Intrauterine pneumonia

Intrauterine pneumonia - acute infectious disease of the fetus and the newborn - occurs as a result of intrauterine infection, proceeds with the defeat of the respiratory parts of the lungs, including alveolar spaces and interstitium.

The disease can be one of the manifestations of a congenital generalized infectious process that occurs with hepatosplenomegaly, rashes on the skin and mucous membranes, CNS damage and other symptoms of congenital infection: chorioretinitis (with rubella and toxoplasmosis); bone changes (with syphilis), etc. Perhaps the course of intrauterine pneumonia as an independent disease caused by intrauterine infection of the lung fetus.

The incidence of intrauterine pneumonia is 1.79 per 1,000 live births.

[1], [2], [3], [4]

What causes intrauterine pneumonia?

The cause of intrauterine pneumonia depends on the pathways of infection.

In case of hematogenous transplacental infection of the fetus, the inflammation of the lungs is most often caused by TORCH pathogens: Toxoplasma gondii, Polynosa rubeolae, Cytomegalovirus hominis, Herpes simplex virus, Treponema pallidum and Listeria monocytogenes. Usually in such cases, intrauterine pneumonia is part of the congenital generalized infectious process and develops during the first 72 hours of life.

The main pathogens of intrauterine pneumonia that develop due to intranatal infection are considered to be microorganisms colonizing the genital tract of the mother: group B streptococci, C. Trachomatis, gram-negative enterobacteria (E. Coli, Klebsiella spp.). Less common are diseases caused by Mycoplasma spp. And Ureaplasma urealyticum.

Group B Streptococcus is the most common cause of congenital inflammation of the lungs (about 50% of cases). According to foreign researchers, they are found in 15-25% of pregnant women (with the colonization of mainly the gastrointestinal tract and genitourinary system), which approximately 1% of cases leads to intranatal infection of the fetus. The risk of infection significantly increases with a long anhydrous period in childbirth, fever in the parturient woman, the development of chorioamnionitis and miscarriage of pregnancy. Most intrauterine pneumonia is caused by serovars I and II. Streptococcus group B serovar III play the role of causative agents of intrauterine pneumonia is much rarer, and the disease usually develops at the 2nd week of life and is of an acquired nature.

The cause of intrauterine pneumonia may become Listeria monocytogenes. They are often found in unpasteurized milk and dairy products, especially in sour cream and soft cheeses. In practically healthy people, they usually do not cause disease. Listeriosis is found mainly in pregnant women with immunodeficiency, their fetuses and newborns. The offspring become infected from mothers as a result of vertical transmission of infection in listeriosis chorioamnionitis, respiratory (influenza-like) or intestinal listeriosis of pregnant women.

Gram-negative bacteria (E coli, Klebsiella spp., Staphylococci) act as causative agents of intrauterine pneumonia rarely.

C. Trachomatis - obligate intracellular parasite, sexually transmitted. According to domestic researchers, almost 26% of women in labor have signs of active infection, which can lead to infection of the child. After infection, chlamydial infection of the respiratory system develops in 13-33,3% of cases, and intrauterine pneumonia - in 10-20%.

The role of U. Urealyticum in the etiology of intrauterine pneumonia has long been questionable. However, the data accumulated in recent years indicate that this causative agent can cause diseases in newborns.

Genital mycoplasmas (M. Hominis) cause inflammation of the lungs only in a special group of patients: deep-in-preterm and newborns receiving immunosuppressive treatment.

Most intrauterine pneumonias develop during the first 3-6 days of life, except mycoplasmal (7 days) and chlamydial (3-6 weeks).

In preterm infants with a body weight of less than 1500 g, inflammation of the lungs can cause Cytomegalovirus hominis (cytomegalovirus), Herpes simplex virus (herpes simplex virus), Varicella zoster virus (Enteric Virus) and Enterovirus (enterovirus).

