CC BY
3922 East European Scientific Journal #11(75), 2021 ...av,...,..
Levchenko L.A.1, Sargsyan H.A.1, Nikoghosyan K. V2.
1 Federal State Autonomous Educational Institution of Higher Education "Russian National Research Medical University after N.I. Pirogov "Ministry of Health of Russia 2 State budgetary institution of health care "Odintsovskaya regional hospital",
Maternity Hospital, Moscow Region
ETIOLOGY AND PATHOGENESIS OF THE CONGENITAL PNEUMONIA IN NEWBORNS
(LITERATURE REVIEW - PART 1)
DOI: 10.31618/ESSA.2782-1994.2021.4.75.177
Abstract. This article focuses on the incidence of intrauterine pneumonia among newborns, with an emphasis on premature babies. So, at the beginning of the 21st century, there is a clear trend in all countries to an increase in the number of births of premature patients. Among the variety of intrauterine infections in premature infants, intrauterine pneumonia deserves close attention. The article presents the main risk factors for preterm birth. The modern views on the etiology of intrauterine pneumonia in newborn infants are presented in detail. The main causative agents of this pathological process are given. The causes of lung lesions in newborns, especially premature babies, are indicated. Clear parallels are drawn between low gestational age and newborn's body weight with the consequences of previous hypoxia (acute and / or chronic), as well as with the emergence and rate of development of intrauterine infection and its influence on the formation and development of the fetal immune system. The combined effect of unfavorable factors subsequently leads to the manifestation of pronounced immunosuppression in the newborn and creates the preconditions for the generalization of the pathological process.
Keywords: premature newborns, intrauterine pneumonia, etiopathogenesis.
In recent decades, a noticeable tendency towards an increase in the number of premature births has been expressed on Earth, and therefore there is an increase in the birth rate of premature babies [1]. According to the literature, about 10-25% of all newborn babies are born prematurely on the planet. [2]. These indicators are tied primarily to the difficult socio-economic and environmental conditions of modern life, as well as with a significant spread of sexually transmitted infections. Not the last place is occupied by bad habits among the population and, in some cases, deterioration in the quality of medical care. The result of the above mentioned is a tendency towards a decrease in the number of women in whom the course of pregnancy and childbirth is possible without complications [3]. At the same time, the age contingent of pregnant women has changed significantly: the number of older women has increased. Among these patients, a high percentage of mothers with chronic diseases were identified. In the history of pregnant women, there is often an indication of the treatment of infertility for a long period of time. All these circumstances predispose to the development of complications during pregnancy and the onset of premature birth [4].
The result of the above mentioned facts is the data of the world literature: 27-36% of children born alive are infected in utero, and among them more than 2/3 are premature babies. Infectious pathology is the determining cause in the structure of newborn mortality and ranges from 11% to 45%, while stillbirth reaches 16% [5].
Of particular medical and social significance in premature infants are infections occurring in the neonatal period [6]. So, early infections in them are manifested in the form of urinary tract infections, bacteremia, meningitis, pneumonia. All of these diseases are characterized by a severe clinical course, and the mortality rate from them reaches 40%. This is 3 times higher than in the absence of infection in
premature infants [7]. It is known that in premature infants the most frequent (30-80%) findings are respiratory disorders, regardless of gestational age [8]. Among the array of intrauterine infections in premature infants, special attention should be paid to intrauterine pneumonias, which are often manifested by severe respiratory disorders and require respiratory correction [7].
According to modern literature data, "Intrauterine pneumonia is an acute infectious and inflammatory disease of the respiratory parts of the lungs as a result of ante- and / or intranatal infection, which has clinical and radiological manifestations in the first 72 hours of a child's life" [3].
In accordance with the ICD, intrauterine pneumonia is divided into: caused by viruses (P 23.0), chlamydia (P 23.1), staphylococcus (P 23.2), group B streptococcus (P 23.3), Escherichia coli (P 23.4), Pseudomonas (P 23.5), other bacterial agents (Haemophilus influenzae, Klebsiella pneumoniae, Mycoplasma, streptococcus with the exception of group B - P 23.6), other pathogens (P 23.8), of unspecified etiology (P 23.9).
Currently, group B streptococci play a special role in the development of infectious pathology in newborns. It is already known that within a few hours after birth, a significant number of children develop pneumonia caused by group B streptococci [7]. It was found that among the pathogenic flora inhabiting the birth canal of the mother, microbes such as group B streptococcus and Escherichia coli predominate in comparison with other pathogens that cause intrauterine pneumonia. According to the literature, "in more than 40-50% of women of childbearing age, the birth canal is colonized by group B streptococcus, and the urinary tract is colonized in 10-40% of pregnant women" [9].
