Congenital pneumonia: clinical guidelines

List of Abbreviations

ABT – antibiotic therapy

AB – antibacterial drug

BP – blood pressure

BPD – bronchopulmonary dysplasia

BP – water-free interval / rupture-to-delivery interval

VAP – ventilator-associated pneumonia

IVH – intraventricular hemorrhage

CHD – congenital heart disease

HFOV – high-frequency oscillatory ventilation

IMV – invasive mechanical ventilation

UTI — urinary tract infection

ABDS – acid-base balance status

CTG – fetal cardiotocography

HC – healthcare organization

NI – neutrophil index

NSG – neurosonography

CBC – complete blood count

UA – urinalysis

VLBW – very low birth weight

NICU / Department of Pathology of Newborns and Preterm Infants – Department of Pathology of Newborns and Preterm Infants

NICU – neonatal intensive care unit

ORC – open resuscitation care system / open radiant warmer

ICU – intensive care unit

PCT – Blood procalcitonin level test (acute phase inflammatory protein)

RDS – respiratory distress syndrome

RCT – randomized controlled trial

RT – respiratory therapy

GBS – group B Streptococcus

CRP – C-reactive protein (acute phase inflammatory protein)

SIRS – systemic inflammatory response syndrome

PCR – polymerase chain reaction

US – ultrasound examination

RR – respiratory rate

HR – heart rate

ECG – electrocardiography (recording of an electrocardiogram)

ELBW – extremely low birth weight

EchoCG – echocardiography

AUC – area under the curve

INSURE – surfactant administration method (INtubate-SURfactant-Extubate) – Intubation-surfactant-extubation and transition to non-invasive respiratory therapy.

CPAP – continuous positive airway pressure / respiratory therapy method – continuous positive airway pressure

FiO2 – fraction of inspired oxygen in the breathing gas mixture

pCO₂ – partial pressure of carbon dioxide

PEEP – positive end-expiratory pressure

PIP – peak inspiratory pressure

SpO2 – oxygen saturation, blood oxygen saturation measured by pulse oximetry

Terms and Definitions

Congenital pneumonia – an acute polyetiological infectious disease with predominant involvement of the respiratory parts of the lungs and accumulation of inflammatory exudate within the alveoli, detected by physical and radiological examination, as a rule, in the first 72 hours of life.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Congenital pneumonia – an acute polyetiological infectious disease with predominant involvement of the respiratory parts of the lungs and accumulation of inflammatory exudate within the alveoli, detected by physical and radiological examination, as a rule, in the first 72 hours of life [1,2].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The cause of congenital pneumonia is intrauterine or intrapartum infection of the fetus with microorganisms via transplacental, ascending, or contact routes. The main causative agents of congenital pneumonia are [2–7]:

Bacteria: Group B Streptococcus, Escherichia coli, Enterobacter spp., Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus viridans, Neisseria gonorrhoeae, Listeria monocytogenes and others.

Atypical and other pathogens: Chlamydia trachomatis, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, Mycoplasma pneumoniae, Treponema pallidum, Mycobacterium tuberculosis,

Viruses: Herpes simplex virus, Cytomegalovirus (CMV), Rubella, enteroviruses, measles virus.

Various types of yeasts and molds: Candida spp., Aspergillus spp. and others.

A major role in the development of congenital pneumonia is played by infectious and inflammatory diseases of the maternal urinary and reproductive systems (pyelonephritis, endometritis, etc.); the degree of fetal maturity, malformations of the bronchial tree, prior intrauterine hypoxia, birth asphyxia, and meconium aspiration. Prematurity, respiratory distress syndrome (RDS), and fetal hypoxia can cause functional, morphological, and immunological immaturity of the lung tissue, contributing to the development of the infectious process.

The disease develops as a result of transplacental transmission of the pathogen or via an ascending route, due to infection of the lungs upon entry of amniotic fluid (contaminated in endometritis, chorioamnionitis, etc.), as well as upon aspiration of infected birth canal contents (intrapartum route) [1,3]. The multiplication of bacteria or viruses in the distal airways and the associated inflammatory response lead to alveolar cell damage, which impairs gas exchange, alters pulmonary circulation, and hinders normal respiratory mechanics. Damage to the alveolar surface impedes surfactant action, may promote transudation of fluid from pulmonary vessels up to pulmonary edema, and ultimately leads to alveolar collapse. The accumulation of bacterial breakdown products and cellular elements (neutrophils, macrophages) in the airways and lung tissue, combined with smooth muscle contraction induced by inflammatory mediators, impairs effective ventilation and contributes to the development of atelectasis, "air trapping," and subsequent ventilation-perfusion mismatch. Inflammatory procoagulants and vasoconstrictors released by activated endothelial cells and platelets increase pulmonary vascular resistance, causing elevated pulmonary artery pressure. Surfactant deficiency is exacerbated [8,9]. These changes lead to the occurrence of postnatal hypercapnia, hypoxemia, mixed acidosis, and hypoxia. As a result of progressive hypoxia, acidosis, and microcirculatory disorders, multiple organ dysfunction syndrome develops very rapidly—initially cardiopulmonary, and subsequently involving other organs.

1.3 Epidemiology of the Disease or Condition

In world literature, there is practically no data on the isolated incidence of congenital pneumonia. This disease is part of the concept of early-onset neonatal sepsis, the incidence of which ranges from 0.17 to 1.19 per 1000 live births in economically developed countries, with a mortality rate of 10-15% [10–15].

According to official statistics in the Russian Federation for 2021, the incidence of congenital pneumonia is 0.85% of cases among term newborns and 10% among preterm infants with a birth weight of 1000 g or more; mortality is 0.7% and 0.92%, respectively. The detection rate of congenital pneumonia among extremely low birth weight infants is 26%, with a mortality rate exceeding 8.3% (Form No. 32 for 2021). In 2014, according to Rosstat data, congenital pneumonia was the underlying cause of death in 8.34% of cases in newborns during the first 6 days of life [16].

1.4 Features of Coding the Disease or Condition

P23 Congenital pneumonia

P23.0 Viral congenital pneumonia

P23.1 Chlamydial congenital pneumonia

P23.2 Staphylococcal congenital pneumonia

P23.3 Congenital pneumonia due to streptococcus group B

P23.4 Congenital pneumonia due to Escherichia coli

P23.5 Congenital pneumonia due to Pseudomonas

P23.6 Congenital pneumonia due to other bacterial agents

P23.8 Congenital pneumonia due to other organisms

P23.9 Congenital pneumonia, unspecified

In cases where pneumonia is one of the manifestations of a congenital generalized infection, the code for the corresponding infection is used – P35, P37. Pneumonia associated with early congenital syphilis is coded under A50.

1.5 Classification of the disease or condition

Congenital pneumonias are classified:

- by etiology: viral, bacterial (microbial), parasitic, fungal, mixed;

- by extent of involvement: focal, segmental, lobar, unilateral, bilateral;

- by severity: mild, moderate, severe;

- by course: with complications (pneumothorax, pleural effusion, pulmonary hypertension) or without complications.

