List of Abbreviations
BP — blood pressure
ALT - alanine aminotransferase
AST - aspartate aminotransferase
ABT - antibiotic therapy
ATC - Anatomical Therapeutic Chemical classification system
UA — upper airways
IVH — intraventricular hemorrhage
HFO - high-frequency oscillatory ventilation
GA — gestational age
GERD — gastroesophageal reflux disease
DNA - deoxyribonucleic acid
GIT - gastrointestinal tract
IMV - invasive mechanical ventilation
ABB — acid-base balance of blood
Drug - medicinal product
MAP — mean airway pressure
PCC — pulmonary circulation
MO - medical organization
NSG - neurosonography
NI — neutrophil index
NEC - necrotizing enterocolitis
VLBW — very low birth weight (less than 1500 g)
NICU - neonatal intensive care unit
PCA — postconceptional age
ACA — anterior cerebral artery
PEEP — positive end-expiratory pressure
TPN - total parenteral nutrition
RASPM - Russian Association of Perinatal Medicine Specialists
RDS - respiratory distress syndrome
CSF - cerebrospinal fluid
CRP - C-reactive protein
TTN — transient tachypnea of the newborn
US — ultrasound examination
FRC — functional residual capacity of the lungs
CVC - central venous catheter
CNS - central nervous system
HR – heart rate
RR — respiratory rate
ECG - electrocardiography
ELBW — extremely low birth weight (999 g and less)
ETT - endotracheal tube
EchoCG – echocardiography
CPAP — continuous positive airway pressure — a method of respiratory therapy based on creating constant positive airway pressure
FiO2 — fraction of inspired oxygen in the air-oxygen mixture
NCPAP (nasal constant positive airway pressure) is the most frequently used method of non-invasive respiratory support in preterm and term newborns, which is based on generating continuous positive airway pressure using specialized nasal cannulas.
NIPPV (nasal intermittent positive pressure ventilation) is a method of non-invasive respiratory support administered to newborns using specialized nasal cannulas and a mechanical ventilator, based on generating intermittent positive airway pressure in the airways.
pH (from Lat. pondus Hydrogenii — "weight of hydrogen") is a measure of hydrogen ion activity in a solution, which quantitatively expresses its acidity. It is a logarithmic scale used to determine the acidity or basicity of aqueous solutions.
PO2 — partial pressure of oxygen in arterial blood
PCO2 — partial pressure of carbon dioxide (CO2) in arterial blood
PEEP (positive end expiratory pressure) — positive pressure at the end of expiration
SpO2 — blood oxygen saturation index
V/Q — ventilation-perfusion ratio
ESCMID (European Society of Clinical Microbiology and Infectious Diseases)
Terms and Definitions
Apnea of prematurity is a pause in breathing that lasts for more than 15–20 seconds, or is of shorter duration but accompanied by bradycardia (< 100 bpm) and/or desaturation (< 85%), in an infant with a gestational age of less than 37 weeks, in the absence of any known underlying disease causing apnea.
Respiratory center is a collection of neurons located in the medulla oblongata that ensure the automatic rhythm of respiratory movements and match respiration to the body's metabolic demands.
Central apnea is a complete cessation of inspiration with no signs of upper airway obstruction.
Obstructive apnea is the absence of effective respiratory movements caused by an obstruction to airflow in the upper airways.
Mixed apnea is the absence of breathing resulting from a combination of central and obstructive components.
Apnea is considered severe if a newborn experiences more than 4 episodes of breathing pauses per hour and/or requires non-invasive mechanical ventilation (CMV) to relieve them more than twice within an hour [1].
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Apnea of prematurity is a pause in breathing that lasts for more than 15–20 seconds, or is of shorter duration but accompanied by bradycardia (< 100 bpm) and/or desaturation (< 85%), in an infant with a gestational age (GA) of less than 37 weeks, in the absence of any known disease causing apnea.
Apnea is considered severe if a newborn experiences more than 4 episodes of breathing pauses per hour and/or requires non-invasive mechanical ventilation to relieve them more than twice within an hour [1].
The leading causes of apnea of prematurity in newborns are immaturity of the central and peripheral respiratory regulation, as well as structural characteristics of the chest and airways in the preterm infant [2–7].
The diagnosis of "apnea of prematurity" implies the absence of pathological conditions that can act as independent causes and triggering factors of apnea in preterm infants. These include neonatal infections, central nervous system pathology (intraventricular hemorrhage (IVH), neonatal seizures, etc.), metabolic disorders (hypo- or hyperglycemia, electrolyte disturbances, etc.), anemia, polycythemia, gastroesophageal reflux, mechanical upper airway obstruction by secretions, and others; see Section 2 "Diagnostics" and Section 7 "Differential Diagnosis" [8,9].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The main component of central respiratory regulation in humans is the respiratory center, located in the medulla oblongata, which functions based on the continuous receipt of signals regarding the state of the body's internal environment.
Control over the respiratory process is carried out via central chemoreceptors (which primarily detect changes in pH and pCO2 in the body) and peripheral chemoreceptors (sensitive to changing pO2), as well as mechanoreceptors of the upper and lower airways, lungs, and respiratory muscles. The continuous interaction of these systems ensures the constancy of blood gas composition in response to changing pH, pO2, and pCO2. Through a system of nerve impulses directed to the respiratory muscles, the respiratory center influences the rate and depth of respiratory movements.
Among the causes leading to the development of respiratory pauses (apnea) in newborns, prematurity occupies one of the leading places (Diagram 1).