If in the first stage of labor there is a pronounced deviation of the fetal heart rate from the norm, then this
IJ«
Its®]«
East European Scientific Journal #11 (75), 2021 23
process is often considered as a typical manifestation of intrauterine pneumonia caused by group B streptococcus [2]. According to the literature, 50-70% of children become infected with group B streptococcus when passing through the vaginal birth canal, while the development of intrauterine pneumonia occurs only in 1-2% of them [1].
1. According to reports of individual authors [10], it has been established that in the United States the most common causative microbial agent of sexually transmitted infections is Chlamydia trachomatis. At the same time, approximately 75% of infected women and 50% of infected men have practically no or minor symptoms of chlamydial infection, as a result of which they do not seek qualified medical care. All this creates the preconditions for the latent course of the infection. In newborns chlamydia causes conjunctivitis and spreads along the lacrimal duct into the nasopharynx, and the result, sooner or later, is intrauterine pneumonia in about 33% of children. However, 11-20% of newborns from infected and untreated mothers also develop pneumonia, although there are no signs of conjunctivitis.
2. Other authors [7] indicate that in addition to group B streptococcus and Chlamydia, Listeria, genital Mycoplasmas, and Candida fungi can be the causative agents of intrauterine pneumonia in newborns. Infection of the fetus with these pathogens also occurs when passing through the birth canal of the mother [4].
3. According to other literature sources [3], the etiological significance of Mycoplasma hominis and Ureaplasma urealyticum in the occurrence of intrauterine pneumonia is not firmly substantiated, therefore, studies of these intracellular microorganisms continue in this direction. In some cases, the causative agent of pneumonia in premature infants may be Pneumocystis carini [4].
4. Intrauterine infections are characterized by a mixed infection (bacterial-fungal, viral-bacterial, viral-bacterial-fungal), isolated from various foci [10].
5. Shabalov N.P. (2009) indicates: the etiology of pneumonia in newborns is often difficult to establish due to the fact that the secondary bacterial flora quickly joins the intrauterine or postnatal viral infection, and the microbe sown from the throat of the patient (and even the tracheal aspirate) in only 25 - 30% of cases is a true causative agent of pneumonia.
It is known that the complex of relationships in the mother-placenta-fetus system is complex; therefore, the presence of foci of infection in a pregnant woman is a real risk factor for the occurrence of various pathological conditions of the fetus and newborn [4]. Risk factors for the development of intrauterine pneumonia in newborns are, first of all, the presence in a pregnant woman chronic infectious process, infection of the urinary system, acute infectious diseases during pregnancy, premature rupture of membranes, chorioamnionitis, a long anhydrous period of labor (more than 24 hours), various interventions during pregnancy and significant colonization of the mother with virulent flora [7, 10].
It was found that the risk of infection is inversely proportional to gestational age and birth weight, and is directly proportional to the severity of the newborn's condition [4, 7].
There is literary evidence regarding the occurrence of intrauterine pneumonia, which is associated with maternal chorioamnionitis, due to which infection of the amniotic fluid and / or colonization of microbes occurs. These pathological processes lead to respiratory problems and fetal asphyxia. The result is the aspiration of the infected amniotic fluid by the fetus, which subsequently leads to the development of intrauterine pneumonia [1, 6].
With hypoxia and hypoxemia, diffuse inhibition of the central nervous system occurs, as a result of which shallow breathing is observed, the breathing rhythm is disturbed (episodes of apnea, periodic breathing - Cheyne-Stokes respiration, changes in inhalation-exhalation ratio, irregular amplitude, asynchrony in the work of the chest and diaphragmatic muscles, participation in the act of breathing additional muscles, etc.). Hypercapnia, toxicosis, reflex influences from the affected areas of the lungs, impaired rheological properties of blood and hemodynamics are also a consequence of the imbalance in the functions of the central nervous system [7, 9].
A "vicious circle" is formed: progressive respiratory disorders cause disturbances in the homeostasis system, which further aggravates the disturbances in external respiration. Hemodynamic changes depend on the severity of these pathological processes. In the future, newborns develop pulmonary hypertension, overload of the right heart on the background of energetic-dynamic insufficiency, often edematous syndrome and anemia [1, 9].
Immaturity of bronchopulmonary structures, surfactant deficiency, tendency to atelectasis, respiratory distress syndrome, severity of metabolic disorders, and circulatory disorders in the lungs are of importance among the causes of lung damage in newborns, especially premature infants [1, 2].
Modern research has established the following pathways of fetal infection: transplacental (hematogenous), intraamnial (ascending or descending), intranatal (during the passage of the fetus through the birth canal) [1, 7].
Considering the transplacental route of infection in the etiology of neonatal pneumonia, the special role of cytomegalovirus and herpes infections, as well as the causative agents of tuberculosis, syphilis, and rubella, should be noted [4, 7].
