List of Abbreviations
BiPAP / Biphasic / DuoPAP – a method of non-invasive respiratory therapy involving the creation of two levels of continuous positive airway pressure.
DLP – Double Lung Point – ultrasound sign "double lung point".
HFNC – High Frequency Nasal Cannula – high-frequency nasal cannula - single-use nasal cannula for high-flow oxygen therapy.
FiO2 – Fraction of inspired oxygen – oxygen concentration in the air-oxygen mixture.
NCPAP – Nasal Continuous Positive Airway Pressure – a method of respiratory therapy based on creating continuous positive airway pressure using specialized nasal interfaces (single-use nasal oxygen cannulas or nasal masks for CPAP/BPAP mechanical ventilation devices).
NHFOV – Nasal High-Frequency Oscillatory Ventilation – nasal high-frequency oscillatory ventilation.
NIPPV – Nasal Intermittent Positive Pressure Ventilation – nasal intermittent positive pressure ventilation.
SpO2 – blood oxygen saturation index.
HFNC – High Frequency Nasal Cannula – single-use nasal cannula for high-flow oxygen therapy.
GA – gestational age.
IMV – artificial lung ventilation.
ABB – acid-base balance of blood.
NI – neutrophil index.
NICU – neonatal intensive care unit.
CRP – C-reactive protein.
TTN – transient tachypnea of the newborn.
US – ultrasound examination.
Terms and Definitions
Respiratory disorders constitute a complex of clinical symptoms that arise during the establishment of postnatal external respiration, including those characterizing respiratory distress in newborns [1], [2].
Respiratory failure is the inability of the respiratory system to maintain normal blood gas composition, or maintaining it through the extreme strain of compensatory mechanisms [1], [2].
Prematurity – birth of an infant before 37 completed weeks of pregnancy. Depending on gestational age, preterm newborns are categorized as extremely preterm (< 28 weeks of gestation), very preterm (28–31 weeks of gestation), moderately preterm (32–33 weeks of gestation), and late preterm.
Late preterm infants – newborns born between 34 weeks and 6 weeks 6 days of gestation (from 239th to 259th day of gestation).
Tachypnea in a newborn is an increase in the respiratory rate of more than 60 breaths per minute.
Transient tachypnea of the newborn is a parenchymal lung disease characterized by transient pulmonary edema due to delayed resorption of fetal lung fluid [3–5].
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Transient tachypnea of the newborn is a parenchymal lung disease characterized by transient pulmonary edema due to delayed resorption of fetal lung fluid [3–5].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The development of the disease is associated with impaired resorption of alveolar fetal fluid, which normally begins a few days before the onset of labor and continues during labor and after birth [6], [7]. During intrauterine development, type II alveolar epithelial cells (type II pneumocytes) actively secrete chloride ions, followed by sodium ions and water into the alveolar lumen, ensuring the production of alveolar fluid necessary for normal growth and development of the fetal lungs [8]. An increase in catecholamine and thyroid hormone levels in late gestation and with the onset of labor leads to the activation of sodium channels on the apical surface of type II alveolar epithelial cells, shifting the function of pneumocytes from secretion to resorption of alveolar fluid [9], [10]. Chloride ion production ceases, and sodium begins to actively move from the alveolar lumen into the interstitium. Following sodium ions, there is a passive movement of water, which is reabsorbed into the lesser circulation and lymphatic vessels. After birth, an increase in the partial pressure of oxygen enhances the expression of sodium channel genes, accelerating the triggered process of fetal fluid reabsorption. Passive clearance of alveolar fluid also occurs due to the oncotic pressure gradient between the alveolar space, interstitium, and blood through aquaporin channels in type I pneumocytes (AQP4 and AQP5). Mechanical pressure exerted on the fetus during vaginal delivery also contributes to the clearance of alveolar fluid.