1.6 Clinical presentation of the disease or condition

Early clinical symptoms of congenital pneumonia are nonspecific. Physical examination reveals signs of infectious toxicity: thermoregulation disorders (temperature instability (≥ 38.5⁰C or ≤ 36.0⁰C)), skin mottling, grayish skin color or skin pallor with perioral cyanosis and/or acrocyanosis, which increases with agitation or feeding, decreased tissue turgor, decreased or absent sucking reflex, refusal to feed, lethargy, muscle hypotonia, or conversely, increased neuroreflex excitability, tachycardia > 180 bpm or bradycardia less than 110 bpm, muffled heart sounds, abdominal distension; enteral feeding intolerance; signs of respiratory distress: decreased blood oxygen saturation; tachypnea > 60/min or apnea episodes (respiratory pause > 15–20 s or > 10 s with bradycardia); expiratory grunt; chest retractions; weakened breathing, localized fine crackles or crepitations in the lungs; decreased effectiveness of ongoing respiratory therapy, including an increase in mechanical ventilation parameters [1–3,7].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis of congenital pneumonia

To confirm the diagnosis, the presence of radiological changes (ultrasound or CT signs) and/or clinical and laboratory data is required (tables 1 and 2).

Main diagnostic criterion for congenital pneumonia:

Presence of infiltrative or focal shadows on the chest X-ray.

Comments: Radiological symptoms of congenital pneumonia lack the necessary specificity and are quite variable, making it difficult to draw conclusions about the etiological factor of the inflammatory process based solely on them. Bilateral lung tissue involvement is possible, usually manifested as a heterogeneous lung pattern—a combination of areas of lung tissue consolidation and compensatory increased aeration, pleural effusion is possible [17,18]. Heterogeneous changes in the pulmonary pattern combined with pleural effusion strongly suggest congenital pneumonia, primarily caused by group B Streptococcus [17,19]. Areas of lung tissue consolidation may be present. Pronounced consolidation limited to a single, isolated lobe is relatively rare in newborns [20]. Congenital pneumonia should be ruled out if new infiltrative shadows appear or if radiological changes persist for 48 hours after birth. Radiologically distinguishing respiratory distress syndrome from congenital pneumonia in preterm infants in the first 72 hours is difficult; therefore, potential radiological signs favoring congenital pneumonia in preterm infants compared to RDS may include the appearance of coarse and fine focal shadows against the background of a coarse reticular pulmonary pattern, accentuation of the pulmonary pattern in the perihilar zones, and a cardiothoracic index of less than 0.5 at 72 hours of life [3].

Auxiliary diagnostic criteria for congenital pneumonia:

The table below reflects general signs used for diagnosing sepsis and pneumonia in newborns and can be used as auxiliary diagnostic criteria for congenital pneumonia.

Table 1. Clinical and laboratory signs of the infectious process in infants with a postmenstrual age of less than 44 weeks:

Clinical signs of the infectious process
Respiratory disorders apnea episodes (respiratory pause > 15–20 s or > 10 s with bradycardia) [22] AND/OR episodes or persistent tachypnea (> 60, in preterm infants > 80 per min.) AND/OR expiratory grunt AND/OR increasing oxygen requirement need for respiratory therapy
Manifestations of cardiovascular failure bradycardia (mean HR less than 110 bpm) (in the absence of beta-blocker therapy or data for congenital heart disease) AND/OR tachycardia (mean HR over 180 bpm in the absence of external stimuli, prolonged medication, and pain stimuli) other cardiac arrhythmias arterial hypotension (mean arterial pressure less than the 5th percentile for gestational age) skin mottling centralization of circulation with impaired skin perfusion (capillary refill time > 3 seconds)
Altered body temperature body temperature less than 36.0°C or fever ≥ 38.5°C [20,21] AND/OR temperature instability
Manifestations of renal failure decreased urine output less than 0.5 ml/kg/h on the 1st day of life, less than 1 ml/kg/h at an age older than 1 day of life
Skin and subcutaneous tissue changes grayish skin color sclerema
Gastrointestinal manifestations enteral feeding intolerance abdominal distension weakened or absent bowel sounds on auscultation
Neurological manifestations lethargy hypotonia hyperesthesia excitability seizure syndrome
Manifestations of hemorrhagic syndrome petechial rash or ecchymoses gastric bleeding pulmonary hemorrhage gross hematuria bleeding from injection sites
Other manifestations presence of fluid in the pleural cavities (excluding extravasation from central venous catheters) early-onset jaundice hepatomegaly (in infants with birth weight > 1500 g – more than 2.5 cm along the midclavicular line, and more than 2 cm in infants < 1500 g), splenomegaly (in the absence of signs of hemolytic disease of the newborn) presence of other purulent-inflammatory foci in the infant during the first three days of life
Laboratory signs of the infectious process
White blood cell count leukopenia less than 5 * 109/l OR leukocytosis on days 1–2 of life greater than 30 * 109/l; on day 3 of life and later greater than 20 * 109/l;
Absolute neutrophil count neutrophilia greater than 20 * 109/l on days 1–2 of life; greater than 7 * 109/l on day 3 of life and later neutropenia [21,22]
Ratio of immature forms to the total neutrophil count (immature-to-total neutrophil ratio (I/T ratio)) greater than 0.2.
Neutrophil morphological abnormalities (investigated in doubtful cases) toxic granulation vacuolation appearance of Döhle bodies (basophilic cytoplasmic inclusions)
Thrombocytopenia in the first 3 days of life less than 123×109/L for infants ≥ 33 weeks of gestation; less than 104×109 /L for infants ≤ 32 weeks of gestation [23]
Elevated levels of laboratory markers of systemic inflammatory response syndrome (SIRS) C-reactive protein (CRP) in blood (the upper limit of normal for CRP is determined by the assay method and analyzer type used) Other SIRS markers accepted in a specific medical organization (procalcitonin [PCT] ≥ 2.5 ng/mL in the first 72 hours of life [24], presepsin [PSP], and other markers)
Metabolic acidosis: serum lactate greater than 2 mmol/L
Placental examination: placental findings such as deciduitis, villitis, funisitis, and infiltration of placental tissues may indirectly indicate the development of an infectious process in the newborn and serve as an additional factor in diagnosing neonatal pneumonia (depending on the level of the healthcare facility providing neonatal care)
Episodes of glucose intolerance registered at least twice (at an age-appropriate rate of glucose administration) hypoglycemia less than 2.6 mmol/L, hyperglycemia greater than 10 mmol/L

Criteria for the diagnosis of congenital pneumonia (Table 2).

Table 2. Criteria for the diagnosis of congenital pneumonia

The diagnosis is established in the presence of the main criterion (Column I).

If it is absent, a combination of auxiliary criteria is used with all 3 items present (Column II).

If laboratory signs of an ongoing infectious process are absent (item 3, Column II), additional criteria are used (Column III) – requiring the presence of 3 or more additional criteria.

