Sudden Infant Death Research Articles

Why do pacifiers/dummies have a protective effect in sudden infant death Syndrome? A new hypothesis

The American Academy of Pediatrics recommends pacifier/dummy use to help prevent sudden infant death syndrome (SIDS). This recommendation is based on studies that have shown pacifier use reduces the risk of SIDS even under conditions regarded as increasing the risk of SIDS. Several unrelated mechanistic explanations have been used to explain this. These prior suggested mechanisms purported to underly the observed protective effect of pacifiers have not proven satisfactory and highlight the need for a more plausible explanation. Pacifier use is associated with increased salivary production. Saliva contains numerous antibacterial compounds that could provide a protective effect against bacterial colonisation. Infection is considered a key player in SIDS pathogenesis given that most SIDS risk factors relate to or align with infection, whereas mainstream research focusses on central homeostatic control of breathing, arousal and heart function. These, however, lack association with risk factors. Given infection is significant in the SIDS story, the increased production and antibacterial effect of saliva could provide an alternative mechanism worthy of consideration in the context of known preventable risk factors in the drive to reach a better understanding of SIDS pathogenesis and further decrease the incidence of SIDS.

Parental obesity and the risk of sudden unexpected infant death.

To clarify the possible role of accidental asphyxiation/suffocation for infants in shared sleeping situations. As it has recently been shown that there is an association between maternal obesity and sudden unexpected infant death (SUID) an index was calculated by dividing parental body mass index (BMI) by the shared sleeping surface area. A much higher index was derived for an obese individual on a narrow sleeping area such as a sofa (50) compared to a thin adult on a queen-sized mattress (5). The index may be a way of semi-quantitating high, and low, risk shared sleeping situations.

Maternal Obesity and Sudden Unexpected Infant Death.

Maternal Obesity and Sudden Unexpected Infant Death.

Collaboration to Reduce Sudden Unexpected Infant Death With Child Fatality Review and Outreach.

Sudden unexpected infant death (SUID) is the leading cause of postneonatal infant mortality in the United States, with disproportionately high rates in Baltimore City and Baltimore County in Maryland. This Advocacy Case Study describes the collaboration between the City and County Child Fatality Review teams to decrease infant mortality. B'more for Healthy Babies, formed in 2009 by the Bureau of Maternal Child Health in Baltimore City with the goal of reducing infant mortality through policy change, service improvements, community mobilization, and behavior change has had a sustained effort to respond to SUID. Recognizing that infants born in Baltimore City often reside in Baltimore County (and vice versa), collaboration with Baltimore County has been essential to increasing B'more for Healthy Babies' scope, reach, and effectiveness. Public health messaging campaigns, creation, and dissemination of a "SLEEP SAFE" testimonial video, and Safe Sleep Summits have involved caregivers, healthcare providers, and community partners. Outcomes of this ongoing collaboration demonstrate a decrease in sleep-related infant mortality rates. Our findings also highlight the need for continued, real time monitoring of sleep-related infant mortality trends with a coordinated, multidisciplinary, and crossjurisdictional response. This initiative can serve as a model of cross-sector communication that can be replicated in other similar geographic locations to further reduce SUID.

Improving Consistency in Classifying Child Maltreatment for Sudden Unexpected Infant Deaths.

Develop guidelines for child death review teams that will improve the consistency in classifying child maltreatment (CM) and distinguish between classification of exposure to hazards and neglect for sleep-related sudden unexpected infant deaths (SUID). Sleep-related SUID (n = 25 797) were identified from the National Fatality Review-Case Reporting System between 2004 and 2018. Key variables considered when classifying CM among sleep-related SUID were identified. Logistic regression was used to assess the strength of associations and identify factors that distinguished between exposure to hazards and neglect. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Guidelines were developed based on these findings. Among the 13 034 sleep-related SUID with CM identified, hazards in the infant sleep environment were strongly associated with classification of both exposure to hazards and neglect, as were supervisor impairment and child welfare substantiation of the death. Comparing neglect to exposure to hazards, there was no association with sleep environment hazards with ORs ranging from 0.8 to 1.3 (95% CI 0.4-3.0), but sleep-related SUID were approximately twice as likely to be classified as neglect when the supervisor was impaired (OR 2.3, 95% CI 2.0-2.7) or child welfare action was taken (OR 1.8, 95% CI 1.5-2.0). The guidelines recommend classification of exposure to hazards for sleep environment hazards with elevation to neglect if the supervisor was impaired or child welfare substantiated the death. Among sleep-related SUID, classification of exposure to hazards is based on presence of sleep environment hazards, whereas neglect is based on supervisor impairment and child welfare action.

