Somatic, emotional, and gastrointestinal symptom severity are increased among children and adolescents with COVID-19.

BACKGROUND: Post-infectious disorders of gut-brain interaction (PI-DGBI) have significant impact on children and adolescents. The effect of COVID-19 on PI-DGBI-associated symptoms in this population, however, is unknown. METHODS: We performed electronic medical record searches to identify patients 8-17 years old with a SARS-CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April-October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms-Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID-19 test or the test result. RESULTS: One hundred and ninety-six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self-reported their child's COVID-19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID-19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID-19 testing that was highest among patients with a positive COVID-19 test. Abdominal pain and diarrhea prior to COVID-19 testing predicted higher NP scores. CONCLUSIONS: Among symptomatic COVID-19 tested children, we found increased severity of nausea-associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID-19 test.

Intrapyloric Botulinum Toxin Injection for Refractory Nausea and Vomiting in Pediatric Patients.

OBJECTIVES: Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders. METHODS: Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders. RESULTS: At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding ( P < 0.0001) and shorter duration of pylorospasm ( P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists. CONCLUSIONS: Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.

Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Impact of Sleep Disturbance on Fatigue, Nausea, and Pain: Mediating Role of Depressive Symptoms Among Youth With Disorders of Gut-Brain Interaction.

OBJECTIVES: A high degree of sleep disturbance is reported among youth with disorders of gut-brain interaction (DGBIs). Given that sleep quality impacts a range of pediatric health outcomes including somatic sensations (eg, pain) and depressive mood occurs relatively frequently among youth with DGBIs, there is a dire need to disentangle the unique contributions of sleep and depressive mood on the somatic sensations experienced by youth with DGBIs. We aimed to examine whether depressive mood mediates the relations among sleep disturbance and pain intensity, nausea, and fatigue among youth with DGBIs. METHODS: One hundred eighteen patients aged 8-17 years ( Mage = 14.05, SD = 2.88; 70.34% female), 83.05% White/non-Hispanic recruited at a pediatric neurogastroenterology clinic completed measures of sleep disturbance, nausea, fatigue, pain intensity, and depressive mood. Three mediation models examined the effect of sleep disturbance on nausea, fatigue, and pain, with depressive mood as a mediator. RESULTS: Participants reported moderate sleep disturbance. Depressive mood partially mediated the significant, respective relations between greater sleep disturbance and more severe nausea and fatigue. Sleep disturbance was significantly associated with higher pain intensity; however, depressive mood was not a significant mediator of this relation. CONCLUSIONS: Sleep quality is a major concern among youth with DGBIs. Low sleep quality may worsen nausea and fatigue via co-occurring increases in depressive mood symptoms. In contrast, sleep disturbance may directly increase pain, regardless of youths' depressive mood symptoms. Future research should explore these relations through prospective studies leveraging a combination of subjective and objective assessment approaches.

Creating a data dictionary for pediatric autonomic disorders.

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders. METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition. RESULTS: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses. CONCLUSION: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary.

Use of Cluster Analysis to Identify Subtypes of Pediatric Functional Nausea.

OBJECTIVE: The aim of the study was to evaluate whether there are clinical subtypes in children with functional nausea based on comorbidities and responses to the Nausea Profile questionnaire. METHODS: Patients from the Neurointestinal and Motility Program clinical registry at Lurie Children's Hospital were included if they met Rome IV criteria for functional nausea. Patients completed the Nausea Profile, a multidimensional measure of nausea with gastrointestinal, emotional, and somatic subscales. Comorbidities were assessed by chart review and self-report measures. Latent class analysis was used to identify patient groups based on comorbidities. To assess if model-identified groups were predictive of differences in nausea quality, Nausea Profile subscale means were compared between groups and used to predict group membership. Conversely, k-means analysis was used to divide the sample into groups based upon Nausea Profile subscale scores, to determine if identified groups had different comorbidities. RESULTS: Seventy-two patients (n = 53 girls) with a mean age (±SD) 14.5 ±â€Š2.9 were included. Two clinical subtypes were identified based on comorbidities, with responses on the emotional subscale of the Nausea Profile predicting group membership (P < 0.04). When patients were grouped by nausea quality, the resulting clusters differed on psychiatric comorbidities (P < 0.001). CONCLUSIONS: Our findings support the existence of nausea subtypes within the broad diagnosis of functional nausea. One such subtype is an emotional predominant nausea supporting the notion that anxiety and depression constitute a subset of patients with nausea. Thus, patients may benefit from a treatment approach that integrates both GI assessment and psychiatric support in their care.

