Apnea in infants
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《美国医学杂志》
1 Clinic of Sleep Disorders, School of Medicine, National University of Mexico ; Laboratory of Cognitive Neurophysiology, National Institute of Rehabilitation, Mexico City,2 Department of Neonatology, National Medical Center "20th of November", ISSSTE ; Department of Neonatology, General Hospital n. 32, IMSS, Mexico City,3 Mexican Center for Neuropediatrics, Mexico City,
Abstract
Objective. The main objective of this study was to describe frequency of risk factors in newborns who present different types of apnea in polysomnographic (PSG) recordings in neonatal care units. Methods. The study was carried out in neonatal care units of a perinatal tertiary level institution in Mexico City between August 2002 and August 2003. Infants were selected from among 223 infants if they presented any type of apnea event in sleep PSG recordings. Results. Nearly 25% of patients from a neonatal care unit presented apnea events. Infants with apnea showed lower values of age, weight, and cephalic perimeter at birth than infants without apnea, but did not show more neurologic risk factors. Central apnea events were more frequent in infants with preterm birth (birthweight <1,500 g), obstructive apnea events were observed in infants with hyperbilirubinemia and gastro-esophageal reflux, while mixed events were seen in infants with sepsis, and hyperbilirubinemia. Sleep PSG recordings detected that 36% of infants with apnea have no previous clinic suspicion of the problem. Conclusion. Central events of apnea were found more frequent in infants with preterm birth, obstructive events in newborns with hyperbilirubinemia and gastroesophagic reflux, while infants mixed apnea had more frequent hyperbilirubinemia and sepsis.
Keywords: Newborns; Apnea; Polysomnography
Apnea in newborns is defined as absence of breathing for 20 sec or longer, or at a shorter time if bradycardia of < 100 beats/min, cyanosis, and/or hypotension is present.[1],[2] Apnea is classified as central, obstructive, and mixed. Central apnea is present when epochs of absence of nasal air flow and thoracic breathing are identified, obstructive apnea is recognized when respiratory thoracic movements are present but nasal air flow is inadequate, and mixed type is present when events begin or end with central or obstructive apnea and change to the other type of apnea.[3]
Sleep polysomnography (PSG) is the most adequate electrophysiologic test to identify apnea in preterm and at-term newborns, and must be performed in all infants with risk factors. Because there is no consensus with regard to the alterations related with each type of apnea in newborns, the objective of this research was to describe frequency of risk factors in newborns for presenting each type of apnea in a sample of infants at two of the main neonatal care units in Mexico City.
Materials and methods
Subjects
The study was carried out at a tertiary-level medical center for care of high-risk newborns at Intensive Neonatal Care Unit and at the Transitional Neonatal Care Unit, between August 15, 2002 and August 9, 2003 in Mexico City. Newborns were selected if they presented any risk factor for apnea during neonatal period (such as preterm birth, low Apgar score, sepsis, and others) when infants were stable and not mechanically ventilated. The sample was divided in infants that presented and those that did not presented apnea events on PSG studies. Newborns were studied by a neurologic examination, transfontanelar ultrasonography, and laboratory tests. Two hundred twenty three patients were studied
[Table - 1]. One hundred twenty nine were females (57.84%). One hundred thirty one patients were born weighting <1,500 g (58.74%). Apgar score at 1 min was = or <3 in 53 patients, other clinical data were obtained from hospital records. Apnea events were recognized in 55 patients (24.66%). The study was approved by research committee of the hospital and parents of infants signed approbation.
