Intussusception Initially Diagnosed as a Brief Resolved Unexplained Event (BRUE)

A brief resolved unexplained event (BRUE) describes an event associated with a change in muscle tone, color, respiration, and responsiveness that is unexplained after an appropriate examination. Some infants with higher risk BRUE may undergo endoscopy as part of their evaluation. This retrospective study aimed to identify the endoscopic findings in infants who have experienced a higher risk BRUE. We also compared the characteristics, prenatal, natal, and postnatal risk factors between 23 infants who underwent endoscopic evaluation and 23 race-matched/sex-matched/term-matched/preterm-matched infants who did not undergo endoscopic evaluation. This was a retrospective descriptive study. Infants were identified from a query of medical records using the ICD-10 code for BRUE (R68.13). Of 119 infants with BRUE, 23 infants with higher risk BRUE underwent an esophagogastroduodenoscopy and flexible sigmoidoscopy. Apnea (87%) was the most common presentation of BRUE. Most were female (57%) with a mean age at BRUE presentation of 2.73 months. We found 10 (43.5%) term infants and 13 (56.5%) preterm infants in our study. There were no significant differences in characteristics, prenatal, natal, and postnatal risk factors between the infants who underwent endoscopy and those who did not undergo endoscopy. The most common abnormal endoscopic finding was lymphonodular hyperplasia (LNH) associated with eosinophilia in the rectosigmoid colon. The proportion of females in the LNH group was significantly higher than the non-LNH group. Rectosigmoid LNH and eosinophilia, which are associated with milk soy protein intolerance (MSPI), were the most common findings on endoscopic evaluation. Although there is no proof of causation between MSPI and BRUE, MSPI should be considered in the differential diagnosis for higher risk BRUE.

In 2016, brief resolved unexplained events (BRUEs) were proposed as alternative concepts to apparent life-threatening event (ALTE). The clinical utility of managing ALTE cases according to the BRUE classification is controversial. To verify the clinical utility of the BRUE criteria, we evaluated the proportion of ALTE patients who met and those who did not meet the BRUE criteria and assessed the diagnoses and outcomes of each group. We retrospectively investigated patients with ALTE younger than 12 months who visited the emergency department of the National Center for Child Health and Development from April 2008 to March 2020. The patients were classified into the higher-risk and lower-risk BRUE groups; however, those who did not meet the BRUE criteria were classified into the ALTE-not-BRUE group. We evaluated the diagnoses and outcomes of each group. Adverse outcomes included death, recurrence, aspiration, choking, trauma, infection, convulsions, heart disease, metabolic disease, allergies, and others. Over the period of 12 years, a total of 192 patients were included, among which 140 patients (71%) were classified into the ALTE-not-BRUE group, 43 (22%) into the higher-risk BRUE group, and 9 (5%) into the lower-risk BRUE group. Adverse outcomes occurred in 27 patients in the ALTE-not-BRUE group and 10 patients in the higher-risk BRUE group. No adverse outcome occurred in the lower-risk BRUE group. Many of the patients with ALTE were classified into the ALTE-not-BRUE group, suggesting that replacing ALTE with BRUE is difficult. Although patients classified as lower-risk BRUE showed no adverse outcomes, there were only a few of them. In the pediatric emergency medicine setting, the BRUE risk classification may be beneficial for certain patients.

The American Academy of Pediatrics published guidelines for evaluation and management of lower-risk infants for a brief resolved unexplained event (BRUE). The guideline identified gaps in knowledge related to caregiver satisfaction, anxiety, and family-centered educational strategies to improve caregiver experience and patient outcomes. The objective of this study was to understand caregivers' experience with hospitalization for infants with BRUE, including their perception of the hospital stay, the diagnosis of BRUE, and their feelings toward the upcoming discharge from the hospital. We conducted a qualitative study using semistructured interviews with caregivers of infants aged 0 to 12 months who were admitted to a quaternary care children's hospital for a BRUE. Interviews were conducted within 24 hours of discharge. Two investigators coded transcripts and identified themes using consensus. Eighteen caregivers of 13 infants were interviewed. No infants met criteria for being low risk according to the American Academy of Pediatrics guidelines. The coding scheme produced 3 major themes. First, parents felt reassured by hospital monitoring, diagnostic evaluation, and staff support in the hospital. Second, parents felt unsettled by the uncertainty of the child's condition and whether BRUE's "unexplainable" quality is understood as being part of normal infant behavior. Third, these themes manifested as conflicting emotions about caregivers' readiness for discharge. Although hospital monitoring may provide reassurance for some caregivers, they continue to struggle with the uncertainty of the diagnosis. Caregiver perspectives can inform physicians' strategies to improve hospital experience and discharge readiness.