When any of these mechanisms are impaired, fetal fluid accumulates in the alveoli, pulmonary interstitium, and interlobar spaces, significantly reducing lung compliance. The retention of fluid in the alveoli prevents normal ventilation, leads to decreased gas exchange, impaired ventilation-perfusion ratio, and increased pulmonary vascular resistance. Accumulation of fluid in peribronchial lymphatic vessels and interstitium can lead to partial collapse of bronchioles and subsequent air trapping.
Risk factors:
Complicated maternal medical history: TTN develops 2–3 times more frequently in newborns of mothers with diabetes mellitus, bronchial asthma, and/or obesity [11–13].
Pregnancy course and delivery characteristics: arterial hypertension during pregnancy, absence of antenatal corticosteroid prophylaxis, preterm birth, cesarean section [14–17].
Male sex – the incidence of TTN in boys is 1.5 times higher than in girls [18].
1.3 Epidemiology of the Disease or Condition
TTN is the most common cause of respiratory disorders in newborns. The incidence of TTN is 4–10 cases per 1,000 live births and is inversely proportional to gestational age (GA). TTN develops in approximately 10% of newborns at 33–34 weeks GA, and in 5% at 35–36 weeks GA [19–20]; among term newborns, this figure is 0.36–0.57% [18]. TTN develops in approximately 10% of newborns at 33–34 weeks GA, and in 5% at 35–36 weeks GA [19–20].
1.4 Features of Coding the Disease or Condition
P22.1 Transient tachypnea of newborn
1.5 Classification of the disease or condition
There is no separate classification for transient tachypnea of the newborn.
1.6 Clinical presentation of the disease or condition
The disease most frequently develops in term and late preterm newborns within the first 2 hours of life. Newborns develop symptoms of respiratory failure: tachypnea, nasal flaring, intercostal retractions, xiphoid depression, jugular notch retraction, grunting, cyanosis, and decreased SpO2 (blood oxygen saturation). Physical examination may also reveal an increased anteroposterior chest diameter. Auscultation reveals weakened breath sounds and sometimes moist rales of various calibers. In most cases, symptoms resolve within 12–24 hours, although cases of longer persistence of respiratory disorders (up to 72 hours of life) and/or development of severe respiratory failure requiring mechanical ventilation have been described [18]. In addition, data have been published on a malignant course of TTN, in which newborns develop persistent pulmonary hypertension due to increased pulmonary vascular resistance caused by retained fetal lung fluid [21].
The described clinical manifestations are nonspecific and can be observed in newborn infants in the context of other diseases.
2. Diagnostics, medical indications and contraindications for diagnostic methods
Criteria for diagnosing transient tachypnea of the newborn
The diagnosis of TTN is established based on the combination of the following criteria:
– respiratory disorders debuting in the first 24 hours of life,
– radiological signs of TTN,
– absence of evidence for another etiology of respiratory disorders (congenital pneumonia or sepsis, respiratory distress syndrome, air leak syndrome, meconium aspiration syndrome, congenital malformations of the lungs and diaphragm).
2.1 Complaints and Anamnesis
See section 1.6 "Clinical presentation of the disease or condition".
2.2 Physical Examination
A newborn infant with respiratory disorders and suspected TTN is recommended to undergo a physical therapeutic visual examination [22-25].
LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)
Comments: visual therapeutic examination includes:
– measurement of respiratory rate [26], [27];
– assessment of heart rate, evaluation of auscultatory findings [28];
– assessment of the severity of respiratory disorders using the Silverman-Andersen score (Appendix G1) [22], [24], [25], [29], [30].
– assessment of signs of infectious toxicosis ("mottled" and grey skin coloration, pale skin with perioral cyanosis and/or acrocyanosis that increases with agitation or feeding, decreased tissue turgor, decreased or absent suck reflex, refusal to feed, lethargy, drowsiness or neurological status changes, tachycardia > 180 bpm, muffled heart sounds, abdominal distension; enteral feeding intolerance; signs of respiratory failure: decreased blood oxygen saturation; tachypnea > 60/min or apnea episodes (respiratory pause > 20 s).
