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 Table of Contents  
Year : 2022  |  Volume : 11  |  Issue : 1  |  Page : 13-18

Respiratory patterns in neonates hospitalized with brief resolved unexplained events

1 Department of Pediatrics, Division of Neonatology, Children's Medical Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Pediatrics, Division of Neonatology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Pediatrics, Division of Neonatology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Pediatrics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission28-May-2021
Date of Decision31-Aug-2021
Date of Acceptance03-Sep-2021
Date of Web Publication03-Jan-2022

Correspondence Address:
Kayvan Mirnia
Department of Pediatrics, Division of Neonatology, Children's Medical Center, School of Medicine, Tehran; University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcn.jcn_69_21

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Objective: The objective of this study is aimed at investigating and evaluating respiratory patterns between infants hospitalized with brief resolved unexplained event (BRUE) and the control group. Methods: A convenient sampling method was used to select 52 patients presented at an urban, tertiary, and teaching pediatric hospital fitting the American Academy of Pediatrics' criteria of a lower-risk BRUE from December 2019 to December 2020. A random probability sampling method was used to select 52 patients as a control group. A NINIX apnea monitoring device was used to record respiratory time patterns and analyzed with SPSS 25. Results: A total of 104 participants participated in the study. Our study found that inspiration time (0.31 ± 0.04), expiratory time (0.93 ± 0.14), respiratory rate (38.48 ± 4.38), body temperature (37.11 ± 0.20), and heart rate (137.90 ± 6.60) were not statistically different between both groups. Mean birth weight in the control group and BRUE were respectively (3.43 ± 0.39, 3.23 ± 0.35). Mean gestational age in the control and BRUE groups were respectively (38.94 ± 1.01, 39.0 ± 1.04). Mean postnatal age in the control and BRUE groups were respectively (17.19 ± 6.07, 17.32 ± 7.35). Birth weight (P = 0.08) was statistically significant between both groups. In one patient, we recorded breath arrest for more than 20 s. Conclusion: There were no significant differences in respiratory patterns between infants hospitalized with BRUE and the control group. Low birth weight and low APGAR score are possible risk factors for infants experiencing BRUE, and more investigations are required to establish underlying causes.

Keywords: Apparent life-threatening event, brief resolved unexplained event, neonate

How to cite this article:
Kadivar M, Sangsari R, Saeedi M, Mirnia K, Kaveh M, Maleki MR, Makuku R. Respiratory patterns in neonates hospitalized with brief resolved unexplained events. J Clin Neonatol 2022;11:13-8

How to cite this URL:
Kadivar M, Sangsari R, Saeedi M, Mirnia K, Kaveh M, Maleki MR, Makuku R. Respiratory patterns in neonates hospitalized with brief resolved unexplained events. J Clin Neonatol [serial online] 2022 [cited 2022 Dec 4];11:13-8. Available from: https://www.jcnonweb.com/text.asp?2022/11/1/13/334737

  Introduction Top

Since antiquity, parents, and infant clinicians observed sudden, short-lived apnea episodes, cyanosis, hypertonia/hypotonia, choking/gagging without a prior explanatory medical history, and were disjointed to the excellent prognosis afterward. Years before 1986, such events were termed “near miss” for sudden infant death syndrome (SIDS)[1],[2] and were linked to prolonged physiologic sleep apnea and importantly hypothesized to be part of the etiology of SIDS.[3] However, further preceding studies did not support this hypothesis,[4] and a new quest to develop a clearly expressing terminology arose.

The National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring in 1986 coined the term: Apparent life-threatening event (ALTE) as “an episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking, or gagging.”[5] The same conference went on to encourage abandonment of previously used terminology such as “aborted crib death” or “near-miss SIDS” citing high chances of a deceptively close association between this type of event and SIDS.

Thirty years after the conference mentioned above, pediatricians and researchers kept on investigating and understood that the clinicopathology of ALTE was not life threatening as previously agreed.[6] The term ALTE was deemed broad, vague, subjective, extensive, too imprecise, and symptom-based, lacking a clinical diagnostic perspective leading to unnecessary costs from investigations and hospitalizations.[7] To address this concern, in 2016, the American Academy of Pediatrics (AAP) published a standardized, clinical practice guideline with risk stratification and clinical decision-oriented approach and named it brief resolved unexplained event (BRUE), replacing ALTE.[7],[8] According to AAP, a BRUE is an unexpected, brief, and now resolved episode event happening in an infant <1 year old, and the observer mentions at least one of the following: (i) cyanosis or pallor; (ii) absent, decreased, or irregular breathing; (iii) marked change in tone (hypertonia or hypotonia); and (iv) altered level of responsiveness,[9] in a setting of no significant history and physical examination.