Polysomnography
PSG studies were carried out during a period of a 45 min of sleep or more time until an awake-sleep period was completed. Electrode impedance was always <5 kilo-Ohms. Recordings were performed in a 24-channel digital polysomnographer (Bravo, Nicolet, Madison, WI, USA) with 16 channels for electroencephalography (EEG), an additional channel for electromyography (EMG), two additional channels for electro-oculography (EOG), one additional channel for electrocardiography (ECG), and four channels for respiration (pneumography). Gold disk electrodes were placed according to the 10-20 International System modified for newborns.[4] The authors used bipolar EEG montage. Band pass filters were set between 0.1 and 35 Hertz (Hz). Technician recorded any change in infant behavior during the recording session according criteria of behavioral states.[5] Brain electric activity was divided into following frequency bands: delta (0.1-3.75 Hz); theta (4-7.75 Hz); alpha (8-13 Hz) and beta (14-35 Hz) and topographically divided in the following regions: frontal, central, parietal, occipital, and temporal. The PSG study was evaluated using epochs of 30 sec for identifying indeterminate, active, and quiet sleep.[6],[7] EMG recording was performed at the chin and was qualified as presence or absence of myogenic potentials. EOG activity was measured at external angles of eye and qualified as presence or absence of eye movements. ECG was measured by placing electrodes on thorax under clavicles and was evaluated for variations in QRS frequency in search for bradycardia. Respiration was measured by means of a nasal thermistor, and impedance pneumatic electrodes it was visually revised in search of apnea events.
Statistical Analysis
Descriptive analysis was performed to determine arithmetic mean, and standard deviation (SD), and percents. We performed Student t test and analyses of variance comparisons for continuous variables, Tukey tests were performed post-hoc to pinpoint differences between types of apnea. For binomial variables we use Fisher exact test. Alpha value a priori was <0.05.
Results
The authors detected apnea events in 55 patients (24.66%). Comparison of clinic characteristics between infants with and without apnea is shown in [Table - 2], significant differences were found with regard to age, weight, and cephalic perimeter at birth, with lower values in the group of infants with apnea as expected by previous literature. No statistical differences in main risk factors such as: sepsis, intraventricular hemorrhage, hyperbilirubinemia, hypoxic-ischemic encephalopathy, meningitis and TORCH in infants with and without apnea were seen. Although each patient can have more than one type of apnea, forty patients showed central apnea events (72.72%), six manifested obstructive events (10.90%), and nineteen demonstrated mixed events (34.54%). Some infants presented only one type of apnea: central ( n = 31), obstructive ( n = 5) and mixed ( n = 10). Comparison of characteristics among these groups showed significant differences in weight at birth, cephalic perimeter, and one-min Apgar score with lower values in infants with central and obstructive apnea than infants with mixed apnea [Table - 3] Tukey test revealed significant differences in weight at birth between central and mixed groups with regard to infants with obstructive events; and in cephalic perimeter among group of mixed apnea to the other two groups; and in Apgar score at one min in groups of obstructive and mixed apnea to group of infants with central events. Frequency of three main risk factors identified in patients with only one type of apnea showed significant differences when compared with infants without apnea in birthweight <1,500 g in the group of infants with central apnea; and in hyperbilirubinemia and gastroesophagic reflux in infants with obstructive apnea; and in hyperbilirubinemia and sepsis in infants with mixed events of apnea [Table - 4]. The main pharmacologic agents used for apnea treatment were theophylline ( n = 21, 38.18%) and aminophylline ( n = 14, 25.45%), nonetheless twenty patients (36.36%) were without treatment at time of study because they were not identified as having apnea events previously.
Discussion
The authors search for risk factors frequency in infants with different types of apnea documented by PSG in neonatal care units. They found that nearly one quarter of infants experienced apnea events. Two previous studies report frequency of apnea in newborns,[8],[9] however because their definition of apnea is absence of breathing for six and three seconds respectively results is not comparable to our data.
Data from our work underlines PSG usefulness to detect apnea including infants in whom clinic vigilance has not identified events (such as obstructive and mixed). In pre-term infants, recurrent apnea represent a clinical problem and are dangerous for short- and long-term[10],[11] neurologic status, thus, it is mandatory to study the pathophysiology of events for a therapeutic rationality.