2.1 Complaints and Anamnesis

Comments: Maternal risk factors for congenital pneumonia include:

- presence of an acute infection in the mother or exacerbation of a chronic one, especially within the 2 weeks prior to delivery;

- maternal laboratory findings before delivery: elevated CRP level, leukocytosis (excluding leukocytosis following recent administration of glucocorticoids [ATC code H02AB]);

- colonization of the maternal birth canal with group B Streptococcus (GBS);

- premature rupture of membranes, pre-labor rupture of amniotic membranes (PROM ≥ 18 hours);

- maternal fever during labor ≥ 38°C or higher lasting for more than 2 hours;

- signs of chorioamnionitis;

- intrauterine procedures during the current pregnancy;

- antibacterial therapy administered to the mother immediately before or during labor with beta-lactamase-resistant penicillins (J01CF Beta-lactamase-resistant penicillins) or systemic antibacterial drugs (ATC code J01) (reserve drugs);

- premature birth.

Maternal risk factors for congenital pneumonia specific to certain perinatal infections:

- maternal consumption of raw meat, raw eggs, raw milk, or contaminated vegetables and fruits, or contact with cat feces during pregnancy (Toxoplasma gondii);

- vaginal delivery in the presence of a primary maternal infection caused by herpes simplex virus type 1 or 2 (herpes simplex virus);

- seronegative mothers who develop a primary infection during pregnancy (cytomegalovirus) or reactivation of cytomegalovirus infection in seropositive pregnant women (see Clinical Guidelines "Congenital Cytomegalovirus Infection");

- maternal HIV infection;

- consumption of dairy and inadequately heat-treated products (Listeria monocytogenes);

- bacteriuria during pregnancy.

2.2 Physical Examination

• It is recommended that a newborn with respiratory disorders and suspected congenital pneumonia undergo a physical examination of the therapeutic type [1,3,8,39–41].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments: see section 1.6. Clinical Presentation.

In a newborn with respiratory disorders and suspected congenital pneumonia lung auscultation typically reveals diminished or harsh breath sounds, localized fine crackles, and crepitation; when foci coalesce, bronchial breath sounds may be heard. When breath sounds are diminished, crackles may be absent.

All described clinical manifestations are nonspecific and may be observed in newborn infants in the presence of other respiratory system diseases; therefore, risk factors for the realization of the infectious process in the neonate, as well as radiological and laboratory examinations, are of great importance in the diagnosis of congenital pneumonia.

Neonatal risk factors for the development of congenital pneumonia include prematurity, low birth weight, and male sex.

• It is recommended that a newborn with respiratory disorders undergo a visual examination for lung and bronchial diseases and auscultation for lung and bronchial diseases using the Silverman-Andersen score to assess the severity of respiratory distress and determine respiratory therapy tactics [42,43].

GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).

Comments: see Appendix G1.

2.3 Laboratory Diagnostics

• It is recommended that a newborn with suspected congenital pneumonia undergo a microbiological (culture) blood test for sterility and determination of microorganism susceptibility to antimicrobial chemotherapeutic agents to identify the pathogen and determine antimicrobial therapy tactics [8,32,44–46].

GCR CLEL 4Level of Evidence C (Level of Likelihood of Evidence – 4).

• It is recommended that a newborn with suspected congenital pneumonia in the event of tracheal intubation undergo a microbiological (culture) sputum test for aerobic and facultatively anaerobic microorganisms, sputum for fungi (yeast and mold), and determination of microorganism susceptibility to antimicrobial chemotherapeutic agents to identify the pathogen and determine antimicrobial therapy tactics [8,32,44,45].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

• In a newborn with suspected congenital pneumonia, it is recommended to perform a study of complete (clinical) blood count with differential white blood cell count and calculation of the neutrophil index to detect inflammatory changes, with a repeat study at 48–72 hours of age if the diagnosis of congenital pneumonia has not been established, and at the end of the course of antimicrobial therapy to decide on discontinuation or prolongation of antimicrobial therapy [14,45,47–52].

GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).

Comments: A high neutrophil index (NI) and low absolute neutrophil count are predictors of infection in neonates, mainly at an age of > 4 hours of life. The sensitivity of the absolute neutrophil count is 78%, specificity is 73%, NI sensitivity is 78%, and specificity is 75% [47–50].

• It is recommended that a newborn with suspected congenital pneumonia undergo a serum C-reactive protein (CRP) test to detect laboratory signs of a systemic inflammatory response, with a repeat test at 48–72 hours of age if a diagnosis of congenital pneumonia has not been established, and at the end of the course of antimicrobial therapy to decide on discontinuing or prolonging antimicrobial therapy [46,53–56].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1).

Comments: The upper limit of normal CRP values is determined by the method used and the type of analyzer in a specific medical organization.

CRP begins to be produced in the liver 4–6 hours after stimulation by an infectious agent and reaches its maximum peak at 36–48 hours. Studies have shown that determining CRP in the first 6–8 hours after birth has a low sensitivity of 35–50% and a high rate of false-positive results of 30% [57,58]. The optimal time for testing is considered to be 24–48 hours after birth; serial dynamic testing increases sensitivity to 74–98% and specificity to 71–94% [58–61]. An elevated CRP level is an early sign of bacterial infection in term infants, whereas such a correlation between its blood concentration in preterm infants and the presence of infectious pathology has not been definitively proven (sensitivity 68.5%, specificity 85.5%) [54]. An elevation in CRP levels in the first 24–48 hours after birth can also be influenced by noninfectious conditions of the newborn, such as trauma, ischemic tissue damage, and hemolysis [54,62].

It is also acceptable to additionally use other laboratory markers of systemic inflammatory response syndrome (SIRS), depending on the capabilities of the specific medical organization: blood presepsin level (soluble CD14) (sensitivity for early infection 81%–91%, specificity 60%–86%, AUC 0.76–0.94) [63,64], and blood procalcitonin level in accordance with the cutoff threshold depending on age (hours) after birth (minimum 2.5 ng/mL) (sensitivity 75%, specificity 83%) [24].

Combinations of various laboratory markers of SIRS increase the diagnostic capability of identifying an infectious state [65,66].

To decide on changing, prolonging, or discontinuing a course of antimicrobial therapy, C-reactive protein levels and, if available at the specific medical organization, procalcitonin levels should be used. Blood presepsin levels are not used to determine further tactics of antimicrobial therapy (discontinuation, change, prolongation of the course), but only for the early diagnosis of an infectious disease.

• In cases of prolonged hospital stay of the mother during the current pregnancy, repeated courses of antibacterial, hormonal, and/or cytotoxic therapy, presence of implanted organs or devices in the mother (artificial valves), as well as in the presence of risk factors for infection or clinical and/or laboratory signs of ongoing infection in the mother, for a newborn with suspected congenital pneumoniarecommendedselective determination of cytomegalovirus DNA (Cytomegalovirus), human herpesvirus type 6 DNA (HHV6), Toxoplasma DNA (Toxoplasma gondii), rubella virus RNA (Rubella virus) by PCR in peripheral and cord blood, quantitative assay, DNA determination Treponema pallidum, Chlamydia DNA (Chlamydia spp.), Streptococcus agalactiae (SGB),  Streptococcus pyogenes (SGA), Haemophilus influenzae DNA (Haemophilus influenzae), Mycobacterium tuberculosis DNA (Mycobacterium tuberculosis complex), varicella-zoster virus DNA (Varicella-Zoster virus) in blood by PCR, quantitative assay, herpes simplex virus types 1 and 2 DNA (Herpes simplex virus types 1, 2), Listeria DNA (Listeria monocytogenes), Pseudomonas aeruginosa, by PCR in blood, quantitative assay, molecular biological urine test for Ureaplasma (Ureaplasma spp.) with species identification, molecular biological test of upper respiratory tract discharge for Mycoplasma hominis (Mycoplasma hominis), molecular biological test of bronchoalveolar lavage fluid, sputum, endotracheal aspirate for methicillin-sensitive and methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus spp, molecular biological test of sputum, bronchoalveolar lavage fluid for cytomegalovirus (Cytomegalovirus) to identify causative agents of congenital pneumonia [1,8,67,68].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: performing a blood test by PCR depends on the technical capabilities of the medical organization's laboratory. If quantitative testing is not available, qualitative testing is permissible.