In a preterm infant, the control of respiratory function is characterized by marked immaturity and the persistence of fetal mechanisms of respiratory regulation [1,6]. Fetal respiratory movements during the intrauterine period are periodic and do not perform the primary function, as the placenta serves as the organ of gas exchange. Their physiological role is to stimulate the development of the respiratory system. Fetal mechanisms persisting in preterm infants manifest as a pronounced central inhibitory influence: attenuation of respiratory activity in response to increased pCO2, a paradoxical reaction to hypoxia, and an enhanced apnea reflex upon laryngeal stimulation, resulting in frequent episodes of apnea and periodic breathing [10–13]. It is believed that the primary mechanism underlying apnea of prematurity is the depression of respiration in response to CO2 accumulation [9,11,12].
The sensitivity of central chemoreceptors, which respond primarily to hypoxia, is reduced in preterm newborns, manifesting as a biphasic response: the initial reaction of the body to hypoxia is an increase in minute ventilation, followed in the second phase by a decrease in respiratory intensity [13].
Apnea may manifest both during periods of active wakefulness and during sleep. However, as a rule, during the "slow-wave" sleep phase, when central nervous system (CNS) excitation is replaced by depression, apnea occurs significantly more often.
Diagram 1. Causes leading to the development of apnea in newborns [7]
Diagram 2. Pathogenesis of apnea of prematurity [7]
Diagram 3. Interrelation of apnea, bradycardia, and desaturation [14]
The mechanisms linking apnea with bradycardia are not fully understood. It is believed that bradycardia occurs as a result of hypoxic stimulation of carotid body chemoreceptors. On the other hand, bradycardia may occur simultaneously with apnea under the influence of laryngeal receptor stimulation, which is a manifestation of a vagal central mechanism that independently causes both apnea and a decrease in heart rate (HR).
1.3 Epidemiology of the Disease or Condition
The frequency and severity of apnea are inversely proportional to the GA of newborns. According to global literature, apnea is diagnosed in 80% of preterm infants born before 33 weeks of gestation, 16% of infants born at 34–35 weeks of gestation, and 5% of infants born after 36 weeks of gestation. According to other data, apnea occurs in extremely low birth weight (ELBW) newborns with a frequency approaching 100%, and in more than 50% of very low birth weight (VLBW) newborns at birth [15]. The frequency of apnea decreases with increasing postnatal age and by 43–44 weeks of postmenstrual age (PMA) corresponds to that of term infants.
Notably, the inverse relationship between the infant's gestational age and the frequency of apnea is associated not only with the degree of immaturity of the respiratory center, but also with the fact that extremely premature infants spend significantly more time in a state of sleep, which appears to be a triggering factor in the development of apnea of various origins.
1.4 Features of Coding the Disease or Condition
P28.3 Primary sleep apnea of newborn
P28.4 Other apnea of newborn
1.5 Classification of the disease or condition
According to the mechanism of occurrence, apnea is divided into:
Central apnea — complete cessation of inspiration without signs of upper airway obstruction. This condition is generally caused by immaturity of the respiratory center neurons that control the breathing process. The pathophysiology is not fully understood, but a number of studies have shown that the occurrence of apnea of this origin is due to a specific (paradoxical) response of immature carotid sinus chemoreceptors to hypoxia and hypercapnia.
Obstructive apnea — the absence of effective respiratory movements caused by an obstruction to airflow in the upper airways (upper airway obstruction by subglottic soft tissues during neck flexion, impaired nasal breathing (including various malformations), reflex laryngospasm, narrowing/collapse of the upper airway lumen due to impaired muscle tone, etc.).
Mixed apnea is the absence of breathing resulting from a combination of central and obstructive components. In premature newborns, as a rule, 50–75% of all apnea episodes are mixed in nature.
Despite the differences in the processes triggering apnea, all three types of apnea are associated with the immaturity of respiratory regulation in the premature infant [16,17].
1.6 Clinical presentation of the disease or condition
The clinical presentation of apnea of prematurity consists of the absence of respiratory movements for at least 15–20 seconds, or ineffective respiratory movements of shorter duration accompanied by secondary symptoms of hypoxia: central and peripheral cyanosis, and bradycardia, with instrumental signs including a decrease in blood oxygen saturation (SpO2) and heart rate. A decrease in SpO2 levels according to continuous transcutaneous monitoring manifests faster than bradycardia in the vast majority of cases [5,16].
2. Diagnostics, medical indications and contraindications for diagnostic methods
Apnea of prematurity accounts for the highest incidence of apnea as a symptom complex, which requires special vigilance regarding newborns with an 80% or higher probability of developing this condition—infants with very low birth weight (VLBW), extremely low birth weight (ELBW), and a gestational age < 32 weeks [18].
The diagnosis of apnea of prematurity is established based on a combination of data: anamnesis (body weight, gestational age, time and circumstances of onset, frequency), clinical features (absence of spontaneous breathing for 15–20 seconds or more, ineffective respiratory movements during a shorter respiratory pause, cyanosis), and instrumental findings (decrease in SpO2 below 85%, heart rate dropping below 100 beats per minute). Since the diagnosis of "apnea of prematurity" implies the absence of other pathological conditions that may act as independent causes and triggers of apnea in premature infants, ruling them out may require additional analysis of anamnestic and clinical data, along with expanded laboratory and instrumental investigations [7,11,19–23].
The typical time of onset for apnea of prematurity is between the 2nd and 7th day of life [9]. Occurrence earlier or later does not rule out the diagnosis, but merely increases the likelihood of apnea of another etiology. Furthermore, arguments supporting the diagnosis of apnea of prematurity include the onset of apnea unrelated to enteral feeding, the absence of visible signs of airway obstruction by secretions/enteral nutrition substrate, predominantly occurring during sleep, the absence of clinical signs of infectious toxicity, and a number of other differential diagnostic features.
