Case #1
A 2-month-old male infant presents to the emergency department (ED) via ambulance in complete cardiorespiratory arrest. On the day of presentation, his mother had left him with a babysitter. After a feeding, the babysitter had put him down to sleep. When she checked on him approximately 30 minutes later, she found him pale, not breathing, and limp. She called 911 and began attempts at CPR (cardiopulmonary resuscitation). En route, CPR was continued, and the patient was intubated, an intraosseous line was placed, and two doses of epinephrine were administered.
Past Medical History: The patient was born at term via spontaneous vaginal delivery with a birth weight of 3.4 kg (7 lbs, 8 oz). There were no complications, and he was discharged home from the hospital with his mother on day of life 2. He has been well since then.
Exam: VS T 35 degrees C, pulse and chest rise with CPR, without CPR apneic and pulseless. The infant is mottled without spontaneous movements. Pupils are fixed and dilated.
Clinical Course: Resuscitation is continued in the ED. There is no response to these measures and the infant is pronounced dead after 30 minutes.
Case #2
A 2-month-old female infant presents to the ED after her mother noted that she appeared to stop breathing at home after a feeding. This episode lasted about 10 seconds and the patient appeared to turn blue around the mouth, prompting her mother to call 911. When EMS arrived, the patient appeared well but due to her mother's concerns she was brought to the emergency department for further evaluation.
Past Medical History: The patient was born at term via spontaneous vaginal delivery with a birth weight of 3.4 kg (7 lbs, 8 oz). There were no complications, and she was discharged home from the hospital with her mother on day of life 2. She has been well since then.
Exam: VS T 37 degrees C, P 140, RR 24, BP 80/50. The infant appears well, with a normal physical exam.
Clinical Course: The patient remains well appearing in the ED without any abnormalities in her vital signs. She is admitted to the hospital for further observation and monitoring.
Sudden infant death syndrome (SIDS) is defined as infant deaths that cannot be explained after a thorough case investigation, including a scene investigation, autopsy, and review of the clinical history. After the scene investigation, though, it appears that many of these deaths are secondary to accidental suffocation or unknown cause, leading to the new broader nomenclature of sudden unexpected infant death (SUID) or sudden unexpected death in infancy (SUDI). SUID is used to describe any sudden death, whether explained or unexplained (including SIDS) that occurs during infancy (1,2).
In the United States, there are about 3,400 yearly cases of sudden unexpected infant deaths with 41% attributed to SIDS (1). SIDS has evolved to be the leading cause of death among infants 1 month to 1 year of age in the United States, with peak incidence between 2 and 4 months of age. In 1994, the Back to Sleep campaign was initiated with a steady decline in deaths until 2000. However, since 2001, the SIDS rate has shown only a slight decline. Racial and ethnic disparities exist, with Asian Americans having lower risk and African American infants and American-Indian/Alaska Native infants having higher mortality rates (1). Other risk factors include parental age younger than 20 years of age or cigarette smoking by the mother during her pregnancy. Infant risk factors include preterm birth, low birth weight and male gender. Environmental risk factors such as a prone sleeping position or second-hand smoke exposure are also contributory. (1,2)
SUIDs may be found to be secondary to suffocation, asphyxia, entrapment, infection, ingestions, metabolic diseases, arrhythmia-associated cardiac channelopathies, and trauma (accidental or non-accidental). SIDS, on the other hand, is a diagnosis of exclusion. It is a multifactorial condition in that the combination of a critical developmental period, intrinsic vulnerability (possibly dysfunctional and/or immature cardiorespiratory and/or arousal systems) and exogenous stressors (prone sleep position, over-bundling, airway obstruction) lead to a failure of protective responses. This results in progressive asphyxia, bradycardia, hypotension, metabolic acidosis, and ineffectual gasping, that ultimately lead to death. At this time, it is unclear what mechanisms are responsible for the intrinsic vulnerability. Associations that have been found include brainstem abnormalities involving the medullary serotonergic 5-hydroxytryptamine system and tobacco smoking, as well as mutations in the cardiac sodium or potassium channel genes that result in long QT syndrome. (2)
As currently there is no definitive test to diagnose SIDS, an infant death should be determined to be attributable to SIDS when all the following are true (3):
1. A complete autopsy is performed, and findings are compatible with SIDS.
2. There is no evidence of acute or remote inflicted trauma, significant bone disease, or significant and contributory unintentional trauma.