Dynamic assessment of respiratory disorders is necessary not so much for diagnostic purposes as to evaluate the efficacy of ongoing respiratory therapy or as an indication for its initiation [22], [30], [31-33].
2.3 Laboratory Diagnostics
A newborn infant with suspected TTN is recommended to undergo a complete (clinical) blood count with differential leukocyte count (leukocyte formula) and calculation of the neutrophil index to detect inflammatory changes in the first day of life in order to exclude an infectious etiology of respiratory disorders and concomitant disorders requiring correction [34-39], [40].
GCR BLEL 3Grade of Recommendation B (Level of Evidence – 3)
Comment: evaluation of the complete (clinical) blood count enables differential diagnosis between TTN and acute infectious diseases of the early neonatal period [34], [41-46]. In the complete (clinical) blood count, inflammatory changes should be assessed (presence of leukocytosis or leukopenia, neutrophilia or neutropenia, shift to the left in the leukocyte formula with young forms, elevated neutrophil index (NI) > 0.2, thrombocytopenia). Special attention should be paid to red blood cell indices (total blood hemoglobin level, hematocrit evaluation) to exclude or confirm polycythemia or anemia in the newborn. There are no specific changes in complete blood count parameters in TTN.
A newborn infant with suspected TTN is recommended to determine the serum C-reactive protein (CRP) level to detect laboratory signs of systemic inflammation in order to exclude an infectious etiology of respiratory disorders [47-51].
GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)
Comments: it is advisable to repeat the CRP level determination and complete blood count (CBC) after 24–48 hours [47],[48] if making a diagnosis is difficult during the first day of life. An increase in laboratory markers of systemic inflammatory response syndrome (SIRS): CRP above reference normal values may indicate the presence of an infectious disease in the child. TTN is characterized by negative SIRS markers and negative results of microbiological (cultural) blood cultures for sterility. In certain cases, to rule out an infectious process and determine patient management tactics, it is advisable to additionally determine the levels of other laboratory markers of SIRS (such as blood procalcitonin testing, etc.) [48],[50],[52]. The upper limit of normal CRP values is determined by the method used and the type of analyzer in a specific medical organization.
In a newborn infant with respiratory disorders and suspected infection, it is recommended to perform a microbiological (cultural) blood test for sterility and a microbiological (cultural) blood test for yeast fungi to rule out an infectious genesis of the respiratory disorders [53–58].
LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)
In a newborn infant with respiratory disorders, it is recommended to test the acid-base balance (ABB) and blood gases, blood lactate level, and blood glucose level to assess hypoxia and metabolic disorders, with repeated testing of the acid-base balance and blood gases to determine further respiratory therapy tactics and parameter adjustment for an objective assessment of the severity of respiratory and metabolic disorders and to determine management tactics [59],[60].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: testing the acid-base balance (ABB) and blood gases may reveal bidirectional nonspecific changes as well as their absence. The frequency of testing depends on the clinical condition of the infant and the ongoing respiratory therapy. Determination of blood lactate levels depends on the technical capabilities of the stat laboratory and its availability.
2.4 Instrumental Diagnostics
In a newborn infant with suspected transient tachypnea, it is recommended to perform a chest X-ray in order to identify characteristic radiological signs of TTN and perform differential diagnosis [61–65].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: radiological signs of TTN include:
– increased or normal chest volume,
– lung hyperaeration, flat diaphragm,
– dilation of the lung roots,
– diffuse decrease in lung tissue transparency. Changes can be asymmetric, with predominant involvement of the right lung,
– enhancement of the pulmonary vascular pattern, «sunburst» pattern — white lines radiating from the root of the lung (so-called «perihilar pattern»),
– accentuation of interlobar fissures,
– moderately severe cardiomegaly.