Differential diagnosis is performed with conditions such as: respiratory distress syndrome, infectious diseases with systemic manifestations, central nervous system pathology (intraventricular hemorrhage, neonatal seizures, etc.), metabolic disorders (hypo- and hyperglycemia, electrolyte disturbances, etc.), anemia, polycythemia, gastroesophageal reflux, mechanical obstruction by secretions, and others; see section 7 "Differential Diagnosis" [8,9].
Indications for an expanded scope of examination and differential diagnosis may include the presence of severe apnea (see "Terms and Definitions"), the lack of positive dynamics during treatment, or the appearance of new clinical symptoms in the patient [2,9,24,25].
The diagnostic and treatment algorithm for apnea in a premature newborn is presented in Appendix B.
2.1 Complaints and Anamnesis
Complaints and medical history are described in section 1.6 "Clinical Presentation".
2.2 Physical Examination
It is recommended that a premature newborn with apnea or suspected apnea undergo a visual therapeutic examination to identify clinical manifestations of apnea [6,10,26,27].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comments: if apnea is suspected, the presence and rate of respiratory movements, signs of respiratory distress, and signs of upper airway obstruction should be assessed immediately, and the heart rate should be determined to decide on the need for resuscitation [28].
It is advisable to assess the skin color (pale, cyanotic, grayish skin tint, etc.), the presence of signs of infectious toxicity, characterize microcirculation by determining the capillary refill time (in seconds), signs of urinary output disorders (oligo- and/or anuria), dyspeptic disorders (abdominal distension, weakened peristalsis, poor enteral nutrition tolerance), jaundice, and hepatosplenomegaly.
2.3 Laboratory Diagnostics
To rule out pathologies whose symptom is apnea, a comprehensive complete blood count is recommended for a premature newborn with apnea [29–31].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: in the comprehensive complete blood count, inflammatory changes should be assessed (presence of leukocytosis or leukopenia, neutrophilia or neutropenia, shift to the immature forms in the leukocyte formula, elevated neutrophil index > 0.2, thrombocytopenia). Special attention should be paid to red blood cell parameters (hemoglobin, hematocrit) to rule out or confirm polycythemia or anemia in the newborn.
A general biochemical blood test (including blood glucose, sodium, potassium, total calcium, total magnesium, total bilirubin, and conjugated bilirubin levels) is recommended for a premature newborn with apnea to rule out pathological conditions causing apnea [9,32–37].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
An assessment of acid-base balance and blood gases (including blood pH, carbon dioxide level, and buffer substances level) is recommended for a premature newborn with severe apnea for timely correction of disorders [38–43].
GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).
Comment: during the onset of a single, brief episode of apnea in preterm infants, blood gas changes may be minimal due to the compensatory mechanisms of the body's buffer systems. However, in VLBW, ELBW infants, and those with a GA < 32 weeks, characteristic signs of transient hypoxemia may be reflected in acid-base status (ABS) parameters even with minor apnea due to their metabolic characteristics. To obtain informative results, it is recommended to assess the patient's blood gas composition immediately after the episode. The main laboratory signs of apnea of prematurity according to ABS and blood gas analysis include respiratory/mixed acidosis, base deficit, and elevated lactate levels.
The determination of serum C-reactive protein (CRP) level is recommended for a premature newborn with apnea to verify infectious diseases with a systemic inflammatory response and to rule out an infectious etiology of apnea [44–49].
GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).
Comment: elevated laboratory markers of the systemic inflammatory response syndrome—specifically CRP above reference normal values (determined by the specifics of the laboratory method used)—may indicate the presence of an infectious disease in the infant.
It is also permissible to additionally use other markers of systemic inflammatory response syndrome if available at the specific medical organization: determination of blood presepsin (soluble CD14) levels (sensitivity for early infection 81%–91%, specificity 60–86%, cutoff threshold from 305 to 672 ng/L; for late infection—sensitivity 81%, specificity 100%, cutoff threshold from 801 to 885 ng/L), blood procalcitonin levels according to age-based (hours) cutoff thresholds (minimum 2.5 ng/mL for early neonatal sepsis [sensitivity 75%, specificity 83%], minimum 2.0 ng/mL for late neonatal sepsis [sensitivity 79%, specificity 63%]), and others [50–53].
Using a combination of various laboratory markers of systemic inflammatory response improves the diagnostic capabilities for identifying infectious diseases [54].
Microbiological (cultural) blood testing for sterility and microbiological (cultural) blood testing for yeast fungi are recommended for a premature newborn with severe apnea to verify infectious diseases and rule out an infectious etiology of apnea [55–58].
GCR BLOE 2Grade of Recommendation B (Level of Evidence – 2).
Comment: according to the 2012 ESCMID guidelines, microbiological (culture) blood tests for yeast fungi should be performed in newborns in a volume of at least 2.0 ml at least 2 times a day for 3 consecutive days. However, given the significant technical difficulties associated with puncturing intact veins in preterm newborns, as well as taking into account the circulating blood volume in VLBW and ELBW infants at birth (90.0 ml per 1 kg of body weight), it is permissible to take at least 1.0 ml of blood for testing as a single sample. In this case, the required blood volume is collected in accordance with the manufacturer's instructions for hematology analyzer bottles [59].
If a specific medical organization has the technical capability, in doubtful cases or for rapid diagnosis in the event of patient deterioration, it is also advisable for preterm newborns to undergo molecular biological testing to detect bacterial and fungal DNA in various biological material samples (blood, oral swab, stool, endotracheal aspirate) for rapid pathogen identification when a newborn with apnea deteriorates [60,61].