3. Other causes and/or mechanisms of death are sufficiently excluded, including meningitis, sepsis, aspiration, pneumonia, myocarditis, trauma, dehydration, fluid and electrolyte imbalance, significant congenital defects, inborn metabolic disorders, asphyxia, drowning, burns, or poisoning.
4. There is no evidence of toxic exposure to alcohol, drugs, or other poisoning.
5. Thorough death and/or incident scene investigation and review of the clinical history reveal no other cause of death.
Investigations are conducted by a multi-disciplinary team consisting of first-responders, child welfare or child protection services, physicians, pathologists, law enforcement, for all unexplained infant deaths. First-response teams are trained to make observations of the scene (such as position of infant, marks on the body, position of clothing and bedding) and to distinguish between normal postmortem findings and those that may be attributable to abuse. Guidelines are also available for investigation of the circumstances of SUIDs. As parents are typically distressed, those involved in the investigation should be compassionate, empathetic, supportive, and non-accusatory. The majority of infants who die from SIDS are not victims of child abuse, with estimates ranging from about 1 to 5 percent. During the investigation, there are certain circumstances that should raise concern for intentional suffocation (3): 1) Previous recurrent cyanosis, apnea, or brief resolved unexplained event (BRUE), previously known as apparent life-threatening event (ALTE) while in the care of the same person. 2) Age of death older than 6 months. 3) Previous unexpected or unexplained deaths of 1 or more siblings. 4) Simultaneous or nearly simultaneous death of twins. 5) Previous death of infants under the care of the same person. 6) Evidence of previous pulmonary hemorrhage.
During prenatal counseling and well-child checks, physicians should provide anticipatory guidance to families to prevent SIDS and SUIDS. The 2022 American Academy of Pediatrics (AAP) Policy Statement on SIDS and Other Sleep-Related Infant Deaths recommends the items in table 1 below (2,4):
Table 1: AAP sleep recommendations (2)
| 1. Infants should be placed in a supine (back) sleep position, not prone or side-sleeping until 1 year of age. |
| 2. Use a firm, flat, non-inclined sleep surface to avoid suffocation or wedging/entrapment. |
| 3. Feeding of human milk is recommended for its associated risk reduction of SIDS. |
| 4. Room-sharing but on a separate surface specific for infants until the child is at least 6 months old. |
| 5. Keep soft objects (e.g., blankets, pillows, soft toys, comforters, mattress toppers, etc.) and loose bedding (e.g., blankets, non-fitted sheets) out of the crib. |
| 6. Consider offering a pacifier at nap time and bedtime, after breastfeeding is well established. |
| 7. Avoid cigarette smoking and nicotine exposure during and after birth. Pregnant mothers should also avoid exposure to second-hand smoking. |
| 8. Avoid alcohol, marijuana, opioids, and illicit drug use during and after pregnancy. |
| 9. Overheating and head coverings in infants should be avoided. |
| 10. Pregnant women are recommended to obtain regular prenatal care. |
| 11. Immunize infants in accordance with AAP and CDC guidelines.. |
| 12. Avoid commercial devices that are inconsistent with safe sleep recommendations. |
| 13. Home cardiorespiratory monitors should not be used to prevent SIDS. |
| 14. Place infants in supervised, awake tummy time, beginning with short periods of time, then gradually increasing to at least 15 to 30 minutes a day by 7 weeks of age. |
| 15. Avoid swaddling an infant. Otherwise, if unavoidable, swaddled infants should always be placed on their backs. |
| 16. Physicians, non-physician clinicians, hospital staff, and childcare providers should promote infant sleep guidelines from the beginning of pregnancy. |
| 17. Media and manufacturers are advised to follow safe sleep guidelines in their products, productions, and promotions. |
| 18. Continuation of the Eunice Kennedy Shriver National Institute of Health and Human Development "Safe to Sleep" campaign. |
| 19. Research/surveillance of the risk factors, causes and mechanisms causing sleep-related deaths should be continued. |
The emphasis of supine sleep position in the Back to Sleep campaign has drastically decreased the number of deaths due to SIDS. However, current efforts are still being made to target this message to populations with higher incidences, such as African Americans and other infant caregivers such as babysitters and daycare personnel. The sleep environment is also important, with attempts made to minimize the risk of suffocation from bedding and other individuals. The AAP encourages breastfeeding; infants may be brought to the bed for feeding and comforting but should be returned to their own crib or bassinet when the parent is ready to return to sleep. It also does not recommend the use of positioning devices, drop-down cribs, or bumper pads. It does note that prone positioning is acceptable when the infant is awake and supervised to promote motor development and minimize positional plagiocephaly (a.k.a. "tummy time" by 7 weeks of age). (2)