Respiratory pattern (absent, decreased, or irregular breathing) is arguably an essential component of a BRUE, evidenced by the earlier hypothesis of sleep apnea etiology in SIDS and is not well characterized in the literature.[3] This 1-year prospective case-control study aimed at investigating and evaluating respiratory patterns.

  Methods Top

Study design

This is an observational, prospective case-control study, giving an analytical perspective into the respiratory patterns of BRUE patients and associated risk factors. The study was conducted for 1 year (December 21, 2019-December 21, 2020) at Children Medical Center's neonatal intensive care unit (NICU), teaching, and tertiary pediatric facility owned by Tehran University of Medical Sciences (TUMS), Tehran, Iran. The NICU admitted 758 patients during this study; Fifty-two cases and 52 controls were selected for the study. A Ninix apnea alarm monitoring device (Behineh Dadepardazan Raymon, IRAN) was installed on the abdomen of infants, and respiratory pattern data were generated, recorded, and analyzed by the device manufacturer. The IBM SPSS Statistics for Windows, Version 25.0. (Armonk, NY: IBM Corp., USA) was used for the statistical analysis of results.

Selection of participants

Inclusion criteria: The study included patients admitted at Children's Medical Center's NICU with gestational age 37 weeks or more and <30 days of age after birth [Table 1]. According to the American Association of Pediatrics, we considered the patient's chief complaint, the reason for admission, and medical history to be consistent with the 2016 definition of BRUE.
Table 1: Frequency of demographic variables in neonates of the two groups brief resolved unexplained events and control

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Exclusion criteria: Our study excluded patients with a confirmed diagnosis, a history of prematurity (gestational Age <37 weeks), an adjusted current age of fewer than 37 weeks, a history of untreated congenital heart disease, a history of chronic lung disease in need of treatment, patients with a history of seizures such as tonic/clonic/myoclonic movements, altered gaze, and uncontrolled eye movements were also excluded from the study.

Data collection

Data were collected in three ways: History taking, regular clinical examinations, and paraclinical investigations. Qualified pediatricians performed clinical examinations on patients, took the patient history from their mothers/guardians, and interpreted clinical investigation results. The three data collection tools had a standard checklist to ensure reliability and validity and were adjusted by reviewing literature and consulting experts' opinions. On the last day of discharge, information recorded on the Ninix monitoring device was extracted and statistically analyzed.

Data analysis

Data extracted from the Ninix device were entered into the statistical software SPSS version 25. The mean and standard deviation for quantitative variables and frequency for qualitative variables were computed using descriptive statistical analysis. Chi-square statistical tests compared qualitative variables, and an independent t-test was used to compare quantitative variables. Statistical significance was P < 0.05.

Ninix device

It is an apnea alarm that is installed on the neonate's nappy. This device changes the abdominal pattern of respiration to signals that the Ninix engineers interpret. Data are shown as a respiratory pattern and mean inspiratory, and expiratory duration was extracted from the respiratory pattern. Vital signs as heart rate and oxygen saturation are collected online by a pulse oximeter, and the temperature was measured online by probes of the warmer. The respiratory arrest of more than 15 s or more than 10 s, accompanied by desaturation or bradycardia, was defined as apnea that required treatment.

Ethical approval and informed consent

Tehran University Medical Sciences Tehran, Iran ethics committee IR sought this study's ethical approval. TUMS.CHMC.REC.1399.014. Medical procedures were performed based on each patient's clinical needs and according to clinical and laboratory findings. Patients were not exposed to unnecessary investigations. Written consent was obtained from the patient's parents or guardians, and information was kept confidential and generally reported.

  Results Top

This study found the incidence of apnea, color change, tone change, and respiratory arrest in the group at 69.2%, 92.3%, 78.8%, and (5.8%), respectively, not observed in the control group [Figure 1].
Figure 1: Sign frequency evaluation in brief resolved unexplained event neonates

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We could detect only one case in the BRUE group with apnea. This neonate was 17 days old, delivered by C/S route, Apgar of minute one-nine and five-ten, and birth weight of 3500 g. From 52 neonates with BRUE at arrival, we could document the diagnosis in 12 patients [Figure 2].
Figure 2: Abnormal respiratory pattern

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  Discussion Top

BRUE is a joint presentation of infants in pediatric emergency facilities, often posing a challenge to the attendant because patients often refer well. Within a year, 40 of 758 patients admitted at our hospital were diagnosed, BRUE, computing a prevalence of 5.3%. Our result is higher than the previously reported range of 0.6% to 1.7% among emergent infant visits[7],[10],[11],[12] and 0.6%–2.6% in 1000 live births.[13] Notwithstanding limitations, the prevalence of BRUE may be hypothesized higher than the global average in the Iranian population for reasons yet to be uncovered.

