Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study

ABSTRACT

Background

Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents’ fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement.

Methods

Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated.

Results

The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35–6.04), P =0.01].

Conclusion

VPA therapy reduces CBHS’ frequency. Mood improvement is a suggestive effective mechanism.

Clinical trial registration

www.clinicaltrials.gov identifier is NCT04482764

KEYWORDS:

• Breath holding spells
• cyanosis
• iron deficiency anemia
• piracetam
• valproic acid

Article highlights

• Cyanotic breath-holding spells (CBHS) are self-limited common conditions among toddlers.

• Frequent CBHS are frightening events to parents even after reassurance.

• Autonomic nervous system dysfunctions are reported in 1/4-1/2 of younger children with CBHS.

• Low doses of valproic acid may provide effectiveness in reduction of spells’ frequency or stopping them.

• Mood improvement and/or enhancement of GABA are possible beneficiary mechanisms.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.