A method for predicting violations adaptation of newborns from mothers with chronic inflammatory gynecological diseases

 

(57) Abstract:

The invention relates to medicine, namely to Pediatrics, and can be used to predict the disorders in the postnatal adaptation of the newborn. The essence of the method is that in cord blood define the subpopulation of T-lymphocytes with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+ and identifying improvement subpopulations of lymphocytes with receptors BG3+ SD+ above 7%, BG3+ SD+ above 12% and LED3+ SD+ above 15% predicted disorder in newborns. The technical result is to increase the accuracy of predicting the disorder of newborns at the subclinical stage.

The invention relates to medicine, namely to Pediatrics, and will find use for prosthetics violations in the period posatales adaptation of newborns and selection of children for further treatment.

Newborns depending on the health pediatricians are divided into two groups: physiological and complicated course of early postnatal adaptation. Children with saline during the early period of adaptation have no somatic or neurological disorders, while the child is aqueous or more foci of infection (pneumonia, the omphalitis, hepatitis and others), in connection with which he prescribed antibiotics (N.N. Volodin et al. “The role of Pro - and anti-inflammatory cytokines in the immune adaptation babies” International Journal on Immunorehebilitation, 2000. Volume 2, Number 1. - P. 175-184). Thus, complicated adaptation of the newborn is closely linked with the development of infectious-toxic processes in the organism of the child.

In recent years, an increasing number of women of childbearing age who are infected with such pathogens as cytomegalovirus, herpes viruses, enteroviruses, chlamydia, Mycoplasma, hepatitis b and C, Epstein-Barr (G. A. Samigina, 1997), leading to increased chronic inflammatory gynecological diseases and further manifested by the birth of children with disorders of adaptation, leading to the development of infection.

Diagnosis of disorders of adaptation in the newborn from the point of view of the forecast of development of intrauterine infection in the neonatal period in the last decade carried by the following methods.

When intrauterine infection in children 1-2 day life is determined by increasing the concentration of interleukin-8 in the concentration range 190-100 mg/ml, concentration of C-reactive protein to 2.66+0.6 mg/DL,annoy adaptation of newborn children” International Journal on Immunorehebilitation, 2000. Volume 2, Number 1).

In the case of bacterial infections in newborns is a significant increase in levels of interleukin-1, tumor necrosis factor - (M. C. Degtyareva, 1995, Diss. Kida. the honey. Sciences “a Comprehensive study of proinflammatory immunocytokines and functional status of lymphocytes in infants with normal and pathological conditions”).

In infants with pneumonia bacterial origin is determined by the low level of production of active forms of oxygen polymorph-nuclear leukocytes. Determination of sensitivity of T-lymphocytes of newborns to the activation of apoptosis indicates massive intrauterine bacterial infection (C. Y. Talalaev, 2000, Pediatrics, No. 3).

The reduced production of reactive oxygen species polymorph-nuclear leukocytes determined by the method Lomonosovskiy chemiluminescence (up to 2,571,37) allows you to diagnose various infections in newborns (L. C. Gankovsky et al., 2000, International Journal on Immunorehabilitation, 2000. Volume 2, Number 1).

Intrauterine infection is characterized by a significant decrease in the content of BG3+ (average to 45.3±4.2%) and DM 4+ (average to 29,33,1%) populations of lymphocytes (G. A. Samigina, 1997, Pediatrics, No. 5, 1997).

Newborns from overdue pregnancy serum determine the level of thyroxine in the first and fifth day of life and reduction of this rate to 25% and more on the fifth day forecast high degree of incidence in neonates (RF patent No. 2014613, 1994).

Mothers of newborns who underwent intrauterine hypoxia, during the winter period is defined in the colostrum the first day after birth indicators of nonspecific protection and their changes in the direction of reducing the functional activity of neutrophils, the number of cationic non-enzymatic proteins, increasing the total content of leukocytes, lymphocytes and macrophages predict in the early postnatal period of development of local inflammatory processes in their infants with hypoxia in 80% (RF application No. 99116922/14, 1999).

When diagnosing the condition of children, by definition, in the blood degree of chemiluminescence observed a number of shortcomings. First of all it should be noted that the chemiluminescence is an integral indicator of free-radical oxidation and does not take into account certain reactions of their formation. The latter reduces the possibility of specific targeted therapy. For example, the characteristic reduction of reactive oxygen species, caused by other pathological processes. Therefore, these methods do not allow the way of distinguishing the type of metabolic disorders for the specific treatment methods.