It is recommended that newborns with suspected transient tachypnea undergo a selective lung ultrasound to detect characteristic signs of TTN and perform differential diagnosis, provided a specialist proficient in this method is available [65],[66],[67].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: lung ultrasound is a highly accurate diagnostic tool that can serve as an alternative to radiography in diagnosing TTN. Lung ultrasound can help differentiate TTN from other conditions accompanied by respiratory failure in the first days of life [68].
Lung ultrasound differs from the imaging of other organs in that it combines the interpretation of real anatomical images with the interpretation of artifacts generated by the ultrasound beam at the air-fluid interface [69]. In normally aerated lung tissue, the majority of the ultrasound signal is reflected by the air contained within the lungs. Therefore, visualizing unchanged lung tissue is not possible. However, when morphological abnormalities occur and consequently alter the physical properties of the lung tissue, acoustic effects are produced that can be detected during ultrasound [70].
“A-lines” represent reflections from the pleural line deeper into the image as a result of the reverberation effect and appear as horizontal, hyperechoic, repeating lines spaced at equal intervals. This artifact is a sign of normal or excessive air content in the alveolar space.
“B-lines” are hyperechoic “comet-tail” artifacts caused by ultrasound reflection at the gas-fluid boundary. They originate from the pleura and extend vertically across the entire screen. “B-lines” are an artifact indicating increased density of the examined lung area and decreased aeration. “B-lines” appear when the ultrasound beam strikes the interface between a thickened interlobular septum and aerated alveoli, i.e., at the boundary of media with vastly different acoustic impedances, resulting in multiple vertical reverberations. The presence of this ultrasound phenomenon is not a specific sign, but rather indicates interstitial changes (interstitial syndrome). The substrate of this ultrasound phenomenon is considered to be the accumulation of excess fluid in the interstitial space of the lung parenchyma or thickening of the interlobular septa [71]. As interstitial changes progress, the number of “B-lines” increases, and they merge with one another up to the appearance of a unified echo-positive image. This phenomenon is termed the “white lung” (and upon longitudinal scanning perpendicular to the ribs, the “waterfall sign”) and reflects alveolar-interstitial syndrome.
One of the most frequent ultrasound signs in TTN is the “double lung point” (DLP). The “double lung point” (DLP) is a clear echogenicity boundary between the lower lung fields (characterized by a hyperechoic thin pleural line and compact “B-lines”) and the upper lung fields (typically characterized by normal echogenicity) [74] (the sensitivity range of this sign varies widely [45.6 – 100%]; specificity range 94.8 – 100%).
The “double lung point”, the presence of “B-lines”, and the “white lung” are the main ultrasound characteristics of TTN [72]. However, the ultrasound presentation of TTN can be variable, for example, partial or complete disappearance of “A-lines” (hyperechoic horizontal lines at equal intervals from the pleural line and from each other, indicating normal lung aeration) in the early stage of the disease, the appearance of 3 or more “B-lines”, and the “white lung” (confluent “B-lines”) in severe manifestations [67]. TTN can be ruled out if pulmonary consolidations and air bronchograms are present [67],[73].
Ultrasound criteria for TTN: a combination of the “double lung point” (DLP) and “B-lines” signs [67].
The combination of ultrasound signs (the “double lung point” [DLP] and the presence of “B-lines”) is a more accurate diagnostic criterion compared to assessing DLP alone (pooled sensitivity – 98%; pooled specificity – 99%).
Newborns with respiratory disorders and suspected TTN, especially those requiring respiratory therapy, are recommended to undergo 24-hour bedside monitoring of vital functions and parameters (oxygen saturation by pulse oximetry [SpO2], heart rate [HR], blood pressure [BP], respiratory rate [RR], body temperature, diuresis) for the timely administration of symptomatic and etiotropic therapy [74-87].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Newborns with respiratory disorders and suspected TTN are recommended to undergo a selective echocardiography (EchoCG) in order to rule out other causes of respiratory disorders [88-90].