Using Sudden Unexpected Infant Death-Case Registry Data to Drive Prevention.

Sudden unexpected infant death (SUID) is a major contributor to infant death and a persistent public health issue. After an initial decline after the 1994 "Back to Sleep" campaign, SUID numbers plateaued. Currently, ∼10 infants die suddenly and unexpectedly each day in the United States. In 2019, we established a surveillance system for SUID in Cook County, Illinois, partnering our academic medical center, the Cook County Medical Examiner's Office, and child death review to create the Cook County SUID Case Registry. Our data show that, in Cook County, including the city of Chicago, ∼1 infant dies unexpectedly during sleep every week. Of these SUID, ∼25% were because of suffocation/possible suffocation. SUID peaks at 30 to 60 days old. SUID rates are 15 times higher in non-Hispanic Black infants and 3 times higher in Hispanic infants, compared with white infants. Nearly all involved 1 or more unsafe sleep factors. SUID are concentrated in community areas experiencing high hardship. Through our Community Partnership Approaches for Safe Sleep-Chicago team, we have developed collaborative prevention approaches in affected communities, allowing for conversations with families and those who support them to better understand barriers to safe sleep that they experience. These partnerships and our data allow for tailoring of informed prevention approaches to address upstream factors driving disproportionate infant mortality in historically disinvested communities, as well as optimizing the immediate risks posed by the infant sleep environment. Data from our system show the number of SUID declining modestly since our prevention work began.

Unexplained Infant Deaths Without Unsafe Sleep Factors: 2011 to 2020.

To describe sudden unexpected infant deaths (SUIDs) occurring in safe sleep environments and explore differences in selected characteristics. We examined SUID from 22 jurisdictions from 2011 to 2020 and classified them as unexplained, no unsafe sleep factors (U-NUSF). Data were derived from the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry, a population-based Centers for Disease Control and Prevention surveillance system built on the National Center for Fatality Review and Prevention's child death review program. SUID classified as U-NUSF included infants who were (1) awake, under supervision, and witnessed to become unresponsive or (2) found unresponsive in a safe sleep environment after sleep (unwitnessed). We calculated frequencies and percentages for demographics, birth and environmental characteristics, medical history, and death investigation findings. Most of the 117 U-NUSF SUID occurred before 4 months of age. Witnessed deaths most commonly occurred at <1 month of age (28%), whereas unwitnessed deaths most commonly occurred at ages 2 to 3 months (44%) Among all U-NUSF, 69% occurred in the infant's home (62% witnessed, 77% unwitnessed). All unwitnessed deaths occurred in a crib; most witnessed deaths occurred while being held (54%) or in a car seat traveling (18%). Most infants (84%) had no history of abuse or neglect. Abnormal autopsy findings were reported in 46% of deaths (49% witnessed, 42% unwitnessed). Characterizing these deaths is key to advancing our knowledge of SUID etiology. Our study revealed a heterogeneous group of infants, suggesting physiologic, genetic, or environmental etiologies.

Evaluating Educational Patterns and Methods in Infant Sleep Care: Trends, Effectiveness, and Impact in Home Settings—A Systematic Review

Background: Sleep care is crucial for the health and development of infants, with proper sleep patterns reducing the risk of sudden infant death syndrome (SIDS) and other sleep-related incidents. Educational interventions targeting caregivers are essential in promoting safe sleep practices. Methods: This systematic review adhered to PRISMA guidelines, searching databases such as PubMed, MEDLINE, Scopus, and the Cochrane Library. Inclusion criteria focused on studies involving home-based interventions for infants aged 0–12 months, including parental education and behavioral interventions. Exclusion criteria included studies in clinical settings and non-peer-reviewed articles. Data extraction and synthesis were performed by two independent reviewers, using a narrative approach to categorize interventions and outcomes. Results: Twenty-three studies met the inclusion criteria. Key findings indicate that home-based educational interventions, including hospital-based programs, home visits, and mobile health technologies, significantly improve parental knowledge and adherence to safe sleep practices. These interventions also enhance parental satisfaction and contribute positively to infant health outcomes. Conclusions: Educational interventions have demonstrated effectiveness in promoting safe sleep practices among caregivers, particularly in home settings. These interventions, including hospital-based programs, home visits, and digital tools, improve parental knowledge, adherence to guidelines, and overall satisfaction. The impact is evident in the reduction of unsafe sleep behaviors and enhanced infant health outcomes. However, variability in the intervention methods and delivery, cultural contexts, and geographic focus suggest a need for more tailored, long-term, and comprehensive studies. Future research should standardize outcome measures and assess the sustained impact of these educational strategies on infant sleep patterns and caregiver practices over time. This will provide deeper insights into the trends and long-term effectiveness of educational patterns and methods in diverse home environments.