Risk factors

• Infectious diseases of the mother during pregnancy (defeat of the urinary system, intestines, vaginitis, vulvovaginitis, etc.).
• Fever in the parturient woman.
• Chorioamnionitis, cervicitis, vaginitis, endometritis in the parturient woman.
• Intrauterine fetal hypoxia, asphyxia in childbirth.
• Aspiration syndrome (especially the syndrome of meconial aspiration of the newborn).
• Prematurity, respiratory distress syndrome (SDR), impaired cardiopulmonary adaptation.

How does intrauterine pneumonia develop?

A major role in the development of intrauterine pneumonia is played by:

• Infectious and inflammatory diseases of the urinary and reproductive organs of the mother (endometritis, etc.);
• gestational maturity of the fetus, the state of the surfactant and bronchopulmonary apparatus, the developmental defects of the bronchial tree, intrauterine hypoxia, asphyxia in labor, aspiration of meconium, amniotic fluid, etc. The disease develops as a result of hematogenous dribbling of the pathogen in the last days or weeks of pregnancy or as a result of infection of the lungs with the admission of amniotic fluid (infected with endometritis, chorionnionitis, etc.) or aspiration of infected contents of the birth canal.

Prematurity, SDR, impaired cardiopulmonary adaptation, fetal hypoxia contribute to the development of the infectious process due to functional, morphological and immunological immaturity of the lung tissue.

In all cases, bilateral lung lesions are detected (both alveoli and interstitium). It causes the emergence after the birth of hypercapnia, hypoxemia, mixed acidosis and hypoxia, a deterioration in the synthesis of surfactant, which causes the appearance of atelectasis, parenchymal edema of the lungs, increased intrapulmonary pressure. As a result of progressive hypoxia, acidosis and microcirculation disorders, multi-organ failure (first cardiopulmonary, then other organs) very quickly develops.

For intrauterine pneumonia caused by Group B streptococci, a combination of respiratory disorders and hyaline membrane disease is characteristic. In their formation, the leading importance is attached to two mechanisms:

• microorganisms, affecting alveolar pneumocytes and endothelial cells of capillaries, cause exudation of plasma proteins in the alveoli, followed by deposition of fibrin and the formation of hyaline membranes;
• immune complexes consisting of the complement component of C3, and fibrin lumps, damage the lung tissue.

Usually in the first 24 hours of life an inflammatory reaction develops in the interstitial tissue of the lungs, multiple small diffuse atelectasis is formed.

Symptoms of intrauterine pneumonia

In the newborn, from the very first hours of life, dyspnoea, inclusion of an ancillary musculature of the chest, respiratory apnea and cyanosis, foamy discharge from the mouth are observed in the act of breathing. Score Silverman 4-6 points. They note the growing lethargy, pallor of the skin (often with a cyanotic shade), tachycardia, an increase in liver size. Quite often develop a sclera, hemorrhage. Pneumonia is accompanied by a marked violation of the general condition: the child becomes sluggish or restless, appetite decreases, regurgitation, vomiting, flatulence, upset of the stool, symptoms of cardiovascular failure, and CNS dysfunction are added.

Preterm neonates are characterized by a dominance in the clinical picture of symptoms of CNS depression, increasing respiratory insufficiency (periorbital and perioral cyanosis, the appearance of apneas); observed a decrease in body weight.

Pneumonia caused by group B Streptococcus develops primarily in premature newborns, usually in the first 24-72 hours of life. Observed increasing dyspnea, a violation of the rhythm of breathing (apnea, guspsy). Characteristic is the appearance of wheezing noisy exhalation, swelling and a decrease in the elasticity of the chest, diffuse cyanosis, progressive hypoxemia. An X-ray examination reveals a symptom of aerial bronchography, a reticular-nodose mesh (due to multiple small atelectasis) and inflammatory infiltration of interstitium.

Pneumonia caused by non-negative bacteria is severe: with fever, apnea, hemodynamic disorders, respiratory distress syndrome, pulmonary hypertension, infectious-toxic shock. When an X-ray study shows signs similar to the hyaline membrane syndrome, the appearance of a reticular nodose net.

Listeriosis intrauterine pneumonia does not have any clinical and radiological features.