GCR CLoE 3Grade of Recommendation C (Level of Evidence – 3)
2.5 Other Procedures
Not applicable.
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
3.1.1 Respiratory Therapy / Oxygen Therapy
Newborns with respiratory disorders and suspected TTN are recommended to receive non-invasive mechanical ventilation for therapeutic purposes [12],[91-93].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: the main mechanism of action of non-invasive respiratory therapy in TTN is an increase in functional residual capacity of the lungs and the surface area of the lungs available for gas exchange throughout the respiratory cycle, which in turn reduces the work of breathing [94]. The preferred method of initial respiratory therapy for TTN is nasal CPAP (NCPAP), the use of which, compared to oxygen therapy, significantly reduces the duration of respiratory disorders and tachypnea without increasing the rate of complications [91],[95].
Non-Invasive Positive Pressure Ventilation (NIPPV) in TTN, according to randomized controlled trials, is not more effective than NCPAP: it does not lead to a reduction in the duration of respiratory therapy, tachypnea, and/or hospitalization [96]. One RCT showed that patients with TTN > 34 weeks of gestation in the nasal high-frequency oscillatory ventilation (NHFOV) group required a shorter duration of non-invasive respiratory support compared to NCPAP [97].
There are extremely few studies on the use of high-flow nasal cannula (HFNC) therapy in newborns with TTN. According to a retrospective study involving 106 patients with a gestational age ≥ 34 weeks, the use of HFNC compared to NCPAP demonstrated a higher requirement for supplemental oxygenation [98]. At the same time, the selective use of this technique is advisable in patients as a simple, safe, and cost-effective method of respiratory therapy [99-101]. According to a recent meta-analysis, the use of HFNC compared to NCPAP as the initial method of non-invasive respiratory therapy in preterm infants revealed no differences in intubation rates, whereas the incidence of nasal trauma was lower with HFNC [102]. HFNC facilitates carbon dioxide elimination from the dead space and can also generate some positive end-expiratory pressure (2–5 cm H2O) [103],[104], which may contribute to increased patient oxygenation and reduced work of breathing. The optimal flow rate of heated and humidified gas mixture when using HFNC should be 4–6 L/min, and the outer diameter of the nasal oxygen cannula should not exceed ½–¾ of the diameter of the nasal passages [94],[102],[105],[106],[107].
Late preterm and term newborns with minimal respiratory disorders (Silverman-Andersen score < 3) without the need for supplemental oxygenation and in the absence of technical capabilities may be observed without non-invasive respiratory therapy for 2 hours after birth, provided normothermia is maintained and vital functions are monitored. If respiratory disorders do not regress and/or the need for supplemental oxygenation arises after 2 hours, prompt initiation of respiratory therapy is recommended [108].
In newborns with TTN or suspected TTN in whom non-invasive respiratory therapy methods have proven ineffective, it is recommended to perform invasive mechanical ventilation (MV) to treat respiratory failure [3],[109],[110].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comment: the probability of requiring invasive respiratory therapy with a confirmed diagnosis of TTN is extremely low [111]. However, during differential diagnosis (e.g., with respiratory distress syndrome, congenital pneumonia, and sepsis (until the diagnosis of TTN is established)), the probability of non-invasive respiratory therapy failure is significantly higher [110].
The need for escalation of respiratory therapy is indicated by an increase in the severity of respiratory disorders (score ≥ 3) and respiratory rate over time (see Appendices B, G1) [22],[24],[25],[30],[31],[112],[113]. During non-invasive respiratory therapy, assessment is performed without disconnecting the patient from the ventilator circuit. Dependence on supplemental oxygenation during non-invasive respiratory therapy is not typical for patients with TTN. The need to increase FiO2 ≥ 0.3 to maintain SpO2 at 91–95% indicates the failure of ongoing non-invasive respiratory therapy. Absolute indications for intubation and transfer to mechanical ventilation are [109]:
– tachypnea greater than 90–100/min [109],
– severe apnea (more than 4 episodes of breathing pauses per hour and/or the need for non-invasive mechanical ventilation (MV) to resolve them more than 2 times per hour [114],
– pronounced acidosis: pH < 7.2 and/or hypercapnia PCO2 > 65 mmHg [109],
– generalized seizures,
– shock,
– tension pneumothorax.
