The onset of AOP is typically within the first 48 hours of life although it can take up to a week to manifest. Typically, a lower GA is correlated to a lengthier duration of this condition.

Bradycardia occurs in the different subtypes of apnea, especially in infants with longer episodes of the disorder. Moreover, this phenomenon is observed in 75% of apneic events that continue for more than 20 s where is it is seen in 10% of spells that last 10s to 14s. Typically, the drop in the heart rate is more than 30% from the baseline.

Additionally, one study discovered that oxygen desaturation precedes bradycardia although the latter recovers first [5]. Bradycardia may occur without desaturation as well.

Physical exam

Neonates with apnea demonstrate notable findings such as absent wall movement, cyanosis, and hypotonia [1]. The patient is typically gasping for air during these episodes. Additionally, auscultation of the lungs yields no breath sounds [8].

The NICU staff should obtain the antenatal history, examine the patient, and order the relevant studies. Additionally, all premature neonates should be monitored closely especially in terms of the cardiac, respiratory, and neurologic status.

Physical exam

Observation of the neonate's vital signs is a key component of the exam. The patient should be placed on a cardiorespiratory monitor, which allows the NICU staff to detect apnea and measure the blood pressure. The patient's heart rate and blood pressure will exhibit findings that are indicative of reflex. Additionally, a pulse oximeter is used to obtain the oxygen saturation levels, which reflects the degree and the duration of apnea.

Additionally, the clinicians should monitor the neonate's breathing patterns, oxygen levels, and heart rate during feeding, awake and sleep times and in the prone and supine positions.

Laboratory tests

Infectious causes are investigated with a complete blood count (CBC), and blood, urine, and cerebrospinal fluid cultures. An electrolyte panel including glucose and mineral levels helps evaluate stressful events, metabolic conditions, or long-term hypoventilation. Also, metabolic diseases should be excluded with plasma and urine organic acid concentration as well as ammonia and amino acid measurements.

Imaging

Neonates with wheezing and/or regurgitation should have chest radiography to assess the lower airway status. A milk scan may also be beneficial [9]. Patients featuring difficulties with swallowing or display anomalies such as tracheoesophageal fistula should undergo a barium swallow study. Finally, infants suspected to have pyloric stenosis or motility dysfunction warrant an abdominal ultrasound and gastric-emptying study.

The treatment of neonates with primary apnea takes into consideration the GA in addition to other factors related to the cause of the premature birth and the measurements of heart rate, oxygen saturation, and physical exam. The delivery room and NICU should be equipped with trained personnel who are able to resuscitate apneic infants according to the neonatal resuscitation program (NRP) algorithm.

Medication

Caffeine and other methylxanthines such as theophylline and aminophylline improve apnea by stimulating the respiratory drive [3] and central nervous system. Preterm neonates receive caffeine or theophylline until they reach a GA of 34 to 35 weeks. Specifically, caffeine is administered orally or intravenously at a dose of 20 mg/kg, which is subsequently followed by a maintenance dose of 5 mg/kg daily [10]. The IV form of theophylline is aminophylline [11], which is given at a loading dose of 5–6 mg/kg and a daily maintenance with 2 to 6 mg/kg split into several doses [12].

Assisted ventilation

Another important component in the treatment of these patients is continuous positive airway pressure (CPAP), which is delivered at 4 to 6 cm H2O to prevent atelectasis of the alveoli and pharyngeal collapse. Another option is the nasal intermittent positive pressure ventilation (NIPPV).

Other

Further interventions include the particular positioning of the newborn while in the NICU. The prone position is effective in decreasing the frequency apneic episodes [13] as it provides chest wall stability and reduces thoracoabdominal asynchrony [14].

Home monitoring

From the cardiopulmonary standpoint, patients with AOP remain in hospital until they achieve resolution of apneic episodes. Moreover, discharge criteria typically include a 3 to 10 day period of no events while on continuous monitoring. Additionally, all infants must pass the car seat test prior to discharge.

Patients who experience these episodes that resolve without intervention may be eligible for home monitoring. These newborns are sent home with a cardiorespiratory monitor and possibly oral caffeine.

Education for parents and caretakers is paramount. They should learn how to utilize the monitor, understand when to intervene and how to perform cardiopulmonary resuscitation (CPR).

Apnea usually resolves in newborns as they reach 37 weeks of GA.

Initially, there can be a rise int he stroke volume, leading to systemic blood pressure and cerebral hypoperfusion that may eventually lead to brain injury.While severe cases of apnea may impact the neural development of the infant, the possible coexistence of other factors or conditions may impact this as well. Hence, no clear relationship has been established between apnea and long-term neurodevelopmental outcomes [7].

AOP, the most prevalent type of primary apnea, is idiopathic although experts indicate that this condition reflects the immature management of respiratory control in preterm infants. Specifically, an underdeveloped respiratory drive and an imbalance between the parasympathetic and sympathetic tones are factors that contribute to the development of AOP.

Additionally, primary apnea may occur secondary to disorders emerging from prematurity. There may be a genetic predisposition as well according to studies that have observed a familial association.