Brief resolved unexplained events (BRUEs) are frequently encountered in infants younger than 1 year. By definition, these events require the infant to be asymptomatic and at baseline at the time of presentation, with no significant abnormalities on examination and no discernible explanatory diagnosis. Research has shown that less than 5% of BRUE cases are attributable to serious underlying conditions, with no increased mortality risk and no increased risk of sudden infant death syndrome. Despite these findings, approximately 63% of patients with BRUEs are hospitalized and up to 82% undergo diagnostic tests, which predominantly result in false-positive findings. Such results may lead to unnecessarily prolonged hospital stays, additional tests or consultations, and increased parental anxiety. The management of a patient who has experienced a BRUE can be challenging for providers and parents alike. Although risk is known to be low in these infants, providers may be compelled to explain the event and provide reassurance. Caregivers oftentimes are concerned that the events may reoccur and be a harbinger of a missed diagnosis. Shared decision-making can be used to explain risk and the benefit of additional testing and hospitalization. This family-centered strategy can align care with the family's values, provide reassurance, and decrease decisional conflict.

ObjectiveA brief resolved unexplained event (BRUE) is a recent clinical entity that has now replaced the term “infant discomfort”. Despite the availability of recent recommendations, identification of patients requiring further examination remains difficult. MethodWe aimed to identify factors associated with severe pathology and/or recurrence by studying the medical files of 767 patients admitted to the pediatric emergency department of a French university hospital for a BRUE. ResultsOverall, 255 files were studied; 45 patients had a recurrence and 23 patients had a severe diagnosis. The most frequently found etiology was gastroesophageal reflux in the benign diagnosis group and apnea or central hypoventilation in the severe diagnosis group. Prematurity (p = 0.032) and time since last meal >1 h (p = 0.019) were the main factors associated with severe disease. Most of the routine examination results remained non-contributive to the etiology. ConclusionAs prematurity is a factor associated with severe diagnosis, special attention should be given to this population, without subjecting them to multiple tests, since the main complication was found to be apnea or central hypoventilation. Prospective research is needed to establish the usefulness and prioritization of diagnostic tests for infants who are at “high risk” of experiencing a BRUE.

The American Academy of Pediatrics (AAP) higher-risk criteria for brief resolved unexplained events (BRUE) have a low positive predictive value (4.8%) and misclassify most infants as higher risk (>90%). New BRUE prediction rules from a US cohort of 3283 infants showed improved discrimination; however, these rules have not been validated in an external cohort. To externally validate new BRUE prediction rules and compare them with the AAP higher-risk criteria. This was a retrospective multicenter cohort study conducted from 2017 to 2021 and monitored for 90 days after index presentation. The setting included infants younger than 1 year with a BRUE identified through retrospective chart review from 11 Canadian hospitals. Study data were analyzed from March 2022 to March 2024. The BRUE prediction rules. The primary outcome was a serious underlying diagnosis, defined as conditions where a delay in diagnosis could lead to increased morbidity or mortality. Of 1042 patients (median [IQR] age, 41 [13-84] days; 529 female [50.8%]), 977 (93.8%) were classified as higher risk by the AAP criteria. A total of 79 patients (7.6%) had a serious underlying diagnosis. For this outcome, the AAP criteria demonstrated a sensitivity of 100.0% (95% CI, 95.4%-100.0%), a specificity of 6.7% (95% CI, 5.2%-8.5%), a positive likelihood ratio (LR+) of 1.07 (95% CI, 1.05-1.09), and an AUC of 0.53 (95% CI, 0.53-0.54). The BRUE prediction rule for discerning serious diagnoses displayed an AUC of 0.60 (95% CI, 0.54-0.67; calibration intercept: 0.60), which improved to an AUC of 0.71 (95% CI, 0.65-0.76; P < .001; calibration intercept: 0.00) after model revision. Event recurrence was noted in 163 patients (15.6%). For this outcome, the AAP criteria yielded a sensitivity of 99.4% (95% CI, 96.6%-100.0%), a specificity of 7.3% (95% CI, 5.7%-9.2%), an LR+ of 1.07 (95% CI, 1.05-1.10), and an AUC of 0.58 (95% CI, 0.56-0.58). The AUC of the prediction rule stood at 0.67 (95% CI, 0.62-0.72; calibration intercept: 0.15). Results of this multicenter cohort study show that the BRUE prediction rules outperformed the AAP higher-risk criteria on external geographical validation, and performance improved after recalibration. These rules provide clinicians and families with a more precise tool to support decision-making, grounded in individual risk tolerance.