Newborns with TTN or suspected TTN are not recommended to receive routine oxygen therapy for the treatment of respiratory failure [115].
LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)
Comment: according to the study by Buckmaster et al. [115], the administration of oxygen therapy prior to initiating non-invasive respiratory support in late preterm and term infants is associated with an increased rate of complications, the need for mechanical ventilation, and its prolonged duration compared to using non-invasive respiratory support as the initial treatment method.
3.1.2 Pharmacotherapy
Not applicable.
3.2 Surgical Treatment
Not applicable.
3.3 Other Treatment
A newborn with TTN or suspected TTN must be provided with a thermoneutral environment, body temperature monitoring, and a protective care regimen (limiting sensory stimulation: protection from light, noise, and touch) to create optimal conditions for nursing. If respiratory support is necessary, transfer to a neonatal intensive care unit (NICU) or an intermediate care unit is indicated.
The infant is indicated for adequate enteral and, if necessary, parenteral nutrition. Preference in enteral feeding is given to breast milk. In case of insufficient lactation or maternal contraindications to breastfeeding, the newborn is fed with an adapted infant formula.
Newborn infants who develop respiratory disorders within the first day of life are not recommended to undergo routine fluid restriction for the treatment of TTN [116],[117].
GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)
Comment: newborns with TTN are recommended to receive a physiological fluid volume (40–60 ml/kg/day on the first day of life, 60–80 ml/kg/day for preterm infants) [118]. Fluid restriction in newborns with TTN is associated with more pronounced weight loss, hyperbilirubinemia, and hypoglycemia. Studies demonstrating the benefits of fluid restriction for treating TTN, including economic feasibility, have certain limitations: 1) small sample sizes (total number of patients 64–70 newborns with a gestational age of 34–42 weeks) and 2) fluid restriction was compared only against a baseline higher fluid volume recommended by the internal protocol of the medical institution [119].
A newborn infant with transient tachypnea is recommended to receive selective infusion therapy and parenteral nutrition to provide fluids and electrolytes, proteins, fats, and carbohydrates based on physiological requirements and pathological losses, and to maintain the body's water-electrolyte balance [120].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: parenteral nutrition is performed using parenteral nutrition solutions (ATX code B05BA) when it is impossible to provide the required gestational-age-appropriate levels of proteins, fats, carbohydrates, electrolytes, and fluid volume via enteral feeding. Fluid, protein, fat, carbohydrate, and electrolyte requirements depending on gestational age and birth weight are specified in the Clinical Guidelines «Congenital Pneumonia». Parenteral nutrition utilizes: amino acids for parenteral nutrition (ATX code B05BA01), fat emulsions for parenteral nutrition (ATX code B05BA02), carbohydrates (ATX code B05BA03), electrolyte solutions (ATX code B05XA), and calcium preparations (ATX code A12AA).
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Not applicable.
5. Prevention and Dispensary Observation
Not applicable.
6. Organization of Medical Care
Treatment of preterm newborns with transient tachypnea is carried out in an inpatient setting.
Indications for patient discharge from a medical organization:
1) Stable, satisfactory condition of the child;
2) Stabilization of laboratory parameters;
3) There are no other contraindications to discharge.
7. Additional Information
The long-term prognosis is favorable in newborns who have undergone TTN.
Criteria for Evaluating the Quality of Medical Care
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Appendix A1. Working Group Composition
Andreev Artem Vladimirovich – PhD in Medical Sciences, Anesthesiologist-Intensivist at the Neonatal and Pediatric Intensive Care Unit No. 2, 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, Moscow.
