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Apnea of Prematurity Eric C CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care Apnea of Prematurity Eric C. Eichenwald, MD, FAAP, COMMITTEE ON FETUS AND NEWBORN Apnea of prematurity is one of the most common diagnoses in the NICU. abstract Despite the frequency of apnea of prematurity, it is unknown whether recurrent apnea, bradycardia, and hypoxemia in preterm infants are harmful. Research into the development of respiratory control in immature animals and preterm infants has facilitated our understanding of the pathogenesis and treatment of apnea of prematurity. However, the lack of consistent defi nitions, monitoring practices, and consensus about clinical signifi cance leads to signifi cant variation in practice. The purpose of this clinical report is to review the evidence basis for the defi nition, epidemiology, and treatment of apnea of prematurity as well as discharge recommendations for preterm infants diagnosed with recurrent apneic events. BACKGROUND This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have Apnea of prematurity is one of the most common diagnoses in the NICU. fi led confl ict of interest statements with the American Academy of Pediatrics. Any confl icts have been resolved through a process Despite the frequency of apnea of prematurity, it is unknown whether approved by the Board of Directors. The American Academy of recurrent apnea, bradycardia, and hypoxemia in preterm infants are Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. harmful. Limited data suggest that the total number of days with apnea and resolution of episodes at more than 36 weeks’ postmenstrual age Clinical reports from the American Academy of Pediatrics benefi t from expertise and resources of liaisons and internal (AAP) and external (PMA) are associated with worse neurodevelopmental outcome in reviewers. However, clinical reports from the American Academy of preterm infants.1,2 However, it is difficult to separate any potential Pediatrics may not refl ect the views of the liaisons or the organizations or government agencies that they represent. adverse effects of apnea from the degree of immaturity at birth, because the incidence of apnea is inversely proportional to gestational age.3 The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking Research into the development of respiratory control in immature into account individual circumstances, may be appropriate. animals and preterm infants has facilitated our understanding of the All clinical reports from the American Academy of Pediatrics pathogenesis and treatment of apnea of prematurity (Table 1). However, automatically expire 5 years after publication unless reaffi rmed, the lack of consistent definitions, monitoring practices, and consensus revised, or retired at or before that time. about clinical significance leads to significant variation in practice.4–6 DOI: 10.1542/peds.2015-3757 The purpose of this clinical report is to review the evidence basis for PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). the definition, epidemiology, and treatment of apnea of prematurity as Copyright © 2016 by the American Academy of Pediatrics well as discharge recommendations for preterm infants diagnosed with recurrent apneic events. To cite: Eichenwald EC and AAP COMMITTEE ON FETUS AND NEWBORN. Apnea of Prematurity. Pediatrics. 2016;137(1):e20153757 Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 137 , number 1 , January 2016 :e 20153757 FROM THE AMERICAN ACADEMY OF PEDIATRICS DEFINITION AND CLASSIFICATION 38 weeks’ PMA is higher in infants Preterm infants with resolved apnea who were 24 to 26 weeks’ gestational also may have clinically unapparent An apneic spell is usually defined age at birth compared with those intermittent hypoxia events. In a as a cessation of breathing for 20 born at ≥28 weeks’ gestation.8 recent study in former preterm seconds or longer or a shorter pause Infants with bronchopulmonary infants after discontinuation of accompanied by bradycardia (<100 dysplasia may have delayed medical therapy for apnea, the mean beats per minute), cyanosis, or pallor. maturation of respiratory control, number of seconds/hour of oxygen In practice, many apneic events in which can prolong apnea for as long saturation less than 80% was 20.3 preterm infants are shorter than 20 as 2 to 4 weeks beyond term PMA.8 at 35 weeks’ PMA, decreasing to 6.8 seconds, because briefer pauses in In most infants, apnea of prematurity seconds/hour at 40 weeks’ PMA.12 airflow may result in bradycardia follows a common natural history, or hypoxemia. On the basis of with more severe events that require respiratory