2.4 Instrumental Diagnostics
For a preterm newborn with apnea, to determine the frequency and duration of apnea episodes and to diagnose comorbid conditions, it is recommended to perform continuous 24-hour bedside monitoring of vital functions and parameters: peripheral capillary oxygen saturation ($ ext{SpO}_2$) by pulse oximetry, heart rate (HR), blood pressure (BP) in peripheral arteries, respiratory rate (RR), and core body temperature [2,62,63].
GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).
Comments: pulse oximetry is used in routine practice to assess the continuous non-invasive oxygenation level in preterm newborns. However, there are a number of factors that can potentially reduce the reliability of the data obtained: poor peripheral perfusion in the distal extremities, hypothermia, motion artifact susceptibility, and ongoing phototherapy.
Continuous electrocardiogram recording makes it possible to exclude arrhythmias, which can also cause episodes of bradycardia with decreased oxygen saturation in preterm infants.
For a preterm newborn with apnea, it is recommended to perform echocardiography to identify cardiovascular pathology as a possible cause of apnea [9,64–66].
GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).
Comment: echocardiography in apnea is necessary to rule out cardiac causes of the newborn's respiratory pauses, such as congenital heart defects, congenital heart block, hypoplastic left heart syndrome, and transposition of the great arteries [9].
For a preterm newborn with apnea, it is recommended to perform neurosonography to identify central nervous system pathology as a possible cause of apnea [67–70].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: neurosonography should be performed in all preterm infants with apnea, as these respiratory pauses may be symptoms of developing intraventricular hemorrhage (IVH) or its complications. Clinical manifestations of IVH may include seizures, apnea, fontanelle tension and bulging, poor tolerance of enteral feeding, and regurgitation. In grade 3 IVH, apnea occurs in 50% of cases [69,70].
For a preterm newborn with severe apnea, it is recommended to perform chest radiography and/or lung ultrasound to rule out diseases and pathological processes in the lung parenchyma whose symptoms may include respiratory disorders, including apnea [9,35,36].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
Comment: there are no specific radiological signs of apnea of prematurity. Radiography makes it possible to rule out upper and lower respiratory tract diseases, the manifestations of which may also include apnea in preterm newborns (focal and infiltrative changes in the lung parenchyma due to pneumonia, atelectasis, air leak syndrome, etc.).
Lung ultrasound can be an effective alternative to targeted chest radiography for diagnosing lung diseases, avoiding ionizing radiation exposure, especially in preterm newborns when performed by a specialist skilled in this method [63,71]. In the presence of pneumonia, areas of lung consolidation with blurred margins and air bronchograms may be detected, as well as pathological pleural lines, pulmonary edema with signs of stratification, and pleural effusion [71].
2.5 Other Procedures
To identify rare causes of apnea (see Section 7 "Differential Diagnosis"), other diagnostic tests may be used, the scope of which is determined individually.
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
For the treatment of apnea of prematurity (primary apnea) in a preterm newborn, it is recommended to prescribe xanthine derivatives (ATC code: N06BC) — caffeine citrate [25,72–83].
GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).
Comments: the main effect of caffeine citrate (ATC code: N06BC) in the treatment of apnea of prematurity is central nervous system stimulation. Caffeine citrate (ATC code: N06BC) produces the following systemic effects: stimulation of the respiratory center, increased minute ventilation, lowered threshold of sensitivity to hypercapnia, enhanced response to hypercapnia, and increased diaphragmatic tone, which enhances chest excursion, especially during sleep.
The drug is approved for intravenous and oral administration. In clinical practice, due to the severity of the condition in preterm infants developing apnea, the drug is initially administered intravenously, with subsequent consideration of switching to the oral form once the condition of the preterm newborns has stabilized.
Dosing regimen: for infants who have not previously received caffeine citrate (ATC code: N06BC) therapy, the recommended starting loading dose is 20 mg/kg/day administered as a slow intravenous infusion over 30 minutes. Starting from the second day of therapy, the recommended "maintenance" dose is 5 mg/kg/day administered as a slow intravenous infusion over 10 minutes. The drug should be diluted with the following solutions: parenteral nutrition solutions (ATC code: B05BA) — dextrose** (5% intravenous solution), saline solutions (ATC code: B05CB) — sodium chloride** (0.9% injection solution or solvent for preparation of dosage forms for injection).
If the therapeutic effect of caffeine citrate (ATC code: N06BC) treatment is insufficient (recurrent apnea persisting despite caffeine citrate therapy), it is permissible to increase the "maintenance" dose of the drug up to 10 mg/kg/day, divided into 2 doses at 12-hour intervals [84].
Increasing the daily dose of caffeine citrate (ATC code: N06BC) above 10 mg/kg/day is not recommended by the product labeling and entails the risk of adverse systemic effects and the need for therapeutic drug monitoring in the blood [5,85].
When following the recommended dosing regimen, routine therapeutic drug monitoring of blood drug levels (caffeine) is not required, as in the majority of preterm infants, including those with impaired liver and kidney function, drug concentrations remain within the therapeutic range [86,87].
The decision to discontinue caffeine citrate (ATC code: N06BC) therapy is made based on the totality of clinical data (absence of apnea episodes during a 5–7 day observation period) [6] or when the infant reaches 37 weeks of postmenstrual age (PMA), provided there is no ongoing need for respiratory support. However, this timeframe may be revised on an individual basis depending on the clinical situation, response to treatment, persistence of apnea episodes despite treatment, and/or other clinical considerations.
If apnea therapy with the specified daily dose of caffeine citrate (ATC code: N06BC) is ineffective, respiratory support for the preterm newborn should be considered.
3.2 Respiratory therapy
For a preterm infant with apnea, when pharmacotherapy is ineffective, it is recommended to provide non-invasive mechanical ventilation (CPAP, NCPAP, NIPPV) and invasive mechanical ventilation for therapeutic purposes [88–91].
GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).
Comments: the criterion for switching to non-invasive mechanical ventilation is the absence of positive dynamics during therapy with caffeine citrate (ATX code N06BC): persistence of the frequency and/or severity of apnea episodes. However, if a preterm infant experiences 4 or more apnea episodes per hour and/or requires mask ventilation more than twice an hour (criteria for so-called "severe apnea"), intubation and switching the patient to invasive mechanical ventilation should be considered [1]. Traditionally, a step-by-step approach to respiratory therapy in newborns is followed: the starting method is non-invasive mechanical ventilation with positive airway pressure (according to medical service nomenclature, this definition includes CPAP, NCPAP, NIPPV). Transition to the next "step" (intubation, invasive mechanical ventilation) is carried out when the previous one is ineffective.
Direct clinical evidence of the benefits of non-invasive mechanical ventilation for the treatment of apnea of prematurity is limited. Non-invasive mechanical ventilation helps improve upper airway patency and increase oxygenation by establishing functional residual capacity (FRC), which prevents atelectasis of the distal respiratory tract due to insufficient endogenous surfactant in preterm infants [5,13].
In 2022, in China, the consensus experts on the diagnosis and management of apnea of prematurity (Subspecialty Group of Neonatology, the Society of Pediatrics, Chinese Medical Association) concluded that non-invasive positive pressure ventilation with a positive end-expiratory pressure (PEEP) of 4–6 cm H₂O reduces the frequency and severity of obstructive apnea by maintaining upper airway patency and increasing end-expiratory lung volume [92,93].
Variable-flow NCPAP is more effective than constant-flow NCPAP as it reduces the infant's work of breathing [25,89,94,95].
The starting parameters for non-invasive mechanical ventilation via CPAP are: FiO2 0.21 – 0.3, PEEP 4-6 cm HO [80].
When selecting respiratory therapy parameters, one should be guided by acid-base balance and blood gas parameters, as well as continuous pulse oximetry monitoring data [96].
The use of caffeine citrate (ATX code N06BC) is a safe and effective strategy that increases the efficacy of non-invasive and invasive mechanical ventilation in the treatment of apnea of prematurity. Therapy with caffeine citrate (ATX code N06BC) shortens the duration of non-invasive mechanical ventilation and reduces the number of failed extubation attempts when invasive mechanical ventilation is required [87].
The decision to discontinue respiratory therapy in preterm newborns diagnosed with apnea is made individually by the attending physician based on the totality of the clinical and laboratory data mentioned above, provided there are no clinical manifestations of the apnea symptom complex against the background of ongoing therapies.
3.3 Surgical Treatment
In uncomplicated apnea of prematurity, surgical treatment is not performed.
3.4 Other treatment
A preterm infant with apnea is recommended to undergo tactile stimulation to stimulate breathing and reduce the frequency of apnea [85,97].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comments: sensory stimulators, such as tactile stimulation, have a beneficial effect in the treatment of an apnea attack. Tactile stimulation has an excitatory, non-specific effect on neurons in the brainstem center, which in turn promotes more intensive respiratory effort in the preterm infant [85,97]. Tactile stimulation methods include rubbing and stroking the palms and soles (both sides) of the infants, gentle massage of the palms and soles (both sides) with the thumb, and passive movements in the limbs by flexing them at major joints (shoulder, elbow, knee) for several minutes [97].
A preterm infant with apnea is recommended to undergo measures to secure and maintain upper airway patency in order to eliminate potential mechanical obstructions to airflow in the airways [5].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
Comments: in the event of apnea, mechanical airway obstruction by foreign contents, upper airway malformations causing obstruction, and incorrect head and neck positioning (especially hyperextension or excessive neck flexion, which can cause tracheal occlusion and obstructive apnea) should be ruled out.
Prone positioning improves thoracoabdominal synchrony and stabilizes the chest wall without significantly affecting the breathing pattern or SpO2. Positional therapy should be provided only in combination with respiratory and drug therapy, as its efficacy as monotherapy has not been proven [5].
The diagnostic and treatment algorithm for apnea in a preterm newborn is presented in Appendix B.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Not applicable.
5. Prevention and Dispensary Observation
Preterm newborns with a birth weight of less than 1500 g and/or gestational age of less than 32 weeks, breathing spontaneously or receiving non-invasive mechanical ventilation [98–102] in the first 72 hours of life, as well as those on invasive mechanical ventilation during weaning from the ventilator [99,103], are recommended to be prescribed xanthine derivatives – #caffeine citrate (ATX code N06BC) for the prevention of apnea, minimization of the need for and duration of invasive mechanical ventilation, and long-term complications [91,99,100,102,104–112].
GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).
Comments. Drawing a boundary between therapeutic and prophylactic administration of #caffeine citrate (ATX code N06BC) is rather difficult in VLBW and ELBW patients receiving respiratory therapy, since, on the one hand, the incidence of apnea of prematurity in this cohort is extremely high, ranging from 50 to 100%, and on the other hand, respiratory therapy, as an independent method of treating apnea, partially or completely neutralizes the clinical manifestations of the disease.
Prophylactic administration of #caffeine citrate (ATX code N06BC) has become widespread based on the results of retrospective cohort studies, despite the risk of bias, as early initiation of treatment was found to be associated with a decrease in the number of apnea episodes, the need for respiratory therapy, the incidence of bronchopulmonary dysplasia (BPD), hemodynamically significant patent ductus arteriosus (hsPDA), and retinopathy of prematurity [79,87,99,113].