Our investigation showed that nutrition, gender, and age distribution were similar between cases and controls, as with previous investigations.[14],[15] Previous studies have reported possible alterations of infant brain structures from fetal hypoxia and metabolic toxins such as nicotine, affecting arousal maturation.[15] Maternal smoking is a known risk factor for low birth weight, intrauterine growth retardation, and preterm delivery,[16],[17] which may logically increase BRUE incidence; alas, our study showed no relationship between BRUE and passive smoking from guardians. Besides, we failed to establish a relationship between infant delivery routes and BRUE [Table 2].
Table 2: Frequency of qualitative demographic variables in infants of brief resolved unexplained events and control groups

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Postdelivery 1 min APGAR score is a limited tool for assessing an infant's physiology because it provides subjective data, hence broadly discouraging predicting infants' clinical outcomes.[18] Evidence from this investigation supports the transition from ALTE to BRUE by the AAP[9] as a clinical diagnostic tool with higher specificity and sensitivity. Our study only recorded a combination of apnea, discoloration, and tonicity in the case group; 69.2%, 92.3%, and 78.8%, respectively, and not in the control group [Table 3]. Mittal MK et al. previously reported that positive pneumography for apnea or reflux does not foretell an ALTE/BRUE.[10] Congruent to our study, average inspiration and expiration times, respiratory rate, and even heart rate had no statistical relevance between the BRUE and control groups [Table 4].
Table 3: Evaluation of the frequency of qualitative clinical variables in the brief resolved unexplained events group

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Table 4: Evaluation of the vital sign variables in neonates of brief resolved unexplained events and control groups

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Our study revealed eight neonates' symptoms during feeding, which may be due to laryngeal chemoreflex (LCR).[19] The pediatric gastroesophageal reflux clinical practice guidelines list BRUE as one of gastroesophageal reflux disease (GERD) symptoms since 2018.[20] In ten neonates, half an hour after feeding, symptoms were demonstrated. Gastroesophageal reflux can explain this event, but as proving reflux in neonates requires PH-impedance, we rendered it.[21] However, Nadeem Z. Jilani's study showed that GERD is not a component of BRUE.[22]

Time relation is a new event that we noticed during our study. Most events occurred in the second half of the day [Table 5]. As this was an accidental result, we had no plan to see whether the neonate was sleeping or not. In preterm neonates, apnea occurs during sleep due to premature patterns of breath.[23] Polysomnography is a feasible tool to monitor sleep-wake patterns in the term. Unfortunately, our method could not predict it. Both groups' inspiratory and expiratory duration were not statistically different except in one patient that inspiratory time was increased and this patient had a respiratory arrest [Table 6]. Pulmonary stretch receptors are capable of modulating respiratory time in neonates by input from afferent neurons. This response is called the Hering-Breuer reflex. This reflex inhibits inspiration and prolongs expiration. If there is an end-expiration obstruction due to secretions and the lung inflation is preserved, the inspiratory time increases, and compensating during airway obstruction. This compensatory mechanism can result in apnea events. Prolonged supine position and decreased. Defensive mechanisms for clearing secretions in neonates may lead to obstruction.
Table 5: Investigating the relationship between brief resolved unexplained events attacks and feeding by history (n=40)

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Table 6: Evaluation of mean inhalation and exhalation time in neonates with respiratory arrest and nonrespiratory arrest in brief resolved unexplained events group

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The majority of infants (40%) admitted at our center for BRUE were discharged with unknown diagnoses compared to a handful (7%) from the control group after thorough investigations and monitoring [Table 7]. Noted diagnoses in this study were few and widely dispersed in both groups: Clinical sepsis, paraclinical sepsis, viral infections, and seizures. Icterus was only diagnosed in the control group. Our study affirms that most BRUE patients are low-risk infants with an excellent prognosis; hence do not need thorough investigations always.
Table 7: Frequency of diagnosis during discharge in neonates with brief resolved unexplained events

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Limitations of the study

Polysomnography concomitant with apnea alarm helps us to unify data of sleep and respiratory pattern. This study could measure the inspiratory and expiratory patterns and could not describe their relationship with sleep. Proving GERD due to its issues in neonates may reveal the LCR role in apnea. Unfortunately, proving GERD in neonates is difficult.