• It is recommended that a newborn with respiratory disorders undergo an acid-base balance and blood gas test, blood lactic acid level, and blood glucose level to assess hypoxia and metabolic disorders, with a repeat acid-base balance and blood gas test to determine further respiratory therapy tactics and parameter adjustments [8,69–75].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments: The frequency of testing depends on the clinical condition of the infant and the ongoing respiratory therapy. Determination of blood lactic acid levels depends on the technical capabilities and availability of the rapid laboratory.

2.4 Instrumental Diagnostics

• All newborns with respiratory disorders are recommended to undergo chest X-ray to assess lung tissue changes and diagnose congenital pneumonia [1,3,17,19,41,45,76,77].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments: see section Criteria for Establishing Diagnosis

• It is recommended that a newborn with respiratory disorders selectively undergo a targeted lung ultrasound examination to detect signs of pneumonia if a specialist proficient in this method is available [78–84].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: Ultrasound signs of pneumonia manifest as consolidation and dynamics of air bronchograms, B-lines, and pleural effusion; abnormal pleural lines and reduced lung sliding may also be noted [85]. Based on the results of meta-analyses, lung ultrasound is a more accurate method than X-ray examination [78,83,84].

Today, lung ultrasound is an affordable, noninvasive, and easily reproducible research method. Given the absence of ionizing radiation, it can be performed repeatedly directly at the patient's bedside. The sensitivity of lung ultrasound for pneumonia in newborns is 93%–100%, and specificity is 96%–100% [79–81].

Normally, lung tissue is not visible on ultrasound; only the echogenic pleural line with artifacts extending from it is visualized.

The main sign of pneumonia is consolidation.

In pneumonia, inflamed and edematous lung tissue, rich in fluid, becomes visible on ultrasound

1. Tissue-like sign

Upon consolidation, the lung resembles liver tissue on echograms ("hepatization" of the lung tissue);

2. Shred sign

In subpleural lesion localization, the superficial pleural border is smooth, while the lower border appears as a hyperechoic jagged line (delineating the consolidation zone from healthy aerated lung tissue);

3. Dynamic "air-bronchogram" – multiple small linear hyperechoic structures moving within the consolidation zone, representing residual air within the bronchioles;

4. "Fluid-bronchogram" – anechoic tubular structures representing fluid within or along the bronchioles. This sign is less common than the air-bronchogram.

Color Doppler mapping helps differentiate a fluid-bronchogram from pulmonary vessels.

B-lines can be detected during the exudation phase, but may also manifest in other respiratory pathological conditions.

Pleural effusion may occur in pneumonia [86].

• It is recommended that a newborn with congenital pneumonia undergoes echocardiography, neurosonography, complex abdominal ultrasound, and renal and adrenal ultrasound to detect complications of congenital pneumonia [87–98].

GCR BLEL 3Grade of Recommendation B (Level of Evidence – 3).

Comments: In case of concomitant disorders of various organs and systems, echocardiography (EchoCG), neurosonography (NSG), and ultrasound of the abdominal cavity, kidneys, and adrenal glands can contribute to the timely prescription and adjustment of symptomatic therapy.

• In a newborn with respiratory disorders and suspected congenital malformations, it is recommended to selectively perform computed tomography of the chest organs for differential diagnosis with congenital lung malformations, congenital surfactant protein deficiency, and other interstitial lung diseases [99–102].

GCR BLEL 1Grade of Recommendation B (Level of Evidence – 1) – for congenital lung malformations.

GCR CLEL 4Grade of Recommendation C (Level of Evidence – 4) – for congenital surfactant protein deficiencies and other interstitial lung diseases.

Comments: computed tomography depends on the technical capabilities of the medical institution.

Computed tomography may require anesthetic support (total intravenous anesthesia, combined inhalation anesthesia, or balanced anesthesia).

• In a newborn with congenital pneumonia presenting with cardiac abnormalities such as arrhythmia, pronounced bradycardia, or tachycardia, it is recommended to perform an electrocardiogram (ECG) to identify the nature of cardiac rhythm disturbances [103–106].

GCR CLEL 4Grade of Recommendation C (Level of Evidence – 4).

• In newborns with respiratory disorders, especially those requiring respiratory therapy, it is recommended to perform continuous bedside monitoring of vital functions and parameters (heart rate, respiratory rate, blood pressure, SpO₂, body temperature, diuresis) for the timely prescription of symptomatic and etiotropic therapy [105,107–119].

GCR BLEL 3Grade of Recommendation B (Level of Evidence – 3).

2.5 Other Procedures

Not used.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Treatment of congenital pneumonia includes:

- Etiotropic therapy – targeting the disease pathogen directly;

- Pathogenetic therapy – treatment of respiratory failure;

- Symptomatic therapy – correction of metabolic disorders and organ system failure.

Etiotropic therapy

• In a newborn with congenital pneumonia or suspected congenital pneumonia, it is recommended to prescribe systemic antimicrobials (ATC code J) for primary etiological treatment [120–122].

GCR ALEL 1Grade of Recommendation A (Level of Evidence – 1).

Comments: Antimicrobial therapy (AMT) for suspected congenital pneumonia should be initiated as early as possible after birth in the following categories of infants with respiratory disorders: extremely low birth weight (ELBW) and very low birth weight (VLBW) infants, as well as newborns requiring invasive respiratory therapy from birth. It is preferable to start AMT no later than 2 hours of life. The initial dose of the starting AMT regimen is administered simultaneously.

In newborns with a birth weight of more than 1500 g, AMT is prescribed when indicated based on the results of initial clinical and laboratory evaluations.

AMT initiated empirically on the first day of life is discontinued if clinical, laboratory, and instrumental findings do not confirm congenital pneumonia within 72 hours of life;

Once pneumonia is diagnosed, the empirical AMT regimen is continued for 7 days (the minimum course of AMT for congenital pneumonia), followed by a clinical and laboratory evaluation with monitoring of systemic inflammatory response syndrome (SIRS) markers to decide on discontinuing or intensifying AMT. If signs of AMT failure persist after 72 hours of life, switching the AMT regimen should be considered.

Upon normalization of SIRS laboratory markers and the complete blood count, AMT is discontinued.

The duration and strategy of antimicrobial therapy are determined on an individual basis, depending on the severity of the child's condition and the normalization of clinical and laboratory data. Persistence of residual radiological changes such as enhanced bronchovascular markings and hypoventilation areas, in the presence of normalized clinical and laboratory findings, is not an indication to continue therapy.