The term BRUE (brief resolved unexplained event) was introduced by the AAP in 2016 to replace the term apparent life-threatening events (ALTE), just as ALTEs replaced the previously used terms "aborted SIDS" or "near-miss SIDS" in 1986. BRUE is characterized as an incident in an infant under the age of 1, where the observer reports a sudden, brief, yet resolved episode involving significant change in at least one of the following: 1) color, 2) breathing, 3) muscle tone, 4) level of responsiveness. (5)
BRUE and ALTE are not identical terms. A BRUE requires an event to be "unexplained" after taking an appropriate history and performing a physical examination; at which point the diagnosis is not apparent (e.g., if the patient’s presentation and initial testing are suggestive of a seizure disorder or severe infection) (6). BRUEs are further stratified as low-risk and high-risk. Low-risk infant criteria include age >60 days old, gestational age >=32 weeks, postconceptional age >=45 weeks, first and single BRUE with no previous episodes, an event lasting <1 minute, no CPR required by a trained medical provider, and no concerning medical history or physical exam features (5). Those that do not meet the low-risk criteria are considered to be high-risk by default. (5,6)
Breathing abnormalities may often be a point of confusion and is worthwhile to distinguish these findings as pathologic or normal. Periodic breathing, in which three or more pauses occur, each lasting more than three seconds but with less than 20 seconds, with normal respiration between pauses, is normal. In contrast, pathologic apnea occurs when the respiratory pause lasts for 20 seconds or more, and is accompanied by bradycardia, cyanosis, hypotonia, or other signs of compromise. In addition, apnea of prematurity is periodic breathing with pathologic apnea associated with preterm delivery. It usually resolves by 34 to 36 weeks gestation but may continue for a few weeks beyond term gestation. It is due to an immature central respiratory center control, as opposed to obstructive apnea, which occurs secondary to conditions such as craniofacial abnormalities or hypotonia. Apnea of infancy is usually reserved for infants who present with a BRUE in whom no plausible etiology is identified. (7)
BRUEs are relatively uncommon, with an incidence between 0.6 and 5.0 per 1000 live births. Most occur in children younger than one year of age, with a peak incidence between one week and two months of age. Those who are born premature are at increased risk for a BRUE but not for SIDS. (8)
BRUE does not refer to a single diagnosis, but rather a clinical condition. There are many potential causes for BRUE, but only approximately 50 percent of cases will result in an identifiable diagnosis. The most common diagnoses include gastroesophageal reflux, lower respiratory tract infection, and seizure. Infants less than two months of age with a BRUE and those with recurrent BRUEs are more likely to have significant disorders. (5)
Table 2: Differential Diagnosis of BRUE (9): (The following list is not exhaustive. Refer to (9) for a more comprehensive list)
| Gastrointestinal (GI): gastroesophageal reflux, gastroenteritis, intussusception, swallowing abnormalities (dysphagia, choking, esophageal dysmotility), bowel obstruction, tracheoesophageal fistulas, other GI abnormalities |
| Neurologic: seizure disorder, febrile seizure, central nervous system (CNS) bleeding, neurologic conditions affecting breathing, CNS infection, malignancy, hydrocephalus, demyelinating disorder |
| Respiratory: respiratory compromise from infection (e.g., RSV, pertussis, pneumonia), obstructive sleep apnea, conditions affecting respiratory control (e.g., prematurity, central hypoventilation), airway obstruction due to congenital abnormalities, foreign-body aspiration |
| Cardiac: channelopathies (prolonged QT syndrome, Brugada syndrome, short QT syndrome), arrhythmia, congenital heart disease, myocarditis/cardiomyopathy, ventricular pre-excitation (Wolff-Parkinson-White syndrome) |
| Otolaryngologic: maxillary hypoplasia, micrognathia, macroglossia, obstructive sleep apnea, subglottic stenosis, adenotonsillar hypertrophy |
| Infectious: sepsis, bronchiolitis, pneumonia, croup, upper respiratory infection, urinary tract infection, sepsis, meningitis, specific organisms (pertussis, RSV, other respiratory viruses) |
| Metabolic abnormalities: inborn errors of metabolism, urea cycle disorders, hypocalcemia, hypoglycemia, mitochondrial disorders, endocrine or electrolyte disorders |
| Child maltreatment: smothering (unintentional or intentional), Munchausen syndrome by proxy, poisoning, abusive head trauma |
| Toxin exposure: medication adverse effect, environmental exposure, vaccine reaction |
| Other: acrocyanosis, hypothermia, breath-holding spell, idiopathic |
A BRUE can only be diagnosed if there is no other qualifying event which is discerned through a thorough history and physical exam. It is helpful to approach a suspected BRUE by identifying infants younger than 1 year who present with a BRUE who are categorized either as 1) lower-risk with a history and physical exam that have evidence-based recommendations for the evaluation and management or 2) higher-risk with a history and physical exam that may need further investigation and treatment but does not have evidence-based recommendations (5). Important historical features to inquire when evaluating for a possible BRUE are detailed in Table 3.
