Accessible Requires Authentication Published by De Gruyter September 18, 2018

Seasonality of month of birth in children and adolescents with autoimmune thyroiditis: a continuing conundrum

Ioannis Kyrgios, Styliani Giza, Vasiliki Rengina Tsinopoulou, Ioanna Maggana, Anna-Bettina Haidich and Assimina Galli-Tsinopoulou

Abstract

Background

The aim of this study was to analyze the seasonal birth month pattern in young patients with autoimmune thyroiditis and compare it with youth controls.

Methods

Medical records of a total of 298 children and adolescents of Greek origin, with a diagnosis of Hashimoto thyroiditis (HT) before the age of 21 years that were born from 1987 to 2010 were retrospectively reviewed. In addition, 298 consecutive subjects that were born from 1988 to 2012 and evaluated in a tertiary unit for any reason, served as controls, provided that they had no personal or family history of thyroid or any other autoimmune disease.

Results

Significant differences were found between children and adolescents with HT and healthy controls in the yearly pattern of month of birth distribution (p=0.029). During month-by-month analysis, it was shown that the highest and lowest predispositions to HT were among those born in spring (March) (odds ratio [OR] 2.34, p=0.005), and autumn (November) (OR 0.49, p=0.035), respectively. A binary logistic regression model also revealed that season of birth and sex were the only factors that remained related to HT disease, even after adjustment for confounding factors such as year of birth and age (p<0.001, Nagelkerke r-square 0.151).

Conclusions

This study suggests that the effect of certain seasonal factors during fetal development, reflected by the seasonal differences in birth pattern, in children and adolescents with autoimmune thyroiditis could contribute to long-term programming of an autoimmune response against the thyroid gland. Further studies are needed to demonstrate a clear cause and effect relationship between month of birth and HT.


Corresponding author: Assimina Galli-Tsinopoulou, MD, PhD, Professor in Pediatrics-Pediatric Endocrinology, 4th Department of Pediatrics, Faculty of Health Sciences, Medical School, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Ring Road Nea Efkarpia, 56403 Thessaloniki, Greece, Phone/Fax: +302310991537

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y. Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. Endocr Rev 2008;29:697–725. Search in Google Scholar

2. Lee HJ, Li CW, Hammerstad SS, Stefan M, Tomer Y. Immunogenetics of autoimmune thyroid diseases: a comprehensive review. J Autoimmun 2015;64:82–90. Search in Google Scholar

3. Ott J, Meusel M, Schultheis A, Promberger R, Pallikunnel SJ, et al. The incidence of lymphocytic thyroid infiltration and Hashimoto’s thyroiditis increased in patients operated for benign goiter over a 31-year period. Virchows Arch 2011;459:277–81. Search in Google Scholar

4. Ajjan RA, Weetman AP. The pathogenesis of Hashimoto’s thyroiditis: further developments in our understanding. Horm Metab Res 2015;47:702–10. Search in Google Scholar

5. Dietert RR, Dietert JM. Early-life immune insult and developmental immunotoxicity (DIT)-associated diseases: potential of herbal- and fungal-derived medicinals. Curr Med Chem 2007;14:1075–85. Search in Google Scholar

6. McKinney PA, EURODIAB Seasonality Of Birth Group, Europe and Diabetes. Seasonality of birth in patients with childhood Type I diabetes in 19 European regions. Diabetologia 2001;44(Suppl 3):B67–74. Search in Google Scholar

7. Kahn HS, Morgan TM, Case LD, Dabelea D, Mayer-Davis EJ, et al. SEARCH for Diabetes in Youth Study Group. Association of type 1 diabetes with month of birth among US youth: The SEARCH for Diabetes in Youth Study. Diabetes Care 2009;32:2010–5. Search in Google Scholar

8. Willis JA, Scott RS, Darlow BA, Lewy H, Ashkenazi I, et al. Seasonality of birth and onset of clinical disease in children and adolescents (0–19 years) with type 1 diabetes mellitus in Canterbury, New Zealand. J Pediatr Endocrinol Metab 2002;15:645–7. Search in Google Scholar

9. Kida K, Mimura G, Ito T, Murakami K, Ashkenazi I, et al. Incidence of Type 1 diabetes mellitus in children aged 0–14 in Japan, 1986–1990, including an analysis for seasonality of onset and month of birth: JDS study. The Data Committee for Childhood Diabetes of the Japan Diabetes Society (JDS). Diabet Med 2000;17:59–63. Search in Google Scholar

10. Dobson R, Giovannoni G, Ramagopalan S. The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude. J Neurol Neurosurg Psychiatry 2013;84:427–32. Search in Google Scholar

11. Torkildsen O, Aarseth J, Benjaminsen E, Celius E, Holmøy T, et al. Month of birth and risk of multiple sclerosis: confounding and adjustments. Ann Clin Transl Neurol 2014;1:141–4. Search in Google Scholar

12. Disanto G, Chaplin G, Morahan JM, Giovannoni G, Hyppönen E, et al. Month of birth, vitamin D and risk of immune-mediated disease: a case control study. BMC Med 2012;10:69. Search in Google Scholar

13. Berkun Y, Lewy H, Padeh S, Laron Z. Seasonality of birth of patients with juvenile idiopathic arthritis. Clin Exp Rheumatol 2015;33:122–6. Search in Google Scholar

14. Namatovu F, Lindkvist M, Olsson C, Ivarsson A, Sandström O. Season and region of birth as risk factors for coeliac disease a key to the aetiology? Arch Dis Child 2016;101:1114–8. Search in Google Scholar

15. Sonnenberg A. Date of birth in the occurrence of inflammatory bowel disease. Inflamm Bowel Dis 2009;15:206–11. Search in Google Scholar

