Association between vitamin D deficiency and otitis media with effusion in children: a systematic review and meta-analysis
Keywords:
child, otitis media with effusion, systematic review, vitamin D deficiency
Abstract
Background Vitamin D plays a crucial role in the regulation of inflammation. However, its effect on the development of otitis media effusion (OME), an inflammatory disease of the middle ear without signs of infection, remains largely unknown.
Objective To assess the association between vitamin D deficiency and OME in children by systematic review and meta-analysis of the literature.
Methods Eligible studies retrieved from PubMed, ProQuest, Embase, Cochrane databases and trial registries published up to 30 October 2022 were included in this review. The risk of bias of the included articles was assessed with the JBI Critical Appraisal Checklist for observational studies. The certainty of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation framework.
Results We included eight studies (six case-control and two cross-sectional studies) involving 1,114 children, of which four studies were eligible for meta-analysis due to the significant clinical heterogeneity. We found that vitamin D deficiency (defined as vitamin D concentration of 20 ng/mL or less, i.e., ?50 nmol/L) might increase the odds of developing OME by 66.0% (n=514; OR 1.66; 95%CI 1.09 to 2.54; I2=20%), albeit with a very low certainty of evidence.
Conclusion There is a very low quality of evidence indicating that vitamin D deficiency is associated with the development of OME in children. Further large, high-quality cohorts and adjusting for confounding factors are warranted to confirm our findings, ideally by exploring the dose-response relationship between vitamin D concentration and the development of OME.
References
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3. Choudhary DS, Verma DP, Singh DBK. Undiagnosed otitis media with effusion in children: Incidence & effect. Int J Med Biomed Stud. 2019;3. DOI: https://doi.org/10.32553/ijmbs.v3i6.310
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5. Erdivanli OC, Coskun ZO, Kazikdas KC, Demirci M. Prevalence of otitis media with effusion among primary school children in Eastern Black Sea, in Turkey and the effect of smoking in the development of otitis media with effusion. Indian J Otolaryngol Head Neck Surg. 2012;64:17–21. DOI: https://doi.org/10.1007/s12070-011-0131-z
6. Wu X, Zheng Y, Gao X, Li G, Cao Q. Association between Helicobacter pylori infection and otitis media with effusion risk in children: a systematic review and meta-analysis. Otolaryngol - Head Neck Surg (United States). 2020;163:654–61. DOI: https://doi.org/10.1177/0194599820921861
7. Alho OP, Oja H, Koivu M, Sorri M. Risk factors for chronic otitis media with effusion in infancy: each acute otitis media episode induces a high but transient risk. Arch Otolaryngol Neck Surg. 1995;121:839–43. DOI: https://doi.org/10.1001/archotol.1995.01890080011002
8. Wu ZH, Tang Y, Niu X, Sun HY, Chen X. The relationship between otitis media with effusion and gastroesophageal reflux disease: a meta-analysis. Otol Neurotol. 2021;42:E245–53. DOI: https://doi.org/10.1097/MAO.0000000000002945
9. Alles R, Parikh A, Hawk L, Darby Y, Romero JN, Scadding G. The prevalence of atopic disorders in children with chronic otitis media with effusion. Pediatr Allergy Immunol. 2001;12:102–6. DOI: https://doi.org/10.1046/j.0905-6157.2000.00008.x
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20. Bergman P. Can vitamin D supplementation prevent chronic otitis media with effusion? Acta Paediatr Int J Paediatr. 2017;106:1385–6. DOI: https://doi.org/10.1111/apa.13943
21. Weinreich H, Daly K. The relationship between vitamin D, otitis media, and weight. Otolaryngol Neck Surg. 2011;145:248. DOI: https://doi.org/10.1177/0194599811415823a371
22. Linday LA, Shindledecker RD, Dolitsky JN, Chen TC, Holick MF. Plasma 25-hydroxyvitamin D levels in young children undergoing placement of tympanostomy tubes. Ann Otol Rhinol Laryngol. 2008;117:740–4. DOI: https://doi.org/10.1177/000348940811701006