Assessing universal considerations in infant mortality across the globe: A descriptive observational study of sudden infant death syndrome knowledge and reduction coverage on YouTube

Assessing universal considerations in infant mortality across the globe: A descriptive observational study of sudden infant death syndrome knowledge and reduction coverage on YouTube

Supine Sleep-Promoting Baby Mattress: SIDS Prevention and Athlete Injury Relief

Sudden Infant Death Syndrome (SIDS) is a leading cause of death in infants aged one to 12 months, primarily occurring during sleep. Consequently, there is considerable interest among researchers and healthcare professionals regarding the sleeping environment and potential risk factors. One identified risk factor is infants sleeping prone (on their stomach), making supine (on the back) sleeping the recommended position. Associate Research Fellow Shing-Jye Chen from the Department of Sports Science Research at the Taiwan Institute of Sports Science (TISS) is developing a hammock-like air-based baby mattress covered with breathable mesh. This mattress is designed to promote supine sleeping and prevent babies from rolling onto their stomachs during sleep. It features air tubing within tensioned mesh fabric that automatically adjusts to suspend and support the baby’s weight. This design increases the contact surface area between the baby and the mattress, reduces contact pressure, and provides evenly distributed support as the baby grows. Chen takes an interdisciplinary approach, collaborating with experts in baby breathing, sleeping patterns, and biomechanics to develop solutions aimed at reducing the risk of SIDS based on scientific evidence, safety, and effectiveness. In a pilot study, Chen collected data on the mattress’s performance using weights to simulate babies of different ages. His team will explore the relationship between weight and the measured pressure values at different internal air pressures within the inflatable tubing design. The potential application of this product design may extend to injured athletes, particularly in areas where injuries contact the mattress surface, thereby reducing stress.

Insights into the aetiology and temporal trends in cardiac mortality in the young: a 21-year review of national and registry data in the united kingdom

Abstract Background An accurate representation of the incidence and aetiology of cardiac and sudden cardiac death (SCD) is vital for healthcare policymakers to effectively allocate resources for preventative strategies. Purpose We aimed to report on the incidence and causes of cardiac and SCD among individuals under 35-years-old in England and Wales for 21 years (2001-2021), with a focus on identifying any temporal trends. Methods Annual mortality data from the Office for National Statistics (ONS) pertaining to cardiovascular (CV) and possible CV deaths in individuals under 35-years-old were analyzed using International Classification of Diseases-10 codes. Deaths were categorized into four-classes: A1- definitive cardiac deaths without identifiable structural heart disease (consistent with sudden arrhythmic death syndrome, SADS); A2- definitive cardiac deaths with identified structural heart disease; A3- definitive cardiac deaths with indeterminate cause; and B- potential cardiac deaths. Incidence rates were computed based on annual ONS census data. Additionally, insights were gleaned from the Cardiac Risk in the Young Centre for Cardiac Pathology (CRYCCP) nationwide registry. Results The mean annual number of definitive cardiac deaths (classes A1+A2+A3) was 414 (SD 27.4), resulting in an incidence of young cardiac and SCD of 1.68/100,000 individuals/year. Ischaemic heart disease (28.4%), cardiomyopathies (25.9%), and SADS (21.8%) were the most prevalent cardiac conditions. Cardiomyopathies and SADS related mortality peaked in the 10-to-19 age group, while ischaemic heart disease peaked in the 30-to-35 age group. A mean of 573 (SD 76.6) possible cardiac deaths (class B) occurred, these primarily included ill-defined causes (33.5%), epilepsy (32.4%), sudden infant death syndrome (24.2%), and drowning (7%). Definitive and possible cardiac deaths showed a male preponderance (male to female ratios: 2.3:1 and 1.6:1, respectively). A declining trend in cardiac mortality was observed with a 1.3% (95%CI: 1.0%-1.7%) incidence rate reduction/year (p&amp;lt;0.001). This was associated with a 2.5% annual incidence rate reduction for deaths attributed to structural heart disease (p&amp;lt;0.001), but an 8.5% annual incidence rate increase for deaths attributed to SADS (p&amp;lt;0.001). These trends corelated with increasing numbers of deaths referred to the CRYCCP where an expert cardiac pathologist diagnosed SADS in over 52% of cases. Conclusions Over 21 years in England and Wales, national datasets suggest the incidence of young cardiac and SCD is 1.68/100,000/year, with a small but appreciable declining mortality trend. The rise in SADS rates and contemporaneous decline in deaths attributed to structural heart disease may signify increased awareness and accessibility to expert cardiac pathologists. Ensuring accurate mortality coding is crucial for thoroughly assessing first-degree family members in cases of suspected inherited cardiac conditions.