Children with chronic nausea and orthostatic intolerance have unique brain network organization: A case-control trial.

BACKGROUND: Determine whether subjects with chronic nausea and orthostatic intolerance share common alterations in key brain networks associated with central autonomic control: default mode, salience, and central executive networks, and the insula, a key component of the salience network. METHODS: Ten subjects (ages 12-18 years; 8 females, 2 males) with nausea predominant dyspepsia, orthostatic intolerance, and abnormal head-upright tilt test were consecutively recruited from pediatric gastroenterology clinic. These subjects were compared with healthy controls (n = 8) without GI symptoms or orthostatic intolerance. Resting-state fMRI and brain network modularity analyses were performed. Differences in the default mode, salience, and central executive networks, and insular connectivity were measured. KEY RESULTS: The community structure of the default mode network and salience network was significantly different between tilt-abnormal children and controls (p = 0.034 and 0.012, respectively), whereas, no group difference was observed in the central executive network (p = 0.48). The default mode network was more consistently "intact," and the consistency of the community structure in the salience network was reduced in tilt-abnormal children, especially in the insula. CONCLUSIONS AND INFERENCES: Children with chronic nausea and orthostatic intolerance have altered connectivity in the default mode network and salience network/insula, which supports over-monitoring of their body and altered processing of bodily states resulting in interoceptive hyper self-awareness. The connectivity of the salience network would not support optimal regulation of appropriate attention to internal and external stimuli, and the hyper-connected default mode network may result in a persistent self-referential state with feelings of emotion, pain, and anxiety.

Food protein-induced enterocolitis syndrome: Dynamic relationship among gastrointestinal symptoms, immune response, and the autonomic nervous system.

OBJECTIVE: To explore the relationship among gastrointestinal (GI) symptoms, immune response, and autonomic nervous system (ANS) in food protein-induced enterocolitis syndrome (FPIES) in relation to the current understanding of disease phenotype and pathogenesis. DATA SOURCES: Relevant studies related to FPIES, GI symptomatology, and ANS were reviewed. Literature search was performed using PubMed, with keyword combinations including but not limited to FPIES, allergic GI disorders, ANS, autonomic dysfunction, dysautonomia, GI, diarrhea, vomiting, neuroimmune, and clinical phenotyping tools. STUDY SELECTIONS: Peer-reviewed case-control studies, observational studies, reviews and guidelines, and systematic reviews related to FPIES and ANS were selected for review. RESULTS: There is limited research directly relating GI symptoms and FPIES to the ANS and immunologic response. To support the proposed mechanisms of action related to patient symptoms, studies relevant to coexisting GI-autonomic processes and FPIES immunologic triggers were examined. These related disease processes were extrapolated to FPIES based on the current knowledge of FPIES phenotype and pathogenesis. CONCLUSION: The etiology of FPIES and the underlying mechanisms triggering symptoms are not well understood. On the basis of the exaggerated GI symptoms and hemodynamic response observed, the ANS likely plays an important role in FPIES, possibly as a compensatory response. The trigger for this cascade of symptoms may be related to the disruption of immunologic homeostasis that typically contributes to immune tolerance. To more accurately evaluate FPIES pathophysiology necessitates understanding the diverse spectrum of presenting symptoms. A consistent and comprehensive symptom assessment tool may improve our understanding of this dynamic relationship.

The Emerging Importance of High-Resolution Manometry in the Evaluation and Treatment of Deglutition in Infants, Children, and Adults: New Opportunities for Speech-Language Pathologists.

Purpose Diagnostic precision and prolonged testing before, during, and after deglutition is lacking across the age spectrum. Conventional clinical evaluation and radiologic methods are widely used but are reliant on human perception, carrying the risk of subjectivity. High-resolution manometry (HRM) is an emerging clinical and research tool and has the capability to objectively measure the dynamics, kinetics, regulatory, and correlation aspects of deglutition. Method We review the basics of manometry and the methods, metrics, and applications of this technology across the age spectrum. The goal is to aid in the translation of HRM from research tool to clinical use by the speech-language pathologist in the development of better global plans to understand normal and abnormal deglutition. Results HRM is an easily adaptable precise diagnostic tool that can be used to examine deglutition phases and abnormalities across the age spectrum from neonates to nonagenarians and can be a valuable adjunct to specialty evaluation of persistent deglutition disorders. Conclusion New opportunities will emerge upon further research for larger-scale translation once normative data and recognition of biomarkers of abnormality are ascertained.