23. Dündar Y, Timurkaynak Y, Demirba? E, Birinci M, Özergin Z, Akcan F, et al. The role of vitamin D in patients with otitis media with effusion. Kulak Burun Bo?az Ve Ba? Boyun Cerrahisi Derg. 2018;26:33–9. DOI: https://doi.org/10.24179/kbbbbc.2017-56598
24. Mandour YM, Shendy M, Ramadan SA, Mohammady AA, Badae S. Vitamin d level in children with secretory otitis media. Otorhinolaryngol Clin. 2021;13:18–22. DOI: https://doi.org/10.5005/jp-journals-10003-1366
25. Li HB, Tai XH, Sang YH, Jia JP, Xu ZM, Cui XF, et al. Association between vitamin D and development of otitis media: a PRISMA-compliant meta-analysis and systematic review. Medicine (Baltimore). 2016;95. DOI: https://doi.org/10.1097/MD.0000000000004739
26. Cayir A, Turan MI, Ozkan O, Cayir Y, Kaya A, Davutoglu S, et al. Serum vitamin D levels in children with recurrent otitis media. Eur Arch Oto-Rhino-Laryngology. 2014;271:689–93. DOI: https://doi.org/10.1007/s00405-013-2455-7
27. Elemraid M, Mackenzie I, Fraser W, Brabin B. Nutritional factors in the pathogenesis of ear disease in children: a systematic review. Arch Dis Child. 2010;95:A49.1-A49. DOI: https://doi.org/10.1136/adc.2010.186338.107
28. Park M, Lee JS, Lee JH, Oh SH, Park MK. Prevalence and risk factors of chronic otitis media: The Korean National Health and Nutrition Examination Survey 2010-2012. PLoS One. 2015;10:e0125905. DOI: https://doi.org/10.1371/journal.pone.0125905
29. della Volpe A, Ricci G, Ralli M, Gambacorta V, Lucia ADE, Minni A, et al. The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (H122), Arabinogalactans, Vitamin D, vitamin E and Vitamin C in otitis media with effusion in children: A randomized controlled trial. Eur Rev Med Pharmacol Sci. 2019;23:6360–70. DOI: https://doi.org/10.26355/eurrev_201907_18460
30. Mohamed AA, EL-Begermy MM, Teaima AA, Abdelghafar MA. Vitamin D levels in children with otitis media with effusion. QJM An Int J Med. 2021;114. DOI: https://doi.org/10.1093/qjmed/hcab094.017
31. T A. Adenoidektomi ve kulaklara ventilasyon Tüpü Tak?lan Çocuklarda vitamin A, vitamin D, Çinko ve Demir Düzeyleri. Konuralp T?p Derg. 2014;2014:28. DOI: https://doi.org/10.18521/ktd.04379
32. Kazi MY, Aamir K, Rana MN, Farooq MA. Frequency of vitamin D3 deficiency in children presenting with frequent sino-pulmonary infections. Pakistan Paediatr J. 2013;37:101–5.
33. Akcan FA, Dündar Y, Akcan HB, Uluat A, Cebeci D, Sungur MA, et al. Clinical role of vitamin D in prognosis of otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2018;105:1–5. DOI: https://doi.org/10.1016/j.ijporl.2017.11.030
34. Asghari A, Bagheri Z, Jalessi M, Salem MM, Amini E, GhalehBaghi S, et al. Vitamin D levels in children with adenotonsillar hypertrophy and Otitis media with effusion. Iran J Otorhinolaryngol. 2017;29:29–33. DOI: https://doi.org/10.22038/ijorl.2016.8066
35. Abu-Elnasr A, Abd El-Galil HM, EL-Madbouly AA. Serum 25-hydroxy vitamin D level in otitis media with effusion and its relation to the risk of recurrence among preschool children. AL-Azhar Assiut Med J. 2015;13.
36. Walker RE, Bartley J, Camargo CA, Flint D, Thompson JMD, Mitchell EA. Higher serum 25(OH)D concentration is associated with lower risk of chronic otitis media with effusion: A case–control study. Acta Paediatr Int J Paediatr. 2017;106:1487–92. DOI: https://doi.org/10.1111/apa.13908
37. Abhari MB, Majidinia H, Beyranvand F, Tehrani Banihashemi A, Dehghani Firouzabadi F, Dehghani Firouzabadi M, et al. Relationship between serum vitamin D levels and serous otitis media in children with adenoid hypertrophy based on age. Thrita. 2020;8:e98796. DOI: https://doi.org/10.5812/thrita.98796
38. Hosseini S, Khajavi M, Eftekharian A, Akbari N. Vitamin D levels in children with otitis media with effusion: a case-control study. Thrita. 2016;5:10–3. DOI: https://doi.org/10.5812/thrita.31977
39. Mohammed GA, Rashed RAA, Elsayed AF, Mostafa SY. Role of vitamin D in children with otitis media with effusion. Al-Azhar Assiut Med J. 2021;19:569. DOI: https://doi.org/10.4103/AZMJ.AZMJ_39_21
40. Ahmed AANA, Mohamed AA, Elbegermy MM, Abdelghafar MA, Teaima AA, Nabil A, et al. Vitamin D level in Egyptian children with otitis media with effusion. Egypt J Otolaryngol. 2022;38:31–8. DOI: https://doi.org/10.1186/s43163-021-00188-5
