Hypovitaminosis D as a risk factor for severe autism spectrum disorder
Abstract
Background Vitamin D is an important risk factor for autism spectrum disorder (ASD). However, research on hypovitaminosis D as a risk factor for severe ASD has been limited. To our knowledge, no such studies have been done in Indonesia.
Objective To evaluate hypovitaminosis D as a risk factor for severe ASD.
Methods This cross-sectional study included children aged 2-18 years who fulfilled the ASD DSM-5 diagnostic criteria. Subjects were consecutively sampled from April - June 2019 at the Child Growth and Polyclinic, Dr. Sardjito General Hospital, Yogyakarta. Assessment of ASD severity was carried out using the Childhood Autism Rating Scale Second Edition (CARS-2) questionnaire. Serum 25(OH)D examination was done in the Clinical Laboratory, Dr. Sardjito General Hospital.
Results Of 36 children with ASD, 36.1% had hypovitaminosis D (<30 ng/mL) and 69.4% had severe ASD, based on the CARS-2 questionnaire (≥37-60). Bivariate analysis revealed that children with hypovitaminosis D had more severe CARS-2 values ​​(92.3%) compared to those with normal vitamin D levels (56.5%) (PR 1.633; 95%CI 1.10 to 2.42; P=0.031). Multivariate analysis with logistic regression revealed that hypovitaminosis D increased the risk of severe ASD (PR 1.65; 95%CI 1.06 to 2.56; P=0.037). However, other variables such as gender, parental education, attention deficit and hyperactivity disorder (ADHD), epilepsy, sleep disorders, pharmacotherapy and non-pharmacotherapy had no significant relationships with severe ASD.
Conclusion Children with ASD and hypovitaminosis D have a 1.65 times higher risk of severe ASD compared to children with ASD and sufficient vitamin D levels. We recommend that children with ASD undergo serum 25(OH)D monitoring.
References
2. Cannell JJ. Vitamin D and autism, what’s new? Rev Endocr Metab Disord. 2017;18:183–93. DOI: 10.1007/s11154-017-9409-0.
3. Saad K, Abdel-rahman AA, Elserogy YM, Al-Atram AA, Cannell JJ, Bjørklund G, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci. 2016;19:346–51. DOI: 10.1179/1476830515Y.0000000019.
4. Sidjaja FF, Newcombe PA, Irwanto, Sofronoff K. The Diagnosis of Autism Spectrum Disorder in Urban Indonesia: A Brief Report. Int J Dev Disabil. 2017;64:33–44. DOI: 10.1080/1034912X.2016.1162768.
5. Lai MC, Lombardo M V., Baron-Cohen S. Autism. Lancet. 2014;383:896–910. DOI: 10.1016/S0140-6736(13)61539-1.
6. KoÄovská E, Gaughran F, Krivoy A, Meier U-C. Vitamin-D Deficiency As a Potential Environmental Risk Factor in Multiple Sclerosis, Schizophrenia, and Autism. Front Psychiatry. 2017;8:47–57. DOI: 10.3389/fpsyt.2017.00047.
7. Jia F, Shan L, Wang B, Li H, Miao C, Xu Z, et al. Bench to bedside review: Possible role of vitamin D in autism spectrum disorder. Psychiatr Res. 2017;260:360–5. DOI: 10.1016/j.psychres.2017.12.005.
8. KoÄovská E, Fernell E, Billstedt E, Minnis H, Gillberg C. Vitamin D and autism: Clinical review. Res Dev Disab. 2012;33:1541–50. DOI: 10.1016/j.ridd.2012.02.015.
9. Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, et al. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adoles Psy. 2016;25:341–50. DOI: 10.1007/s00787-015-0786-1.
10. Humble MB. Vitamin D, light and mental health. J Photoch Photobio B. 2010;101:142–9. DOI: 10.1016/j.jphotobiol.2010.08.003.