AMT is carried out in accordance with local protocols adopted in the specific medical institution.

Starting AMT regimens (Appendix A3.2) [121,123–125]:

Regimen A: empirical AMT combining broad-spectrum penicillins (ATC code J01CA) (ampicillin**) and other aminoglycosides (ATC code J01GB) (#gentamicin**, amikacin**, netilmicin) [121,123–125]. In case of renal impairment, the discontinuation of other aminoglycosides (ATC code J01CA) should be considered on an individual basis, taking into account the patient's medical history, laboratory, and microbiological findings. Continuation of AMT with a combination of penicillins, including beta-lactamase inhibitor combinations (ATC code J01CR) (Ampicillin+[Sulbactam]**), is acceptable.

Regimen B: provides antimicrobial therapy to newborns whose mothers have a history of risk factors such as chorioamnionitis, intrauterine interventions, prolonged rupture of membranes (more than 18 hours), elevated CRP, intrapartum fever lasting more than 2 hours, maternal AMT immediately before and during delivery, using a combination of penicillins, including beta-lactamase inhibitor combinations (ATC code J01CR) or other beta-lactam antibacterials (ATC code J01D), or group B Streptococcus isolated from the cervical canal. It is advisable to use a combination of penicillins, including beta-lactamase inhibitor combinations (ATC code J01CR) (Ampicillin+[Sulbactam]**) and other aminoglycosides (ATC code J01GB) (#gentamicin**, amikacin**, netilmicin).

Preference is given to parenteral administration of systemic antimicrobial drugs (ATC code J) (intravenous drug administration). It is not recommended to prescribe drugs containing amoxicillin+[clavulanic acid]** (ATC code J01CR) due to the potential adverse effects of clavulanic acid on the intestinal wall, especially in premature newborns. It is inappropriate to include 1st (ATC code J01DB), 2nd (ATC code J01DC), 3rd (ATC code J01DD), and 4th (ATC code J01DE) generation cephalosporins in the starting antimicrobial therapy regimen instead of broad-spectrum penicillins (ATC code J01CA) due to the lack of activity against Listeria monocytogenes and Enterococcus spp., as well as the risk of necrotizing enterocolitis (NEC) and invasive candidiasis in ELBW newborns [126].

Regimen C: targeted antimicrobial therapy.

Targeted antimicrobial therapy is used if the mother has flora resistant to the drugs in initial antimicrobial regimens "A" and "B" and/or after obtaining laboratory tests of the newborn determining the susceptibility of microorganisms to systemic antimicrobial drugs (ATX code J01) [32]. If the isolated pathogens are not susceptible to the initial regimen drugs, it is necessary to switch to systemic antimicrobial drugs (ATX code J) to which susceptibility has been identified. Over the past decade, the incidence of flora resistant to the initial antibacterial therapy regimen as a cause of early-onset neonatal sepsis—including lung involvement (pneumonia)—has increased. This has prompted the revision of local protocols in foreign clinics to include systemic antibacterial drugs (ATX code J01) in the initial antibacterial therapy targeting resistant gram-positive and gram-negative flora if identified in the mother or newborn (vancomycin** (ATX code J01XA), linezolid** (ATX code J01XX), 3rd-generation cephalosporins (ATX code J01DD), carbapenems (ATX code J01DH)) [122,127–134]. (Appendix A3.2.)

If atypical pathogens of congenital pneumonia (Chlamydia trachomatis, Ureaplasma spp., Mycoplasma spp.) are identified, antibacterial therapy is carried out with macrolides (ATX code J01FA), for example, erythromycin (ATX code J01FA01) [1,135].

In cases of invasive candidiasis caused by Candida albicans fungal flora, therapy is carried out with a systemic antifungal drug from the triazole derivative group (ATX code J02AC)—fluconazole** at a dose of 12 mg/kg/day. If invasive candidiasis caused by Candida non-albicans or fluconazole-resistant** Candida albicans fungal flora (ATX code J02AC) is detected, therapy is carried out with another systemic antifungal drug (ATX code J02AX)—micafungin** at an initial dose of 4 mg/kg/day.

Doses of systemic antibacterial drugs (ATX code J01) are presented in Appendix A3.2.

• In a newborn with viral pneumonia, it is recommended to prescribe antiviral therapy depending on the identified pathogen using direct-acting antiviral drugs (ATX code J05A) of the nucleoside and nucleotide group, excluding reverse transcriptase inhibitors (ATX code J05AB) (#ganciclovir**, #valganciclovir**, acyclovir**) for primary etiotropic treatment and reduction of adverse neurological outcomes [136–139].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2) – for cytomegalovirus.

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4) – for herpes viruses.

Comments: Treatment of cytomegalovirus pneumonia is carried out in accordance with the clinical guidelines "Congenital cytomegalovirus infection". The duration of treatment is 6 months. #Ganciclovir** (ATX code J05AB) is prescribed at a single dose of 6 mg/kg 2 times a day by continuous intravenous infusion, followed by a switch to #valganciclovir** (ATX code J05AB) at a single dose of 16 mg/kg 2 times a day orally [136,137].

Congenital pneumonia caused by human herpesvirus type 6 is extremely rare. Based on cases presented in the literature, treatment is carried out with #ganciclovir** (ATX code J05AB), which is prescribed at a single dose of 6 mg/kg 2 times for a duration of 1 month [138].

Treatment of congenital pneumonia caused by herpes simplex virus is carried out with acyclovir** (ATX code J05AB) at a single dose of 20 mg/kg every 8 hours, with a course duration of 21 days [139].

Pathogenetically substantiated intensive care

• Preterm infants with congenital pneumonia and respiratory disorders are recommended selective administration of pulmonary surfactant preparations (ATX code R07AA)—natural phospholipids (ATX code R07AA02)—according to indications, regardless of birth weight, to improve alveolar respiration, reduce the need for respiratory support, and reduce oxygen demand [140–146].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: Pulmonary surfactants (ATX code R07AA)—natural phospholipids (ATX code R07AA02)—poractant alfa**, beractant**, alveofact can be used in newborns with congenital pneumonia with an increasing need for supplemental oxygen supply and intensification of ongoing respiratory therapy. According to several studies, surfactant therapy improves gas exchange in the majority of patients with pneumonia, but the response is slower than in newborns with RDS. A single administration of pulmonary surfactant (ATX code R07AA)—natural phospholipids (ATX code R07AA02)—to newborns with congenital pneumonia is less effective; a large number of children with congenital pneumonia require repeated administration of pulmonary surfactant (ATX code R07AA) [147–151]. Administration of pulmonary surfactants (ATX code R07AA) is contraindicated in air leak syndrome or profuse pulmonary hemorrhage (administration is possible after cessation of hemorrhage or pneumothorax if indicated).

Administration of pulmonary surfactants (ATX code R07AA)—natural phospholipids (ATX code R07AA02)—dose, route, and method of administration should be carried out in accordance with the drug instructions.

