Intrauterine pneumonia

Intrauterine pneumonia is an acute infectious disease of the fetus and newborn; it occurs as a result of intrauterine infection and affects the respiratory parts of the lungs, including the alveolar spaces and interstitium.

The disease may be one of the manifestations of a congenital generalized infectious process, occurring with hepatosplenomegaly, rashes on the skin and mucous membranes, damage to the central nervous system and other symptoms of a congenital infection: chorioretinitis (with rubella and toxoplasmosis); bone changes (with syphilis), etc. It is possible for intrauterine pneumonia to occur as an independent disease caused by intrauterine infection of the lungs of the fetus.

The incidence of intrauterine pneumonia is 1.79 per 1000 live births.

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What causes intrauterine pneumonia?

The cause of the development of intrauterine pneumonia depends on the routes of infection.

In hematogenous transplacental infection of the fetus, pneumonia is most often caused by TORCH infection pathogens: Toxoplasma gondii, Polynosa rubeolae (rubella virus), Cytomegalovirus hominis (cytomegalovirus), Herpes simplex virus (herpes simplex virus), as well as Treponema pallidum and Listeria monocytogenes. Usually, in such cases, intrauterine pneumonia is part of a congenital generalized infectious process and develops in the first 72 hours of life.

The main pathogens of intrauterine pneumonia that developed as a result of intranatal infection are considered to be microorganisms that colonize the mother's genital tract: 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 streptococci are the most common (about 50% of cases) cause of congenital pneumonia. According to foreign researchers, they are found in 15-25% of pregnant women (with the gastrointestinal tract and genitourinary system being colonized mainly), which in approximately 1% of cases leads to intranatal infection of the fetus. The risk of infection increases significantly with a long anhydrous period during labor, fever in the mother, the development of chorioamnionitis and prematurity. Intrauterine pneumonia is mainly caused by serovars I and II. Group B streptococci serovar III play the role of causative agents of intrauterine pneumonia much less often, with the disease usually developing in the 2nd week of life and is acquired.

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

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

C. trachomatis is an obligate intracellular parasite transmitted sexually. According to Russian researchers, almost 26% of women in labor have signs of active infection, which can cause 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, data accumulated in recent years indicate that this pathogen is capable of causing diseases in newborns.

Genital mycoplasmas (M. hominis) cause pneumonia only in a special group of patients: extremely premature infants and newborns receiving immunosuppressive treatment.

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

In very premature infants weighing less than 1500 g, pneumonia can be caused by Cytomegalovirus hominis (cytomegalovirus), Herpes simplex virus (herpes simplex virus), Varicella zoster virus (chickenpox virus) and Enterovirus (enteroviruses).

Risk factors

• Infectious diseases of the mother during pregnancy (damage to the urinary system, intestines, vaginitis, vulvovaginitis, etc.).
• Fever in a woman in labor.
• Chorioamnionitis, cervicitis, vaginitis, endometritis in women in labor.
• Intrauterine fetal hypoxia, asphyxia during childbirth.
• Aspiration syndrome (especially meconium aspiration syndrome of the newborn).
• Prematurity, respiratory distress syndrome (RDS), impaired cardiopulmonary adaptation.

How does intrauterine pneumonia develop?

The following play a major role in the development of intrauterine pneumonia:

• infectious and inflammatory diseases of the urinary and reproductive systems of the mother (endometritis, etc.);
• gestational maturity of the fetus, the state of the surfactant system and the bronchopulmonary apparatus, malformations of the bronchial tree, previous intrauterine hypoxia, asphyxia during childbirth, aspiration of meconium, amniotic fluid, etc. The disease develops as a result of hematogenous introduction of the pathogen in the last days or weeks of pregnancy or as a result of infection of the lungs when amniotic fluid enters them (infected with endometritis, chorioamnionitis, etc.), or when infected contents of the birth canal are aspirated.

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

In all cases, bilateral lung damage is detected (both alveoli and interstitium). It causes hypercapnia, hypoxemia, mixed acidosis and hypoxia after birth, deterioration of surfactant synthesis, which causes atelectasis, parenchymatous pulmonary edema, and increased intrapulmonary pressure. As a result of progressive hypoxia, acidosis and microcirculation disorders, multiple organ failure develops very quickly (first cardiopulmonary, then other organs).

Intrauterine pneumonia caused by group B streptococci is characterized by a combination of respiratory disorders and hyaline membrane disease. Two mechanisms are considered to be of primary importance in their formation:

• microorganisms, affecting alveolar pneumocytes and endothelial cells of capillaries, cause exudation of plasma proteins into the alveoli with subsequent deposition of fibrin and formation of hyaline membranes;
• Immune complexes consisting of complement component C3 and fibrin clumps damage lung tissue.

