Vitamin B12 and Folic Acid Levels in Patients with Breath Holding Spells

Abstract

Objective: Breath holding spells are a benign, non-paroxysmal disorder observed in childhood. The pathogenesis of breath holding spells is still unclear. Dysfunction of the autonomic nervous system, iron deficiency, genetic predisposition, interleukin 1, nitric oxide and cerebral erythropoietin have been implicated in the pathogenesis. The purpose of this study was to compare vitamin B12 and folic acid levels between patients diagnosed with breath holding spells and a healthy group.

Material and Methods: Fifty-one cases diagnosed with breath holding spells in the pediatric neurology clinic were included in the study group (Group 1), and 78 healthy patients presenting to the general clinic in the control group (Group 2). Hemoglobin, hematocrit, mean erythrocyte volume, vitamin B12, folic acid, ferritin, iron, and iron binding capacity levels were compared between the study and the control groups.

Results: Mean folate levels were 18.92±12.83 (5.27-91) ng/mL in the study group and 9.95±8.92 (2-37) ng/mL in the control group. Mean B12 levels were 274.13±214.37 (75-1201) pg/mL in the study group and 408.82±194.18 (120-959) pg/mL in the control group. Statistically significant differences in both vitamin B12 and folic acid levels were observed between the groups (p=0.000 and p=0.002, respectively). No significant difference was determined between the attack groups’ (<15/month, >15/month) vitamin B12 (p=0.570) or folic acid (p=0.643) levels.

Conclusion: Based on this study, vitamin B12 and folic acid levels should be routinely evaluated in patients diagnosed with breath holding spells.

Keywords

• Child
• Folic acid
• Treatment
• Vitamin B12

Katılma Nöbeti Olan Hastalarda B12 Vitamini ve Folik Asit Düzeyleri

Abstract

Amaç: Katılma nöbetleri, çocukluk çağında görülen iyi huylu, paroksismal olmayan bir hastalıktır. Katılma nöbetlerinin patogenezi çok açık değildir. Patogenezde otonom sinir sistemi disfonksiyonu, demir eksikliği, genetik yatkınlık, interlökin 1, nitrik oksit ve serebral eritropoietinin sorumlu olabileceği ileri sürülmektedir. Bu çalışmada katılma nöbeti olan hastalar ile sağlıklı grup arasında B12 vitamini ve folik asit düzeylerinin karşılaştırılması amaçlandı.

Gereç ve Yöntemler: Çocuk nörolojisi kliniğinde katılma nöbeti tanısı konulan 51 olgu çalışma grubuna (Grup 1), genel pediatri kliniğine başvuran 78 sağlıklı hasta kontrol grubuna (Grup 2) alındı. Çalışma ve kontrol gruplarında hemoglobin, hematokrit, ortalama eritrosit hacmi, vitamin B12, folik asit, ferritin, demir ve demir bağlama kapasiteleri karşılaştırıldı.

Bulgular: Çalışma grubunda ortalama folat düzeyi 18.92±12.83 (5.27-91) ng/mL, kontrol grubunda ortalama folat düzeyi 9.95±8.92 (2-37) ng/mL, ortalama B12 düzeyi çalışma grubu 274.13±214.37 (75-1201) pg/mL, kontrol grubunda ortalama B12 düzeyi 408.82±194.18 (120-959) pg/mL’di. Gruplar arasında B12 vitamini ve folik asit düzeylerinde istatistiksel olarak anlamlı fark bulundu (p=0.000, p=0.002). Atak gruplarının (<15/ay, >15/ay) B12 vitamini (p=0.570) ve folik asit (p=0.643) düzeyleri arasında anlamlı fark saptanmadı.

Sonuç: Bu çalışma sonucunda katılma nöbeti olan hastalarda B12 vitamini ve folik asit düzeylerinin rutin olarak değerlendirilmesi gerektiği kanaatine varıldı. 

Keywords

• Çocuk
• Folik asit
• Tedavi
• B12 Vitamini

References

1. DiMario FJ. Prospective study of children with cyanotic and pallid breath-holding spells. Pediatrics 2001;107:265-9.
2. Leung AKC, Leung AAM, Wong AHC, Hon KL. Breath- holding spells in pediatrics: a narrative review of the current evidence. Curr Pediatr Rev 2019;15:22-9.
3. DiMario FJ, Bauer L, Volpe J, Baxter D. Respiratory Sinus Arrhythmia in Children with breath-holding spells. J Child Neurol 1997;12: 260–2.
4. Kolkiran A, Tutar E, Atalay S, Deda G, Cins S. Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiency. Acta Paediatr 2005;94:1227–31.
5. Gastaut H, Gastaut Y. Electroencephalographic and clinical study of anoxic convulsions in children. Electroencephalogr Clin Neurophysiol 1958;10:607–20.
6. Laxdal T, Gomez MR, Reiher J. Cyanotic and pallid syncopal attacks in children (breath-holding spells). Dev Med Child Neurol 1969;11:755–63.
7. Bridge EM, Livingston S, Tietze C. Breath-holding spells. Their relationship to syncope, convulsions, and other phemonema. J Pediatr 1943;23:539–61.
8. Breukels MA, Plötz FB, van Nieuwenhuizen O, van Diemen-Steenvoorde JA. Breath holding spells in a 3-day-old neonate: an unusual early presentation in a family with a history of breath holding spells. Neuropediatrics 2002;33:41-2.