11. Chlebowski C, Green JA, Barton ML, Fein D. Using the CARS to diagnose Autism Spectrum disorders. J Autism Dev Disord. 2013;40:787–99. DOI: 10.1007/s10803-009-0926-x.
12. Perry A, Condillac RA, Freeman NL, Dunn-Geier J, Belair J. Multi-site study of the Childhood Autism Rating Scale (CARS) in five clinical groups of young children. J Autism Dev Disord. 2005;35:625–34. DOI: 10.1007/s10803-005-0006-9.
13. Schopler E, Reichler R, Daly K. The childhood autism rating scale. J Autism Dev Disord. 1980;10:91–103. DOI: 10.1007/BF02408436.
14. Arastoo AA, Khojastehkia H, Rahimi Z, Khafaie MA, Hosseini SA, Mansoori SM, et al. Evaluation of serum 25-Hydroxy vitamin D levels in children with autism Spectrum disorder. Ital J Pediatr. 2018;44:1–5. DOI: 10.1186/s13052-018-0587-5.
15. Meguid NA, Hashish AF, Anwar M, Sidhom G. Reduced Serum Levels of 25-Hydroxy and 1,25-Dihydroxy Vitamin D in Egyptian Children with Autism. J Altern Complement Med. 2010;16:641–5. DOI: 10.1089/acm.2009.0349.
16. Humble MB, Gustafsson S, Bejerot S. Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: Relations with season, age, ethnic origin and psychiatric diagnosis. J Steroid Biochem Mol Biold Biochem. 2010;121:467–70. DOI: 10.1016/j.jsbmb.2010.03.013.
17. Gong ZL, Luo CM, Wang L, Shen L, Wei F, Tong RJ, et al. Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. NeuroReport. 2014;25:23–7. DOI: 10.1097/WNR.0000000000000034.
18. Mazahery H, Camargo CA, Conlon C, Beck KL, Kruger MC, Von Hurst PR. Vitamin D and Autism Spectrum Disorder: A Literature Review. Nutrients. 2016;8:3–35. DOI: 10.3390/nu8040236.
19. Alzghoul L, AL-Eitan LN, Aladawi M, Odeh M, Abu Hantash O. The Association Between Serum Vitamin D3 Levels and Autism Among Jordanian Boys. J Autism Dev Disord. 2019;25:1–6. DOI: 10.1007/s10803-019-04017-w.
20. Mostafa GA, AL-Ayadhi LY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity. J Neuroinflammation. 2012;9:1–7. DOI: 10.1186/1742-2094-9-201.
21. Molloy CA, Kalkwarf HJ, Manning-Courtney P, Mills JL, Hediger ML. Plasma 25(OH)D concentration in children with autism spectrum disorder. Developmental Medicine & Child Neurology. 2010;52:969–71. DOI: 10.1111/j.1469-8749.2010.03704.x.
22. Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, et al. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab. 2011;8:1–12. DOI: 10.1186/1743-7075-8-34.
23. Uʇur Ç, Gürkan CK. Serum vitamin D and folate levels in children with autism spectrum disorders. Res Autism Spectr Disord. 2014;8:1641–7. DOI: 10.1016/j.rasd.2014.09.002.
24. Hashemzadeh M, Moharreri F, Soltanifar A. Comparative study of vitamin D levels in children with autism spectrum disorder and normal children : A case-control study. J Fundam Ment Health. 2015;17:197–201.
25. Ernawati F, Basuki B. Status VItamin D Terkini Anak Indonesia Usia 2,0-12,9 Tahun. Gizi Indon. 2015;38:73–80.
26. Enko D, Kriegshäuser G, Stolba R, Worf E, Halwachs-Baumann G. Method evaluation study of a new generation of vitamin D assays. Biochem Med. 2015;25:203–12. DOI: 10.11613/BM.2015.020.