• Newborns with congenital pneumonia and oxygen dependency are recommended to undergo non-invasive mechanical ventilation (NIPPV, CPAP) for the treatment of respiratory failure and the prevention of lung injury [146,152–156].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

• Newborns with respiratory disorders, in whom non-invasive mechanical ventilation (NIPPV, CPAP) has proven ineffective, are recommended to undergo invasive mechanical ventilation (including high-frequency oscillatory ventilation) for the treatment of respiratory failure [117,146,157–159].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: The duration of invasive mechanical ventilation should be minimized. Mechanical ventilation should be performed with tidal volume control, which shortens its duration and reduces the incidence of complications such as BPD and IVH [160–162]. A prerequisite for the successful use of this type of respiratory therapy in newborns is the ability to regularly monitor blood gas composition. Newborns on mechanical ventilation undergo selective sedation and analgesia when necessary [163].

The ineffectiveness of conventional mechanical ventilation is an indication for transfer to high-frequency (oscillatory) ventilation (HFOV). During HFOV, due to the stabilization of alveolar volume, there is a reduction in atelectasis, an increase in the gas exchange area, and an improvement in pulmonary blood flow. As a result of properly conducted respiratory therapy, the ventilation-perfusion ratio becomes adequate, leading to improved pulmonary gas exchange.

Symptomatic therapy

Symptomatic therapy includes the prescription of medications depending on the clinical manifestations of the infectious disease course (antihemorrhagic, hemostatic, anticonvulsant, sedative, cardiotonic, vasopressor, infusion therapy).

3.2 Surgical Treatment

Not applicable.

3.3 Other Treatment

The therapeutic and protective regimen involves creating optimal conditions for nursing newborns.

- The child is shown a thermoneutral environment, restriction of sensory stimulation (protection from light, noise, touch), postural support, and pain prevention;

- The child is shown adequate enteral and, if necessary, parenteral nutrition. Preference in enteral feeding is given to breast milk. In case of insufficient lactation or contraindications to breastfeeding on the part of the mother, the newborn is fed with a dry adapted milk formula for feeding infants from birth or a dry/ready-made special milk formula for feeding premature and low-birth-weight infants.

• A newborn infant with congenital pneumonia is recommended selective administration of infusion therapy and parenteral nutrition to provide fluids and electrolytes, supply proteins, fats, and carbohydrates based on physiological requirements and pathological losses, and maintain the body's water-electrolyte balance [164–170].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: Parenteral nutrition is carried out with parenteral nutrition solutions (ATX code B05BA) if it is impossible to deliver the level of protein, fat, carbohydrate, electrolyte requirements and fluid volume necessary for gestational age via enteral nutrition. Requirements for fluids, proteins, fats, carbohydrates, and electrolytes depending on gestational age and birth weight are specified in Appendix A3.3. For parenteral nutrition, the following are used: amino acids for parenteral nutrition (ATX code B05BA01), lipid emulsions for parenteral nutrition (ATX code B05BA02), carbohydrates (ATX code B05BA03), electrolyte solutions (ATX code B05XA), calcium preparations (ATX code A12AA).

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation is carried out depending on concomitant pathology and complications by specialized professionals (neurologist, ophthalmologist, pulmonologist, etc.).

5. Prevention and Dispensary Observation

Prevention of congenital pneumonia consists in the timely detection and treatment of infectious diseases in the mother during pregnancy [171,172]. Compliance with the sanitary and anti-epidemic regime in obstetric healthcare organizations is mandatory.

6. Organization of Medical Care

Treatment of newborns with congenital pneumonia is carried out in an inpatient setting. If clinical signs of congenital pneumonia develop, the newborn is subject to transfer to the neonatal intensive care unit (NICU) / intensive care ward or to the department of pathology of newborns and premature infants, depending on the severity of the condition and the degree of respiratory failure.

Indications for discharging a patient from a medical organization:

1) Stabilization of the child's condition is achieved, there are no signs of respiratory failure, and inflammatory changes on the chest X-ray are absent;

2) Normalization of laboratory markers of systemic inflammatory response syndrome (SIRS);

3) There are no other contraindications to discharge.

7. Additional Information

The prognosis of the disease in the absence of concomitant conditions is generally favorable.

In extremely premature infants who have suffered from congenital pneumonia, the risk of developing bronchopulmonary dysplasia increases.

Differential diagnosis of congenital pneumonia is carried out with the following diseases and conditions:

- Transient tachypnea of the newborn;

- Neonatal respiratory distress syndrome;

- Neonatal meconium aspiration;

- Other types of aspiration (blood, milk);

- Air leak syndrome;

- Persistent pulmonary hypertension of the newborn;

- Congenital malformations of the lungs (congenital airway malformation [formerly known as congenital cystic adenomatoid malformation, cystic hypoplasia of the lungs], aplasia, hypoplasia of the lungs, etc.);

- Congenital diaphragmatic hernia;

- Congenital heart defects;

- Interstitial lung diseases;

- Other causes of respiratory disorders of extrapulmonary origin.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Irina V. Andreyeva – PhD in Medical Sciences, Associate Professor, Senior Researcher at the Research Institute of Antimicrobial Chemotherapy, Smolensk State Medical University of the Russian Ministry of Health, Smolensk, member of the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (MACMA)

2. Elena N. Baibarina – MD, Professor, Honored Scientist of the Russian Federation, Chief Researcher at the Department of Pathology of Newborns and Premature Infants, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, member of the Council of the Russian Society of Neonatologists

3. Ekaterina N. Balashova – PhD in Medical Sciences, Leading Researcher at the Prof. A.G. Antonov NICU of the Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Associate Professor at the Department of Neonatology, Institute of Professional Education, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, member of the Council of the Russian Society of Neonatologists

4. Irina A. Belyaeva – MD, Head of the Department of Preconceptional, Antenatal and Neonatal Medicine, Research Institute of Pediatrics and Child Health, Academician V.I. Petrovsky National Medical Research Center of Surgery, Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, member of the Union of Pediatrists of Russia, Honorary Professor of the Russian Association of Perinatal Medicine Specialists

5. Evgenia V. Boytsova – MD, PhD, Professor, Leading Researcher, Department of Therapeutic Pulmonology, Research Institute of Pulmonology, First Saint Petersburg State Medical University named after acad. I.P. Pavlov

6. Nikolay N. Volodin – MD, PhD, Professor, Academician of the Russian Academy of Sciences, President of the Association of Specialists in Perinatal Medicine, Care for Pregnant Women, Fetuses, Newborns, and Children Under 3 Years of Age (ASPM+)

7. Dmitry N. Degtyarev – MD, PhD, Professor, Deputy Director for Research, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Head of the Department of Neonatology, Pediatric Faculty, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University); Member of the Council of the Russian Society of Neonatologists

8. Viktor V. Zubkov – MD, PhD, Director of the Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Head of the Department of Neonatology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Professor, Department of Neonatology, N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University); Member of the Council of the Russian Society of Neonatologists

9. Oleg V. Ionov – MD, PhD, Head of the Prof. A.G. Antonov ICU, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Professor, Department of Neonatology, N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University); President of the Russian Society of Neonatologists

10. Anna L. Karpova – MD, PhD, Head of the Neonatal Inpatient Unit, City Clinical Hospital No. 67 named after L.A. Vorokhobov of the Moscow Healthcare Department; Associate Professor, Professor V.V. Gavryushov Department of Neonatology, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health; Assistant Professor, Department of Outpatient Therapy, Clinical Laboratory Diagnostics, and Medical Biochemistry, Institute of Professional Development, Yaroslavl State Medical University of the Russian Ministry of Health; Member of the Council of the Russian Society of Neonatologists.