41. Atkinson J, Salmond C, Crampton P. NZDep2013 index of deprivation. Wellington: 2014.
42. Cai T, McPherson B. Hearing loss in children with otitis media with effusion: a systematic review. Int J Audiol. 2017;56:65–76. DOI: https://doi.org/10.1080/14992027.2016.1250960
43. Li JD, Hermansson A, Ryan AF, Bakaletz LO, Brown SD, Cheeseman MT, et al. Panel 4: Recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models. Otolaryngol - Head Neck Surg (United States). 2013;148:E52–63. DOI: https://doi.org/10.1177/0194599813479772
44. Kim HB, Lim SH, Cho CG, Choi HS. Influence of vitamin D deficiency on progression of experimental otitis media in rats. Endocrinol Metab. 2018;33:296–304. DOI: https://doi.org/10.3803/EnM.2018.33.2.296
45. Durgut O, Dikici O. The effect of adenoid hypertrophy on hearing thresholds in children with otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2019;124:116–9. DOI: https://doi.org/10.1016/j.ijporl.2019.05.046
46. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017:i6583. DOI: https://doi.org/10.1136/bmj.i6583
2. Anggraeni R, Carosone-Link P, Djelantik B, Setiawan EP, Hartanto WW, Ghanie A, et al. Otitis media related hearing loss in Indonesian school children. Int J Pediatr Otorhinolaryngol. 2019;125:44–50. DOI: https://doi.org/10.1016/j.ijporl.2019.06.019
3. Choudhary DS, Verma DP, Singh DBK. Undiagnosed otitis media with effusion in children: Incidence & effect. Int J Med Biomed Stud. 2019;3. DOI: https://doi.org/10.32553/ijmbs.v3i6.310
4. American Academy of Family Physicians; American Academy of Otolaryngology-Head and Neck Surgery; American Academy of Pediatrics Subcommittee on Otitis Media with Effusion. Otitis media with effusion. Pediatrics. 2004;113:1412–29. DOI: https://doi.org/10.1542/peds.113.5.1412
5. Erdivanli OC, Coskun ZO, Kazikdas KC, Demirci M. Prevalence of otitis media with effusion among primary school children in Eastern Black Sea, in Turkey and the effect of smoking in the development of otitis media with effusion. Indian J Otolaryngol Head Neck Surg. 2012;64:17–21. DOI: https://doi.org/10.1007/s12070-011-0131-z
6. Wu X, Zheng Y, Gao X, Li G, Cao Q. Association between Helicobacter pylori infection and otitis media with effusion risk in children: a systematic review and meta-analysis. Otolaryngol - Head Neck Surg (United States). 2020;163:654–61. DOI: https://doi.org/10.1177/0194599820921861
7. Alho OP, Oja H, Koivu M, Sorri M. Risk factors for chronic otitis media with effusion in infancy: each acute otitis media episode induces a high but transient risk. Arch Otolaryngol Neck Surg. 1995;121:839–43. DOI: https://doi.org/10.1001/archotol.1995.01890080011002
8. Wu ZH, Tang Y, Niu X, Sun HY, Chen X. The relationship between otitis media with effusion and gastroesophageal reflux disease: a meta-analysis. Otol Neurotol. 2021;42:E245–53. DOI: https://doi.org/10.1097/MAO.0000000000002945
9. Alles R, Parikh A, Hawk L, Darby Y, Romero JN, Scadding G. The prevalence of atopic disorders in children with chronic otitis media with effusion. Pediatr Allergy Immunol. 2001;12:102–6. DOI: https://doi.org/10.1046/j.0905-6157.2000.00008.x
10. Vanneste P, Page C. Otitis media with effusion in children: pathophysiology, diagnosis, and treatment. A review. J Otol. 2019;14:33–9. DOI: https://doi.org/10.1016/j.joto.2019.01.005
11. Restuti RD, Safitri ED, Ranakusuma RW, Priyono H, Saleh RR, Sriyana AA, et al. Prospero 2021 CRD42021230843 2021. [cited 2022 May 20]. Available from: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=230843
12. Dekkers OM, Vandenbroucke JP, Cevallos M, Renehan AG, Altman DG, Egger M. COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology. PLoS Med. 2019;16:e1002742. DOI: https://doi.org/10.1371/journal.pmed.1002742
13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372. DOI: https://doi.org/10.1136/bmj.n71
14. Munn Z, Stone J, Aromataris E, Klugar M, Sears K, Leonardi-Bee J, et al. Assessing the risk of bias of quantitative analytical studies: introducing the vision for critical appraisal within JBI systematic reviews. JBI Evid Synth. 2022:12–3. DOI: https://doi.org/10.11124/JBIES-22-00224
15. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158:531–7. DOI: https://doi.org/10.1001/archpedi.158.6.531
16. Deeks JJ, Higgins JPT, Altman DG. Analysing data and undertaking meta-analyses. Cochrane Handb. Syst. Rev. Interv., 2019, p. 241–84. DOI: https://doi.org/10.1002/9781119536604.ch10
17. (RevMan) RM. [Computer program]. Version 5.4. The Cochrane Collaboration; 2020.