Chlamydial intrauterine pneumonia usually develops during the 3rd-6th week of life. In half the cases it is preceded by conjunctivitis (it is detected on the 5th-15th day). It is characterized by the absence of fever, subacute malosymptomnoe beginning and dry non-productive cough (cough stakatto), bronchoobstructive syndrome.

There is no toxicosis. At a physical examination, slight changes in the lungs are revealed. On X-ray diffraction patterns, bilateral diffuse uneven infiltration is noted with the predominance of the interstitial component. In a general analysis of peripheral blood, mild eosinophilia is sometimes found.

Ureaplasma intrauterine pneumonia usually occurs in the second week of life in children born to mothers with this infection. A slow development of the clinical picture is characteristic. Perhaps the only typical symptom is a stubborn, unproductive cough. X-ray features are also absent, they show bilateral lung damage with infiltrative uneven focal shadows. Changes in the general analysis of peripheral blood may be absent.

Diagnosis of intrauterine pneumonia

The basis for the diagnosis is the following: the detection of risk factors for intrauterine pneumonia in a mother's history, increasing dyspnea from the first hours of life (> 50 per minute), an increase in body temperature> 38.5 ° C, typical radiographic findings.

Physical examination. With percussion, sometimes identify tympanitis in the basal zones, shortening of percussion sound in the lower, lower-lying parts of the lungs; at auscultation - crepitation and small bubbling rales. However, it is worth noting that these auscultative phenomena often occur on the 4-7th day of the disease, and the shortening of percussion sound in young children is sometimes absent.

Radiography of the chest. The diagnosis is confirmed by the discovery of the following changes:

• disseminated peribronchial focal infiltration;
• focal shadows on the background of an intensified bronchoconstrictive pattern and emphysematous swollen pulmonary fields.

General analysis of peripheral blood. In prenatal pneumonia, an increase (> 10-12 × ^{10 9} / L) or a decrease (<3 × 10 ⁹ / L) of the number of leukocytes is usually detected ; an increase in the number of neutrophils, an increase in their index (ratio of the number of immature cells to the total number of neutrophils, normal value <0.2), shift of the leukocyte formula to the left; thrombocytopenia.

Biochemical analysis and investigation of the acid-base state of blood. The disease is characterized by mixed acidosis, a decrease in the saturation of blood with oxygen. In the results of biochemical blood tests, a moderate increase in the activity of liver enzymes, a concentration of creatinine and urea, a change in the electrolyte composition of the blood.

Bacteriological (seeding of bronchial aspirate, IFI, PCR), virologic (IFR, PCR) and serological studies (detection of antibodies to viruses, bacteria, chlamydia, mycoplasma). Group B Streptococcus is sometimes isolated from the blood and liquor of a sick child (the latter is possible if intrauterine pneumonia is accompanied by the development of streptococcal meningitis). A faster, informative and sensitive method is the detection of streptococcal antigens in the blood and CSF. The detection of bacteria or their antigens in urine and feces is of no diagnostic significance.

[5], [6], [7], [8],

Differential diagnostics

After the appearance of the assumption of intrauterine pneumonia, differential diagnosis is carried out immediately, since its clinical picture is similar to other diseases different in treatment tactics:

• SDR caused by surfactant deficiency;
• meconial aspiration;
• pneumothorax;
• congenital malformations of the lungs and other organs of the chest (shared emphysema, Wilson-Mikity syndrome, pulmonary coloboma, diaphragmatic hernia);
• thymoma.

For differential diagnosis, data of anamnesis (prematurity, unfavorable course of the labor period, asphyxia in childbirth, low grade on Apgar scale, high on the Silverman scale) are of great importance. However, the decisive role is played by the results of chest radiographs, which allow us to distinguish these states with a high degree of certainty. If necessary (for example, in the case of meconial aspiration complicated by pneumonia), radiographic examination of the lungs should be carried out in dynamics with an interval of 1-3 days. In severe cases, children who are on the IVL, along with X-ray examination, it is advisable to perform a cytological and microbiological study of the tracheobronchial aspirate.