11. Anna R. Kirtbaya – MD, PhD, Head of Clinical Work, Prof. A.G. Antonov ICU, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Professor, Department of Neonatology, N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University); Member of the Russian Society of Neonatologists

12. Roman S. Kozlov – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Rector of Smolensk State Medical University of the Russian Ministry of Health; Honored Worker of Science of the Russian Federation; Chief freelance specialist in clinical microbiology and antimicrobial resistance of the Russian Ministry of Health; President of the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (MACMAH)

13. Daria S. Kryuchko – MD, PhD, Professor, Department of Neonatology, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Member of the Council of the Russian Society of Neonatologists

14. Anna A. Lenyushkina – MD, PhD, Head of Clinical Work, ICU No. 2, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Member of the Council of the Russian Society of Neonatologists.

15. Lyudmila V. Malyutina – MD, PhD, Associate Professor, Department of Neonatology, Moscow Regional Research Clinical Institute named after M.F. Vladimirsky; Member of the Council of the Russian Society of Neonatologists.

16. Inessa I. Mebelova – Deputy Chief Physician for Neonatology, Republican Perinatal Center named after K.A. Gutkin; Chief freelance specialist in neonatology of the Ministry of Health of the Republic of Karelia; Member of the Council of the Russian Society of Neonatologists

17. Aleksey V. Mostovoy – MD, PhD, Head of the Resuscitation and Intensive Care Service, City Clinical Hospital No. 67 named after L.A. Vorokhobov of the Moscow Healthcare Department; Associate Professor, Professor V.V. Gavryushov Department of Neonatology, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health; Assistant Professor, Department of Outpatient Therapy, Clinical Laboratory Diagnostics, and Medical Biochemistry, Institute of Professional Development, Yaroslavl State Medical University of the Russian Ministry of Health; Chief freelance neonatologist of the Russian Ministry of Health in the North Caucasian Federal District; Member of the Council of the Russian Society of Neonatologists

18. Leyla S. Namazova-Baranova – MD, PhD, Professor, Academician of the Russian Academy of Sciences, President of the Union of Pediatricians of Russia; Past President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health, National Medical Research Center No. 2 of the B.V. Petrovsky Russian National Research Center of Surgery; Head of the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health; Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health

19. Irina V. Nikitina – MD, PhD, Leading Researcher, ICU No. 2, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Head of Studies, Professor of the Department of Neonatology, Institute of Professional Education, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov; Member of the Russian Society of Neonatologists

20. Dmitry Yu. Ovsyannikov – MD, PhD, Professor, Head of the Department of Pediatrics, Peoples' Friendship University of Russia named after Patrice Lumumba

21. Tatiana V. Priputnevich – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Director of the Institute of Microbiology, Antimicrobial Therapy, and Epidemiology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Moscow; Professor, Department of Microbiology and Virology, Pediatric Faculty, Pirogov Russian National Research Medical University; Chief freelance specialist in medical microbiology of the Russian Ministry of Health.

22. Vladislav A. Romanenko – MD, PhD, Professor, Honored Doctor of the Russian Federation, Diplomate of the European Academy of Natural Sciences, Chairman of the Chelyabinsk Regional Branch of the Russian Society of Neonatologists.

23. Andrey Yu. Ryndin – PhD in Medical Sciences, Senior Researcher at the Prof. A.G. Antonov ICU, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Associate Professor at the Department of Neonatology, N.F. Filatov Clinical Institute of Children's Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Member of the Russian Society of Neonatologists.

24. Irina I. Ryumina – MD, PhD, Professor, Head of the Department of Pathology of Newborns and Premature Infants, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Member of the Russian Society of Neonatologists.

25. Liliya R. Selimzyanova – MD, PhD, Leading Researcher, Research Institute of Pediatrics and Child Health, National Medical Research Center No. 2 of the B.V. Petrovsky Russian National Research Center of Surgery; Associate Professor, Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University); Associate Professor, Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health; Member of the Union of Pediatricians of Russia

26. Tatiana V. Turti – MD, PhD, Chief Researcher, Department of Preconceptional, Antenatal, and Neonatal Medicine, Research Institute of Pediatrics and Child Health, National Medical Research Center No. 2 of the B.V. Petrovsky Russian National Research Center of Surgery; Professor, Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health; Member of the Union of Pediatricians of Russia

27. Elena A. Filippova – PhD in Medical Sciences, Head of the Department of Ultrasound Diagnostics in Neonatology and Pediatrics, Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Member of the Russian Society of Neonatologists.

No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Methods used for collecting/selecting evidence: electronic database search.

Description of methods used for evidence collection/selection: The evidence base for the recommendations included publications from the Cochrane Library, PubMed, EMBASE, MEDLINE, Scopus, Web of Science, eLIBRARY, clinicaltrials.gov, electronic libraries, and clinical guidelines published by the National Institute for Health and Care Excellence, The European Association of Perinatal Medicine, The European Society for Pediatric Research, The European Foundation for the Care of Newborn Infants, and The European Society for Neonatology. The search depth was 68 years.

Methods used for assessing the quality and strength of evidence:

• expert consensus;

• assessment of significance in accordance with the rating scheme.

Scales for assessing levels of evidence (LE) (Tables 1, 2) for diagnostic, preventive, therapeutic, and rehabilitation methods (diagnostic, preventive, therapeutic, rehabilitation interventions) with definitions, and the scale for assessing grades of recommendation (GR) (Table 3) for preventive, diagnostic, therapeutic, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions).

Methods used for analyzing evidence:

• reviews of published meta-analyses;

• systematic reviews with evidence tables.

Description of methods used for analysis of evidence.

When selecting publications as potential sources of evidence, the methodology used in each study was reviewed to ensure its validity. Methodological evaluation was based on questions focused on study design features that significantly affect the validity of the results and conclusions.

To minimize potential subjective errors, each study was evaluated independently by at least two members of the working group. Any discrepancies in assessments were discussed by the full working group. If consensus could not be reached, an independent expert was involved.

Economic analysis:

Cost analysis was not performed, and pharmacoeconomic publications were not evaluated.

Method of guidelines validation:

• external expert review;

• internal expert review.

Description of the guidelines validation method:

The preliminary version of these guidelines was reviewed by independent experts who were asked to comment primarily on whether the interpretation of the evidence underlying the recommendations was accessible and understandable.

Comments were received from primary care physicians and district pediatricians regarding the clarity of the presentation of the guidelines and their assessment of the importance of the guidelines as a working tool in daily practice.

The draft version was also sent to a non-medically trained reviewer to obtain comments from a patient perspective.

Comments received from experts were carefully systematized and discussed by the chair and members of the working group. Each point was discussed, and resulting modifications to the guidelines were recorded. If no changes were made, the reasons for declining the changes were recorded.