Sociodemographic and Pathological Study of Sudden Death Among Neonates and Infants: An Autopsy Based Study

Children dying within the first year of life is referred to as infant mortality and is an important key indicator for a country’s health and standard of living. Every year, there is an estimated 4.5 million infant deaths around the world, accounting for almost 75% of deaths in children younger than 5 years. The studies based on infant deaths are relatively less in number worldwide.This study investigates the sociodemographic and pathological aspects of infant deaths through autopsy data. The objective of the study was to evaluate the pathology and causes of infant/neonatal deaths and analyze related social and demographic factors. A cross-sectional descriptive autopsy study was conducted at the Government Medical College, Kozhikode, covering 66 medicolegal infant death cases from April 2018 to October 2022. Data were collected via questionnaires and analyzed using SPSS software. Respiratory infections (37.14%) were the leading cause of infant deaths, while perinatal complications and congenital abnormalities each accounted for 25% of neonatal deaths. Most deaths occurred in the postneonatal period (77.1%), predominantly among male infants (63%) from rural areas (84.3%). Key findings included consolidation and bronchopneumonia in lung examinations. Significant associations were found with various factors, including the period of infancy, delivery type, co-sleeping history, and prior hospitalizations. Birth weight and histopathological lung findings were linked to sudden infant death syndrome (SIDS).

Tongue microbiota in relation to the breathing preference in children undergoing orthodontic treatment

BackgroundMouth breathing (MB), a risk factor of oral dysbiosis and halitosis, is linked with craniofacial anomalies and pediatric obstructive sleep apnea. Here, we aimed to analyze tongue microbiota in children from the perspective of their breathing pattern before/during orthodontic treatment.MethodsThis prospective case–control study included 30 children with orthodontic anomalies, 15 with MB and 15 with nasal breathing (NB), matched by age, sex, and body mass index. All underwent orthodontic examination and sleep apnea monitoring. Tongue swabs were collected before starting (timepoint M0) and approx. six months into the orthodontic therapy (timepoint M6). Oral candidas and bacteriome were analyzed using mass spectrometry technique and 16S rRNA sequencing, respectively.ResultsMB was associated with higher apnea–hypopnea index. At M0, oral candidas were equally present in both groups. At M6, Candida sp. were found in six children with MB but in none with NB. No significant differences in bacterial diversity were observed between groups and timepoints. However, presence/relative abundance of genus Solobacterium was higher in children with MB than NB at M0.ConclusionsSignificant links between MB and the presence of genus Solobacterium (M0) as well as Candida sp. (M6) were found in children with orthodontic anomalies, highlighting the risk of halitosis in them.

What Has the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry Learned About Consenting Families for DNA Banking and/or Genomic Research?

Since 2015, the Sudden Unexpected Infant Death (SUID) and Sudden Death in the Young (SDY) Case Registry has characterized sudden and unexpected deaths among young people (0-20 years). Families may provide informed consent to save biospecimens for banking and/or genomic research. We reviewed all consent-eligible cases to describe the frequency, time from death to consent, type (paper, phone, or electronic), and staffing method (Medical Examiner Office-based bereavement counselor vs outsourced genetic counselor). Of 5438 cases from January 2015 to January 2022, 3498 (64%) were eligible for consent and 391 (11%) were successfully consented. Half (54%) were obtained within 60 days of the death, 39% within 48 hours. Most were paper based (73%); 23% were obtained by phone, and 4% electronically. Consent rates varied by site from 3% to 66%. Higher consent rates were achieved within a Medical Examiner Office by a social worker or death investigator. Only 3% of consents attempted by a contracted genetic counselor were successful. Identified barriers include lack of available contact information, inability to reach family using the collected information, and lack of response when contacted. Consent rates were highest shortly after death when families were contacted by the Medical Examiner Office as part of bereavement outreach.

