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Breath-Holding Spells
Introduction
A breath-holding spell is a common benign phenomenon that affects up to 5% of children.[1] These spells can be a frightening experience for children as well as parents. These spells are broken down into 2 types: cyanotic and pallid.[2][3] The cyanotic type is usually precipitated by the child being angry or frustrated, which causes them to hold their breath until the face turns purple or blue.[1][2][3] The pallid type is usually associated with a "sudden scare," after which the child stops breathing. These episodes can last up to a minute, after which the child recovers completely.
These spells occur in children with normal neurological exams and otherwise meeting age-appropriate developmental milestones. These episodes can cause children to lose consciousness and even precipitate a seizure.[4] The frequency of these episodes can be decreased by distracting the child, avoiding emotional triggers, and providing psychosocial help to parents and children.[1][5]
In addition, it is important to rule out certain conditions such as iron deficiency anemia[6][7][8]and long QT syndrome[9] when assessing a child and to follow up on any other red flags with a more detailed workup.[10][11] Thankfully, the prognosis is excellent, and these spells usually resolve by age 6 and do not affect the child's subsequent neurological development.[12]
Etiology
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Etiology
Breath-holding spells were once considered attention-seeking behavior, but studies have shown that these episodes are not intentional and result from an involuntary reflex.[1][13] While cyanotic and pallid are the 2 predominant types of breath-holding spells, some children can have a mixed phenotype.[14] No preceding aura exists in either phenotype, and the spells self-resolve within 60 seconds.[1][3]
Cyanotic breath-holding spells are more common, accounting for over 60% of patients.[15] The trigger for these episodes is the anger or frustration of the child. The child typically cries briefly, becomes silent, stops breathing, and becomes cyanotic.[1] This can result in loss of consciousness and precipitate a seizure, though the episode is self-limiting.[3] A prolonged spell (>60 s) should prompt a workup for an alternate diagnosis.[1]
The pallid form usually follows a painful or frightful experience.[1] After an inciting event, the heart rate slows, the child stops breathing, loses consciousness, and becomes pale. Children may become sweaty and have body jerks or lose bladder control. Episodes are usually brief, and the child regains consciousness without any intervention.[16]
Some studies suggest that a dysfunctional autonomic nervous system may play a role in the cause of the spells, specifically with a maturation delay in parts of the brainstem[13][17]. The underlying cause of breath-holding spells is poorly understood. However, it has been shown that children with cyanotic breath-holding episodes may have some autonomic dysregulation, including higher diastolic blood pressure and a higher resting heart rate.[18] Recent work has shown that these patients have differences in the development of the brainstem and medulla, as measured by MRI.[17] Evidence suggests that respiratory sinus arrhythmia is more common in children with breath-holding spells compared to controls, giving credence to the dysregulation of autonomic function.[19][20]
In addition, iron deficiency anemia has been identified very commonly in these children, and iron supplementation has been found to help even in children without iron deficiency anemia.[21][22][23][24] Furthermore, reduced antioxidant levels in children with breath-holding spells may contribute to these episodes.[25] One study compared 67 children with breath-holding spells with 60 control children. The authors found that selenium, superoxide dismutase, and erythrocyte glutathione peroxidase values were decreased in children with breath-holding spells.[25]
Maternal stress levels (including during pregnancy), maternal depressive traits, and overprotective maternal characteristics are also associated with the development of breath-holding spells, further exacerbating parents' stress and anxiety.[26][27] As for the child, low frustration tolerance has also been associated with the development of breath-holding spells.[27]
Epidemiology
Breath-holding spells are a common problem in the pediatric population, with a frequency of up to 5% of children.[1][3] Most breath-holding spells occur before the child turns 18 months old and generally resolve by age 6.[28] Sometimes there are features of both cyanosis and pallor, termed mixed episodes.[1]
A predominance of males compared to females is reported.[1] In at least one study, there was a positive correlation between the father's age and frequency of breath-holding spells and a negative correlation with birth order.[29] One-third of patients have a positive family history of breath-holding spells.[20] No significant demographic difference has been reported with the types of spells. However, there is some evidence that pallid breath-holding spells have an older age at onset than cyanotic breath-holding spells.[21]
Based on a pedigree analysis of a study looking at severe breath-holding spells, the mode of inheritance seems to be autosomal dominant with reduced penetrance.[30] However, there are also several other conditions, such as familial dysautonomia[31], long QT syndrome[32], and 16p11.2 microdeletion syndrome[33], which seem to predispose patients to breath-holding spells.[1]
Pathophysiology
The exact mechanism for cyanotic breath-holding spells is not clear. Pallid breath-holding is caused by an increased parasympathetic response, causing a reduced blood flow to the brain. This can be demonstrated by the fact that these spells can be incited by increasing the vagal tone via ocular compression.[14] In both types of cases, the association of iron deficiency anemia indicates that if a child's oxygen-carrying capacity is reduced from anemia (including iron deficiency anemia, sideroblastic anemia, or transient erythroblastopenia of childhood), the child may be more prone to these spells and loss of consciousness.[1][34][35]
The lower selenium levels found in patients with breath-holding spells may also explain the underlying pathophysiology, as oxidative stress is a culprit in other neurological disorders such as epilepsy.[25] Selenium is responsible for removing free oxygen radicals, and the lower levels in these patients can indicate that this system is not in balance.[25][36][37]
History and Physical
A complete history should be obtained from the parents of any child with cyanosis or loss of consciousness. In this condition, the account should identify a clear emotional inciting event followed by the development of either a cyanotic or pallid type of breath-holding spell. There should be no aura preceding the event, and the child should not have any postictal signs after recovery.[1]
The physical exam findings should be benign. Any part of the evaluation that does not fit this history should warrant a prompt workup and referral to appropriate specialties, such as pediatric cardiology, pediatric neurology, or genetics.