  Conclusion Top

There were no significant differences in respiratory patterns between infants hospitalized with BRUE and the control group. Most events of BRUE occurred in the second half of the day.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Cornwell AC, Weitzman ED, Kravath RE. Respiratory and cardiac events observed and recorded during and following a “near miss” for Sudden Infant Death Syndrome episode. The International journal of neuroscience 1982;16:231-9.  Back to cited text no. 1
Guilleminault C, Ariagno R, Coons S, Winkle R, Korobkin R, Baldwin R, et al. Near-miss sudden infant death syndrome in eight infants with sleep apnea-related cardiac arrhythmias. Pediatrics 1985;76:236-42.  Back to cited text no. 2
Steinschneider A. Prolonged apnea and the sudden infant death syndrome: Clinical and laboratory observations. Pediatrics 1972;50:646.  Back to cited text no. 3
Hodgman JE. Effect on Sleep Position on Apnea and Bradycardia in High-Risk Infants. J Perinatology 2002;22:163-4.  Back to cited text no. 4
Infantile apnea and home monitoring. National Institutes of Health Consensus Development Conference Consensus Statement 1986;6:1-10.  Back to cited text no. 5
Vigo A, Balagna R, Brazzi L, Costagliola G, Gregoretti C, Lupica MM, et al. Apparent life-threatening events: Helping infants help themselves. Pediatric Emergency Care 2018;34.  Back to cited text no. 6
Arane K, Claudius I, Goldman RD. Brief resolved unexplained event: New diagnosis in infants. Can Fam Physician 2017;63:39-41.  Back to cited text no. 7
Kondamudi NP, Virji M. Brief Resolved Unexplained Event. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC.; 2021.  Back to cited text no. 8
Tieder JS, Bonkowsky JL, Etzel RA, Franklin WH, Gremse DA, Herman B, et al. Brief resolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants. Pediatrics 2016;137:e20160590.  Back to cited text no. 9
Mittal MK, Donda K, Baren JM. Role of pneumography and esophageal pH monitoring in the evaluation of infants with apparent life-threatening event: A prospective observational study. Clinical Pediatrics 2013;52:338-43.  Back to cited text no. 10
Davies F, Gupta R. Apparent life threatening events in infants presenting to an emergency department. Emerg Med J 2002;19:11-6.  Back to cited text no. 11
Monti MC, Borrelli P, Nosetti L, Tajè S, Perotti M, Bonarrigo D, et al. Incidence of apparent life-threatening events and post-neonatal risk factors. Acta Paediatr 2017;106:204-10.  Back to cited text no. 12
Kondamudi NP, Virji M. Brief resolved unexplained event (BRUE). 2017.  Back to cited text no. 13
Ueda R, Nomura O, Maekawa T, Sakai H, Nakagawa S, Ishiguro A. Independent risk factors for recurrence of apparent life-threatening events in infants. European J Pediatrics 2017;176:443-8.  Back to cited text no. 14
Franco P, Montemitro E, Scaillet S, Groswasser J, Kato I, Lin J-S, et al. Fewer spontaneous arousals in infants with apparent life-threatening event. Sleep 2011;34:733-43.  Back to cited text no. 15
Ko TJ, Tsai LY, Chu LC, Yeh SJ, Leung C, Chen CY, et al. Parental smoking during pregnancy and its association with low birth weight, small for gestational age, and preterm birth offspring: A birth cohort study. Pediatrics and Neonatology 2014;55:20-7.  Back to cited text no. 16
Horta BL, Victora CG, Menezes AM, Halpern R, Barros FC. Low birthweight, preterm births and intrauterine growth retardation in relation to maternal smoking. Paediatric and Perinatal Epidemiology 1997;11:140-51.  Back to cited text no. 17
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Xia L, Leiter JC, Bartlett D, Jr. Laryngeal reflex apnea in neonates: effects of CO2 and the complex influence of hypoxia. Respir Physiol Neurobiol 2013;186:109-13.  Back to cited text no. 19
Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, et al. Pediatric gastroesophageal reflux clinical practice guidelines: Joint recommendations of the north american society for pediatric gastroenterology, hepatology, and nutrition and the european society for pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr 2018;66:516-54.  Back to cited text no. 20
Ravi K, Geno DM, Vela MF, Crowell MD, Katzka DA. Baseline impedance measured during high-resolution esophageal impedance manometry reliably discriminates GERD patients. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society 2017;29.  Back to cited text no. 21
Jilani NZ, Hussain A, Al Ansari K, Powell CVE. Gastro-oesophageal reflux is not a major cause of brief resolved unexplained events in infants. Breathe 2019;15:e32.  Back to cited text no. 22
Patel M, Mohr M, Lake D, Delos J, Moorman JR, Sinkin RA, et al. Clinical associations with immature breathing in preterm infants: Part 2-periodic breathing. Pediatr Res 2016;80:28-34.  Back to cited text no. 23


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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