515VP SCN4A loss of function zebra fish model: insights into myopathy and sudden infant death

515VP SCN4A loss of function zebra fish model: insights into myopathy and sudden infant death

Brief Resolved Unexplained Event: Evidence-Based and Family-Centered Management.

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.

Validation of a Textile-Based Wearable Measuring Electrocardiogram and Breathing Frequency for Sleep Apnea Monitoring

Sleep apnea (SA) is a prevalent disorder characterized by recurrent events of nocturnal apnea. Polysomnography (PSG) represents the gold standard for SA diagnosis. This laboratory-based procedure is complex and costly, and less cumbersome wearable devices have been proposed for SA detection and monitoring. A novel textile multi-sensor monitoring belt recording electrocardiogram (ECG) and breathing frequency (BF) measured by thorax excursion was developed and tested in a sleep laboratory for validation purposes. The aim of the current study was to evaluate the diagnostic performance of ECG-derived heart rate variability and BF-derived breathing rate variability and their combination for the detection of sleep apnea in a population of patients with a suspicion of SA. Fifty-one patients with a suspicion of SA were recruited in the sleep laboratory of the Cantonal Hospital St. Gallen. Patients were equipped with the monitoring belt and underwent a single overnight laboratory-based PSG. In addition, some patients further tested the monitoring belt at home. The ECG and BF signals from the belt were compared to PSG signals using the Bland-Altman methodology. Heart rate and breathing rate variability analyses were performed. Features derived from these analyses were used to build a support vector machine (SVM) classifier for the prediction of SA severity. Model performance was assessed using receiver operating characteristics (ROC) curves. Patients included 35 males and 16 females with a median age of 49 years (range: 21 to 65) and a median apnea-hypopnea index (AHI) of 33 (IQR: 16 to 58). Belt-derived data provided ECG and BF signals with a low bias and in good agreement with PSG-derived signals. The combined ECG and BF signals improved the classification accuracy for SA (area under the ROC curve: 0.98; sensitivity and specificity greater than 90%) compared to single parameter classification based on either ECG or BF alone. This novel wearable device combining ECG and BF provided accurate signals in good agreement with the gold standard PSG. Due to its unobtrusive nature, it is potentially interesting for multi-night assessments and home-based patient follow-up.

GFAP expression in the brain during human postnatal development

AbstractGlial fibrillary acidic protein (GFAP) immunohistochemistry was investigated in the developing human brain using two measures; the number of GFAP‐positive cells (density, GFAP+/mm2), and a reactivity score (R‐score), which we recently introduced to indicate astrogliosis, with scores ≥120 indicative of pathological processes. The primary aim was to report on GFAP expression and cell soma size in 26 microscopically defined regions of the amygdala, basal ganglia, cerebellum, hippocampus and medulla, and to determine whether they are affected by postconceptional age (PCA) from 40 to 83 weeks. The secondary aim was to determine if GFAP expression differs according to the classification of sudden infant death syndrome (SIDS) as opposed to infant deaths of known causes, or for the presence of major SIDS risk factors of male sex, cigarette smoke exposure, upper respiratory tract infection (URTI), bed‐sharing and prone sleeping. The cerebellar molecular layer was void of GFAP+ cells, while the internal granular layer (IGL) had the highest density, with &gt;60% of infants having an R‐Score &gt;120. GFAP expression decreased with increasing PCA in the entorhinal and temporal cortex, subiculum and regions of the cerebellum and medulla. GFAP cell soma size corresponded with astrogliosis score and no effect of PCA was evident. Various region‐dependent GFAP expressional differences were seen according to SIDS classification and the risk factors studied. The findings indicate that the density of GFAP decreases in specific regions of the brain within the first year of postnatal development, and that reactive astrocytes are common, particularly within the early postnatal months.

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes.

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters (Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters (Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.