Children with Functional Nausea-Comorbidities outside the Gastrointestinal Tract.

OBJECTIVE: To detail common comorbidities and procedures performed to evaluate functional nausea in children. STUDY DESIGN: In total, 63 children age 7-18 years seen in a tertiary care pediatric clinic who met Rome IV criteria for functional nausea prospectively completed an Intake Questionnaire, the Pediatric and Parent-Proxy PROMIS-25 Profile v 2.0, the Pediatric and Parent-Proxy Pediatric Sleep Disturbance-Short Form 4a, and the COMPASS 31 orthostatic intolerance scale to assess comorbidities. Medical records were reviewed for diagnostic tests performed to evaluate nausea and for additional comorbidities. Summary statistics were used to determine the most common comorbidities and diagnostic yield of the procedures. Intraclass correlation coefficients assessed agreement between parent and child reports on the PROMIS scales. RESULTS: Patients with functional nausea experienced multisystem comorbidities. A majority reported abdominal pain, headache, orthostatic intolerance, fatigue, disturbed sleep, anxiety, constipation, allergies, and vomiting. Agreement between parent-proxy and child report of symptoms on PROMIS scales was good to excellent (intraclass correlation coefficients = .78-.83; all P < .001). Patients underwent extensive diagnostic testing: 96 endoscopic procedures, 199 radiologic tests, and 4 cholecystectomies. Most of the procedures were not diagnostically informative. CONCLUSIONS: Children with functional nausea have comorbidities outside the gastrointestinal tract that warrant evaluation. Gastrointestinal diagnostic tests were of low-yield in identifying a cause. Understanding the relationship with comorbidities may provide insight into etiologies for the nausea and define clinical phenotypes to better tailor care.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

Update on pediatric gastroparesis: A review of the published literature and recommendations for future research.

BACKGROUND: Due to scarcity of scientific literature on pediatric gastroparesis, there is a need to summarize current evidence and identify areas requiring further research. The aim of this study was to provide an evidence-based review of the available literature on the prevalence, pathogenesis, clinical presentation, diagnosis, treatment, and outcomes of pediatric gastroparesis. METHODS: A search of the literature was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines with the following databases: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent reviewers screened abstracts for eligibility. KEY RESULTS: Our search yielded 1085 original publications, 135 of which met inclusion criteria. Most articles were of retrospective study design. Only 12 randomized controlled trials were identified, all of which were in infants. The prevalence of pediatric gastroparesis is unknown. Gastroparesis may be suspected based on clinical symptoms although these are often non-specific. The 4-hour nuclear scintigraphy scan remains gold standard for diagnosis despite lack of pediatric normative comparison data. Therapeutic approaches include dietary modifications, prokinetic drugs, and postpyloric enteral tube feeds. For refractory cases, intrapyloric botulinum toxin and surgical interventions such as gastric electrical stimulation may be warranted. Most interventions still lack rigorous supportive data. CONCLUSIONS: Diagnosis and treatment of pediatric gastroparesis are challenging due to paucity of published evidence. Larger and more rigorous clinical trials are necessary to improve outcomes.

Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla.

Children with orthostatic intolerance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10-18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent 1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high- and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study.NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states.

Evaluating the yield of gastrointestinal testing in pediatric patients in aerodigestive clinic.

OBJECTIVE: To improve understanding of the interrelatedness of airway and esophageal diagnoses by evaluating the yield of procedural and radiographic testing of the gastrointestinal tract in children with airway conditions by their referring diagnoses in a pediatric aerodigestive clinic. METHODS: A retrospective chart review of all 325 patients seen in the aerodigestive program from 2010 to 2013 was performed in a single academic medical center. Demographics and results from esophagogastroduodenoscopies with biopsies (EGD), upper gastrointestinal fluoroscopy studies (UGI), and pH multichannel intraluminal impedance probe (pH-MII) performed within 30 days of the clinic visit were evaluated according to presenting diagnoses. RESULTS: Mean patient age was 3.15 years (range 0.15-24 years) and 41.2% were born premature. 189/325 (58.1%) were on acid suppression. A total of 295 EGD, 193 pH-MII, and 54 UGI were performed. The most common diagnosis with an abnormal pH-MII was asthma. The most common diagnoses with an abnormal EGD were feeding difficulty and tracheal esophageal fistula/ esophageal atresia (TEF/EA). EGDs were normal in 188/295 (63.7%), while 39/295 (13.2%) demonstrated esophagitis, and 22/295 (7.5%) had >15 esophageal eosinophils per high power field. The majority of pH-MII (144/193 [74.6%]) and UGI (47/54 [87%]) were normal. CONCLUSIONS: Children with feeding difficulty, TEF/EA, and asthma were the mostly likely to have a histologic abnormality on EGD or an abnormal pH-MII. The majority of children were previously prescribed acid suppression medication and had a referring diagnosis of gastroesophageal reflux disease but were subsequently found to have normal evaluation. Prospective studies are needed to optimize care of this population.