American Academy of Pediatrics released a clinical practice guideline (CPG) in 2016 recommending the term apparent life-threatening events (ALTE) be replaced by brief resolved unexplained events (BRUE). The CPG provides recommendations for the clinical evaluation and management of infants with this condition based on the risk of a serious underlying disorder or repeat event. The lower-risk CPG was applied to a modelled population, studying predictors of hospital admission, defined as length of stay (LOS)≥24hours. An algorithm was derived using a Pediatric Emergency Care Applied Research Network database. Propensity score weighting, based on probability of following the CPG, determined the adjusted odds ratio (aOR) and 95% confidence interval (CI) of hospital admission. Multiple imputation allowed any missing data problems be addressed and a sensitivity analysis of database robustness. Applying the modelling algorithm, 3116 observations were identified, among whom 1974 (63.4%) the CPG was followed and 1142 (36.6%) not followed. The CPG was followed for 60.1% of infants staying ≥24hours compared with 76.6% of infants staying <24hours (P<.001). After propensity score weighting and multiple imputation, the likelihood of hospital admission was significantly lower when the CPG was followed (aOR=0.49; 95% CI, 0.39-0.62, P<.001). Results suggest that use of the CPG under strict conditions would lead to fewer hospital admissions among infants with a lower-risk BRUE. Implementation of CPGs in modelled populations may help clinicians identify unanticipated factors and address these issues beforehand. We noted differences in care based on race, necessitating further investigation.

Apparent Life-Threatening Event: Multicenter Prospective Cohort Study to Develop a Clinical Decision Rule for Admission to the Hospital

Aortopexy is the most common surgical intervention for pediatric tracheomalacia (TM). The thoracoscopic approach, despite being reported by a few authors, remains controversial due to the different reported techniques and outcomes.We report a retrospective review of our preliminary experience with thoracoscopic aortopexy from 2023 to date. Patients' demographic data and symptoms were collected: age and weight at surgery, comorbidities, presence of brief resolved unexplained event (BRUE), dyspnea, chest infections, and barking cough. The study describes our surgical technique and its evolution. We analyzed the clinical outcome and endoscopic improvement, success and complication rate, operative time, and length of stay. We then compared our findings with the results of open and thoracoscopic aortopexy reported in the current literature.A total of 12 thoracoscopic aortopexies were performed on 10 patients (including two redo). The mean age and weight at operation were 3.2 years (range: 4 months-6 years) and 13.6 kg (range: 3.5-23), respectively. Two patients presented with BRUE, one with dyspnea, in the other cases the indications were recurrent pneumonia (more than six per year or three in 6 months). All patients underwent preoperative flexible bronchoscopy for the diagnosis of TM. The average estimated tracheal collapse was 86% (range: 70-95%). One intraoperative bleeding caused a conversion to open surgery, but no other complications occurred. All patients were extubated on the same day. Two cases required a redo due to suture tearing, and one of them required an additional posterior tracheopexy for persistent symptoms. The remaining patients had significant improvement on follow-up: success rate is 75%. Both patients requiring redo underwent aortopexy without pledgeted sutures or innominate artery (IA) suspension: these steps are associated with a success rate of 88.9% (p = 0.0182). Our refined technique now includes total thymectomy, pericardiotomy, pledgeted horizontal mattress sutures on the aorta, and the IA after full mobilization of the innominate vein.Thoracoscopic aortopexy appears to be a feasible and effective option for pediatric TM, particularly when replicating open surgical principles. Further research is needed to optimize the technique and improve the clinical results.

