Breath-holding Spells and Its Management Study (BAM)

Breath-holding Spells and Its Management: a Prospective Study on Patient and Disease Characteristics, Evaluation of Novel Guidelines, Parental Handling, and Long-term Follow-up in Breath-holding Spells

The goal of this prospective population-based study is to evaluate the new disease description and management guidelines for breath-holding spells in children (Hellström Schmidt et al, Acta Paediatrica 2024) below the age of 5 years in southern Sweden. The main questions it aims to answer are:

• Does the disease description and management guidelines lead to the expected reduction in diagnostic interventions and are the clinical managements guidelines safe to use?
• If iron supplementation is given, does it reduce the frequency and severity of the spells?
• What information and support does parents to children with breath-holding spells need?

Participants will undergo evaluation by a medical doctor and if typical breath-holding spells are diagnosed, be managed according to the new guidelines. If iron deficiency is found, iron supplementation is recommended. Digital surveys will be distributed and parents of patients with frequent spells will be eligible for participation in an interview sub-study.

Study Overview

• Status: Recruiting
• Conditions: Breath-holding Spell
• Intervention / Treatment: Diagnostic test: Guidelines

Detailed Description

Please see the Study plan among the documents.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sanna Hellström Schmidt, MD; Phone Number: +4646177203; Email: sanna.hellstrom_schmidt@med.lu.se
• Study Contact Backup: Name: Cornelis J Pronk, MD, PhD; Email: kees-jan.pronk@med.lu.se

Study Locations

• Sweden
  • Eslöv, Sweden
    • Recruiting
    • Barn- och ungdomsmedicinmottagning Eslöv
    • Contact: Annika Lagström
  • Kristianstad, Sweden
    • Recruiting
    • Capio Barnavårdscentral Kristianstad
    • Contact: Linda Nyberg
  • Lund, Sweden
    • Recruiting
    • Skane University Hospital
    • Contact: Sanna Hellström Schmidt, MD
  • Lund, Sweden
    • Recruiting
    • Barnläkargruppen Sparta
    • Contact: Johanna Bengtsson
  • Malmö, Sweden
    • Recruiting
    • Skane University Hospital
    • Contact: Sanna Hellström Schmidt, MD
  • Malmö, Sweden
    • Recruiting
    • Barnläkargruppen Sparta
    • Contact: Johanna Bengtsson
  • Malmö, Sweden
    • Recruiting
    • BVC Bambino Hyllie
    • Contact: Anna Sövgren
  • Malmö, Sweden
    • Recruiting
    • BVC Bambino Lindängen
    • Contact: Anna Sövgren
  • Malmö, Sweden
    • Recruiting
    • BVC Bambino Mobilia
    • Contact: Anna Sövgren
  • Simrishamn, Sweden
    • Recruiting
    • Barn- och ungdomsmedicinmottagning Simrishamn, Capio närsjukhus
    • Contact: Therése Saksø
  • Sjöbo, Sweden
    • Recruiting
    • Familjecentralen Björken, BVC Sjöbo
    • Contact: Gustav Robertz, MD
  • Ystad, Sweden
    • Recruiting
    • Lasarettet i Ystad
    • Contact: Gustav Robertz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Below 5 years of age
• resident in Region Skåne (Sweden)
• suspected breath-holding spell

Exclusion Criteria:

• previous investigation for breath-holding spell (previous spells are not a reason for exclusion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Typical spells; Patients with typical spells should be investigated according to our guidelines	Diagnostic test: Guidelines; Participant with typical spells will be investigated according to our guidelines. These include that participants with heredity for or signs and symptoms of cardiac disease will be subjected to an ECG and participants with two or more spells should be subjected to blood tests for anemia and iron deficiency
No Intervention: Non-typical spells; Patients with non-typical spells will be investigated individually, as it is done today

