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A 2 year old child is seen in the outpatients department with a history of breath holding spells for the past three months, occurring about 3–4 times per week. These are causing her mother a great deal of concern. You consider whether or not a course of iron would reduce the frequency of these attacks.
Structured clinical question
In a 2 year old child with breath holding spells [patient], will a treatment with iron [intervention] reduce the frequency of episodes [outcome]?
Search strategy and outcome
Secondary searches—Cochrane, Clinical Evidence—none.
Medline 1996–2001, using the OVID interface.
Breath holding spells AND iron therapy, limited to (English & Child)—six hits: two letters, an editorial and three papers as discussed below. See table 1.
Commentary
The literature reviewed suggests that a trial of iron therapy will reduce the frequency of breath holding spells.
All these papers showed a high incidence of iron deficiency anaemia associated with breath holding spells. A full blood count would therefore be warranted in the work up of these children. Treatment is more likely to be successful when there is concomitant iron deficiency anaemia.
Length of treatment varied between 3 and 16 weeks with ferrous sulphate (5–6 mg/kg/day). A course of 8 weeks would seem reasonable—long enough to improve any anaemia.
There was no mention of side effects with ferrous sulphate treatment in any of these papers. Typically these would include nausea, vomiting, diarrhoea, and change in stool colour; the latter presumably making it difficult to complete a double blind study of iron therapy.
There is also the risk of accidental overdose by the patient or siblings to be considered. However, the risk of overdose with paediatric preparations of iron is minimal compared with adult preparations.
The decision to treat also needs to be balanced against the natural course of breath holding spells which are invariably benign and self limiting—both in the short and long term.
▸ CLINICAL BOTTOM LINE
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Iron therapy is of benefit in children with breath holding spells (NNT=2).
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Improvement is more likely in those with concomitant iron deficiency anaemia (NNT=1).
Supplementary materials
Table 1
Citation Study group Study type (level of evidence) Outcome Key result Comments
Daoud et al (1997) 67 children with BHS were randomised to either ferrous sulphate or placebo RCT (level 1b) Frequency of BHS per month after 16 weeks. Complete response (no attacks), partial response ( 
50% reduction),
minimal or no response (<50% reduction)
Complete response in 51.5% treated v 0% in non-treatment group. Partial response in 36.4% treated group v 5.9% in non-treatment group. NNT for any response = 2 (95% CI 2 to 3) The baseline mean Hb in children who showed a response was 86 g/l compared to 106 g/l in those that responded poorly (p=0.004) Mocan et al (1999) 91 children with breath holding spells. 63 with concomitant IDA Case control (level 4) Frequency of BHS over the 3 months study period. Complete response (no attacks), partial response ( 50%
reduction), no response
Complete response in 32% treated group and 21% more had partial response. NNT (for either a partial or complete response) = 2 (95% CI 2 to 3) Only those children with BHS and IDA were treated with iron. The placebo group were those with BHS but normal Hb Bhatia et al (1990) 50 children with BHS Case series (level 4) A reduction in frequency and severity of BHS following a course of iron which was continued until Hb >11 g/dl 96% of the study group had IDA (mean Hb = 8.12 g/dl). 82% showed a response within 2 weeks. After three weeks 100% of cases had shown an improvement Failed to define improvement . Archimedes Update
An update on this article was received in October 2003.
A repeat search on Medline produced only one new article.
This was a case series of 3 children (level 4) with breath holding spells associated with iron deficiency anaemia. The main outcome looked at was autonomic function, assessed with 24 hour Holter recordings of the RR interval. All three received ferrous sulphate solution for 3 months at a dose of 6mg/kg/day.
A significant improvement in autonomic function was reported with an improvement in Hb levels. The authors also reported that severe breath holding spells disappeared in all three children - a number needed to treat of 1.
Reference
Orii et al. Autonomic Nervous System Function After Iron supplementation. J Child Neurol 2002; 17(5):337-40.
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