Apnea of prematurity

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Apnea of prematurity
Specialty Pediatrics

Apnea of prematurity is a disorder in infants who are preterm that is defined as cessation of breathing (apnea) that lasts for more than 20 seconds and/or is accompanied by hypoxia or bradycardia. Apnea of prematurity is often linked to earlier prematurity (younger gestational age). [1]

Contents

Apnea is traditionally classified as either obstructive, central, or mixed:

Over 50% of infants who are born preterm are estimated to be affected by apnea of prematurity. [2] Infants who are born weighing less than 1000g have close to a 100% risk of being affected by apnea of prematurity. Most premature infants are affected by 'central' apnea due to the developmental stage of their respiratory tract. [2]

Apnea of prematurity can increase the risk of chronic health conditions including retinopathy and increases the risk of problems with the infant's neurological development. Apnea lasting more than 60 seconds may result in death or disability. [2]

The main treatment for apnea of prematurity has been pharmaceutical treatment with methylxanthines that have a mechanism of action of bronchodilation and a stimulant of the respiratory system to promote spontaneous breathing. Caffeine, theophylline, and minophylline are the common medications used.

Pathophysiology

Ventilatory drive is primarily dependent on response to increased levels of carbon dioxide (CO2) and acid in the blood. A secondary stimulus is hypoxia. Responses to these stimuli are impaired in premature infants due to immaturity of specialized regions of the brain that sense these changes. In addition, premature infants have an exaggerated response to laryngeal stimulation (a normal reflex that closes the airway as a protective measure). [1]

Diagnosis

Apnea of prematurity can be readily identified from other forms of infant apnea such as obstructive apnea, hypoventilation syndromes, breathing regulation issues during feeding, and reflux associated apnea with an infant pneumogram or infant apnea/sleep study.

It has been reported that the incidence of neonatal apnea happens in almost all infants with gestational age of less than 29 weeks or the birth weight of less than 1000g. [3] [4] [5]

Treatment

Medications

Methylxanthines (theophylline and caffeine) have been used for almost three decades to treat apnea of prematurity. [6] These medications are thought to help by stimulating the preterm infant's respiratory drive, increasing activity of the diaphragm muscles, and by bronchodilation. There is some evidence that these medications can reduce to need for mechanical ventilation in preterm infants. [2] There is no clear evidence to determine which type of methylxanthine formulation is more effective for preterm infants. [2] The long term effects of this treatment approach has not been well studied. There is also not a lot of evidence to support the most effective way to treat very young preterm infants such as those who are born earlier than 28 weeks of gestational age. [2]

Respiratory support

Simple tactile stimulation by touching the skin or patting the infant may stop an apneic episode by raising the infant's level of alertness. Increasing the environmental oxygen level by placing the infant in a tent or hood with supplemental oxygen can diminish the frequency of AOP, and may also help the infant maintain adequate oxygenation during short episodes of apnea. Increased oxygen at low levels can also be delivered using a nasal cannula, which additionally may provide some stimulation due to the tactile stimulation of the cannula. CPAP (continuous positive airway pressure) is sometimes used for apnea when medications and supplemental oxygen are not sufficient. Usually as a last resort, mechanical ventilation is used to support infants whose apnea cannot be controlled sufficiently by other methods and where the potential risk of harm from recurrent hypoxia is felt to outweigh the risks of injury from ventilation.

Monitoring

In-hospital monitors in the NICU typically measure respiratory movements, heartrate, and pulse oximetry. Central apnea can be detected quickly since it results in absence of respiratory movements. Obstructive apnea can be detected when the level of oxygen has declined in the blood and/or results in slowing of the heart rate.

Home apnea monitors (which must be distinguished from infant monitors that are designed only to allow parents to listen to the infant remotely) most frequently measure only respiratory movements and/or heart rate. They are generally used with premature infants who are otherwise ready for discharge, but who continue to require supplemental oxygen or medication for mild residual AOP. Home apnea monitoring is typically required for 6–12 weeks after discharge.

Outcome

Since AOP is fundamentally a problem of the immaturity of the physiological systems of the premature infant, it is a self-limited condition that will resolve when these systems mature. It is unusual for an infant to continue to have significant problems with AOP beyond 43 weeks post-conceptual age.

Infants who have had AOP are at increased risk of recurrence of apnea in response to exposure to anesthetic agents, at least until around 52 weeks post-conceptual age.

There is no evidence that a history of AOP places an infant at increased risk for SIDS. However, any premature infant (regardless of whether they have had AOP) is at increased risk of SIDS. It is important that other factors related to SIDS risk be avoided (exposure to smoking, prone sleeping, excess bedding materials, etc.)

Epidemiology

Apnea of prematurity occurs in at least 85 percent of infants who are born at less than 34 weeks of gestation. The incidence is inversely related to the gestational maturity of the infant, but has considerable individual variability.

Related Research Articles

<span class="mw-page-title-main">Hypoxia (medicine)</span> Medical condition of lack of oxygen in the tissues

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.