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the guidelines	The number of wrongful and missed diagnoses (definition: managed and diagnosed as breath-holding spells at physician assessment within study but later found to be another cause for the symptoms, like long QT syndrome or epilepsy).	From date of inclusion to end of follow up at 36 months
Usability of the guidelines	Assessed according to the following: Number of patients with a diagnostic interventions for each intervention in the guidelines: ECGs and bloodtests.; Number of found pathologies for each intervention (blood tests and ECGs) - for patients with typical spells handled according to the guidelines and those with non-typical spells managed individually. This includes a retrospective assessment of ECG (a complete assessment including rythm, long QT syndrome, AV-block, ST-segment changes) and blood test results (for anemia and iron deficiency; i.e. values outside of the age adapted normal range).; Retrospective analysis of the clinical doctors compliance with managment guidelines, evaluated through the number of interventions for each patient that were not recommended in the guidlines (for instance number of EEGs).	From date of inclusion until last diagnostic intervention, expected to be within 2 weeks from inclusion.
Usability of the disease definition	Assessed according to the following: Adherence to the the prespecified definition of typical spells through comparison of clinical physicians assessment and a retrospective assessment by study physician, i.e. the number of cases with a discrepant judgment of the clinical presentation.; The number of typical spells compared to the number of non-typical spells and other diagnsoses.; Compilation of patient and spell characteristics (defined in the variable list in the attached documents) and comparison with the current definition of typical spells.	From the inclusion date until end of physicians assessment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need of information and support to parents	Through interview study (qualitative study) gather information on given information and support and their need for more information and support. Will be conducted on parents of children with more than 5 spells in total at the 6 month follow up (assessed as frequent spells).	From 6 months after inclusion until interview is performed (expected to be within three months of six month digital survey)
Effect of iron supplement treatment on spell frequency and severity	In cases of iron treatment (initiated by the clinical physician). Assessed according to the following: Comparison of spell frequency (number of spells/time unit) before start of treatment, during treatment and after completion of treament.; Comparison of spell severity (simple or severe spells defined as spells without and with loss of consciousness) before start of treatment, during treatment and after completion of treament.; Anemia and iron deficiency blood test values (Hb, MCV, reticulocytes, ferritin, CRP if signs of infection, iron, iron saturation and transferrin) comparison between patients with effect of iron treatment on spell frequency and severity, versus the group without a clinical effect of iron treatment.; Patient compliance for iron supplementation as per survey question with answer altneratives yes/no/don't know	From the date of inclusion until evaluation of iron treatment, most probably within 12 months from inclusion.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural course of the spells through long term follow-up	Assessed according to the following parameters, through digital surveys: Spells during the last 3 months (yes or no); Number of spells the previous month (0, 1, 2-5, 6-10, >10); Total number of spells (free text); Uncontactable or unconscious (=severity of spells) (Yes, No, Don't know); Alterations in spell semiology? (Yes, No, Don't know)	36 months
Contact with health care during long term follow-up	Evaluation of the following questions: Do parents follow the advice to reach out to health care if the spell semiology change?; Planned follow up? Above questions are assessed in a digital survey: - Further contact with healthcare. Answer alternatives: (Yes, No, Don't know). If yes: (acute or planned)	36 months
Burden of care	Will be assessed through a combined evaluation of the following variables: Number of acute health care visits; Number of planned health care visits including follow-up appointments over phone; Number of over-night hospital stays (number of nights); Number of ambulance rides to the hospital	36 months
Dietary impact on iron status	At first visit, parents will answer questions on the child and family's diet in a questionnaire, to evaluate a possible association between diet and iron status (and further, to breath-holding spell frequency and severity). The questions are as follows: Mark all alternatives that is correct about your childs diet: (breatmilk/formula/cow's milk/taste portions/family meals); Does your child drink more than 3 dl of cow's milk per day? (yes/no)> If yes, estimate the amount of cow's milk your child drink during a day in dl: (a number in free text); Do you eat vegetarian or vegan food only? (yes/no)	From inclusion to blood test results, within 2 weeks from initial visit

Collaborators and Investigators

• Sponsor: Region Skane

Publications and helpful links

General Publications

• Hellstrom Schmidt S, Smedenmark J, Jeremiasen I, Sigurdsson B, Eklund EA, Pronk CJ. Overuse of EEG and ECG in children with breath-holding spells and its implication for the management of the spells. Acta Paediatr. 2024 Feb;113(2):317-326. doi: 10.1111/apa.17020. Epub 2023 Oct 31.
• Hellstrom Schmidt S, Tedgard U, Pronk CJ. Breath-holding spells occur disproportionately more often in children with transient erythroblastopenia. Acta Paediatr. 2016 Sep;105(9):1088-93. doi: 10.1111/apa.13428. Epub 2016 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: September 16, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: iron deficiency anemia; long QT syndrome; electrocardiography; parental support; disease definition
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Metabolic Diseases; Arrhythmias, Cardiac; Hematologic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Anemia; Iron Metabolism Disorders; Anemia, Hypochromic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia, Iron-Deficiency; Long QT Syndrome
• Other Study ID Numbers: 2023-03363-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be share as far as the Swedish law (concerning patient confidentiality) and ethical considerations allows. Decisions will be made from case to case depending on what data are inquired for.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No