Table 3: Important Historical Features to Consider for possible BRUE (5)
| 1. Ruling out child abuse: Are there multiple or varied versions of the initial history? Any history/circumstances that are inconsistent with the patient’s developmental stage? History of unexplained bruising? Inconsistency between caregiver’s perspective and child’s actual developmental stage? |
| 2. Events surrounding the BRUE: General report of event? Who was/is reporting the event? Any witnesses of the event (e.g., parent(s), other children/adults) and their reliability as historian(s)? What was the child doing before the event (i.e., sleeping or awake, position of infant, feeding, nearby hazardous objects that could smother/choke)? What happened during the event (i.e., choking/gagging, actively moving vs. quiet/flaccid, repetitive movements, fever, infant appearance including skin or lip color)? What happened after the event (i.e., how long did the event last, any interventions including gentle stimulation or CPR, abrupt or gradual cessation of event)? What is the patient’s state after the event (i.e., normal, quiet, fussy)? Recent illnesses or injuries? |
| 3. Medical history: History of BRUE? Medical conditions such as prematurity, seizures, reflux, breathing abnormalities or congenital heart disease? Pre/perinatal history? Gestational age? Previous hospitalizations or surgeries? Recent immunizations? |
| 4. Medication history: What medicines does the child take? What other medications are in the home? Alternative or complementary medications? |
| 5. Family history: Cardiac conditions (i.e., arrhythmias, long QT syndrome), genetic or metabolic disorders, neonatal and child deaths, SIDS? |
| 6. Social history: Who was caring for the child at the time of the event? Family structure? Inconsistencies within the story? Social stressors or recent life changes? Infectious exposure? Previous involvement of child protective services or law enforcement? |
| 7. Environmental history: Exposure to tobacco smoke, drugs? Housing exposures (i.e., mold, water damage)? |
During the management of an infant >60 d and <1 year that meets criteria for having experienced a lower-risk BRUE, Table 4 lists the categories of evaluations recommended (and not recommended) by the AAP (5). This listing is very detailed and beyond the scope of this chapter.
Table 4: AAP recommended categories of evaluations for a lower risk BRUE (5)
| 1. Cardiopulmonary evaluation |
| 2. Child abuse evaluation |
| 3. Neurologic evaluation |
| 4. Infectious disease evaluation (need not obtain WBC count, blood culture or CSF analysis/culture for detecting an occult bacterial infection for low-risk BRUE) |
| 5. Gastrointestinal evaluation |
| 6. Inborn Errors of Metabolism (IEM) evaluation |
| 7. Anemia evaluation |
| 8. Patient- and family-centered care |
Routine hospital admission for patients remains controversial; but admission for an observation period is reasonable. Those that present with severe episodes, for example those requiring CPR, or with abnormal results on history and physical exam, should be hospitalized for further evaluation. Hospitalization allows the physician to monitor the infant and provide direct observation for any parental or social issues. However, parents should also be informed that it is unlikely that a treatable cause will be identified. In addition, for those infants with a reassuring history of a benign event and normal physical exam, it may be possible to discharge them home after a period of observation if adequate follow-up can be assured. (5)
A meta-analysis was conducted which incorporated observational studies of patients with ALTE, identified from a published review of the literature from 1970 through 2014 and a PubMed query through February 2017. The study provides evidence that the baseline risk of death for a child who has had a BRUE is similar to a child in the overall population during their first year of life (6).