However, the main cause of intrauterine pneumonia is aspiration or ingestion of infected amniotic fluid or mucus, and often a combination of both. Also, a version has been worked out that lung infection can occur during the first breath of a child due to aspiration by the vaginal microflora [1, 7].
Newborns with HIV infection can develop severe pneumonia, which progresses rapidly. Its etiological reasons are microbes of tuberculosis, syphilis and cytomegalovirus [1, 10].
24 East European Scientific Journal #11 (75), 2021
A common cause of congenital intranatal pneumonia can be pathogens that cause amnionitis and endometritis in the mother with infection of the amniotic fluid. These include: genital mycoplasmas, anaerobic bacteria, including group B and D streptococci; other microbes - green streptococci, hemophilic and tuberculous (very rare) bacilli, listeria [9].
Microbes such as group B streptococci, chlamydiae, genital mycoplasmas, cytomegalovirus, listeria, herpes simplex viruses type II, fungi of the genus Candida, less often other pathogens - green streptococci, Escherichiae, enterococci, Haemophilus influenzae and, possibly, Trichomoniasis cause intranatal pneumonias acquried during passage through the birth canal [3, 7].
For congenital transplacental antenatal and postnatal pneumonias, hematogenous penetration of infectious agents into the lungs is typical. It was found that infectious (in most cases bacterial) agents affecting the alveolar membrane and the interstitial space of the lungs cause the formation of a triad of signs: the development of hyaline membranes (typical for group B streptococci), purulent inflammation and interstitial edema [10, 11].
As a rule, intrauterine pneumonia is focal-confluent, if it occurs mainly through hematogenous penetration of infection. When an infection enters from the amniotic fluid or during the passage of the fetus through the infected birth canal, intrauterine pneumonia also occurs, but this pathological process is already defined as bronchopneumonia [12].
Until now, there is no sufficiently affirmative explanation why, in the case of fetal intrauterine infection in the antenatal or intrapartum period, the "site of application" is mainly the pulmonary system [4].
Often, intrauterine pneumonia is the cause of the development of multiple organ failure. This is due to severe infectious toxicosis and severe secondary metabolic disorders. In such cases, pneumonia is regarded as a symptom of neonatal sepsis [9].
In 67.5% of cases in premature infants the respiratory organs are affected in the presence and aggravation of the septic process with the development of the systemic inflammatory response syndrome [9].
One of the defining reasons leading to the generalization of infectious and inflammatory diseases in premature infants is the immaturity of the immune system, which is unable to produce appropriate protective reactions [4].
At the same time, premature births themselves create a cascade of disorders in the mother-placenta-fetus system, and therefore the supply of the newborn with transplacental immunoglobulin G, which carries out a protective function in the child's body, is disrupted [3].
The relationship between acute and chronic fetal hypoxia, low birth weight, the presence of intrauterine infection with the emergence and development of infectious immunosuppression, followed by
suppression of the immune system of the newborn has been established [5].
In this case, the cellular link of the immune system is primarily affected. Studies have established a decrease in the number of T and B-lymphocytes on the basis of their increased migration from the bloodstream to the inflammation focus [9].
Bacteremia and the accompanying antigenaemia and toxaemia are the causes that trigger a number of successive protective reactions of the body. As a result, activated cells of a monocytic-macrophage nature begin phagocytosis of bacteria and their decay products, which entails an excessive release of biologically active substances (pro-inflammatory cytokines) into the systemic circulation. The most studied of them are: interleukin-1, tumor necrosis factor-a, granulocyte-macrophage colony-stimulating factor, interleukin-6 and interleukin-8 [9].
Considering the wide range of pro-inflammatory cytokines and their high concentrations, a reaction occurs with specific receptors on the membranes of various cells of the body. As a result of such a cascade pathological process, a systemic inflammatory response develops [5]. That are proinflammatory cytokines that activate the center of thermoregulation and contribute to the onset of fever, affect the protein-synthesizing function of the liver, inhibit albumin synthesis and promote the production of proteins of the acute phase of inflammation (C-reactive protein, haptoglobin, orosomucoid) by hepatocytes, contribute to an increase in the catabolic direction of metabolism and the development of cachexia [13].
Neutrophils, heading to the site of infection, interact with adhesion molecules on the surface of vascular endothelial cells, fibroblasts, cells of other tissues and organs. When neutrophils die, the contents of their granules are released, which activates platelet aggregation, release of serotonin, histamine, proteases, derivatives of arachidonic acid, complement system, factors that activate blood clotting, kinin-kalekrein system, etc. The predominance of destructive processes in the mechanism of action of cytokines and other mediators of inflammation leads to impaired function and permeability of the capillary endothelium, impaired microcirculation [3, 6].
An irrefutable fact is that it is intrauterine infection that can be the cause of congenital immunodeficiency. Thus, in newborns with foci of infection, the study of the function of polymorphonuclear leukocytes revealed a deep immaturity of the receptor structures of neutrophils to chemotactically active factors with dysregulated functions, i.e. almost complete "cell blindness" [4, 7].