Consultation and peer review:

Recent changes in these recommendations are presented as a draft for discussion. An updated version for broad discussion was posted on the website of the Russian Society of Neonatologists (RSN) www.neonatology.pro, the Association of Specialists in Perinatal Medicine, Care for Pregnant Women, Fetuses, Newborns, and Children Under 3 Years of Age (ASPM+) www.raspm.ru, and the public discussion portal of the Russian Ministry of Health https://portalcr.minzdrav.gov.ru/ to ensure that all interested parties have the opportunity to participate in discussing and improving the recommendations.

The draft guidelines were reviewed by independent experts who were asked to comment primarily on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.

Target audience for these clinical guidelines:

1. Pediatricians,

2. Neonatologists;

3. Anesthesiologists-intensivists;

4. Pulmonologists;

5. General practitioners (family physicians);

6. Medical students;

7. Residents and interns.

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for methods of prevention, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Scale for assessing the grades of recommendation (GR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Appendix A3.1 Related Documents

These clinical guidelines were developed taking into account the following regulatory legal documents and electronic resources:

1. Federal Law No. 323-FZ "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" dated November 21, 2011.

2. Order of the Russian Ministry of Health No. 203n of May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care."

3. International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) (World Health Organization), 2019 version.

4. Order of the Ministry of Health of Russia No. 804n dated October 13, 2017 (as amended on September 24, 2020, with amendments dated October 26, 2022) "On Approval of the Nomenclature of Medical Services" (Registered with the Ministry of Justice of Russia on November 7, 2017, No. 48808).

5. Rules for the provision of medical care in the specialty "Neonatology" (Order of the Ministry of Health of the Russian Federation No. 921n dated November 15, 2012).

6. Order of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on April 16, 2024) "On Approval of the List of Vital and Essential Drugs, as Well as Lists of Drugs for Medical Use and the Minimum Assortment of Drugs Necessary for the Provision of Medical Care".

7. Methodological Letter of the Ministry of Health of the Russian Federation No. 15-4/I/2-2570 dated March 4, 2020, "Resuscitation and Stabilization of Newborn Infants in the Delivery Room." Edited by E.N. Baybarina. Moscow: Ministry of Health of the Russian Federation; 2020.

8. State Register of Medicinal Products: https://grls.rosminzdrav.ru

Appendix A3.2 Antibacterial therapy

The doses, frequency, and routes of administration of systemic antibacterial drugs used (ATC code J01) in newborns are presented in accordance with the drug instructions or literature data in the case of off-label drugs.

Appendix A3.2.1. Rational antibiotic therapy. Drug dosing regimens.

When prescribing systemic antimicrobial agents (ATC code J), follow the manufacturer's product insert. Dosage regimens and routes of administration may vary between manufacturers!

Appendix A3.3 Fluid, energy, protein, fat, carbohydrate, and electrolyte requirements of the newborn.

Appendix A3.3.1. Approximate fluid requirements in newborns (mL/kg/day) [169].

Appendix A3.3.2. Recommended nutrient doses in total parenteral nutrition [166,168,170].

Calorie provision [167].

The initial recommended energy (E) range is 40 to 60 kcal/kg/day (energy equal to resting energy expenditure). The recommended target total energy value of TPN (amino acids + carbohydrates + fats) is 90–120 kcal/kg/day for preterm infants and 85–100 kcal/kg/day for full-term infants.

• 1 g of protein – 4 kcal

• 1 g of carbohydrates = 4 kcal

• 1 g of fat – 9.25-10 kcal

Appendix A.3.3.3. Daily requirement for electrolytes (potassium, sodium, calcium, phosphorus, and magnesium) during total parenteral nutrition [165].

* – start after establishing diuresis

** – doses are indicated with adequate phosphorus supply; if phosphorus is absent, the calcium dose is reduced by 2–4 times (0.4–0.7 mmol/kg) and prescribed with monitoring of blood calcium levels in the child

*** – in the first days of life, rule out hypermagnesemia if the mother received magnesium sulfate** (ATC code B05XA) before delivery

Appendix B. Physician Action Algorithms

Diagram

Appendix C. Patient Information

Congenital pneumonia in newborns is a disease caused by pathogenic microorganisms. Infection occurs in utero. In some cases, the infection enters the child's body during childbirth.

The most common causative agents of congenital pneumonia are group B Streptococcus and Escherichia coli. An adult has a strong immune system, so it often happens that these microbes, while present in the mother's body, cause no apparent harm to her and do not cause distinct symptoms of any disease. That is why the birth of a sick baby often comes as a complete surprise to the family. The fetus and newborn are much more susceptible to infection due to the immaturity of the immune system. Congenital pneumonia in a newborn can be triggered even by sources of infection that the mother may not notice or feel, such as chronic urinary tract infections, which are particularly dangerous.

Symptoms of congenital pneumonia usually appear already in the delivery room or in the first hours of life; however, the Apgar score may be high, and the baby's behavior and condition immediately after birth may seem completely normal—this is due to the effect of birth stress. However, upon dynamic observation, such doctors quickly catch the neonatologist's attention with loud grunting respiration, shortness of breath, and cyanosis (bluish skin discoloration). Subsequently, they may require observation in an intensive care unit, placement in an incubator, supplemental oxygen, or even mechanical ventilation.

Feeding of a preterm infant with congenital pneumonia is performed via a gastric tube, since their reflexes are sluggish and they lack the strength to suck independently. The baby's body temperature is unstable, can be either above or below normal, and cools rapidly outside the incubator. Preterm infants with congenital pneumonia require a long time for treatment and recovery, as fighting an infection while dealing with immaturity is a difficult task.

In the recent past, congenital pneumonia was accompanied by a high mortality rate. Modern medicine in most cases allows for the timely detection and cure of this disease. It is very important to maintain a positive attitude and support breastfeeding—these two factors are the key to success.

After discharge from the hospital, it is very important to continue regular follow-up with the district pediatrician, follow their recommendations, continue breastfeeding, and under no circumstances refuse routine vaccinations.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Respiratory Distress Scoring Scale

Russian title: Silverman-Andersen Respiratory Severity Score

Original title: The Silverman Andersen respiratory severity score

Source (official developer website, validation publication):

 Silverman W.A., Andersen D.H. A controlled clinical trial of effects of water mist on obstructive respiratory signs, death rate and necropsy findings among premature infants. Pediatrics. 1956;17(1):1-10.[187]

Type: rating scale

Purpose: assessment of respiratory disorders

Content (template) [25,42,43].

Key (interpretation) and explanations:

When assessing respiratory failure using the Silverman-Andersen score, points are calculated depending on clinical manifestations:

• A score of 0 indicates the absence of respiratory distress syndrome (RDS);

• A score of 1 to 3 indicates initial signs of RDS;

• A score of 4–5 indicates moderate RDS (indication for advancing to the next level of respiratory support);

• A total score of 6 or more in newborns indicates severe RDS.

A score of 1–3 indicates a compensated condition of the infant against the background of ongoing therapeutic measures.

A score of 4 or more indicates ineffectiveness of respiratory support and requires stepping up intensive respiratory therapy (switching from CPAP to non-invasive ventilation, and in case of insufficient efficacy of non-invasive ventilation, switching to conventional mechanical ventilation).

An increase in the severity of respiratory failure assessed by the Silverman-Andersen score, along with an increased oxygen requirement in the infant, may serve as an indication for surfactant replacement therapy.