Since there is no evidence that BRUEs are precursors to SIDS, the AAP does not recommend that infant home monitors routinely be used to prevent SIDS. This is due to the high rate of false alarms, parental anxiety, inappropriate use of monitors, and the lack of proven efficacy in the prevention of death. However, monitors may be warranted for infants who are technology dependent, have unstable airways, have rare medical conditions affecting regulation of breathing, or have symptomatic chronic lung disease. All caregivers should be encouraged to become educated in CPR techniques. (2)
Questions
1. True/False: All BRUE episodes are thought to be precursors to SIDS.
2. Intentional suffocation should be considered as a possibility of a SUIDS death when:
a. The infant is younger than 6 months of age
b. Previous BRUEs have occurred under the care of different caregivers
c. Previous death of another family member under the care of the same caregiver
d. No evidence of intrapulmonary hemorrhage
e. No family history of SIDS or BRUE
3. True/False: Co-sleeping is acceptable if a mother is breastfeeding.
4. True/False: Home apnea monitors do not prevent SIDS
References
1. Centers for Disease Control and Prevention. Sudden Unexpected Infant Death and Sudden Infant Death Syndrome - Data and Statistics. April 2021. https://www.cdc.gov/sids/data.htm. Accessed June 2022
2. Moon RY, Carlin RF, Hand I, The Task Force On Sudden Infant Death Syndrome and the Committee on Fetus and Newborn. Sleep-Related Infant Deaths: Updated 2022 Recommendations for Reducing Infant Deaths in the Sleep Environment. Pediatrics. 2022;150(1);e2022057990. doi:10.1542/peds.2022-057990
3. Palusci VJ, Council on Child Abuse and Neglect, Kay AJ, et al. Identifying Child Abuse Fatalities During Infancy. Pediatrics. 2019;144 (3):e20192076. doi:10.1542/peds.2019-2076
4. Centers for Disease Control and Prevention. Sudden Unexpected Infant Death and Sudden Infant Death Syndrome - Parents and Caregivers. October 2021. https://www.cdc.gov/sids/Parents-Caregivers.htm. Accessed June 2022.
5. Tieder JS, Bonkowsky JS, Etzel RA, et al, Subcommittee on Apparent Life Threatening Events. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016;137(5):e20160590. doi:10.1542/peds.2016-0590
6. Brand DA, Fazzari MJ. Risk of Death in Infants Who Have Experienced a Brief Resolved Unexplained Event: A Meta-Analysis. J Pediatr. 2018;197:63-67. doi: 10.1016/j.jpeds.2017.12.028
7. Kondamudi NP, Krata L, Wilt AS. Infant Apnea. [Updated 2023 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441969/
8. Manon DC, Brulé B, Lauzier D, Brossier F, Porcheret. Brief resolved unexplained event: Severity-associated factors at admission in the pediatric emergency ward. Archives de Pédiatrie. 2023;30(6):389-395. doi:10.1016/j.arcped.2023.05.005.
9. Tieder et al, Supplemental Table 6. Pediatrics 2016;137:online: https://aap2.silverchair-cdn.com/aap2/content_public/journal/pediatrics/137/5/10.1542_peds.2016-0590/10/peds_20160590supplementarydata.pdf?Expires=1732296368&Signature=ItLurt3MVBbdbeZJO9~yu22CglTVhz7XPJah6ygjehtMMQDTZCHW64ucoUn3H15rvvf0XoqW0235juomHelLYDYAIEm~FKPMCePfXYMhn64fAG5jT2wbJNan0gbKDSkB9nA9l76xe7V6XeMNogcLHfQwGUUvTmSIkaoEImYUCzJuDLt~Zevnq1JRg~2S8YbKoPqMtpaO29UlNdPAZJ-~XZjsEkzE-8Z17KG05B7Sku5xYj2obMg79qgXbsNI6Fh3T3S0NmJ2M97kw0litWN4Tz5Jr71oLABxpTDTS6o1wStokqfzUfEdKFq7s4uyQ9T6mPLqmLFSaKFGho3wrlUOw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
Answers to questions
1.False, 2.C, 3.False, 4.True