9. Hindley D, Ali A, Robson C. Diagnoses made in a secondary care “fits, faints, and funny turns” clinic. Arch Dis Child 2006;91:214–8.
10. Mocan H, Yildiran A, Orhan F, Erduran E. Breath-holding spells in 91 children and response to treatment with iron. Arch Dis Child 1999;81:261–2.
11. Tsiftsoglou AS, Tsamadou AI, Papadopoulou LC. Heme as key regulator of major mammalian cellular functions: molecular, cellular, and pharmacological aspects. Pharmacol Ther 2006;111:327–45.
12. Mackler B, Person R, Miller LR, Inamdar AR, Finch CA. Iron deficiency in the rat: biochemical studies of brain metabolism. Pediatr Res 1978;12:217–20.
13. Beard JL, Tobin BW, Smith SM. Effects of iron repletion and correction of anemia on norepinephrine turnover and thyroid metabolism in iron deficiency. Proc Soc Exp Biol Med 1990;193:306–12.
14. Hecht EM, Layton MR, Abrams AG. Iron Supplementation for the Treatment of Breath-Holding Spells: A Systematic Review and Meta-Analysis. Clinics Pediatrics 2020;59:819-22.
15. Lahiri S, Roy A, Baby SM, Hoshi T, Semenza GL, Prabhakar NR. Oxygen sensing in the body. Prog Biophys Mol Biol 2006;91:249–86.
16. Calik M, Abuhandan M, Aycicek A, Taskin A, Selek S, Iscan A. Increased oxidant status in children with breath-holding spells. Childs Nerv Syst 2013;29:1015–9.
17. Carman KB, Ekici A, Yimenicioglu S, Arslantas D, Yakut A. Breath holding spells: point prevalence and associated factors among Turkish children. Pediatr Int 2013;55:328–31.
18. Vurucu S, Karaoglu A, Paksu SM, Oz O, Yaman H, Gulgul M, et al. Breath-holding spells may be associated with maturational delay in myelination of brain stem. J Clin Neurophysiol 2014;31:99–101.
19. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006;5:949–60.
20. Coveñas R, Mangas A, Bodet D, Duleu S, Marcos P, Karakas B, et al. Frontiers in vitamin research: new antibodies, new data. Scientific World Journal 2011;11:1226-42.
21. Mangas A, Coveñas R, Geffard K, Geffard M, Marcos P, Insausti R, et al. Folic acid in the monkey brain: an immunocytochemical study. Neurosci Lett 2004;362:258-61.
22. Sen A, Chandrasekhar K. Spinal MR imaging in Vitamin B12 deficiency: Case series; differential diagnosis of symmetrical posterior spinal cord lesions. Ann Indian Acad Neurol 2013;16:255-8.
23. Smith AD, Smith SM, De Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized clinical trial. PLoS One 2010;5:e12244.
24. Stojsavljovic N, Levic Z, Drulovic J, Dragutinović G. A 44-month clinical brain MRI follow-up in a patient with B12 deficiency. Neurology 1997;49:878–91.
25. Scalabrino G. Cobalamin (vitamin B12) in subacute combined degeneration and beyond: traditional interpretations and novel theories. Exp Neurol 2005;192:463–79.
26. Reynolds EH. The neurology of folic acid deficiency. Handbook of Clinical Neurology 2014:120;927-43.
27. Duque-Díaz E, Coveñas R. Mapping of folic acid in the children brainstem. Anat Cell Biol 2021;54:340-9.
28. Abdollahi Z, Elmadfa I, Djazayeri A, Sadeghian S, Freisling H, Mazandarani SF, et al. Folate, vitamin B12 and homocysteine status in women of childbearing age: baseline ßdata of folic acid wheat flour fortification in Iran. Ann Nutr Metab 2008;53:143-50.
29. Tsen CM, Hsieh CC, Yen CH, Lau YT. Homocysteine altered ROS generation and NO accumulation in endothelial cells. Chin J Physiol 2003;46:129-36.
30. Bendall JK, Douglas G, McNeill E, Channon KM, Crabtree MJ. Tetrahydrobiopterin in cardiovascular health and disease. Antioxid Redox Signal 2014;20:3040–77.
31. Li Q, Youn JY, Cai H. Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension. J Hypertens 2015;33:1128–36.
32. Arslan H, Torun E, Akkan J, Guler S, Bayraktar S. The Evaluation of Physiological and Biochemical Parameters and the Autonomic Nervous Systems of Children with Breath-Holding Spells. Neuropediatrics 2014;45:212–6.