The results of peripheral blood tests play an auxiliary role, but an increase or decrease in the number of leukocytes, a neutrophil index> 0.3 indicate an infection process.

[9], [10], [11]

Treatment of intrauterine pneumonia

General principles - the creation of a protective regime: premature babies should be placed in a medical incubator (kuvez) and provide an additional supply of oxygen mixture (15-40%), temperature and humidity determined depending on the maturity of the child.

The choice of the method of feeding (volume, frequency and method) is carried out in accordance with the severity of the condition, the accompanying pathology, the maturity of the organism, take into account the severity of the sucking and swallowing reflexes. Absolute preference is given to mother's milk. If the natural can not be prescribed parenteral nutrition. The volume of the mixture is adjusted taking into account the losses from fever, dyspnea, vomiting and diarrhea.

Oxygen therapy is an obligatory component of the treatment of intrauterine pneumonia, it is performed in accordance with the state of respiratory function of the child.

Antibacterial treatment

The earliest (at the stage of the diagnosis assumption) the appointment of empirical antibiotic therapy is the main kind of treatment of intrauterine pneumonia.

The originality of the pathogens manifested in the first 6 days of life, makes the choice of a combination of ampicillin with aminoglycosides (netilmicin or amikacin). If the effect is absent 48 hours after the start of treatment, cephalosporins of the third generation (cefotaxime, ceftriaxone), can be used in combination with aminoglycosides.

Group B streptococci are sensitive to aminopenicillins, most cephalosporins (except cefoxytin: resistance is sometimes found to it). The action of beta-lactams potentiate aminoglycosides. In view of the foregoing, the most common treatment regimen for suspected pneumonia caused by Group B Streptococcus is a combination of ampicillin with amikacin or netilmicin (cefotaxime or cefuroxime may be used instead of the beta-lactam preparation).

The main drugs for the treatment of intrauterine pneumonia, determining their dose and the frequency of administration, depending on the age and body weight of the patient

Antibiotics	Routes of administration	0-4 weeks, body weight <1200 g	First week		Children 7 days and older
			Body weight 1200-2000 g	Body weight> 2000 g	Body weight 1200-2000 g	Body weight> 2000 g
Aminoglycosides
Amikacin	Intravenous, intramuscular	18 mg / kg for 1 week every 48 hours further 15 mg / kg every 36 hours	18 mg / kg every 36 hours	15 mg / kg every 24 hours	15 mg / kg every 24 hours	15 mg / kg every 24 hours
Gentamicin Tobramycin Nethylmycin	Intravenous, intramuscular	5 mg for 1 week every 48 hours further 4 mg every 36 hours	4.5 mg every 36 hours	4 mg every 24 hours	4 mg every 24 hours	4 mg every 24 hours
Glycopeptides
Vancomycin	Intravenously	15 mg / kg every 24 hours	10-15 mg / kg every 12-18 hours	10-15 mg / kg every 8-12 hours	10-15 mg / kg every 8-12 hours	10-15 mg / kg every 6-8 hours
Macrolides
Erythromycin	Reg os	10 mg / kg every 12 hours	10 mg / kg every 12 hours	10 mg / kg every 12 hours	10 mg / kg every 8 hours	10 mg / kg every 8 hours
Oxazolidinones
Linezolid	Intravenously	10 mg / kg every 8-12 hours	10 mg / kg every 8-12 hours	10 mg / kg every 8-12 hours	10 mg / kg every 8 hours	10 mg / kg every 8 hours