Central apnea was the most frequent type of apnea in preterm infants; evidence related this kind of apnea with breathing control centers immaturity.[12] Authors data are in agreement with this hypothesis: 72.72% of their patients had central apnea and born more frequent with birthweight <1,500 g than infants without apnea. Obstructive apnea had more frequently hyperbilirubinemia and gastro-esophagic reflux. Obstructive events may be associated with hypotonus of the upper air pathway muscles after hiperbilirubinemic encephalopathy and with regurgitation events respectively.[13],[14] An alternative explanation suggests that obstructive apnea may be associated with a postural defect or decrease in muscle tone and a consequent reduction in dimensions of upper respiratory tract.[15] Mixed apneas had most frequently sepsis and hyperbilirubinemia, suggesting that share some pathophysiologic mechanisms with other types of apnea, or may reflect effects of fever and infection in the central nervous system.[16]
Nearly one half of infants with apnea were not under pharmacological treatment because they had not yet been identified at time of study. Theophylline was the most frequent medication used in authors studied population and is in agreement with data from other investigations.[17],[18] Authors data suggest that PSG in newborns with neurologic risk factors must be mandatory to detect apnea in infants, including those in whom apnea events have not been previously identified.[19],[20]
References
1.Task Force on Prolonged Apnea. Prolonged apnea. Pediatrics 1978; 61: 651-652. [PUBMED]
2.Baird TM. Clinical correlates, natural history and outcome of neonatal apnoea. Semin Neonatol 2004; 9: 205-211. [PUBMED] [FULLTEXT]
3.Finer NN, Barrington KJ, Hayes BJ, Hugh A. Obstructive, mixed, and central apnea in the neonate: Physiologic correlates. J Pediatr 1992; 121: 943-950. [PUBMED]
4.Hofmann E, Havens B, Geidel S, Hoppenbrouwers T, Hodgman JE. Long-term, continuous monitoring of multiple physiological parameters in newborn and young infants. Acta Paediatr Scand 1977; suppl 266: 1-24.
5.Prechtl HFR. The behavioral states of the newborn (a review). Brain Res 1974; 76: 185-212.
6.Stockard-Pope JE, Werner JE, Bickford RG. Atlas of neonatal electroencephalography . New York, Raven Press. 1992
7.Cursi-Dascalova L, Mirmiran M. Manuel des techniques d′enregistrement et d′analyse des stades de sommeil et de veille chez le prιmaturι et le nouveau-nι a terme . Paris; éditions INSERM. 1996
8.Hoppenbrouwers T, Hodgman JE, Harper RM, Hofmann E, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life: III. Incidence of apnea and periodic breathing. Pediatrics 1977; 60: 418-425.
9.Kato I, Franco P, Groswasser J, Kelmanson I, Togari H, Kahn A. Frequency of obstructive and mixed sleep apneas in 1,023 infants. Sleep 2000; 23: 487-492.
10.Deykin E, Bauman ML, Kelly DH, Hsieh CC, Shannon D. Apnea of infancy and subsequent neurologic, cognitive, and behavioral status. Pediatrics 1984; 73: 638-645.
11.Poblano A. Neurophysiological studies in early detection of neurological damage (in Spanish). In: Poblano A (ed.). Early detection and intervention in infants with neurological damage . Mιxico, Editores de Textos Mexicanos. 2003; 101-129.
12.Denavi-Saubiι M, Kalia M, Pierrefiche O, Schweitzer P, Foultz AS, Champagnat J. Maturation of brain stem neurons involved in respiratory rhythmogenesis: biochemical, bioelectric and morphological properties. Biol Neonate 1994; 65: 171-175.
13.Scheidt PC, Bryla DA, Nelson KB, Hirtz DG, Hoffman HJ. Phototherapy for neonatal hyperbilirubinemia: Six-year follow-up of the National Institute of Child Health and Human Development. Pediatrics 1990; 85: 455-463.
14.Menon AP, Schefft GL, Thach BT. Apnea associated with regurgitation in infants. J Pediatr 1985; 106: 625-629.
15.Ruggins NR, Milner AD. Site of upper airway obstruction in preterm infants with problematic apnoea. Arch Dis Child 1991; 66: 787-792.
16.Meade RH. Bacterial meningitis in the neonatal infant. Med Clin North Am 1985; 69: 257-267.
17.Scanlon JEM, Chin KC, Morgan MEI, Durbin GM, Hale KA, Brown SS. Caffeine or theophylline for neonatal apnoea. Arch Dis Child 1992; 67: 425-428.
18.Gerhardt T, McCarthy J, Bancalari E. Effects of aminophylline on respiratory center and reflex activity in premature infants with apnea. Pediatr Res 1983; 17: 188-191.
19.Poets CF, Stebbens VA, Samuels MP, Southall DP. The relationship between bradychardia, apnea, and hypoxemia in preterm infants. Pediatr Res 1993; 34: 144-147.