There has been a paradigm shift in pediatrics. In 1986, the concept of “near-miss sudden infant death syndrome” was replaced by the term “apparent life-threatening event” (ALTE).1 The goal was to clearly distinguish that which was uniformly fatal—sudden infant death syndrome—from that which was seldom so. Thirty years later, research has shown that ALTE is rarely life-threatening. Two prospective studies involving >1100 infants with ALTE found no mortality during hospitalization or within 72 hours of discharge from the emergency department.2,3 Thus, the terminology has changed again, and the concept of ALTE has been retired by the American Academy of Pediatrics (AAP). Now called a “brief resolved unexplained event” (BRUE), the wording is purposeful in its intent to highlight the benign nature of these events.4 Regardless of what they are called by clinicians and researchers, these events remain frightening and anxiety provoking for parents and caregivers. That is, after all, why they seek care for their infant. Now, when infants come to medical attention after these odd events, clinicians call it a BRUE, which is exactly what the name implies: a transient alteration in an infant’s color, tone, mental status, or breathing whose etiology remains unclear after a detailed history and physical examination. These well-appearing infants are classified in the AAP clinical practice guideline (CPG) as being at lower or …

Repair of Type C Tracheo-esophageal Fistula/Esophageal Atresia With or Without Trans Anastomotic Tube: A Pilot Randomized Controlled Trial

The term BRUE (Brief resolved unexplained event) was proposed by the American Academy of Pediatrics in 2016 to replace the term ALTE (Apparent life-threatening event), which in turn replaced the so-called near-miss sudden infant death syndrome in 1986. This latest change is intended to avoid unnecessary hospitalizations and reduce the use of high-cost, low-yield laboratory and imaging tests. However, we believe that in the absence of clinical guidelines that guide the management of the BRUE, that objective may not be met. We present a clinical guideline prepared for Hospital Dr. Exequiel González Cortés, in Santiago, Chile.

Gastroesophageal Reflux

This study aimed to formulate a clinical decision rule (CDR) to identify infants with apparent-life threatening event (ALTE) who are at low risk of adverse outcome and can be discharged home safely from the emergency department (ED). This is a prospective cohort study of infants with an ED diagnosis of ALTE at an urban children's hospital. Admission was considered warranted if the infant required significant intervention during the hospital stay. Logistic regression and recursive partitioning were used to develop a CDR identifying patients at low risk of significant intervention and thus suitable for discharge from the ED. A total of 300 infants were enrolled; 228 (76%) were admitted; 37 (12%) required significant intervention. None died during hospital stay or within 72 hours of discharge or were diagnosed with serious bacterial infection. Logistic regression identified prematurity, abnormal result in the physical examination, color change to cyanosis, absence of symptoms of upper respiratory tract infection, and absence of choking as predictors for significant intervention. These variables were used to create a CDR, based on which, 184 infants (64%) could be discharged home safely from the ED, reducing the hospitalization rate to 102 (36%). The model has a negative predictive value of 96.2% (92%-98.3%). Only 12% of infants presenting to the ED with ALTE had a significant intervention warranting hospital admission. We created a CDR that would have decreased the admission rate safely by 40%.