For prophylactic purposes, #caffeine citrate (ATX code N06BC) should be prescribed after obtaining informed consent from the patient's legal representatives. Dosage and duration of prophylactic administration do not differ from those used in the treatment of apnea of prematurity.
Studies evaluating the efficacy of early prophylactic administration of #caffeine citrate (ATX code N06BC) with a prospective randomized design are few and show ambiguous results [91,102,114,115]. The positive effect of early prophylactic administration of #caffeine citrate (ATX code N06BC) has been proven in extremely preterm newborns without the need for invasive mechanical ventilation at the time of the first drug administration [100,102,107]. When #caffeine citrate (ATX code N06BC) was administered within the first 72 hours of life, a reduction in the need for invasive mechanical ventilation and its duration, BPD, retinopathy of prematurity, and hsPDA was observed without an increased risk of necrotizing enterocolitis (NEC), IVH, and mortality compared to newborns receiving placebo or later administration [105,107].
A preterm infant with a gestational age of less than 34 weeks or a birth weight of less than 1500 g is recommended enteral feeding with native breast milk or specialized infant formulas for preterm and low birth weight infants at a temperature of 32-34°C for the prevention of apnea of prematurity [116].
GCR BLOE 2Grade of Recommendation B (Level of Evidence – 2).
6. Organization of Medical Care
Treatment of preterm newborns with manifestations of apnea is carried out in an inpatient setting.
If it is impossible to perform the required scope of laboratory and instrumental examinations and differential diagnostic measures to establish the etiology of apnea, it is advisable to consider transferring the child to a higher-level medical organization.
Indications for discharge of a preterm newborn with apnea of prematurity from a medical organization: absence of clinical manifestations of apnea for 5-7 days after discontinuation of caffeine citrate therapy.
7. Additional Information
In uncomplicated cases of the disease in preterm newborns, the prognosis is favorable.
Differential diagnosis
Apnea of prematurity is a diagnosis of exclusion; therefore, it is important to diagnose and treat the etiological cause of apnea.
Diseases and disorders of various organ systems [9,117–123]
▪ Perinatal asphyxia.
▪ Intraventricular/intracranial or subarachnoid hemorrhage.
▪ Systemic neonatal infections (sepsis).
▪ Neuroinfections (meningitis, meningoencephalitis).
▪ Hydrocephalus with elevated intracranial pressure.
▪ Cerebral infarction.
▪ Seizures.
▪ Birth trauma.
▪ Congenital myopathies or neuropathies.
▪ Congenital malformations.
▪ Respiratory system:
▪ Hypoxia.
▪ Upper airway obstruction/malformation (e.g., Pierre Robin sequence).
▪ Lung diseases: pneumonia/respiratory distress syndrome/aspiration syndromes/bronchopulmonary dysplasia.
▪ Hypercapnia, inadequate respiratory therapy, or premature extubation.
▪ Pulmonary hemorrhage.
▪ Pneumothorax.
▪ Vocal cord paresis/paralysis.
▪ Cardiovascular system:
▪ Chronic heart failure.
▪ Cardiac disorders such as: congenital heart defects, congenital atrioventricular block.
▪ Severe hypovolemia/hypotension/hypertension.
▪ Increased vagal tone. Newborns exhibit increased vagal tone, particularly shortly after birth.
▪ Gastrointestinal tract:
▪ Necrotizing enterocolitis.
▪ Gastroesophageal reflux disease (GERD). All preterm infants and many term infants have GERD. Some signs associated with GERD in newborns include apnea, desaturation, and bradycardia. Studies have shown that in preterm infants, the timing of reflux episodes and apnea is rarely linked.
▪ Diseases and disorders accompanied by abdominal distension (due to decreased lung volume and enhanced vagal stimulation).
▪ Hematopoietic system:
▪ Severe anemia.
▪ Polycythemia.
▪ Other diseases and disorders:
▪ Temperature instability. Any sudden temperature fluctuations, most commonly hyperthermia, but also hypothermia, can trigger apnea and bradycardia in a newborn.
▪ Metabolic/electrolyte imbalance and inherited metabolic disorders. Hypoglycemia, hypo-/hypernatremia, hypermagnesemia, hyperkalemia, hyperammonemia, and hypo-/hypercalcemia can cause apnea and bradycardia.
▪ Acute/chronic pain.
▪ Head/body position. Incorrect neck positioning (especially hyperextension or excessive flexion) can cause tracheal occlusion and obstructive apnea.
▪ Jaundice (unconjugated hyperbilirubinemia) may be associated with central apnea in preterm infants.
▪ Congenital central hypoventilation syndrome (Ondine's curse syndrome).