Balashova Ekaterina Nikolaevna – PhD in Medical Sciences, Leading Researcher at the Professor A.G. Antonov Neonatal and Pediatric Intensive Care Unit, 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; 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 Russian Ministry of Health (Sechenov University), Member of the Council of the Russian Society of Neonatologists, Moscow.
Baskevich Maxim Arkadievich – Anesthesiologist-Intensivist at the Neonatal and Pediatric Intensive Care Unit No. 2, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.
Budina Arina Yurievna – Anesthesiologist-Intensivist at the Neonatal and Pediatric Intensive Care Unit No. 2, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.
Volodin Nikolai Nikolaevich – MD, Professor, Academician of the Russian Academy of Sciences, President of the Association of Specialists in Perinatal Medicine, Healthcare for Pregnant Women, Fetuses, Newborns, and Children Under 3 Years of Age (ASPM+).
Ionov Oleg Vadimovich – MD, Head of the Professor A.G. Antonov Neonatal Intensive Care Unit, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; 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 Russian Ministry of Health (Sechenov University), President of the Russian Society of Neonatologists.
Krog-Jensen Olga Alexandrovna – PhD in Medical Sciences, Anesthesiologist-Intensivist at the Neonatal and Pediatric Intensive Care Unit No. 2, 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 Russian Ministry of Health (Sechenov University), Member of the Russian Society of Neonatologists, Moscow.
Lenyushkina Anna Alekseevna – PhD in Medical Sciences, Head of the Neonatal and Pediatric Intensive Care Unit No. 2, 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, Moscow.
Nikitina Irina Vladimirovna – MD, Leading Researcher at the Neonatal and Pediatric Intensive Care Unit No. 2, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health; Head of Academic Studies, 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 Russian Society of Neonatologists, Moscow.
Prutkin Mark Evgenievich – Head of the Department of Anesthesiology, Reanimation, and Intensive Care for Newborns and Preterm Infants, Perinatal Center No. 1, Regional Children's Clinical Hospital, Yekaterinburg, Member of the Council of the Russian Society of Neonatologists, Yekaterinburg.
Pupysheva Anna Fedorovna – Anesthesiologist-Intensivist, Head of Clinical Work at the Neonatal and Pediatric Intensive Care Unit No. 2, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Moscow.
Romanenko Vladislav Alexandrovich – MD, Professor, Honored Doctor of the Russian Federation, Diploma Laureate of the European Scientific and Industrial Chamber, Chairman of the Chelyabinsk Regional Branch of the Russian Society of Neonatologists, Chelyabinsk, Member of the Council of the Russian Society of Neonatologists.
Shestak Evgeniy Vyacheslavovich – PhD in Medical Sciences, Anesthesiologist-Intensivist, Head of the Neonatal Intensive Care Unit, Yekaterinburg Clinical Perinatal Center; Associate Professor at the Department of Hospital Pediatrics, Pediatric Faculty, Ural State Medical University, Yekaterinburg.
Conflict of interest:
All members of the Working Group have confirmed that they have no financial support or conflicts of interest to disclose.
Conflict of interest: none.
Appendix A2. Methodology for Developing Clinical Guidelines
Methods used for evidence collection/selection: 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 to assess 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 evidence analysis:
reviews of published meta-analyses;
systematic reviews with evidence tables.
Description of methods used for evidence analysis.
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 reviewed.
Method of recommendation validation:
external expert review;
internal expert review.
Description of the guideline 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:
Pediatricians;
Neonatologists;
Anesthesiologists-intensivists;
Pulmonologists;
General practitioners (family physicians);
Medical students;
Residents and interns.
Table 1.Scale for evaluating levels of evidence (LoE) for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
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 rehabilitation interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
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:
Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Health Protection of Citizens in the Russian Federation."
Order of the Russian Ministry of Health No. 203n of May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care."
