Incidence and Risk Factors of Brief Resolved Unexplained Events in Infants presenting to Pediatrics Department of Bab Elsharya University Hospital

Background: Infants who present with a history of an acute event (an unexpected change in an infant's breathing, appearance, or behavior), reported by their parent or caregiver, represent a heterogeneous group of patients of varying ages with diverse pathophysiology. A BRUE is diagnosed only when there is no explanation for the described event after a thorough history and physical examination. Aim of the study: to detect the incidence of Brief Resolved Unexplained events and differentiate Risk Factors according to initial presentation of cases and follow-up. Methods: Prospective application of BRUE criteria on infants younger than 12 months old who presented to emergency room of Bab El Shaaria University Hospital from 1 June 2018 to 1 December 2018. BRUE patients were classified into Lower-risk (LR-BRUE) and Higher-risk (HR-BRUE). History was taken from all caregivers and all patients underwent physical examinations and o2 saturation monitoring by pulse oximetry on room air. Studied infants were followed up 3 to 6 months after discharge either by regular visits or by phone. Results: study included 2462 Infants below 1 years old, the inclusion criteria of BRUE met 39 patients ( 1.58%) 18 of them are males (46 %) and 21 are females(54%), 23 of BRUE cases classified as low


Introduction
Clinicians should use the term BRUE to describe an event occurring in an infant <1 year of age when the observer reports a sudden, brief, and now resolved episode of ≥1 of the following: • Cyanosis or pallor • absent, decreased, or irregular breathing • marked change in tone (hyper or hypotonia) • altered level of responsiveness Further recommendations were made for standardizing the diagnostic evaluation and a risk stratification algorithm for these infants.
Among the recommendations for infants having experienced a lower-risk BRUE (LR-BRUE) was that a minimal diagnostic work-up was indicated and that follow-up in an ambulatory setting was permissible. A BRUE is diagnosed only when there is no explanation for the described event after a thorough history and physical examination. The presence of other features, for example respiratory symptoms or a fever, preclude the diagnosis and should prompt further assessment for a specific cause.

Ethical consideration:
• Written Parent consent for the study was obtained before the study.
• Approval of the local ethical committee in the pediatrics department, college and university were obtained before the study.
•The authors declared no potential conflict of interest with respect to the research & publication of this article.
•All the data of the patient & results of the study are confidential & the patient has the right to keep it.
•the authors received no financial support for the research &publications of the article.

Patients and Methods
The study is a prospective cohort study included 2462 Infants below 1 years old presented to emergency room of Bab Elsharya University Hospital from 1 June 2018 to 1 December 2018. Informed consents were obtained from all caregivers of patients.
All BRUEs patients fulfilled the following criteria:  Inclusion criteria: All patients below 12 months old presented by a sudden, brief (>1minute) and now resolved episode of one or more of the following: -Cyanosis or pallor.
-Marked change in tone ( hypotonia or hypertonia ) -Altered level of responsiveness. -Any recent events was explained or reached the diagnosis through medical history, clinical examination.

Methods:
History was taken from all caregivers, and all patients underwent physical examinations and monitoring O 2 saturation. Studied infants were followed up 3 to 6 months after discharge either by regular visits or by phone to follow any new events, recurrence or sudden death.

1-Personal data:
Patient's name, age, sex, address and method of contact (Mobile or telephone numbers).

Event description
Description of the colour, respiration, and muscle tone of the infant by his caregivers is very imperative. We had to differentiate central cyanosis from acrocyanosis (hands and feet). We asked about presence or absence of apnea..Also if the infant was limp or muscle tone was increased. Seizure like movements was evaluated. We had to ask about any resuscitation required or it was spontaneously resolved.

Past history
Detailed past history, include in pregnancy, birth condition neonatal period , medical or surgical problems.

Family history
Family history of other siblings with a BRUE, consanguinity, numbers of sibling , history of early unexplained deaths, genetic, metabolic, cardiac or neurological problems

Daily life conditions
We Asked about usual sleep conditions including sleep position ambient temperature and bedding materials. Events preceding the BRUE Knowing minor symptoms preceding the event including recent episodes of fever, illness, received medications, immunization or any change in daily life routine.

