70 in 1 minute. Breathing through the nose is not difficult. Heart rate up to 145 in 1 minute and respiratory rate up to 70 in 1 minute. Auscultation was recorded a tendency to weaken breathing and tension of the wings of the nose, as well as retraction of the intercostal space on inspiration in the lower chest. Hard breathing was noted in the lungs.

The diagnosis of the newborn: Intrauterine infection (influenza A virus (H3N2) 1: 16-1: 64). Respiratory distress syndrome of moderate severity. Premature 1 degree.

Example 3

Newborn B. Born from the first pregnancy, which proceeded with symptoms of mild gestosis (nausea, vomiting up to 2 times a day). At 20 weeks, she had the flu A (H3N2), which was accompanied by an increase in temperature to 38.4 ° with an increase in body temperature for 3 days. The duration of intoxication symptoms was 8 days. Signs of acute rhinopharyngitis were noted: serous discharge on the 2nd – 3rd day, mucopurulent discharge on the nose on the 4th – 6th day, severe sore throat and cough with a slight amount of mucopurulent sputum for 8 days. At week 30, moderate swelling of the lower extremities was recorded.

Mother's age is 30 years old, serving. In childhood, there were acute respiratory infections up to 3 times a year. Heredity is not burdened. The antenatal clinic was observed regularly from 9 weeks. Blood type 0 (I), rhesus positive. The birth is first, premature at 36 weeks, through the natural birth canal. Amniotic fluid green.

Clinical diagnosis of the mother: First, premature birth at 36 weeks of gestation. Chronic intrauterine hypoxia of the fetus. Episiotomy Episioraphy.

A boy was born with a weight of 2500 g, length - 48 cm, head circumference - 31 cm and chest - 30 cm. In the maternity ward, an Apgar score of 4/7 points. Blood type 0 (1), rhesus positive. In a serological study using the hemagglutination inhibition reaction, an increase in the titer of antibodies to the influenza A (H3N2) virus 1: 64-1: 256 was observed in the child compared with that in the mother. At birth, the number of white blood cells was 10.0 * 10 ⁹ / l, s / I - 4%, s / I - 22%, lymph. - 56%, mon - 6%. The concentration of medium molecular peptides in the supernatant of the nasopharyngeal aspirate was 0.680 units. opt. density.

After 4 hours, the condition of the newborn is very serious. The skin of the nasolabial triangle with a cyanotic hue. Acrocyanosis. Single elements of vesiculosis. A decrease in activity, muscle tone and tendon reflexes was noted. Physiological reflexes are poorly expressed, and some are not detected. Heart sounds are muffled, rhythmic up to 162 beats per 1 minute. Respiratory rate 90 in 1 minute. During auscultation, significant respiratory depression was recorded. Difficulty breathing through the nose, tension of the wings of the nose and partial retraction of the lower part of the sternum were noted. There was significant retraction of the intercostal space on inspiration in the lower chest.

Diagnosis of the newborn: Intrauterine infection, vesiculosis (influenza A virus (H3N2) (1: 64-1: 256). Severe respiratory distress syndrome. Premature grade 1.

Information sources used:

1. Gorikov I.N. The state of the respiratory organs in newborns during intrauterine infection with the influenza A (H3N2) virus // Problems of infectious pathology in the regions of Siberia, the Far East and the Far North. Abstracts of reports. The second scientific. conf. with international participation. Novosibirsk, Russia, May 29-31, 2002., CERIS, Novosibirsk, 2002. - P.240.

2. Samsonov V.P., Lutsenko M.T., Novik E.V. Diagnosis of various degrees of endotoxemia in case of lung abscesses: guidelines of the Ministry of Health of the RSFSR, Institute of Physiology and Pathology of Respiration, Siberian Academy of Medical Sciences, Blagoveshchensk, 1988. - 10 p.

3. A method for the diagnosis of respiratory distress syndrome in newborns: US Pat. 2342667 Ros. Federation: IPC G01N 33/68 / I.N. Gorikov, V.P. Kolosov, V.P. Samsonov, L.G. Nahamchen; Applicant and patent holder of GU DNTs FPD SB RAMS. - No. 2007136874/15; capt. 10/04/2007; publ. 12/27. 2008, Bull. Number 36.

4. A device for aspirating biological fluid from the nasal cavity and nasopharyngeal space in newborns: US Pat. 2392974 Ros. Federation: IPC A61M 1/00 / I.N. Gorikov, M.T. Lutsenko, V.P. Samsonov, L.G. Nahamchen, E.V. Ushakova, N.O. Kostromina; Applicant and patent holder of GU DNTs FPD SB RAMS. - No. 2008152941/14; capt. 12/31/2008; publ. 06/27. 2010, Bull. No. 18.

5. Puzyreva N.I., Laryushina P.M., Ryzhkova N.K. Respiratory distress syndrome and lung surfactant in newborns. - M.: Medicine, 1987 .-- 144 p.

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7. A.S. 1516980 USSR, MKI ³ A1 G01N 33/53. A method for the diagnosis of intrauterine infection / O.A. Aksenov, Z.A. Osipova, G.P. Kurbatova, V.F. Melnikova (USSR). - No. 429708 / 28-14. Claimed on 05.25.87. Publ. 10/23/89, Bull. Number 39. - 2 p.

Claims (1)

A method for preclinical diagnosis of respiratory distress syndrome of varying severity with intrauterine influenza A (H3N2) in preterm infants, which consists in examining the concentration of medium molecular peptides in the supernatant of the biological fluid of the nasopharyngeal aspirate and at a concentration of medium molecular peptides equal to 0.575-0.600 optical density units mild respiratory distress syndrome, with a concentration of medium molecular peptides equal to 0.601-0.661 optical units density diagnose respiratory distress of moderate severity, a medium molecular peptides at a concentration equal to 0,662-0,722 units of optical density diagnose respiratory distress syndrome, severe severity.