International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) (World Health Organization), 2019 version.
Order of the Russian Ministry of Health 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).
Order of the Russian Ministry of Health No. 222n dated April 17, 2025, "On Approval of the Procedure for Providing Medical Care in the Field of 'Neonatology'." (Registered with the Ministry of Justice of Russia on June 2, 2025, No. 82516).
Methodological Letter of the Russian Ministry of Health 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.
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Transient tachypnea of the newborn (TTN) is a self-limiting respiratory disorder in newborns caused by delayed clearance of lung fluid after birth. It is one of the most common causes of respiratory distress in the first hours of life.
Why does this happen? During pregnancy, the baby's lungs are filled with fluid. With normal labor, this fluid is gradually expelled. Sometimes this process is delayed, especially in infants born via elective cesarean section without labor onset, or following precipitous or preterm delivery. As a result, excess fluid remains in the lungs, impairing normal gas exchange.
What are the manifestations of transient tachypnea? The main symptoms appear shortly after birth and include:
Rapid breathing (more than 60 breaths per minute).
Mild chest retractions during breathing.
Expiratory grunting.
Occasionally, mild cyanosis (bluish discoloration of the skin) if oxygen saturation is decreased.
How is it diagnosed? TTN is diagnosed based on clinical signs and examination findings (pulse oximetry, chest radiography). If necessary, the physician will rule out other, more serious causes of respiratory distress.
How is transient tachypnea treated? In most cases, TTN resolves spontaneously within 12–72 hours. Treatment aims to maintain normal oxygen and carbon dioxide levels and includes:
Maintaining normal body temperature.
Respiratory support (ventilatory support used when a baby cannot breathe normally on their own; it helps deliver oxygen to the body and/or remove carbon dioxide when the lungs cannot cope on their own).
Tube feeding or intravenous nutrition during the period of respiratory support.
Antibiotics and other specific medications are generally not required unless there are signs of infection.
Prognosis
The prognosis for TTN is favorable. Complete recovery occurs without long-term health consequences. TTN does not affect the child's further development.
What is important for parents to know?
Transient tachypnea is a temporary and reversible condition.
It is not associated with congenital malformations or chronic lung diseases.
Once symptoms resolve, the infant does not require special care or treatment.
Medical observation in the first days of life is important for timely condition monitoring.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Appendix G1. Respiratory Distress Scoring Scale
Russian title: Silverman-Andersen Respiratory Severity Score.
Original name: Retraction scoring system, 1956, W. Silverman, D. Andersen.
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.[29].
Type: rating scale.
Purpose: assessment of respiratory disorders.
Content (template)
0 points | 1 point | 2 points | |
|---|---|---|---|
1. Chest wall movements | chest and abdomen move synchronously during breathing | asynchrony between chest and anterior abdominal wall movements | marked asynchrony between chest and anterior abdominal wall movements, seesaw respiration |
2. Intercostal retractions on inspiration | absent | mild retraction | marked retraction |
3. Retraction of the xiphoid process on inspiration | none | mild | marked retraction |
4. Position of the lower jaw | mouth closed, lower jaw stationary | mouth closed, chin drops on inspiration | mouth open, jaw drops on inspiration |
5. Expiratory sounds | breathing calm and even | grunting audible only with a stethoscope auscultation | grunting, noisy respiration, expiratory sounds audible at a distance |
Key (interpretation) and notes:
A score of 1–2 points indicates a compensated condition of the infant during ongoing therapeutic management. An increase in the severity of respiratory disorders to ≥ 3 points [22],[24],[25],[30],[31],[112],[113] indicates the need to escalate respiratory therapy. Serial assessment of respiratory disorders is necessary not so much for diagnostic purposes, but to evaluate the efficacy of ongoing respiratory therapy or as an indication for its initiation. When administering non-invasive respiratory therapy, the assessment is performed without disconnecting the patient from the ventilator circuit.