Table 1. Most common causes of apnea and bradycardia by gestational age [9]
Preterm infants | Term infants | Any gestational age |
|---|---|---|
Apnea of prematurity Respiratory distress syndrome Intraventricular hemorrhage Anemia of prematurity Posthemorrhagic hydrocephalus | Infection Severe birth asphyxia Intracranial hemorrhage Stroke Polycythemia Withdrawal syndrome | Pneumonia Sepsis Necrotizing enterocolitis Meningitis Gastroesophageal reflux disease Post-extubation atelectasis Seizures Asphyxia Hypothermia/Hyperthermia |
Criteria for Evaluating the Quality of Medical Care
References
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Appendix A1. Working Group Composition
Elena S. Akhapkina - Junior Research Fellow, Department of Innovative Development, Department of Regional Cooperation and Integration, 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;
Ekaterina N. Balashova - PhD in Medical Sciences, Leading Research Fellow, Professor A.G. Antonov Intensive Care Unit, 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, Associate Professor at the Department of Neonatology, 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;
Artem A. Burov - PhD in Medical Sciences, Head of Clinical Work, Neonatal Surgery Department, 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;
Nikolay N. Volodin - Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, President of the Russian Association of Perinatal Medicine Specialists, President of the Association of Specialists in Perinatal Medicine, Healthcare Delivery to Pregnant Women and Fetuses, Newborns and Children Under 3 Years of Age (ASPM+), Moscow;
Dmitry N. Degtyarev - Doctor of Medical Sciences, Professor, Deputy Director for Science, 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, 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;
Maria G. Degtyareva - Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Professor at the Department of Neonatology, Faculty of Additional Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health;
Viktor V. Zubkov - Doctor of Medical Sciences, Director of the Institute of Neonatology and Pediatrics, Head of 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, Professor at the Department of Neonatology, 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;
Zuykov Oleg Aleksandrovich — Head of the Pediatric Expertise Department at the Altai Regional Clinical Center for Maternal and Child Health (AKKZHOMD), Chief Freelance Neonatologist of the Ministry of Health of the Altai Krai, Chairman of the Regional Branch of the Russian Society of Neonatologists, Barnaul;
Ionov Oleg Vadimovich — Doctor of Medical Sciences, Head of the Professor A.G. Antonov Department of Reanimation and Intensive Care at the Institute of Neonatology and Pediatrics of the 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 of the I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Chairman of the Russian Society of Neonatologists, Moscow;
Krog-Jensen Olga Aleksandrovna — Candidate of Medical Sciences, Neonatologist at the Reanimation and Intensive Care Department No. 2 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 of the N.F. Filatov Clinical Institute of Children's Health at the 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 — Candidate of Medical Sciences, Head of the Reanimation and Intensive Care Department No. 2 of the Institute of Neonatology and Pediatrics of the 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;
Narogan Marina Viktorovna — Doctor of Medical Sciences, Leading Researcher at the Department of Pathology of Newborns and Premature Infants of the 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 of the N.F. Filatov Clinical Institute of Children's Health at the 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;
Nikitina Irina Vladimirovna — Doctor of Medical Sciences, Leading Researcher at the Reanimation and Intensive Care Department No. 2 of the Institute of Neonatology and Pediatrics, Head of Academic Affairs, Professor at the Department of Neonatology of the Institute of Professional Education of the 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 Premature Infants at Perinatal Center No. 1 of the Regional Children's Clinical Hospital, Yekaterinburg, Member of the Council of the Russian Society of Neonatologists, Yekaterinburg;
Sapun Olga Ilyinichna — Head of the Neonatal Intensive Care Unit No. 2 of the Children's Regional Clinical Hospital, Krasnodar, Chief Freelance Neonatologist of the Ministry of Health of Krasnodar Krai, Assistant at the Department of Pediatrics with a Course in Neonatology at Kuban State Medical University, Member of the Council of the Russian Society of Neonatologists, Krasnodar.
Conflict of interest:
All members of the Working Group have confirmed that they have no financial support or conflicts of interest to disclose.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
specialists with higher medical education in the following specialties:
Neonatology;
Pediatrics;
Anesthesiology and Critical Care Medicine;
Obstetrics and Gynecology;
Clinical Pharmacology;
Microbiology;
Neurology;
Methodology
Methods used for collecting/selecting evidence: electronic database search.
Description of methods used for evidence collection/selection: the evidence base for the guidelines includes publications from the Cochrane Library, EMBASE and MEDLINE databases, and the electronic library (www.elibrary.ru). The search depth was 28 years.
Methods used for assessing the quality and strength of evidence:
8. expert consensus;
9. evaluation of significance according to the rating scheme (Tables A 2.1, A 2.2).
Methods used for analyzing evidence:
10. reviews of published meta-analyses;
11. 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 is examined to ensure its validity. The result of this evaluation affects the level of evidence assigned to the publication, which in turn affects the grade of the resulting recommendations.
Methodological evaluation is based on several key questions focused on those study design features that have a substantial impact on the validity of the results and conclusions. These key questions may vary depending on the study types and the questionnaires used to standardize the publication evaluation process.
The evaluation process is undoubtedly subject to subjective bias. To minimize potential errors, each study was evaluated independently, i.e., by at least two independent members of the working group. Any discrepancies in evaluations were discussed by the full working group. If a consensus could not be reached, an independent expert was involved.
Evidence tables were completed by the members of the working group.
Methods used for formulating recommendations: expert consensus.
Method of recommendation 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. Feedback was obtained from primary care physicians and district general practitioners regarding the clarity of the presentation of the recommendations and their assessment of the importance of the recommendations 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 chairman and members of the working group.
Each item was discussed, and the resulting changes made to the recommendations were recorded. If no changes were made, the reasons for refusing to make changes were recorded.
Consultation and peer review:
The latest changes to these guidelines are presented for discussion in a preliminary version. The preliminary version has been posted for broad discussion on the website of the Russian Association of Perinatal Medicine Specialists (RAPMS) www.raspm.ru, so that individuals not participating in the congress have the opportunity to take part in the discussion and improvement of the guidelines.
The draft recommendations were also 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.
Working Group:
For the final edition and quality control, the guidelines were re-analyzed by the working group members, who concluded that all expert comments and feedback had been taken into account and the risk of bias in the development of the guidelines was minimized.
Table 1. Scale for assessing levels of evidence (LE) 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
These clinical guidelines have been developed taking into account the following regulatory legal documents:
Methodological letter edited by Prof. E.N. Baybarina, "Resuscitation and Stabilization of Newborn Infants in the Delivery Room" dated March 4, 2020.
Procedure for the Provision of Medical Care in the Profile "Obstetrics and Gynecology (Excluding Assisted Reproductive Technologies)" (Order of the Ministry of Health of the Russian Federation No. 1130n dated October 20, 2020).