Typically, in the first 24 hours of life, an inflammatory reaction develops in the interstitial tissue of the lungs, and multiple small, diffusely located atelectases are formed.

Symptoms of intrauterine pneumonia

In the newborn, shortness of breath, inclusion of the accessory muscles of the chest in the act of breathing, attacks of apnea and cyanosis, foamy discharge from the mouth are observed already from the first hours of life. The Silverman assessment is 4-6 points. Increasing lethargy, pale skin (often with a cyanotic tint), tachycardia, an increase in the size of the liver are noted. Sclerema and bleeding often develop. Pneumonia is accompanied by a pronounced deterioration in the general condition: the child becomes lethargic or restless, appetite decreases, regurgitation, vomiting, flatulence, bowel disorder appear, symptoms of cardiovascular insufficiency and dysfunction of the central nervous system are added.

In premature infants, the clinical picture is characterized by the dominance of symptoms of central nervous system depression, increasing respiratory failure (periorbital and perioral cyanosis, the appearance of apnea attacks); a drop in body weight is observed.

Pneumonia caused by group B streptococci develops primarily in premature infants, most often in the first 24-72 hours of life. Increasing dyspnea and respiratory rhythm disturbances (apnea, gasps) are observed. The appearance of a wheezing noisy exhalation, bloating and decreased elasticity of the chest, diffuse cyanosis, and progressive hypoxemia are characteristic. X-ray examination reveals the symptom of air bronchography, a reticular-nodular network (due to multiple small atelectases) and inflammatory infiltration of the interstitium.

Pneumonia caused by non-negative bacteria is severe: with fever, apnea, hemodynamic disturbances, respiratory distress syndrome, pulmonary hypertension, infectious toxic shock. X-ray examination reveals signs similar to hyaline membrane syndrome - the appearance of a reticular-nodular network.

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

Chlamydial intrauterine pneumonia usually develops in the 3rd-6th week of life. In half of the cases, it is preceded by conjunctivitis (it is detected on the 5th-15th day). It is characterized by the absence of fever, subacute low-symptom onset and dry unproductive cough (staccato cough), broncho-obstructive syndrome.

There is no toxicosis. Physical examination reveals minor changes in the lungs. Radiographs show bilateral diffuse uneven infiltration with a predominance of the interstitial component. General peripheral blood analysis sometimes reveals moderate eosinophilia.

Ureaplasma intrauterine pneumonia usually occurs in the second week of life in children born to mothers with the specified infection. Slow development of the clinical picture is characteristic. Perhaps the only typical symptom is persistent unproductive cough. Radiological features are also absent, revealing 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 making a diagnosis is the following: identification of risk factors for the development of intrauterine pneumonia in the mother's medical history, increasing dyspnea from the first hours of life (>50 per minute), an increase in body temperature >38.5 °C, typical radiological findings.

Physical examination. Percussion sometimes reveals tympanitis in the root zones, shortening of the percussion sound in the lower, lower outer parts of the lungs; auscultation reveals crepitation and fine bubbling rales. However, it should be noted that the auscultatory phenomena mentioned above most often occur on the 4th-7th day of the disease, and shortening of the percussion sound in small children is sometimes completely absent.

Chest X-ray. The diagnosis is confirmed by detecting the following changes:

• scattered peribronchial focal infiltration;
• focal shadows against the background of an enhanced bronchovascular pattern and emphysematously inflated lung fields.

General analysis of peripheral blood. Intrauterine pneumonia usually reveals an increase (>10-12x10 ⁹ /l) or decrease (<3x10 ⁹ /l) in the number of leukocytes; an increase in the number of neutrophils, an increase in their index (the ratio of the number of immature cells to the total number of neutrophils, the normal value is <0.2), a shift in the leukocyte formula to the left; thrombocytopenia.

Biochemical analysis and study of the acid-base balance of the blood. The disease is characterized by mixed acidosis, decreased blood oxygen saturation. The results of biochemical blood tests reveal a moderate increase in the activity of liver enzymes, creatinine and urea concentrations, and changes in the electrolyte composition of the blood.

Bacteriological (bronchial aspirate culture, IFI, PCR), virological (IFI, PCR) and serological studies (detection of antibodies to viruses, bacteria, chlamydia, mycoplasma). Group B streptococci are sometimes isolated from the blood and cerebrospinal fluid of a sick child (the latter is possible if intrauterine pneumonia is accompanied by the development of streptococcal meningitis). A faster, more informative and sensitive method is the detection of streptococcal antigens in the blood and cerebrospinal fluid. Detection of bacteria or their antigens in urine and feces has no diagnostic value.