In the invention, using for the diagnosis of intrauterine infections on the level of membrane molecules cells BG3+ and CD4+ T-lymphocyte though and can be used to diagnose its presence, but does not allow you to set the time of infection.

The prototype of the invention was elected “a Method for predicting local purulent-inflammatory processes in newborn infants” (RF application No. 99116646/14, 1999, hubaev I. C. et al.).

The method chosen as a prototype, is that in the early postnatal period in neonates with severe hypoxia determine the indices in the umbilical cord and peripheral blood during the first days of life and their changes in the direction of reducing the functional activity of neutrophils, leukocyte reactivity index, the components of the complete blood count, and increase the level of lipid peroxidation and total content of leukocytes predict the development of local inflammatory processes in the spring-summer season Involves the use of only in neonates with severe hypoxia.

2. Do not allow the differential diagnosis between intrauterine infection and infection.

3. Cannot be used to predict the viral infection.

4. The method is used for diagnostics only local inflammatory processes and does not affect systemic infection.

These drawbacks are eliminated in this present method.

The objective of the invention: improving the accuracy of prediction of infection in the postnatal adaptation of the newborn to the appointment of adequate therapy.

The problem is solved by the fact that children born from clinically healthy mothers with various chronic inflammatory gynecological diseases, carry out the determination of subpopulations of T-lymphocytes from cord blood with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+ and identifying levels of subpopulations of lymphocytes with receptors BG3+ SD+ above 7%, BG3+ SD+ above 12% and LED3+ SD+ above 15% predict the development of infection in the early postnatal adaptation.

This method allows you to subclinical stage diagnosis of the adaptation in infected infants, leading to the development of infection, to conduct differential diagdirection therapy before the onset of disease.

In the monograph by R. M. Haitov (“Immunology”, Moscow, 2000) indicated that T-lymphocytes with receptors BG3+ SD+, BG3+ SD+ used as an early marker of activation, their increase is due to the onset of lymphocyte proliferation, while increasing BG3+ SD+ lymphocyte subpopulations due to run through these receptors intracellular self-destruct mechanism is apoptosis.

However, in literature examples of using these methods in the diagnosis of disorders of adaptation in the newborn. Due to the fact that in early postnatal adaptation of the role of the immune system (Benitz, W. E., 1998), we have investigated the levels of subpopulations of T-lymphocytes from cord blood with receptors BG3+ SD+ LED3+ SD+ as early markers of activation and receptor BG3+ SD+, inducing apoptosis of the cell.

According to our data in women with chronic inflammatory gynecological diseases in 90% of cases there are complications of pregnancy and childbirth, the fetus and newborn, in 53% of cases it manifests itself in the adaptation to their newborns.

All of the above was the basis for determining increase of subpopulations of T-lymphocytes with receptors BG3+ SD+, BG3+ SD+, BG3+ SD="ptx2">The technical result obtained by the proposed method consists of a differentiated approach to the diagnosis and therapy of disorders of adaptation infants born to mothers with chronic inflammatory gynecological diseases. The method allows to assign adequate therapeutic measures aimed at preventing the development of infection in the postnatal adaptation of the newborn, has high accuracy, simple enough.

The implementation of the method and its effectiveness are described in the following examples.

Example 1.

Child R s was born 12.05.2000, (history of births No. 286) among women 25 years of age with complicated obstetric history (non-developing pregnancy). Pregnancy proceeded against the background of vaginitis, cervical erosion. During pregnancy, the woman mentioned ARI, pneumonia. When DNA diagnostics detected Mycoplasma, Ureaplasma. Genera I, in time. The baby was born in a satisfactory condition, with a mass of 3100, length 49 cm, as assessed by the Apgar scale 8-9. The skin is pale pink, clear. In the first days of life the study of subpopulations of T-lymphocytes with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+ in the serum. the new gradient estimate phenotypic characterization of T-lymphocytes by the method of flow cytofluorimetry using monoclonal antibodies (CALTAG) (flow cytometer apparatus COULTEN Epics XL). Use the following antibodies BG3+ (typing of the total population of the Phone) and activation markers BG3+ SD+ (early activation), BG3+ SD+ (receptors for transferrin) and markers of activation of apoptosis BG3+ SD+.

The level of subpopulations Phone with receptors BG3+ SD+: 8%, BG3+ SD+: 13%, BG3+ SD+: 16%, i.e. according to our data the child threaten the development of infection in the postnatal adaptation of the newborn.