<span class="mw-page-title-main">Meconium aspiration syndrome</span> Medical condition affecting newborn infants

Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.

<span class="mw-page-title-main">Theophylline</span> Drug used to treat respiratory diseases

Theophylline, also known as 1,3-dimethylxanthine, is a drug that inhibits phosphodiesterase and blocks adenosine receptors. It is used to treat chronic obstructive pulmonary disease (COPD) and asthma. Its pharmacology is similar to other methylxanthine drugs. Trace amounts of theophylline are naturally present in tea, coffee, chocolate, yerba maté, guarana, and kola nut.

<span class="mw-page-title-main">Preterm birth</span> Birth at less than a specified gestational age

Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 34 weeks, late preterm birth is between 34 and 36 weeks' gestation. These babies are also known as premature babies or colloquially preemies or premmies. Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes and/or the leaking of fluid from the vagina before 37 weeks. Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and problems with their vision. The earlier a baby is born, the greater these risks will be.

Retinopathy of prematurity (ROP), also called retrolental fibroplasia (RLF) and Terry syndrome, is a disease of the eye affecting prematurely born babies generally having received neonatal intensive care, in which oxygen therapy is used because of the premature development of their lungs. It is thought to be caused by disorganized growth of retinal blood vessels and may result in scarring and retinal detachment. ROP can be mild and may resolve spontaneously, but it may lead to blindness in serious cases. Thus, all preterm babies are at risk for ROP, and very low birth-weight is an additional risk factor. Both oxygen toxicity and relative hypoxia can contribute to the development of ROP.

Fetal distress, also known as non-reassuring fetal status, is a condition during pregnancy or labor in which the fetus shows signs of inadequate oxygenation. Due to its imprecision, the term "fetal distress" has fallen out of use in American obstetrics. The term "non-reassuring fetal status" has largely replaced it. It is characterized by changes in fetal movement, growth, heart rate, and presence of meconium stained fluid.

<span class="mw-page-title-main">Infant respiratory distress syndrome</span> Human disease affecting newborns

Infant respiratory distress syndrome (IRDS), also known as surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins.

<span class="mw-page-title-main">Hypocapnia</span> State of reduced carbon dioxide in the blood

Hypocapnia, also known as hypocarbia, sometimes incorrectly called acapnia, is a state of reduced carbon dioxide in the blood. Hypocapnia usually results from deep or rapid breathing, known as hyperventilation.

<span class="mw-page-title-main">Neonatal intensive care unit</span> Intensive care unit specializing in the care of ill or premature newborn infants

A neonatal intensive care unit (NICU), also known as an intensive care nursery (ICN), is an intensive care unit (ICU) specializing in the care of ill or premature newborn infants. The NICU is divided into several areas, including a critical care area for babies who require close monitoring and intervention, an intermediate care area for infants who are stable but still require specialized care, and a step down unit where babies who are ready to leave the hospital can receive additional care before being discharged.

Perinatal asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. It remains a serious condition which causes significant mortality and morbidity. It is also the inability to establish and sustain adequate or spontaneous respiration upon delivery of the newborn, an emergency condition that requires adequate and quick resuscitation measures. Perinatal asphyxia is also an oxygen deficit from the 28th week of gestation to the first seven days following delivery. It is also an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs and may be associated with a lack of ventilation. In accordance with WHO, perinatal asphyxia is characterised by: profound metabolic acidosis, with a pH less than 7.20 on umbilical cord arterial blood sample, persistence of an Apgar score of 3 at the 5th minute, clinical neurologic sequelae in the immediate neonatal period, or evidence of multiorgan system dysfunction in the immediate neonatal period. Hypoxic damage can occur to most of the infant's organs, but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity.

Necrotizing enterocolitis (NEC) is an intestinal disease that affects premature or very low birth weight infants. Symptoms may include poor feeding, bloating, decreased activity, blood in the stool, vomiting of bile, multi-organ failure, and potentially death.

Antenatal steroids, also known as antenatal corticosteroids, are medications administered to pregnant women expecting a preterm birth. When administered, these steroids accelerate the maturation of the fetus' lungs, which reduces the likelihood of infant respiratory distress syndrome and infant mortality. The effectiveness of this corticosteroid treatment on humans was first demonstrated in 1972 by Sir Graham Liggins and Ross Howie, during a randomized control trial using betamethasone.

<span class="mw-page-title-main">Periventricular leukomalacia</span> Degeneration of white matter near the lateral ventricles of the brain

Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis of white matter near the lateral ventricles. It can affect newborns and fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. The white matter in preterm born children is particularly vulnerable during the third trimester of pregnancy when white matter developing takes place and the myelination process starts around 30 weeks of gestational age.

<span class="mw-page-title-main">Bronchopulmonary dysplasia</span> Medical condition

Bronchopulmonary dysplasia is a chronic lung disease which affects premature infants. Premature (preterm) infants who require treatment with supplemental oxygen or require long-term oxygen are at a higher risk. The alveoli that are present tend to not be mature enough to function normally. It is also more common in infants with low birth weight (LBW) and those who receive prolonged mechanical ventilation to treat respiratory distress syndrome. It results in significant morbidity and mortality. The definition of bronchopulmonary dysplasia has continued to evolve primarily due to changes in the population, such as more survivors at earlier gestational ages, and improved neonatal management including surfactant, antenatal glucocorticoid therapy, and less aggressive mechanical ventilation.