effort and airflow, intervention resolving first. Last to MONITORING FOR APNEA/ apnea may be classified as central resolve are isolated, spontaneously BRADYCARDIA (cessation of breathing effort), resolving bradycardic events of obstructive (airflow obstruction uncertain clinical significance.8 Most infants in NICUs are usually at the pharyngeal level), continuously monitored for or mixed. The majority of apneic heart rate, respiratory rate, and episodes in preterm infants are Most studies examining the time oxygen saturation. Cardiac alarms mixed events, in which obstructed course to resolution of apnea are most commonly set at 100 airflow results in a central apneic of prematurity have relied on beats per minute, although lower pause, or vice versa. nurses' recording of events in the medical record; however, alarm settings are acceptable in several studies have shown a lack convalescent preterm infants. EPIDEMIOLOGY AND TIME COURSE TO of correlation with electronically Apnea alarms are generally set RESOLUTION recorded events.9,10 Standard at 20 seconds. However, apnea NICU monitoring techniques are detection by impedance monitoring In an observational study, unable to detect events that are is potentially misleading. Impedance Henderson-Smart3 reported that primarily obstructive in nature. With monitoring is prone to artifact the incidence of recurrent apnea continuous electronic recording, attributable to body movement or increased with decreasing gestational it is evident that some preterm cardiac activity and is unable to age. Essentially, all infants born infants continue to have clinically detect obstructive apnea. Practices at ≤28 weeks’ gestation were unapparent apnea, bradycardia, and differ as to when continuous diagnosed with apnea; beyond 28 oxygen desaturation events even oximetry is discontinued. In a study weeks’ gestation, the proportion of after discharge. The Collaborative investigating the age at last recorded infants with apnea decreased, from Home Infant Monitoring Evaluation apnea and age at discharge from the 85% of infants born at 30 weeks’ Study examined the occurrence of hospital in 15 different NICUs, the gestation to 20% of those born at 34 apnea/bradycardia events in >1000 duration of use of pulse oximetry was weeks’ gestation. This relationship preterm and healthy term infants significantly different among hospital has important implications for NICU 5 monitored at home.11 “Extreme sites. Later discontinuation of pulse policy, because infants born at less events” (apnea >30 seconds and/or oximetry was associated with a later than 35 weeks’ gestation generally heart rate <60 beats per minute for PMA at recorded last apnea and require cardiorespiratory monitoring >10 seconds) were observed most longer length of stay, suggesting that after birth because of their risk frequently in former preterm infants, oximetry may detect events that of apnea. As expected with a decreasing dramatically until about cardiorespiratory monitoring does developmental process, some infants 43 weeks’ PMA. After 43 weeks’ PMA, not. born at 35 to 36 weeks’ gestation “extreme events” in both preterm There are no data to suggest that a may have respiratory control and term infants were very rare. diagnosis of apnea of prematurity is instability, especially when placed in a semiupright position.7 In Henderson-Smart’s study, apneic TABLE 1 Factors Implicated in the Pathogenesis of Apnea of Prematurity spells stopped by 37 weeks’ PMA in Central Mechanisms Peripheral Refl ex Pathways 92% of infants and by 40 weeks’ PMA Decreased central chemosensitivity Decreased carotid body activity in more than 98% of infants.3 The Hypoxic ventilatory depression Increased carotid body activity proportion of infants with apnea/ Upregulated inhibitory neurotransmitters Laryngeal chemorefl ex bradycardia events persisting beyond Delayed central nervous system development Excessive bradycardic response Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS associated with an increased risk of with resultant excitation of gestation who do not require sudden infant death syndrome (SIDS) respiratory neural output, as well as positive pressure support, one or that home monitoring can prevent blockade of excitatory adenosine A2A reasonable approach would be SIDS in former preterm infants. receptors located on γ-aminobutyric to await the occurrence of apnea Although infants born preterm have acidergic neurons. Specific before initiating therapy.20 In the a higher risk of SIDS, epidemiologic polymorphisms in the A1 and A2A Caffeine for Apnea of Prematurity and physiologic data do not support
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