To the Editors: We read the recent publication by Hobbs et al1 on the characteristics and complications of COVID-19 in hospitalized infants with interest. The authors reported that the most severe cases were in infants <6 months of age, with respiratory complications being the most frequent. Among all patients (severe and nonsevere), there were no reports of apnea. To the best of our knowledge publications about COVID-19 associated apnea in infants are scarce2 and published before the delta variant of SARS-CoV-2 became widespread. Here, we present 5 cases of apnea as the initial manifestation of uncomplicated COVID-19 in young infants treated at our hospital in Croatia (November 2021 to February 2022) (Table 1). The definition of apnea agreed by the American Academy of Pediatrics was used. Except for 1 moderate preterm neonate with intraventricular hemorrhage and another newborn with a small patent foramen ovale, the other infants were healthy with unremarkable prenatal and neonatal medical histories. At the time of admission 4 children appeared well with normal vital signs, although 1 child was hypoxic with physical findings suggestive of bronchiolitis. In all patients, we ruled out other common infectious causes of apnea (normal blood tests, excluded other respiratory viruses and pertussis) and several different diagnoses (cardiac and neurological abnormalities). The association between apnea and COVID-19 was further confirmed by documentation of SARS-CoV-2 infection among patient’s family members and rapid clinical improvement with complete recovery with or without methylxanthine treatment. TABLE 1. - Demographic, Clinical, Diagnostic and Treatment Data of Patients Case 1 Case 2 Case 3 Case 4 Case 5 General data Gender Male Female Male Male Female Birth age (wks) 38 39 38 34 40 Comorbidities None None None None None Age (d) 13 91 23 36 32 Date November 15, 2021 November 18, 2021 November 19, 2021 January 28, 2022 February 2, 2022 Apnea (duration) November 15–17, 2021 November 18, 2021 November 20–22, 2021 January 28–29, 2022 February 2–March 2, 2022 Fever/cough +/+ +/+ +/+ +/+ –/– Diagnostic procedures SARS-CoV-2 * + + + + + Respiratory viruses † – – – – – BP/BPP ‡ – – – – – Chest radiograph Normal Normal Normal Normal Normal Cranial ultrasonography Normal Not done Normal IVH § Normal Transthoracic echocardiography PFO ¶ Not done Normal Normal Normal Treatment (d) Oxygen 6 1 1 – – Aminophylline 6 – 4 – – *PCR from NP swab.†Multiplex PCR from NP aspirate for influenza A/B, human metapneumovirus, respiratory syncytial virus, bocavirus, adenovirus, enterovirus, coronaviruses, parainfluenza virus types 1, 2, 3, and 4, parechoviruses and rhinoviruses.‡PCR from NP aspirate for BP/BPP.§IVH (grade 2).¶PFO (3–4 mm).BP/BPP indicates Bordetella pertussis/parapertussis; IVH, intraventricular hemorrhage; NP, nasopharyngeal; PCR, polymerase chain reaction; PFO, patent foramen ovale. Apnea in infants can result from prematurity or other underlying conditions. Infants presenting with apnea were previously categorized as “apparent life-threatening events” but in 2016 American Academy of Pediatrics replaced this term to “brief resolved unexplained events” (BRUE) to distinguish benign events from life-threatening and to improve clinical management. However, based on many clinical guidelines and reports, infants with evidence of apnea are excluded from BRUE and should undergo further cardiac, neurologic, gastroenterologic, and hematologic evaluations to establish the underlying disorder.3,4 Infectious diseases are common causes of apnea in young infants, especially in preterm neonates and infants <2 months of age. Sepsis, central nervous system, or respiratory infections are those which need to be excluded, especially when accompanied by fever or respiratory symptoms. The 2 principal infectious causes of apnea are respiratory syncytial virus and Bordetella pertussis; however, other respiratory viruses have also been reported in a small percentage of cases.3–5 We observed that SARS-CoV-2 can cause apnea in young infants with otherwise asymptomatic or benign COVID-19. We also noticed a cluster of described clinical manifestation during predominant circulation of the delta (until late December 2021) and omicron (from January 2022) variants in the Croatian population. Based on our report, we suggest that testing for SARS-CoV-2 should be part of the initial evaluation of apnea in infants who were <3 months of age presenting to emergency pediatric departments. Additionally, although the majority of neonatal SARS-CoV-2 infections are mild, caregivers should be aware of this potentially life-threatening complication, especially in very young patients who are discharged or treated in outpatient settings.