16. Pazderska A, Fichna M, Mitchell AL, Napier CM, Gan E, et al. Impact of month of birth on the risk of development of autoimmune addison’s disease. J Clin Endocrinol Metab 2016;101:4214–8. Search in Google Scholar

17. Thvilum M, Brandt F, Brix TH, Hegedüs L. Month of birth is associated with the subsequent diagnosis of autoimmune hypothyroidism. A nationwide Danish register-based study. Clin Endocrinol (Oxf) 2017;87:832–7. Search in Google Scholar

18. Hamilton A, Newby PR, Carr-Smith JD, Disanto G, Allahabadia A, et al. Impact of month of birth on the development of autoimmune thyroid disease in the United Kingdom and Europe. J Clin Endocrinol Metab 2014;99:E1459–65. Search in Google Scholar

19. Krassas GE, Tziomalos K, Pontikides N, Lewy H, Laron Z. Seasonality of month of birth of patients with Graves’ and Hashimoto’s diseases differ from that in the general population. Eur J Endocrinol 2007;156:631–6. Search in Google Scholar

20. Cappa M, Bizzarri C, Crea F. Autoimmune thyroid diseases in children. J Thyroid Res 2010;2011:675703. Search in Google Scholar

21. Lleo A, Battezzati PM, Selmi C, Gershwin ME, Podda M. Is autoimmunity a matter of sex? Autoimmun Rev 2008;7:626–30. Search in Google Scholar

22. Merrill SJ, Mu Y. Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity. J Theor Biol 2015;375:95–100. Search in Google Scholar

23. Ghosh S, Klein RS. Sex drives dimorphic immune responses to viral infections. J Immunol 2017;198:1782–90. Search in Google Scholar

24. Yu HJ, Kwon MJ, Woo HY, Park H. Analysis of 25-hydroxyvitamin D status according to age, gender, and seasonal variation. J Clin Lab Anal 2016;30:905–11. Search in Google Scholar

25. Filippi CM, von Herrath MG. Viral trigger for type 1 diabetes: pros and cons. Diabetes 2008;57:2863–71. Search in Google Scholar

26. Svensson J, Lindberg B, Jonsson B, Ericsson UB, Olofsson P, et al. Intrauterine exposure to maternal enterovirus infection as a risk factor for development of autoimmune thyroiditis during childhood and adolescence. Thyroid 2004;14:367–70. Search in Google Scholar

27. Desailloud R, Hober D. Viruses and thyroiditis: an update. Virol J 2009;6:5. Search in Google Scholar

28. Mori K, Yoshida K. Viral infection in induction of Hashimoto’s thyroiditis: a key player or just a bystander? Curr Opin Endocrinol Diabetes Obes 2010;17:418–24. Search in Google Scholar

29. Viskari H, Knip M, Tauriainen S, Huhtala H, Veijola R, et al. Maternal enterovirus infection as a risk factor for type 1 diabetes in the exposed offspring. Diabetes Care 2012;35:1328–32. Search in Google Scholar

30. Elfving M, Svensson J, Oikarinen S, Jonsson B, Olofsson P, et al. Maternal enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age. Exp Diabetes Res 2008;2008:271958. Search in Google Scholar

31. Dahlquist GG, Ivarsson S, Lindberg B, Forsgren M. Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case control study. Diabetes 1995;44:408–13. Search in Google Scholar

32. Gale EA. Congenital rubella: citation virus or viral cause of type 1 diabetes? Diabetologia 2008;51:1559–66. Search in Google Scholar

33. Forrest JM, Menser MA, Burgess JA. High frequency of diabetes mellitus in young adults with congenital rubella. Lancet 1971;ii:332–4. Search in Google Scholar

34. Benvenga S, Guarneri F. Molecular mimicry and autoimmune thyroid disease. Rev Endocr Metab Disord 2016;17:485–98. Search in Google Scholar

35. Akeno N, Blackard JT, Tomer Y. HCV E2 protein binds directly to thyroid cells and induces IL-8 production: a new mechanism for HCV induced thyroid autoimmunity. J Autoimmun 2008;31:339–44. Search in Google Scholar

36. Watad A, Azrielant S, Bragazzi NL, Sharif K, David P, et al. Seasonality and autoimmune diseases: The contribution of the four seasons to the mosaic of autoimmunity. J Autoimmun 2017;82:13–30. Search in Google Scholar

37. Jacobsen R, Moldovan M, Vaag AA, Hypponen E, Heitmann BL. Vitamin D fortification and seasonality of birth in type 1 diabetic cases: D-tect study. J Dev Orig Health Dis 2016;7:114–9. Search in Google Scholar

38. Cashman KD, Dowling KG, Škrabáková Z, Gonzalez-Gross M, Valtueña J, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr 2016;103:1033–44. Search in Google Scholar

39. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 1988;67:373–8. Search in Google Scholar

40. Saggese G, Federico G, Balestri M, Toniolo A. Calcitriol inhibits the PHA-induced production of IL-2 and IFN-gamma and the proliferation of human peripheral blood leukocytes while enhancing the surface expression of HLA class II molecules. J Endocrinol Invest 1989;12:329–35. Search in Google Scholar

41. Khoo AL, Koenen HJ, Chai LY, Sweep FC, Netea MG, et al. Seasonal variation in vitamin D levels is paralleled by changes in the peripheral blood human T cell compartment. PLoS One 2012;7:e29250. Search in Google Scholar

Received: 2018-01-27
Accepted: 2018-08-13
Published Online: 2018-09-18
Published in Print: 2018-10-25

©2018 Walter de Gruyter GmbH, Berlin/Boston