Order of the Russian Ministry of Health dated April 17, 2025, No. 222n "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).
Approved Professional Standard "Neonatologist" by Order of the Ministry of Labor and Social Protection of the Russian Federation No. 136n dated March 14, 2018.
International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) (World Health Organization) 1994.
Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services" (as amended on September 24, 2020).
Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Health Protection of Citizens in the Russian Federation."
Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019, "On Approval of the List of Vital and Essential Drugs for 2020" as amended on November 23, 2020, No. 3073-r.
Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 44 dated December 24, 2020, On Approval of Sanitary Rules SP 2.1.3678-20 "Sanitary and Epidemiological Requirements for the Operation of Premises, Buildings, Structures, Equipment and Transport, as well as the Working Conditions of Business Entities Engaged in the Sale of Goods, Performance of Work or Provision of Services".
Appendix B. Physician Action Algorithms
*Complete clinical blood count (CBC) with differential, general therapeutic biochemical blood analysis (glucose, electrolyte profile, total and direct bilirubin), CRP, neurosonography.
** The expanded scope of examination is determined individually, except for cases of severe apnea, and may include:
- Acid-base balance and blood gas analysis;
- Microbiological (cultural) blood test for sterility;
- Chest X-ray and/or lung ultrasound;
- Echocardiography.
In case of severe apnea, all items of the expanded examination should be performed.
*** When identifying diseases/conditions where one of the symptoms may be apnea (polycythemia, hypo- and hyperglycemia, electrolyte disorders, systemic infectious process, intraventricular hemorrhage, neonatal seizures, etc.), efforts should be directed toward treating these pathological conditions.
Appendix C. Patient Information
Apnea of prematurity is a cessation of breathing lasting more than 15–20 seconds, or of shorter duration but accompanied by bradycardia (< 100 bpm) and/or desaturation (< 85%), in an infant with a gestational age of less than 37 weeks, in the absence of any known underlying disease causing the apnea.
The primary regulatory center for respiration in newborns, as in adults, is the respiratory center located in the medulla oblongata, which functions based on the continuous receipt of signals regarding the internal environment. The respiratory center ensures a constant rhythm of respiratory movements and matches respiration to the metabolic demands of the body.
Through a system of nerve impulses directed to the respiratory muscles, the respiratory center influences the rate and depth of respiratory movements.
In a premature infant, the central and peripheral mechanisms controlling breathing are "tuned" according to intrauterine principles, and spontaneous breathing is unstable, punctuated by frequent breathing pauses. Apnea of prematurity is traditionally associated with immaturity of the respiratory center. The frequency and severity of apnea are inversely proportional to the gestational age at birth.
Central apnea is a complete cessation of inspiration with no signs of upper airway obstruction. This condition is typically caused by the immaturity of neurons in the respiratory center that control the breathing process. It is the most common type of apnea in premature infants.
Risk factors for apnea in premature newborns include: birth at 32 weeks of gestation or earlier, very low or extremely low birth weight, birth trauma, and abnormal blood glucose or electrolyte levels according to biochemical blood tests.
When an episode of apnea occurs in premature newborns, it is necessary to perform a visual examination of the infant, check the patency of the upper airways, and conduct an in-depth examination of the premature infant to rule out neonatal infection and manifestations of seizure syndrome. In the event of an apnea attack in a premature newborn, you should perform tactile stimulation and ensure free movement of the infant's limbs. Tactile stimulation techniques include rubbing and tapping the baby's palms and soles (both sides), gentle massage of the palms and soles (both sides) with the thumb, and passive limb movements by flexing them at major joints (shoulder, elbow, knee) for several minutes. After stabilization, it is advisable to place an infant who has developed apnea in an optimal prone position. Positional therapy should only be provided in combination with respiratory and drug therapy, due to unproven efficacy as a standalone treatment method.
The primary treatment for apnea of prematurity is the administration of caffeine citrate (ATX code N06BC). The leading effect of caffeine citrate (ATX code N06BC) in the treatment of apnea of prematurity is central nervous system stimulation. Caffeine citrate (ATX code N06BC) produces the following effects: stimulates the respiratory center of the premature infant, lowers the threshold of sensitivity to carbon dioxide accumulation in the infant's blood, enhances the body's response to carbon dioxide accumulation, increases the tone of the diaphragm (thoracoabdominal barrier), and increases the amplitude of respiratory chest movements, especially during sleep.
The drug is approved for use in the neonatal period via intravenous administration and orally. In clinical practice, when nursing extremely premature infants in an intensive care unit due to the severity of their condition, the drug is typically administered intravenously first, followed by a switch to oral administration after their condition stabilizes.
The decision to discontinue caffeine citrate (ATX code N06BC) therapy is made in the absence of apnea episodes in the spontaneously breathing premature infant over an observation period of 5-7 days, or when the infant reaches 37 weeks of postconceptual age.
Positive airway pressure via nasal cannulas is an effective treatment method in premature infants who have developed apnea when drug therapy is ineffective. It helps improve upper airway patency, prevents airway collapse, and stimulates spontaneous breathing efforts.
The decision to discontinue respiratory therapy in premature newborns diagnosed with apnea is made individually by the attending physician based on a combination of clinical and laboratory data in the absence of clinical manifestations of apnea during ongoing therapy.
Methods for preventing apnea in premature newborns do exist.
Extremely premature newborns who are breathing spontaneously or receiving non-invasive respiratory therapy, as well as those on mechanical ventilation prior to planned extubation, are recommended early administration of #caffeine citrate (ATX code N06BC) for the prevention of apnea, minimization of the need for and duration of invasive mechanical ventilation, and long-term complications.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not applicable.