20.Alvarez JE, Bodani J, Fajardo CA, Kwiakowski K, Cates DB, Rigatto H. Sighs and their relationship to apnea in the newborn infant. Biol Neonate 1993; 63: 139-146.(Poblano Adrian, Marquez Aida, Hernandez )
Abstract
Objective. The main objective of this study was to describe frequency of risk factors in newborns who present different types of apnea in polysomnographic (PSG) recordings in neonatal care units. Methods. The study was carried out in neonatal care units of a perinatal tertiary level institution in Mexico City between August 2002 and August 2003. Infants were selected from among 223 infants if they presented any type of apnea event in sleep PSG recordings. Results. Nearly 25% of patients from a neonatal care unit presented apnea events. Infants with apnea showed lower values of age, weight, and cephalic perimeter at birth than infants without apnea, but did not show more neurologic risk factors. Central apnea events were more frequent in infants with preterm birth (birthweight <1,500 g), obstructive apnea events were observed in infants with hyperbilirubinemia and gastro-esophageal reflux, while mixed events were seen in infants with sepsis, and hyperbilirubinemia. Sleep PSG recordings detected that 36% of infants with apnea have no previous clinic suspicion of the problem. Conclusion. Central events of apnea were found more frequent in infants with preterm birth, obstructive events in newborns with hyperbilirubinemia and gastroesophagic reflux, while infants mixed apnea had more frequent hyperbilirubinemia and sepsis.
Keywords: Newborns; Apnea; Polysomnography
Apnea in newborns is defined as absence of breathing for 20 sec or longer, or at a shorter time if bradycardia of < 100 beats/min, cyanosis, and/or hypotension is present.[1],[2] Apnea is classified as central, obstructive, and mixed. Central apnea is present when epochs of absence of nasal air flow and thoracic breathing are identified, obstructive apnea is recognized when respiratory thoracic movements are present but nasal air flow is inadequate, and mixed type is present when events begin or end with central or obstructive apnea and change to the other type of apnea.[3]
Sleep polysomnography (PSG) is the most adequate electrophysiologic test to identify apnea in preterm and at-term newborns, and must be performed in all infants with risk factors. Because there is no consensus with regard to the alterations related with each type of apnea in newborns, the objective of this research was to describe frequency of risk factors in newborns for presenting each type of apnea in a sample of infants at two of the main neonatal care units in Mexico City.
Materials and methods
Subjects
The study was carried out at a tertiary-level medical center for care of high-risk newborns at Intensive Neonatal Care Unit and at the Transitional Neonatal Care Unit, between August 15, 2002 and August 9, 2003 in Mexico City. Newborns were selected if they presented any risk factor for apnea during neonatal period (such as preterm birth, low Apgar score, sepsis, and others) when infants were stable and not mechanically ventilated. The sample was divided in infants that presented and those that did not presented apnea events on PSG studies. Newborns were studied by a neurologic examination, transfontanelar ultrasonography, and laboratory tests. Two hundred twenty three patients were studied
[Table - 1]. One hundred twenty nine were females (57.84%). One hundred thirty one patients were born weighting <1,500 g (58.74%). Apgar score at 1 min was = or <3 in 53 patients, other clinical data were obtained from hospital records. Apnea events were recognized in 55 patients (24.66%). The study was approved by research committee of the hospital and parents of infants signed approbation.
Polysomnography
PSG studies were carried out during a period of a 45 min of sleep or more time until an awake-sleep period was completed. Electrode impedance was always <5 kilo-Ohms. Recordings were performed in a 24-channel digital polysomnographer (Bravo, Nicolet, Madison, WI, USA) with 16 channels for electroencephalography (EEG), an additional channel for electromyography (EMG), two additional channels for electro-oculography (EOG), one additional channel for electrocardiography (ECG), and four channels for respiration (pneumography). Gold disk electrodes were placed according to the 10-20 International System modified for newborns.[4] The authors used bipolar EEG montage. Band pass filters were set between 0.1 and 35 Hertz (Hz). Technician recorded any change in infant behavior during the recording session according criteria of behavioral states.[5] Brain electric activity was divided into following frequency bands: delta (0.1-3.75 Hz); theta (4-7.75 Hz); alpha (8-13 Hz) and beta (14-35 Hz) and topographically divided in the following regions: frontal, central, parietal, occipital, and temporal. The PSG study was evaluated using epochs of 30 sec for identifying indeterminate, active, and quiet sleep.[6],[7] EMG recording was performed at the chin and was qualified as presence or absence of myogenic potentials. EOG activity was measured at external angles of eye and qualified as presence or absence of eye movements. ECG was measured by placing electrodes on thorax under clavicles and was evaluated for variations in QRS frequency in search for bradycardia. Respiration was measured by means of a nasal thermistor, and impedance pneumatic electrodes it was visually revised in search of apnea events.