27. Le Goff C, Cavalier E, Souberbielle JC, González-Antuña A, Delvin E. Measurement of circulating 25-hydroxyvitamin D: A historical review. Pract Lab Med. 2015];2:1–14. DOI: 10.1016/j.plabm.2015.04.001.
28. Sarmah D, Sharma B. Interpreting the laboratory reports for Vit D. J Assoc Physicians India. 2014;62:797–800.
29. Cooper K, Smith LGE, Russell AJ. Gender Identity in Autism: Sex Differences in Social Affiliation with Gender Groups. J Autism Dev Disord. 2018;48:3995–4006. DOI: 10.1007/s10803-018-3590-1.
30. Werling D, Geschwind D. Sex differences in autism spectrum disorder. Curr Opin Neurol. 2013;26:69–86. DOI: 10.4324/9780429454646.
31. Saad K, Abdel-Rahman AA, Elserogy YM, Al-Atram AA, El-Houfey AA, Othman HAK, et al. Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. J Child Psychol Psychiatry. 2016;59:20–9. DOI: 10.1111/jcpp.12652.
32. Frazier TW, Hardan AY. Equivalence of symptom dimensions in females and males with autism. Autism. 2017;21:749–59. DOI: 10.1177/1362361316660066.
33. Su X, Cai RY, Uljarević M. Predictors of Mental Health in Chinese Parents of Children with Autism Spectrum Disorder (ASD). J Autism Dev Disord. 2018;48:1159–68. DOI: 10.1007/s10803-017-3364-1.
34. Mannion A, Leader G. Comorbidity in autism spectrum disorder: A literature review. Res Autism Spectr Disord. 2013;7:1595–616. DOI: 10.1016/j.rasd.2013.09.006.
35. Sprenger L, Bühler E, Poustka L, Bach C, Heinzel-Gutenbrunner M, Kamp-Becker I, et al. Impact of ADHD symptoms on autism spectrum disorder symptom severity. Res Dev Disab. 2013;34:3545–52. DOI: 10.1016/j.ridd.2013.07.028.
36. Mannion A, Leader G. Epilepsy in autism spectrum disorder. Res Autism Spectr Disord. 2014;8:354–61. DOI: 10.1016/j.rasd.2013.12.012.
37. Viscidi E, Johnson A, Spence S, Buka S, Morrow E, Triche E. The association between epilepsy and autism symptoms and maladaptive behaviors in Children with Autism Spectrum Disorder. Autism. 2014;18:1–21. DOI: 10.1038/jid.2014.371.
38. Ewen JB, Marvin AR, Law K, Lipkin PH. Epilepsy and Autism Severity: A Study of 6,975 Children. Autism Res. 2019;0:1–9. DOI: 10.1002/aur.2132.
39. Adams HL, Matson JL, Cervantes PE, Goldin RL. The relationship between autism symptom severity and sleep problems: Should bidirectionality be considered? Res Autism Spectr Disord. 2014;8:193–9. DOI: 10.1016/j.rasd.2013.11.008.
40. Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. Autism spectrum disorder. Lancet. 2018;392:508–20. DOI: 10.1016/S0140-6736(18)31129-2.
41. Levine SZ, Kodesh A, Goldberg Y, Reichenberg A, Furukawa TA, Kolevzon A, et al. Initial severity and efficacy of risperidone in autism: Results from the RUPP trial. Eur Psychiatry. 2016;32:16–20. DOI: 10.1016/j.eurpsy.2015.11.004.
42. Salomone E, Beranová Š, Bonnet-Brilhault F, Briciet Lauritsen M, Budisteanu M, Buitelaar J, et al. Use of early intervention for young children with autism spectrum disorder across Europe. Autism. 2016;20:233–49. DOI: 10.1177/1362361315577218.
Copyright (c) 2021 Diyah Rakanita Undang, Mei Neni Sitaresmi, Roni Naning
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Accepted 2021-03-02
Published 2021-03-02