Thus, summarizing the idea of the development of the pathogenesis of intrauterine pneumonia in premature infants, it is necessary to distinguish the following stages leading to the pathological process: fetal hypoxia, aspiration of infected amniotic fluid followed by microbial colonization of the upper respiratory tract, the development of severe acidosis and impaired homeostasis on the background of
IJ«
It!®]«
East European Scientific Journal #11 (75), 2021 25
immune depression and morphofunctional immaturity [1].
LITERATURE:
1. Abramyan R.A. Analysis of the structure of preterm labor and associated perinatal losses (20062010) / R.A. Abramyan, V.F. Grigoryan // Neonatology, surgery and perinatal medicine. - 2011. -Vol. 1, No. 1. - pp. 26-29.
2. Avramenko I. Yu. Dynamics of nitrite anion and endothelin-1 in congenital heart defects accompanied by pulmonary hypertension / / Perinatology and pediatrics. - 2009. - № 2 (38). -P. 37-39.
3. Al Aboud Mazen Heiro. Detection of infectious and inflammatory diseases in the early neonatal period: abstract of the dissertation for the degree of candidate of science. Medical Sciences: spec. 14.01.10 "Pediatrics" / Heiro Al Aboud Mazen. Odessa, 2008, 19 p. (in Russian).
4. Abramova I. V., Kuznetsova V. A. Biochemical indicators of blood in premature newborns with intrauterine infection// Clinical laboratory diagnostics. 2008, No. 9, pp. 7a-7.
5. Avramenko I. Yu. The role of endothelial dysfunction in congenital heart defects in young children: abstract of the dissertation for the degree of candidate of science. 14.01.10 "Pediatrics" / I. Yu. Avramenko. Lviv, 2008, 22 p. (in Russian).
6. Avdeeva M. G., Lebedev V. V., Shubich M. G. Molecular mechanisms of infection process development // Clinical laboratory diagnostics. 2007, No. 4, pp. 15-22.
7. Zagashtokova A. Kh., Kushnareva M. V., Efimov M. S. Activity of the elastase-inhibitory system in infectious and non-infectious lung pathology in premature babies with extremely low body mass [etc.] // Questions of gynecology, obstetrics and perinatology. 2009, No. 6, pp. 58-61.
8. Smiyan I. S., Pavlishin G. A., Stetsenko V. V. Analysis of birth and survival indicators of children with extremely low body weight [etc.] // The materials of the I-th Congress of neonatologists of Ukraine, October 24-25, 2007 - Odessa, 2007. - pp. 102-103.
9. Cherkasova T. M., Remneva O. V., Nesterov Yu. N. Obstetric and perinatal factors of the risk of
formation of intrauterine pneumonias [etc.] //Russian pediatric journal. 2008, No. 3, pp. 11-14.
10. Abaev Yu. K. Inflammatory diseases of newborns / Yu. K. Abaev. Rostov N / A: Feniks publ., 2007, 256 p. (in Russian).
11. Antonov A. G., Badyuk E. E., Tilkidzhi Yu. Homeostasis of the newborn (physical and chemical indicators) - L.: Meditsina, 1984. - 184 P.
12. Aryaev M. L. Neonatology / M. L. Aryaev. Kiev: ADEF-Ukraine, 2003, 756 p. (in Russian).
13. Gerasimov I. G., Zaitsev I. A., Kotelnitsky M. N. The analysis of spinal fluid tensiograms using a kinetic model [etc] //Bulletin of experimental biology and medicine. - 2004. - № 5. - pp. 597-600.
For correspondence:
Lyudmila A. Levchenko, MD, PhD, DSc, Professor
Russian National Research Medical University after N.I. Pirogov, Moscow, Russian Federation
Department of Hospital Pediatrics a$Tep V.A. Tabolina
Address: 1 Ostrovityanov str., Moscow, 117997, Russian Federation
Phone: +79850586344
ORCID: https://orcid.org/0000-0003-0172-0520 Information about co-authors: Heghine A. Sargsyan, MD, PhD, Associate professor, Academician V.A.Tabolin Department of Hospital Paediatrics, Paediatric Faculty, Pirogov Russian National
Research Medical University Address: 1 Ostrovityanov str., Moscow, 117997, Russian Federation
Phone: +79250702357
ORCID: https://orcid. org/0000-0001-7305-9036 Knarik V. Nikoghosyan, MD, PhD
State budgetary institution of health care "Odintsovskaya regional hospital", Maternity Hospital, c. Odintsovo, Moscow Region, Russian Federation
Address: 3B Marshal Biryuzova str., Odintsovo, Moscow region, 143003, Russian Federation Phone: +79680554440
ORCID: https://orcid.org/0000-0003-1347-5489