Penicillins
Ampicillin	Intravenous, intramuscular	25-50 mg / kg every 12 hours	25-50 mg / kg every 12 hours	25-50 mg / kg every 8 hours	25-50 mg / kg every 8 hours	25-50 mg / kg every 6 hours
Oxacillin	Intravenous, intramuscular	25 mg / kg every 12 hours	25-50 mg / kg every 12 hours	25-50 mg / kg every 8 hours	25-50 mg / kg every 8 hours	25-50 mg / kg every 6 hours
Cephalosporins of the second generation
Cefuroxime	Intravenous, intramuscular	25-50 mg / kg every 12 hours	25-50 mg / kg every 12 hours	25-50 mg / kg every 8 or 12 hours	25-50 mg / kg every 8 hours	25-50 mg / kg every 8 hours
Third generation cephalosporins
Cefotaxime	Intravenous, intramuscular	50 mg / kg every 12 hours	50 mg / kg every 12 hours	50 mg / kg every 8 or 12 hours	50 mg / kg every 8 hours	50 mg / kg every 6 or 8 hours
Ceftazidime	Intravenous, intramuscular	30-50 mg / kg every 12 hours	30-50 mg / kg every 12 hours	30-50 mg / kg every 8 or 12 hours	50 mg / kg every 8 hours	50 mg / kg every 8 hours
Ceftriaxone	Intravenous, intramuscular	50 mg / kg every 24 hours	50 mg / kg every 24 hours	50 mg / kg every 24 hours	50 mg / kg every 24 hours	50-75 mg / kg every 24 hours

Treatment of listeriosis intrauterine pneumonia is ampicillin in combination with aminoglycosides (netilmicin, amikacin).

If the inflammation of the lungs is caused by other pathogens (which it is desirable to prove by additional methods of research), then use alternative groups of antibacterial drugs:

• Gram-negative bacteria - cephalosporins of the third generation (cefotaxime, ceftriaxone, ceftazidime) alone or in combination with aminoglycosides;
• staphylococcus - oxacillin, vancomycin or linezolid alone or in combination with aminoglycosides (amikacin, netilmicin).

Mycoplasmas, ureaplasms, chlamydia are not sensitive to ampicillin and aminoglycosides; in such cases, the appointment of macrolides inside (spiramycin, azithromycin) or intravenously (erythromycin) is indicated.

Unfortunately, the determination of the causative agent requires a certain time, and in connection with the treatment of prematurity with high-risk factors in the lung inflammatory process of atypical nature (miscarriage, chronic salpingo-oophoritis, diagnosed infection of the urogenital system in the mother), along with beta-lactams and aminoglycosides, it is expedient to immediately use macrolide antibiotic.

[12], [13], [14], [15], [16], [17]

Immunotherapy

Intrauterine pneumonia, especially in prematurity, always develops against the background of transient humoral immunodeficiency, so in severe cases it is necessary (along with antibiotics) to carry out immunotherapy - as early as possible (on the 1st-3rd day of treatment), human immunoglobulins (most preferably pentaglobin) .

The medications are prescribed daily or every other day at usual doses (500-800 mg / kg body weight), a mandatory minimum course of 2-3 injections, if necessary, increase it to 5. The goal of the treatment is to increase the concentration in the patient's blood> 800 mg%. In severe hospital intrauterine pneumonia, intraglobin and octagam have a good effect. Domestic immunoglobulin for intravenous administration is not significantly different from foreign analogues, but more often it causes side effects (allergic rashes, hyperthermia).

A number of researchers recommend the appointment of lycopid during the period of symptoms of acute toxicosis.

Symptomatic treatment

The choice of drugs for symptomatic therapy depends on the manifestations of the disease, but almost always use mucolytics, the best consider ambroxol. It dilutes the bronchial secret, and also increases the synthesis of the surfactant by the alveocytes of the second order and slows down its disintegration. Depending on the condition of the child, the drug is administered orally or inhaled through a nebulizer or spacer.

Bibliography

Grebennikov VA, Ionov OI, Mostova AB, etc. Respiratory Disorders // Neonatology: National Leadership / Under total. Ed. HH Volodina. - Moscow: GEOTAR-Media, 2007.

Samsygin G.A. Intrauterine pneumonia // Rational pharmacotherapy of childhood diseases: A guide for doctors / Ed. AA Baranova, HH Volodina, G.A. Samsygin. - Moscow: Litterra, 2007. - Book. 1.

Shabalov N.P. Neonatology. - T. 1. - Moscow: MEDpress-inform, 2004.

Bartlett JG Management of Respiratory Tract Infections. - Philadelfia, 2001.

[18], [19], [20], [21], [22], [23], [24],