Statistical Analysis
Descriptive analysis was performed to determine arithmetic mean, and standard deviation (SD), and percents. We performed Student t test and analyses of variance comparisons for continuous variables, Tukey tests were performed post-hoc to pinpoint differences between types of apnea. For binomial variables we use Fisher exact test. Alpha value a priori was <0.05.
Results
The authors detected apnea events in 55 patients (24.66%). Comparison of clinic characteristics between infants with and without apnea is shown in [Table - 2], significant differences were found with regard to age, weight, and cephalic perimeter at birth, with lower values in the group of infants with apnea as expected by previous literature. No statistical differences in main risk factors such as: sepsis, intraventricular hemorrhage, hyperbilirubinemia, hypoxic-ischemic encephalopathy, meningitis and TORCH in infants with and without apnea were seen. Although each patient can have more than one type of apnea, forty patients showed central apnea events (72.72%), six manifested obstructive events (10.90%), and nineteen demonstrated mixed events (34.54%). Some infants presented only one type of apnea: central ( n = 31), obstructive ( n = 5) and mixed ( n = 10). Comparison of characteristics among these groups showed significant differences in weight at birth, cephalic perimeter, and one-min Apgar score with lower values in infants with central and obstructive apnea than infants with mixed apnea [Table - 3] Tukey test revealed significant differences in weight at birth between central and mixed groups with regard to infants with obstructive events; and in cephalic perimeter among group of mixed apnea to the other two groups; and in Apgar score at one min in groups of obstructive and mixed apnea to group of infants with central events. Frequency of three main risk factors identified in patients with only one type of apnea showed significant differences when compared with infants without apnea in birthweight <1,500 g in the group of infants with central apnea; and in hyperbilirubinemia and gastroesophagic reflux in infants with obstructive apnea; and in hyperbilirubinemia and sepsis in infants with mixed events of apnea [Table - 4]. The main pharmacologic agents used for apnea treatment were theophylline ( n = 21, 38.18%) and aminophylline ( n = 14, 25.45%), nonetheless twenty patients (36.36%) were without treatment at time of study because they were not identified as having apnea events previously.
Discussion
The authors search for risk factors frequency in infants with different types of apnea documented by PSG in neonatal care units. They found that nearly one quarter of infants experienced apnea events. Two previous studies report frequency of apnea in newborns,[8],[9] however because their definition of apnea is absence of breathing for six and three seconds respectively results is not comparable to our data.
Data from our work underlines PSG usefulness to detect apnea including infants in whom clinic vigilance has not identified events (such as obstructive and mixed). In pre-term infants, recurrent apnea represent a clinical problem and are dangerous for short- and long-term[10],[11] neurologic status, thus, it is mandatory to study the pathophysiology of events for a therapeutic rationality.