Chronic nausea and orthostatic intolerance: Diagnostic utility of orthostatic challenge duration, Nausea Profile Questionnaire, and neurohumoral measures.

BACKGROUND: Chronic nausea in pediatrics is a debilitating condition with unclear etiology. We aimed to define hemodynamic and neurohumoral characteristics of chronic nausea associated with orthostatic intolerance in order to improve identification and elucidate mechanism. METHODS: Children (10-18 years) meeting Rome III criteria for functional dyspepsia with nausea and symptoms of orthostatic intolerance (OI) completed a Nausea Profile Questionnaire followed by prolonged (45 minutes rather than the traditional 10 minutes) head-upright tilt (HUT) (70° tilt up) test. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured supine and after 15 minutes into HUT. Beat-to-beat heart rate and blood pressure were continuously recorded to calculate their variability and baroreflex sensitivity. KEY RESULTS: Within 10 and 45 minutes of HUT, 46% and 85% of subjects, respectively, had an abnormal tilt test (orthostatic hypotension, postural orthostatic tachycardia, or syncope). At 15 and 45 minutes of HUT, nausea was elicited in 42% and 65% of subjects respectively. Higher Nausea Profile Questionnaire scores correlated with positive HUT testing at 10 minutes (P = 0.004) and baroreflex sensitivity at 15 minutes (P ≤ 0.01). Plasma vasopressin rose 33-fold in subjects with HUT-induced nausea compared to twofold in those who did not experience HUT-induced nausea (P < 0.01). CONCLUSIONS AND INFERENCES: In children with chronic nausea and OI, longer duration HUT elicited higher frequency of abnormal tilt testing and orthostatic-induced nausea. The Nausea Profile Questionnaire predicted the orthostatic response to tilt testing. Exaggerated vasopressin release differentiated patients with HUT-induced nausea (vs those without nausea), suggesting a possible mechanism for chronic nausea in childhood.

Pediatric Disorders of Orthostatic Intolerance.

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.

Anxiety and physiological responses to the Trier Social Stress Test for Children in adolescents with cyclic vomiting syndrome.

This study compared anxiety and physiological responses during the Trier Social Stress Test for Children (TSST-C) in adolescents. 38 subjects (26 females) were enrolled: 11 cyclic vomiting syndrome (CVS), 11 anxiety, and 16 controls. Salivary cortisol, α-amylase and heart rate variability (HRV) were assessed during the TSST-C. Anxiety was measured by the Screen for Childhood Anxiety Related Emotional Disorders (SCARED), Anxiety Disorders Interview Schedule, and State-Trait Anxiety Inventory for Children (STAI-C). 11 anxiety and 7 CVS subjects had ≥1 anxiety disorder. 82% in the anxiety and CVS groups met criteria for an anxiety disorder on the SCARED. Combining groups, cortisol increased from baseline to recovery during the TSST-C (p=0.0004) and the stressor to recovery (p=0.005). α-amylase did not differ during the TSST-C for the total sample, but increased for anxiety compared to controls from baseline to recovery (p=0.01). HRV decreased during the stressor (p=0.0001) and increased at recovery (p=0.004). No associations were found between biomarkers and trait anxiety. Associations were found between baseline HRV and pre-test state anxiety (r=-0.406, p=0.012) and between recovery HRV and post-test state anxiety (r=-0.501, p=0.002) for the total sample. Anxiety is prevalent in CVS warranting screening. HRV may serve as a biomarker for evaluating stress as a potential trigger for CVS episodes. State but not trait anxiety was associated with changes in HRV, suggesting acute anxiety may be more relevant in linking stress and CVS episodes.