The incidence of AOP occurs more frequently in preterm neonates born at lower GAs. For example, almost all newborns born less that 29 weeks or weigh below 1,000 grams have AOP [2], in comparison to 55% of newborns with a GA of 30 to 31weeks and 7% at GA of 34 to 35 weeks [3].

There are 3 subtypes of apnea, which are central (10% to 25% of cases), obstructive (10% to 25% of cases), and mixed (at least half of all cases) [4]. They vary in terms of pathophysiology and clinical picture.

Central apnea is characterized by the absence of respiratory effort secondary to a failure in the central respiratory centers to stimulate afferent peripheral nerves and produce stimulation of the respiratory muscles. This lack of communication between the brain and respiratory muscles in response to hypercapnia is observed in premature neonates due to immaturity. Note that there are secondary causes such head trauma and toxin-induced apnea but these are beyond the scope this topic.

Patients with obstructive apnea develop this due to a partial or complete occlusion of the airway while the mixed subtype features elements of both central and obstructive apnea.

Neurologic effects

Preterm infants with AOP exhibit episodes of oxygen desaturation and possibly reflex bradycardia, which are two variables that promote changes in the cerebral hemodynamics. For example, shortly after hypoxemia, the heart rate falls and the stroke volume increases [5]. However, this is not sustained in prolonged episodes of apnea and bradycardia, which are characterized by systemic hypotension and cerebral hypoperfusion [6]. These mechanisms may lead to hypoxic brain injury [6].

One of the main approaches to preventing poor outcomes in the discharged infant is by proper placement of the infant in the supine position [13] with the head centered and the neck kept neutrally.

Apnea refers to an interruption of respiratory airflow or a cessation of airflow. Apnea is usually classified as central, obstructive, or mixed according to the underlying pathophysiology. The most common type of primary apnea is known as apnea of prematurity (AOP), which usually occurs in an infant born prior to 37 weeks of gestational age (GA). Specifically, the definition of AOP [1] is a pause in breathing that is 1) greater than 20 seconds or 2) accompanied by oxygen desaturation with or without bradycardia.

The clinical picture manifests early in the neonatal period, usually within the first 2 days. The infant usually gasps or demonstrates labored breathing and/or cyanosis. Generally, the risk of AOP is inversely related to the GA. Note that brief pauses lasting 5 to 10 seconds are normal in the preterm neonate.

All newborns undergo full physical exams immediately after birth. High-risk infants such as those who are born preterm are placed in the neonatal intensive care unit (NICU) where they are monitored carefully in terms of their cardiopulmonary status and other important elements such as feeding, weight gain, etc. The medical team should also ascertain the antenatal and family history. All causes of apnea should be investigated and hence pertinent laboratory and imaging studies should be obtained as well.

Patients with AOP are treated with caffeine or other methylxanthines to increase the respiratory drive and the diaphragm contractility [1]. Additionally, assisted ventilation is also usually required in these patients to help to achieve the above goals.

While the long-term consequences of apnea are not understood, this condition may hinder neurological development and produce unfavorable outcomes although the exact relationship has not been fully elucidated.

The most common form of primary apnea is referred to as apnea of prematurity. As the name suggests, this occurs in babies born prematurely, which is before 37 weeks of gestational age. These patients do not have any other condition or disorder that lead to apnea, and therefore it is presumed the apneic episodes develop due to the immaturity of the central nervous system, obstruction of the airways, or a combination of both.

Specifically, the criteria of apnea are:

• A pause in breathing that lasts more than 20 seconds or
• Shorter pause that is accompanied with a low oxygen saturation and/or bradycardia (slow heartbeat)

The apneic episodes start in the first week, especially in the first 2 days of the newborn's life. The following features are usually seen:

• Gasping for breath
• Bluish discoloration of the skin
• Weak muscle tone
• No movement of the chest
• No breath sounds

The obstetric and neonatal teams should be prepared when babies are born preterm. The medical personnel should be trained in performing CPR in order to resuscitate babies experiencing difficulty with breathing.

Preterm neonates are admitted to the neonatal intensive care unit (NICU) where they are placed on heart and oxygen monitors to monitor their breathing, heart rate, blood pressure, and respiratory rate. Additionally, the medical staff will observe the infant's breathing patterns while feeding, sleeping, and other times.

A series of blood tests, possibly chest X-rays and other imaging tests are performed to rule out other disease or causes of apnea.

The main goal is to stimulate breathing, which can be achieved by:

• Treatment with caffeine
• Assisted ventilation

Also, the positioning of the neonate is very important. While in the NICU, the baby should sleep on his/her belly. However, once discharged at home, the patient should lay on his/her back, with the head kept midline and in a neutral position.

Babies are observed carefully and closely. If they have not had any episodes with breathing trouble for a certain period of time, they may be discharged. The neonates should have close follow-up appointments with the doctor. Also, parents should be educated on signs of breathing trouble and when to seek immediate medical care.

The prognosis is good as most cases resolve as the newborn reaches 37 weeks of gestational age.

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