18. Oxman AD. Grading quality of evidence and strength of recommendations. Br Med J. 2004;328:1490–4. DOI: https://doi.org/10.1136/bmj.328.7454.1490
19. Walker RE, Bartley J, Camargo CA, Mitchell EA. Vitamin D and otitis media. Curr Allergy Asthma Rep. 2019;19. DOI: https://doi.org/10.1007/s11882-019-0866-2
20. Bergman P. Can vitamin D supplementation prevent chronic otitis media with effusion? Acta Paediatr Int J Paediatr. 2017;106:1385–6. DOI: https://doi.org/10.1111/apa.13943
21. Weinreich H, Daly K. The relationship between vitamin D, otitis media, and weight. Otolaryngol Neck Surg. 2011;145:248. DOI: https://doi.org/10.1177/0194599811415823a371
22. Linday LA, Shindledecker RD, Dolitsky JN, Chen TC, Holick MF. Plasma 25-hydroxyvitamin D levels in young children undergoing placement of tympanostomy tubes. Ann Otol Rhinol Laryngol. 2008;117:740–4. DOI: https://doi.org/10.1177/000348940811701006
23. Dündar Y, Timurkaynak Y, Demirba? E, Birinci M, Özergin Z, Akcan F, et al. The role of vitamin D in patients with otitis media with effusion. Kulak Burun Bo?az Ve Ba? Boyun Cerrahisi Derg. 2018;26:33–9. DOI: https://doi.org/10.24179/kbbbbc.2017-56598
24. Mandour YM, Shendy M, Ramadan SA, Mohammady AA, Badae S. Vitamin d level in children with secretory otitis media. Otorhinolaryngol Clin. 2021;13:18–22. DOI: https://doi.org/10.5005/jp-journals-10003-1366
25. Li HB, Tai XH, Sang YH, Jia JP, Xu ZM, Cui XF, et al. Association between vitamin D and development of otitis media: a PRISMA-compliant meta-analysis and systematic review. Medicine (Baltimore). 2016;95. DOI: https://doi.org/10.1097/MD.0000000000004739
26. Cayir A, Turan MI, Ozkan O, Cayir Y, Kaya A, Davutoglu S, et al. Serum vitamin D levels in children with recurrent otitis media. Eur Arch Oto-Rhino-Laryngology. 2014;271:689–93. DOI: https://doi.org/10.1007/s00405-013-2455-7
27. Elemraid M, Mackenzie I, Fraser W, Brabin B. Nutritional factors in the pathogenesis of ear disease in children: a systematic review. Arch Dis Child. 2010;95:A49.1-A49. DOI: https://doi.org/10.1136/adc.2010.186338.107
28. Park M, Lee JS, Lee JH, Oh SH, Park MK. Prevalence and risk factors of chronic otitis media: The Korean National Health and Nutrition Examination Survey 2010-2012. PLoS One. 2015;10:e0125905. DOI: https://doi.org/10.1371/journal.pone.0125905
29. della Volpe A, Ricci G, Ralli M, Gambacorta V, Lucia ADE, Minni A, et al. The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (H122), Arabinogalactans, Vitamin D, vitamin E and Vitamin C in otitis media with effusion in children: A randomized controlled trial. Eur Rev Med Pharmacol Sci. 2019;23:6360–70. DOI: https://doi.org/10.26355/eurrev_201907_18460
30. Mohamed AA, EL-Begermy MM, Teaima AA, Abdelghafar MA. Vitamin D levels in children with otitis media with effusion. QJM An Int J Med. 2021;114. DOI: https://doi.org/10.1093/qjmed/hcab094.017
31. T A. Adenoidektomi ve kulaklara ventilasyon Tüpü Tak?lan Çocuklarda vitamin A, vitamin D, Çinko ve Demir Düzeyleri. Konuralp T?p Derg. 2014;2014:28. DOI: https://doi.org/10.18521/ktd.04379
32. Kazi MY, Aamir K, Rana MN, Farooq MA. Frequency of vitamin D3 deficiency in children presenting with frequent sino-pulmonary infections. Pakistan Paediatr J. 2013;37:101–5.