However, in the first 7 days, when the child was in the hospital, the clinical manifestations of the disease were not. After discharge from the hospital, the child began to grow hysterical skin, which persisted for 1 month, appeared hypermia throat, appeared purulent discharge from the left ear, the temperature rose up to subfebrile figures, the child does not have gained weight in the first month of life, was marked symptoms of intoxication in the form of weakness, adynamia, regurgitation, poor appetite.

Child at 28 days of life hospitalized in a neonatal care unit, NIIAP.

Child while in hospital at 28 days of life, a General analysis of blood, which was determined leukocytosis, neutrophilia with a shift to stab, laboratory and functional tests:

In the study of bilirubin in the serum at 28 days of life revealed hyperbilirubinemia (110 µmol/l) due to the indirect fraction.

When viewed from an ENT physician diagnosed left purulent otitis media.

In the analysis of a blood on sterility, crops discharge from the pharynx growth of microorganisms was not determined.

The child was diagnosed with Intrauterine infection of unspecified etiology: left purulent otitis media, pharyngitis, conjugation jaundice.

Assigned antibacterial, detoxification therapy, interferon therapy.

Example 2.

Child B s born 6.04.2000, (history of births No. 158) women 34 years, pregnancy which occurred at the background of chronic adnexitis, colpitis. When DNA diagnostics detected Ureaplasma, Mycoplasma, Gardnerella.

Genera I, in time, by caesarean section. The baby was born in a satisfactory condition, the weight of 3700, length 52 cm, with rating on a scale of Apgar 8-9. The skin is pale pink, pure.

In the first days of life the study of subpopulations Phone with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+.

The level of subpopulations Phone with receptors BG3+ SD+: 7%, BG3+ SD+: 12%, BG3+ SD+: 15%.

Our d is Leno that the baby is healthy, during the first month didn't hurt.

Example 3.

Child B s born 4.04. (history of births No. 151) in women 22 years of age with complicated obstetric history (1 miscarriage), pregnancy which occurred at the background of chronic adnexitis, colpitis. When DNA diagnostics detected Ureaplasma.

Genera I, in time. The baby was born in a satisfactory condition by the weight of 2900, length 49 cm, with rating on a scale of Apgar 8-9. The skin is pale pink, clear. In the first days of life the study of subpopulations of T-LF with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+.

The level of subpopulations Phone with receptors BG3+ SD+: 6%, BG3+ SD+: 11%, BG3+ SD+: 14%.

According to our data the neonatal period should be positive.

During the examination of a child under the age of 1 month revealed that the baby is healthy and on the first month of life does not hurt.

Diagnosis of intrauterine infection was carried out in newborns whose mothers had chronic inflammatory gynecological diseases as chronic adnexitis, endometritis, vaginitis. Infants were divided into 2 groups:

- children with disabilities in early postnatal adaptation of the static type, perinatal CNS lesions(61%) - I gr.

- children with clinical and laboratory examination found no visible lesions (39%) of group II.

All the children of the first group received basic antibacterial and palindromoa therapy, while in the newborn group II was observed physiological during the early period of adaptation.

Thus, we examined 32 newborn child born to mothers with chronic inflammatory diseases of the genitals in the form of chronic adnexitis, endometritis, vaginitis. In the hospital, all children were clinically healthy. After discharge from the hospital newborn infants were divided into 2 groups: children with physiological neonatal period and complicated. In children with complicated during the neonatal period was noted vesiculopustules, otitis, malnutrition, pneumonia, conjugation jaundice. In the blood was determined leukocytosis, neutrophilia with the manifestation of the disease.

The level of subpopulations of lymphocytes with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+ in the blood of the umbilical cord was possible to predict abnormalities in the postnatal adaptation of the newborn. All the neonates had a value of DM shows the high accuracy of the proposed method.

We use the indicators enable early diagnosis of the occurrence of the pathological process in infected infants.

Our proposed method is quite simple, retraumatized, as used umbilical cord blood, allows for subclinical stage diagnosis of the adaptation in infected infants, leading to the development of infection, to identify it to manifestation of the disease and, thus, the differential diagnosis between infection and infection, on the basis of this be treated with antibiotics not all newborns at risk, and differentiated.

Tested in maternity and neonatal care unit, NIIAP.

A method for predicting violations adaptation of newborns from mothers with chronic inflammatory gynecological diseases, through research, umbilical cord blood, wherein define subpopulations of T-lymphocytes from cord blood with receptors BG3+ SD+, BG3+ SD+, BG3+ SD+ and identifying improvement subpopulations of T-lymphocytes with receptors BG3+ SD+ above 7,0%, SD 3+ SD 71+ above 12.0% and SP 3+ SD 95+ above 15,0% predicted disorder of newborns are being

 

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