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Differential diagnostics

Once a suspicion of intrauterine pneumonia has arisen, differential diagnostics are carried out immediately, since its clinical picture is similar to other diseases that differ in treatment tactics:

• SDR due to surfactant deficiency;
• meconium aspiration;
• pneumothorax;
• congenital malformations of the lungs and other organs of the chest (lobar emphysema, Wilson-Mikity syndrome, coloboma of the lung, diaphragmatic hernia);
• thymoma.

For differential diagnostics, anamnesis data are of great importance (prematurity, unfavorable course of the labor period, birth asphyxia, low Apgar score, high Silverman score). However, the results of chest X-rays play a decisive role, allowing to differentiate the above conditions with a high degree of reliability. If necessary (for example, in the case of meconium aspiration complicated by pneumonia), chest X-rays should be performed dynamically at intervals of 1-3 days. In severe cases, in children on mechanical ventilation, along with X-ray examination, it is advisable to conduct cytological and microbiological examination of the tracheobronchial aspirate.

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

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Treatment of intrauterine pneumonia

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

The choice of feeding method (volume, frequency and method) is carried out in accordance with the severity of the condition, concomitant pathology, maturity of the organism, taking into account the severity of the sucking and swallowing reflexes. Absolute preference is given to mother's milk. If natural is impossible, parenteral nutrition is prescribed. The volume of the mixture is adjusted taking into account losses from fever, shortness of breath, vomiting and diarrhea.

Oxygen therapy is a mandatory component of the treatment of intrauterine pneumonia; it is carried out in accordance with the state of the child’s respiratory function.

Antibacterial treatment

The earliest possible (at the stage of presumptive diagnosis) prescription of empirical antibacterial therapy is the main type of treatment for intrauterine pneumonia.

The peculiarity of the pathogens of the disease, which manifested itself in the first 6 days of life, makes the combination of ampicillin with aminoglycosides (netilmicin or amikacin) the drugs of choice. If there is no effect after 48 hours from the start of treatment, then third-generation cephalosporins (cefotaxime, ceftriaxone) are used, possibly in combination with aminoglycosides.

Group B streptococci are sensitive to aminopenicillins, most cephalosporins (the exception is cefoxitin: resistance to it is sometimes detected). The action of beta-lactams is potentiated by aminoglycosides. Given the above, the most common treatment regimen for suspected pneumonia caused by group B streptococci is a combination of ampicillin with amikacin or netilmicin (cefotaxime or cefuroxime can be used instead of a beta-lactam drug).

The main drugs for the treatment of intrauterine pneumonia, determining their dose and 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 then 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 Netilmicin	Intravenous, intramuscular	5 mg for 1 week every 48 hours then 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
Cephalosporins of the third generation
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 - ampicillin in combination with aminoglycosides (netilmicin, amikacin).

If pneumonia is caused by other pathogens (which should preferably be proven by additional research methods), then alternative groups of antibacterial drugs are used:

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

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

Unfortunately, identifying the pathogen requires a certain amount of time, and therefore, when treating premature babies with high-risk factors for the development of an atypical inflammatory process in the lungs (miscarriage; chronic salpingo-oophoritis, diagnosed infection of the genitourinary system in the mother), along with beta-lactams and aminoglycosides, it is advisable to immediately use a macrolide antibiotic.

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Immunotherapy

Intrauterine pneumonia, especially in premature babies, always develops against the background of transient humoral immunodeficiency, therefore, in severe cases, immunotherapy is mandatory (along with antibiotics) - as early as possible (on the 1st-3rd day of treatment), human immunoglobulins are administered (pentaglobin is best).

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

A number of researchers recommend prescribing licopid during the period of subsiding symptoms of acute toxicosis.

Symptomatic treatment

The choice of drugs for symptomatic therapy depends on the manifestations of the disease, but mucolytics are almost always used, with ambroxol considered the best. It liquefies bronchial secretions, and also increases the synthesis of surfactant by second-order alveocytes and slows down its decay. Depending on the child's condition, the drug is administered orally or by inhalation through a nebulizer or spacer.

References

Grebennikov V.A., Ionov O.I., Mostovoy A.V., et al. Respiratory disorders // Neonatology: National guidelines / Under the general editorship of N.N. Volodin. - M.: GEOTAR-Media, 2007.

Samsygina G.A. Intrauterine pneumonia // Rational pharmacotherapy of childhood diseases: Guide for doctors / Ed. AA Baranov, HN Volodin, G.A. Samsygina. - M.: Litterra, 2007. - Book 1.

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

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

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