33. Akcan FA, Dündar Y, Akcan HB, Uluat A, Cebeci D, Sungur MA, et al. Clinical role of vitamin D in prognosis of otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2018;105:1–5. DOI: https://doi.org/10.1016/j.ijporl.2017.11.030
34. Asghari A, Bagheri Z, Jalessi M, Salem MM, Amini E, GhalehBaghi S, et al. Vitamin D levels in children with adenotonsillar hypertrophy and Otitis media with effusion. Iran J Otorhinolaryngol. 2017;29:29–33. DOI: https://doi.org/10.22038/ijorl.2016.8066
35. Abu-Elnasr A, Abd El-Galil HM, EL-Madbouly AA. Serum 25-hydroxy vitamin D level in otitis media with effusion and its relation to the risk of recurrence among preschool children. AL-Azhar Assiut Med J. 2015;13.
36. Walker RE, Bartley J, Camargo CA, Flint D, Thompson JMD, Mitchell EA. Higher serum 25(OH)D concentration is associated with lower risk of chronic otitis media with effusion: A case–control study. Acta Paediatr Int J Paediatr. 2017;106:1487–92. DOI: https://doi.org/10.1111/apa.13908
37. Abhari MB, Majidinia H, Beyranvand F, Tehrani Banihashemi A, Dehghani Firouzabadi F, Dehghani Firouzabadi M, et al. Relationship between serum vitamin D levels and serous otitis media in children with adenoid hypertrophy based on age. Thrita. 2020;8:e98796. DOI: https://doi.org/10.5812/thrita.98796
38. Hosseini S, Khajavi M, Eftekharian A, Akbari N. Vitamin D levels in children with otitis media with effusion: a case-control study. Thrita. 2016;5:10–3. DOI: https://doi.org/10.5812/thrita.31977
39. Mohammed GA, Rashed RAA, Elsayed AF, Mostafa SY. Role of vitamin D in children with otitis media with effusion. Al-Azhar Assiut Med J. 2021;19:569. DOI: https://doi.org/10.4103/AZMJ.AZMJ_39_21
40. Ahmed AANA, Mohamed AA, Elbegermy MM, Abdelghafar MA, Teaima AA, Nabil A, et al. Vitamin D level in Egyptian children with otitis media with effusion. Egypt J Otolaryngol. 2022;38:31–8. DOI: https://doi.org/10.1186/s43163-021-00188-5
41. Atkinson J, Salmond C, Crampton P. NZDep2013 index of deprivation. Wellington: 2014.
42. Cai T, McPherson B. Hearing loss in children with otitis media with effusion: a systematic review. Int J Audiol. 2017;56:65–76. DOI: https://doi.org/10.1080/14992027.2016.1250960
43. Li JD, Hermansson A, Ryan AF, Bakaletz LO, Brown SD, Cheeseman MT, et al. Panel 4: Recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models. Otolaryngol - Head Neck Surg (United States). 2013;148:E52–63. DOI: https://doi.org/10.1177/0194599813479772
44. Kim HB, Lim SH, Cho CG, Choi HS. Influence of vitamin D deficiency on progression of experimental otitis media in rats. Endocrinol Metab. 2018;33:296–304. DOI: https://doi.org/10.3803/EnM.2018.33.2.296
45. Durgut O, Dikici O. The effect of adenoid hypertrophy on hearing thresholds in children with otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2019;124:116–9. DOI: https://doi.org/10.1016/j.ijporl.2019.05.046
46. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017:i6583. DOI: https://doi.org/10.1136/bmj.i6583
Published
2024-10-21
How to Cite
1.
Restuti R, Safitri E, Ranakusuma R, Sriyana A, Priyono H, Saleh R, Marpaung D, Lazarus G. Association between vitamin D deficiency and otitis media with effusion in children: a systematic review and meta-analysis. PI [Internet]. 21Oct.2024 [cited 21Nov.2024];64(5):419-9. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/3519
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Copyright (c) 2024 Ratna Dwi Restuti, Eka Dian Safitri, Respati Wulansari Ranakusuma, Ayu Astria Sriyana, Harim Priyono, Rangga Rayendra Saleh, Dora A Marpaung, Gilbert Lazarus
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Received 2023-07-20
Accepted 2024-10-21
Published 2024-10-21
Accepted 2024-10-21
Published 2024-10-21