3-Full clinical examination:
Full clinical examination to assess general condition of patient and give clue for initial diagnosis including evaluations of the cardiac, respiratory, and neurological systems. It included: -Vital signs with oxygen saturation.
-Measurement of height, weight, and head circumference.
-Respiratory examination of respiratory rate, pattern of breathing and breath sounds.
-Cardiovascular examination heart rate, murmur and pulse oximetry -Examination for physical signs of trauma (bruising, subconjunctival or retinal hemorrhage, bulging anterior fontanel) -Abdominal examination for distension or tenderness to exclude acute intestinal obstruction should be done -Neurologic examination, including alertness, tone and reflexes.
-Inguino-scrotal examination to exclude testicular torsion or incarcerated inguinal hernia -Developmental assessment, including assessment of neonatal reflexes -An observation period, especially while the infant is feeding.

Laboratory and radiological work up:
Our study depended on full history and cautious physical examination which can direct to risk stratification of the patients , and laboratory investigation according to the guideline was as the following :

Low Risk group :
Briefly monitored patients with contentious pulse oximetry for 1-4 hours.

High risk group
They are more likely to have a serious underlying conditions and possibly future events , however the guideline didn't recommend specific  Lumbar puncture, brain imaging were done when we suspect CNS infection.
 ECG, ECHO for suspected cardiac causes.
 Brain imaging and EEG for seizures.

Statistical analysis
Data were analyzed with SPSS version 21.
Qualitative data were described using number and percent.
Association between categorical variables was tested using Chi-square test.
Continuous variables were presented as mean ± SD (Standard deviation) for parametric data and Median for non-parametric data.
For all above mentioned statistical tests done, the threshold of significance is fixed at 5% level (p-value).
The results were considered: -Non-significant when the probability of error is more than 5% (p > 0.05).
-Significant when the probability of error is less than 5% (p ≤ 0.05).
-Highly significant when the probability of error is less than 0.1% The smaller the p-value obtained, the more significant were the results

Results
All results are demonstrated in the following tables.   There was no statistical significance between circumstances and environment prior to event to the classification of risk of BRUE. There is statistical significance of High BRUE in patients presented by hypotonia and pallor (p-value 0.010, 0.022) respectively. There is statistical significance of High BRUE in patients presented by duration of the event more than 60 seconds (p-value = 0.031)  Recurrence rate is statistically significant in patient below 2 months old , preterm infants , infants with history of underlying diseases, and those whose o2 saturation above 90 , p-value ( 0.009-0.002-0.017-0.040) respectively.  Risk of death is statistically significant in infants with history of underlying diseases , History of NICU admission and those whose presented by high Risk BRUE , p-value ( 0.022 -0.040 -0.031 ) respectively. The main risk factors for acute events in infants described as BRUE was feeding difficulties, recent upper respiratory symptoms, and age younger than two months, or a history of previous episodes. As regard the demographic data of the studied group, Male Patients represent 46 %, while female patients represent 54 % of the studied group ranged from 12 days to 12 months old (median age 2.8 months), while previous retrospective study on ALTE done in Tel-Aviv medical center found that 52% of the studied infants were boys between the ages of 1

Recurrence attacks of BRUE
week and 1 year (median age 6 weeks) (Weiss et al., 2010). Recurrence rate is statistically significant in patient below 2 months old , preterm infants , infants with history of underlying diseases , and those whose O 2 saturation above 90%.
There was no statistical significance between the final diagnosis of High Risk group and recurrence nor death.
Risk of death is statistically significant in infants with history of underlying diseases , History of NICU admission and those whose presented by high Risk BRUE .

Limitation of the study:
The study is based on a single, tertiary hospital site in Egypt, cairo thus limiting the external validity and generalizability of our results.

 Conclusion
Since BRUE can present without signs of acute illness and it is often associated with significant medical conditions, Pediatricians should be aware of its clinical importance.
Applying the recent AAP BRUE guidelines and risk stratification to patients presented by acute events is a safe and cost-effective approach. -Careful out-patient follow-up is recommended as two of our patients with a LR-BRUE had a recurrence.