Evaluation
No specific diagnostic testing is universally accepted for breath-holding spells. The diagnosis is usually made from the description of the episode. A history of any inciting event should be elicited, especially to distinguish any seizure disorder, as history is typical for breath-holding spells.
The patient's color during the episode may help differentiate the type of episode as cyanotic or pallid. Iron studies should be obtained as iron deficiency is prevalent among these children.[1][38] An EKG is another mainstay of evaluation to rule out a potentially important cardiac cause of these spells.[9][39]
Distinguishing seizure disorders from breath-holding spells may be confusing; therefore, an electroencephalogram (EEG) may be performed. Nonetheless, an EEG is usually not recommended without any red flags.[40] If an EEG is performed, an ocular compression test may differentiate a seizure from a breath-holding spell.[41]
Neuroimaging studies are unnecessary since these patients have normal anatomy. Other causes of syncope and seizures should be ruled out, such as epileptic disorders and cardiac arrhythmias. In most cases, without other signs or concerning symptoms for a different etiology, a referral usually does not result in additional evaluation or treatment.[3]
Treatment / Management
Behavioral Interventions
Since breath-holding spells do not have any long-term effects, parents should be advised to minimize their attention to the episodes to keep the child from developing behavioral problems.[14] However, it can be stressful for parents to see their child having breath-holding spells; working with a professional counselor may help parents cope.(B3)
In one randomized control study, psychoeducational therapy the anxiety and depression levels of the mother as well as showed a reduction in the number of breath-holding spells.[5] Thus, reassurance and behavior intervention remains the gold standard of treatment.[1] While other treatments are discussed below and may be effective, the benefits and risks of treatments must be weighed carefully, given the self-limiting nature of this disease.(A1)
Iron Supplementation
Several studies suggest that there may be an association between iron deficiency anemia and breath-holding spells. Iron supplementation can decrease the frequency of breath-holding spells[42], with a starting dose of 3 to 6 mg/kg/d.[6][42][43] Iron treatment can be given even if the child does not have iron deficiency since it may decrease the frequency of spells.[43] (A1)
Levetiracetam/Piracetam
Increasing evidence shows piracetam or levetiracetam can reduce the instances of breath-holding spells.[44] In randomized controlled trials piracetam (40mg/kg/d), significantly decreased breath-holding spells compared to placebo.[45][46] A recent head-to-head comparison in a randomized control trial between levetiracetam and piracetam showed better efficacy of levetiracetam[44], though more studies are needed. Another study showed that combining iron and levetiracetam was more efficacious than levetiracetam alone in controlling breath-holding spells.[45][47](A1)
Differential Diagnosis
Breath-holding spells are quite common; however, differential diagnoses to consider include the following:
- Congenital laryngeal stridor
- Arrhythmia
- Apnea of prematurity
- Genetic disorders
- Epilepsy
- Sepsis
- Nonaccidental trauma
- PDA-dependent congenital heart lesion
Prognosis
Breath-holding spells are not harmful and do not result in brain damage. Neurologic development outcome, if already normal, will remain normal.[1] Most children will no longer have the episodes by age 6.[1][48] In a study using magnetic resonance spectroscopy, when comparing patients with breath-holding spells to controls, no difference in brain metabolite values was noted. This gives biochemical evidence to clinical findings that there is no permanent brain damage in these patients.[49]
Complications
These episodes are quite stressful for the family and the child; the episodes may increase stress in the home environment.[26][27]
While iron therapy can theoretically have complications, the adverse effects are minimal when prescribed for this condition and usually do not require any treatment modification.[24][50]
Consultations
Treating breath-holding spells can require a collaborative approach, including collaboration with the following specialties:
- Child and adult psychiatry for behavioral interventions aimed at parents and children.
- Pediatric cardiology if LQTS is suspected.
- Pediatric neurology if seizure or other neurological disorder is suspected.
- Genetics if an underlying genetic disease is suspected based on physical exam or family history.
Deterrence and Patient Education
Parents should be educated on handling the events and receive reassurance that breath-holding spells have no long-term effects. Given some parental stress levels associated with these episodes, parents may also benefit from a counselor if these episodes create stress and affect family dynamics. In addition, parents should receive assistance to cope with the stress and should be educated about discipline techniques.
Enhancing Healthcare Team Outcomes
Breath-holding spells may be benign, but they can be highly distressing for caretakers; therefore, reassurance and proper explanation are the treatment's mainstay. Underlying medical causes should be addressed, and treatment options should be considered if these spells interfere with patients' or parents' regular daily activities.
Individual therapies, online support groups, and mental health nurse and clinician education may be offered to the families. Pediatric neurology, genetics, and pediatric cardiology may be consulted if there are any red flags or if the initial evaluation findings are abnormal.
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