<span class="mw-page-title-main">Analeptic</span> Drug class

An analeptic, in medicine, is a central nervous system stimulant. The term "analeptic" typically refers to respiratory stimulants. Analeptics are central nervous system (CNS) stimulants that include a wide variety of medications used to treat depression, attention deficit hyperactivity disorder (ADHD), and respiratory depression. Analeptics can also be used as convulsants, with low doses causing patients to experience heightened awareness, restlessness, and rapid breathing. The primary medical use of these drugs is as an anesthetic recovery tool or to treat emergency respiratory depression. Other drugs of this category are prethcamide, pentylenetetrazole, and nikethamide. Nikethamide is now withdrawn due to risk of convulsions. Analeptics have recently been used to better understand the treatment of a barbiturate overdose. Through the use of agents, researchers were able to treat obtundation and respiratory depression.

Anemia of prematurity (AOP) refers to a form of anemia affecting preterm infants with decreased hematocrit. AOP is a normochromic, normocytic hypoproliferative anemia. The primary mechanism of AOP is a decrease in erythropoietin (EPO), a red blood cell growth factor.

Wilson–Mikity syndrome, a form of chronic lung disease (CLD) that exists only in premature infants, leads to progressive or immediate development of respiratory distress. This rare condition affects low birth babies and is characterized by rapid development of lung emphysema after birth, requiring prolonged ventilation and oxygen supplementation. It is closely related to bronchopulmonary dysplasia (BPD), differing mainly in the lack of prior ventilatory support. All the initial patients described with Wilson–Mikity syndrome were very low birth weight infants that had no history of mechanical ventilation, yet developed a syndrome that clinically resembled BPD. Upon the death of some of these infants, autopsies showed histologic changes similar to those seen in BPD.

Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated with a reduction in blood oxygen saturation. CSA is usually due to an instability in the body's feedback mechanisms that control respiration. Central sleep apnea can also be an indicator of Arnold–Chiari malformation.

Late preterm infants are infants born at a gestational age between 34+0⁄7 weeks and 36+6⁄7 weeks. They have higher morbidity and mortality rates than term infants due to their relative physiologic and metabolic immaturity, even though they are often the size and weight of some term infants. "Late preterm" has replaced "near term" to describe this group of infants, since near term incorrectly implies that these infants are "almost term" and only require routine neonatal care.

Infantile apnea is a rare disease that is characterized by cessation of breathing in an infant for at least 20 seconds or a shorter respiratory pause that is associated with a slow heart rate, bluish discolouration of the skin, extreme paleness, gagging, choking and/or decreased muscle tone. Infantile apnea occurs in children under the age of one and it is more common in premature infants. Symptoms of infantile apnea occur most frequently during the rapid eye movement (REM) stage of sleep. The nature and severity of breathing problems in patients can be detected in a sleep study called a polysomnography which measures the brain waves, heartbeat, body movements and breathing of a patient overnight. Infantile apnea can be caused by developmental problems that result in an immature brainstem or it can be caused other medical conditions. As children grow and develop, infantile apnea usually does not persist. Infantile apnea may be related to some cases of sudden infant death syndrome (SIDS) however, the relationship between infantile apnea and SIDS is not known.

References

  1. 1 2 3 4 5 Martin R.J.; et al. (2002). "Pathophysiologic Mechanisms Underlying Apnea of Prematurity". NeoReviews. 3 (4): e59–e65. doi:10.1542/neo.3-4-e59.
  2. 1 2 3 4 5 6 Moresco, Luca; Sjögren, Alice; Marques, Keri A; Soll, Roger; Bruschettini, Matteo (2023-10-04). Cochrane Neonatal Group (ed.). "Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants". Cochrane Database of Systematic Reviews. 2023 (10). doi:10.1002/14651858.CD015462.pub2. PMC   10548499 . PMID   37791592.
  3. ↑ Dong LB, Li YF, Zhang Y, Qiao S. A pilot study of limb stimulation for the treatment of neonatal apnea. Medicine (Baltimore). 2018;97(49):e12827. doi:10.1097/MD.0000000000012827.
  4. ↑ Martin RJ, Abu-Shaweesh JM, Baird TM. Apnoea of prematurity.Paediatr Resp Rev 2004;5(suppl A):S377–82
  5. ↑ Robertson CM, Watt MJ, Dinu IA. Outcomes for the extremelypremature infant: what is new? And where are we going. Pediatr Neurol2009;40:189–96.
  6. ↑ Baird, T.M.; et al. (2002). "Clinical Associations, Treatment, and Outcome of Apnea of Prematurity". NeoReviews. 3 (4): e66–e70. doi:10.1542/neo.3-4-e66.
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