Central apnea was the most frequent type of apnea in preterm infants; evidence related this kind of apnea with breathing control centers immaturity.[12] Authors data are in agreement with this hypothesis: 72.72% of their patients had central apnea and born more frequent with birthweight <1,500 g than infants without apnea. Obstructive apnea had more frequently hyperbilirubinemia and gastro-esophagic reflux. Obstructive events may be associated with hypotonus of the upper air pathway muscles after hiperbilirubinemic encephalopathy and with regurgitation events respectively.[13],[14] An alternative explanation suggests that obstructive apnea may be associated with a postural defect or decrease in muscle tone and a consequent reduction in dimensions of upper respiratory tract.[15] Mixed apneas had most frequently sepsis and hyperbilirubinemia, suggesting that share some pathophysiologic mechanisms with other types of apnea, or may reflect effects of fever and infection in the central nervous system.[16]
Nearly one half of infants with apnea were not under pharmacological treatment because they had not yet been identified at time of study. Theophylline was the most frequent medication used in authors studied population and is in agreement with data from other investigations.[17],[18] Authors data suggest that PSG in newborns with neurologic risk factors must be mandatory to detect apnea in infants, including those in whom apnea events have not been previously identified.[19],[20]
References
1.Task Force on Prolonged Apnea. Prolonged apnea. Pediatrics 1978; 61: 651-652. [PUBMED]
2.Baird TM. Clinical correlates, natural history and outcome of neonatal apnoea. Semin Neonatol 2004; 9: 205-211. [PUBMED] [FULLTEXT]
3.Finer NN, Barrington KJ, Hayes BJ, Hugh A. Obstructive, mixed, and central apnea in the neonate: Physiologic correlates. J Pediatr 1992; 121: 943-950. [PUBMED]
4.Hofmann E, Havens B, Geidel S, Hoppenbrouwers T, Hodgman JE. Long-term, continuous monitoring of multiple physiological parameters in newborn and young infants. Acta Paediatr Scand 1977; suppl 266: 1-24.
5.Prechtl HFR. The behavioral states of the newborn (a review). Brain Res 1974; 76: 185-212.
6.Stockard-Pope JE, Werner JE, Bickford RG. Atlas of neonatal electroencephalography . New York, Raven Press. 1992
7.Cursi-Dascalova L, Mirmiran M. Manuel des techniques d′enregistrement et d′analyse des stades de sommeil et de veille chez le prιmaturι et le nouveau-nι a terme . Paris; éditions INSERM. 1996
8.Hoppenbrouwers T, Hodgman JE, Harper RM, Hofmann E, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life: III. Incidence of apnea and periodic breathing. Pediatrics 1977; 60: 418-425.
9.Kato I, Franco P, Groswasser J, Kelmanson I, Togari H, Kahn A. Frequency of obstructive and mixed sleep apneas in 1,023 infants. Sleep 2000; 23: 487-492.
10.Deykin E, Bauman ML, Kelly DH, Hsieh CC, Shannon D. Apnea of infancy and subsequent neurologic, cognitive, and behavioral status. Pediatrics 1984; 73: 638-645.
11.Poblano A. Neurophysiological studies in early detection of neurological damage (in Spanish). In: Poblano A (ed.). Early detection and intervention in infants with neurological damage . Mιxico, Editores de Textos Mexicanos. 2003; 101-129.
12.Denavi-Saubiι M, Kalia M, Pierrefiche O, Schweitzer P, Foultz AS, Champagnat J. Maturation of brain stem neurons involved in respiratory rhythmogenesis: biochemical, bioelectric and morphological properties. Biol Neonate 1994; 65: 171-175.
13.Scheidt PC, Bryla DA, Nelson KB, Hirtz DG, Hoffman HJ. Phototherapy for neonatal hyperbilirubinemia: Six-year follow-up of the National Institute of Child Health and Human Development. Pediatrics 1990; 85: 455-463.
14.Menon AP, Schefft GL, Thach BT. Apnea associated with regurgitation in infants. J Pediatr 1985; 106: 625-629.
15.Ruggins NR, Milner AD. Site of upper airway obstruction in preterm infants with problematic apnoea. Arch Dis Child 1991; 66: 787-792.
16.Meade RH. Bacterial meningitis in the neonatal infant. Med Clin North Am 1985; 69: 257-267.
17.Scanlon JEM, Chin KC, Morgan MEI, Durbin GM, Hale KA, Brown SS. Caffeine or theophylline for neonatal apnoea. Arch Dis Child 1992; 67: 425-428.
18.Gerhardt T, McCarthy J, Bancalari E. Effects of aminophylline on respiratory center and reflex activity in premature infants with apnea. Pediatr Res 1983; 17: 188-191.
19.Poets CF, Stebbens VA, Samuels MP, Southall DP. The relationship between bradychardia, apnea, and hypoxemia in preterm infants. Pediatr Res 1993; 34: 144-147.
20.Alvarez JE, Bodani J, Fajardo CA, Kwiakowski K, Cates DB, Rigatto H. Sighs and their relationship to apnea in the newborn infant. Biol Neonate 1993; 63: 139-146.(Poblano Adrian, Marquez Aida, Hernandez )