Occurrence and Correlates of Vitamin D and Iron Deficiency in Children with Autism Spectrum Disorder
Abstract
1. Introduction
2. Materials and Methods
2.1. Sample
2.2. Criteria for Vitamin D and Iron Deficiency
2.3. Factors Associated with Deficiencies
2.4. Statistical Analysis
3. Results
3.1. Characteristics of the Study Population
3.2. Vitamin D
3.3. Iron
4. Discussion
Clinical Implications
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| ADOS-2 | Autism Diagnostic Observation Schedule |
| [25(OH)D] | 25-hydroxyvitamin D |
References
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5™, 5th ed.; American Psychiatric Publishing, Inc.: Arlington, VA, USA, 2013; pp. 205–224. [Google Scholar] [CrossRef] [Scilit]
- Wong, C.M.; Aljunied, M.; Chan, D.K.L.; Cheong, J.M.Y.; Chew, B.; Chin, C.H.; Choo, S.H.T.; Chua, A.H.L.; Foo, M.T.S.; Goh, T.J.; et al. 2023 clinical practice guidelines on autism spectrum disorder in children and adolescents in Singapore. Ann. Acad. Med. Singap. 2024, 53, 541–552. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Bandini, L.G.; Anderson, S.E.; Curtin, C.; Cermak, S.; Evans, E.W.; Scampini, R.; Maslin, M.; Must, A. Food selectivity in children with autism spectrum disorders and typically developing children. J. Pediatr. 2010, 157, 259–264. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Nogueira-de-Almeida, C.A.; de Araújo, L.A.; da V. Ued, F.; Contini, A.A.; Nogueira-de-Almeida, M.E.; Martinez, E.Z.; Ferraz, I.S.; Del Ciampo, L.A.; Nogueira-de-Almeida, C.C.J.; Fisberg, M. Nutritional Factors and Therapeutic Interventions in Autism Spectrum Disorder: A Narrative Review. Children 2025, 12, 202. [Google Scholar] [CrossRef] [Scilit] [PubMed] [PubMed Central]
- Institute of Medicine (US); Food and Nutrition Board; Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D; Ross, A.C., Taylor, C.L., Yaktine, A.L., Del Valle, H.B., Eds.; The National Academies Press: Washington, DC, USA, 2011. [Google Scholar] [CrossRef] [Scilit]
- Baeke, F.; Takiishi, T.; Korf, H.; Gysemans, C.; Mathieu, C. Vitamin D: Modulator of the immune system. Curr. Opin. Pharmacol. 2010, 10, 482–496. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Becker, A.; Eyles, D.W.; McGrath, J.J.; Grecksch, G. Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats. Behav. Brain Res. 2005, 161, 306–312. [Google Scholar] [CrossRef] [Scilit]
- Guillot, X.; Semerano, L.; Saidenberg-Kermanac’h, N.; Falgarone, G.; Boissier, M.C. Vitamin D and inflammation. Jt. Bone Spine 2010, 77, 552–557. [Google Scholar] [CrossRef] [Scilit]
- Mutua, A.M.; Mogire, R.M.; Elliott, A.M.; Williams, T.N.; Webb, E.L.; Abubakar, A.; Atkinson, S.H. Effects of vitamin D deficiency on neurobehavioural outcomes in children: A systematic review. Wellcome Open Res. 2020, 5, 28. [Google Scholar] [CrossRef] [Scilit]
- Wang, Z.; Ding, R.; Wang, J. The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis. Nutrients 2020, 13, 86. [Google Scholar] [CrossRef] [Scilit]
- Jayanath, S.; Fong, C.Y.; Sarvananthan, R. Autism spectrum disorder and vitamin D status: A cross-sectional study of children in a developing country in Southeast Asia. Res. Autism Spectr. Disord. 2021, 84, 101786. [Google Scholar] [CrossRef] [Scilit]
- Saad, K.; Abdel-Rahman, A.A.; Elserogy, Y.M.; Al-Atram, A.A.; Cannell, J.J.; Bjorklund, G.; Abdel-Reheim, M.K.; Othman, H.A.; El-Houfey, A.A.; Abd El-Aziz, N.H.; et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. 2016, 19, 346–351. [Google Scholar] [CrossRef] [Scilit]
- Mostafa, G.A.; Al-Ayadhi, L.Y. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity. J. Neuroinflamm. 2012, 9, 201. [Google Scholar] [CrossRef] [Scilit]
- Kittana, M.; Ahmadani, A.; Stojanovska, L.; Attlee, A. The Role of Vitamin D Supplementation in Children with Autism Spectrum Disorder: A Narrative Review. Nutrients 2021, 14, 26. [Google Scholar] [CrossRef] [Scilit]
- McCann, J.C.; Ames, B.N. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am. J. Clin. Nutr. 2007, 85, 931–945. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Fretham, S.J.; Carlson, E.S.; Georgieff, M.K. The role of iron in learning and memory. Adv. Nutr. 2011, 2, 112–121. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Lozoff, B.; Beard, J.; Connor, J.; Barbara, F.; Georgieff, M.; Schallert, T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr. Rev. 2006, 64, S34–S43, discussion S72–S91. [Google Scholar] [CrossRef] [Scilit]
- Lozoff, B.; Jimenez, E.; Hagen, J.; Mollen, E.; Wolf, A.W. Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000, 105, E51. [Google Scholar] [CrossRef] [Scilit]
- Bilgiç, A.; Gürkan, K.; Türkoğlu, S.; Akça, Ö.F.; Kılıç, B.G.; Uslu, R. Iron deficiency in preschool children with autistic spectrum disorders. Res. Autism Spectr. Disord. 2010, 4, 639–644. [Google Scholar] [CrossRef] [Scilit]
- Herguner, S.; Kelesoglu, F.M.; Tanidir, C.; Copur, M. Ferritin and iron levels in children with autistic disorder. Eur. J. Pediatr. 2012, 171, 143–146. [Google Scholar] [CrossRef] [Scilit]
- Reynolds, A.; Krebs, N.F.; Stewart, P.A.; Austin, H.; Johnson, S.L.; Withrow, N.; Molloy, C.; James, S.J.; Johnson, C.; Clemons, T.; et al. Iron status in children with autism spectrum disorder. Pediatrics 2012, 130 (Suppl. S2), S154–S159. [Google Scholar] [CrossRef] [Scilit]
- Sidrak, S.; Yoong, T.; Woolfenden, S. Iron deficiency in children with global developmental delay and autism spectrum disorder. J. Paediatr. Child Health 2014, 50, 356–361. [Google Scholar] [CrossRef] [Scilit]
- Lord, C.; Rutter, M.; DiLavore, P.; Risi, S.; Gotham, K.; Bishop, S. Autism Diagnostic Observation Schedule–2nd Edition (ADOS-2); Western Psychological Corporation: Los Angeles, CA, USA, 2012; Volume 284, pp. 474–478. [Google Scholar]
- WHO. WHO Guideline on Use of Ferritin Concentrations to Assess Iron Status in Individuals and Populations. Available online: https://www.ncbi.nlm.nih.gov/pubmed/33909381 (accessed on 21 April 2020).
- Chew, E.C.S.; Lam, J.C.M. Diagnosis and Management of Iron Deficiency Anaemia in Children—A Clinical Update. Proc. Singap. Healthc. 2012, 21, 278–285. [Google Scholar] [CrossRef] [Scilit]
- Ministry of Health Singapore. National Health Survey. 2010. Available online: https://www.moh.gov.sg/others/resources-and-statistics/reports-national-health-survey-2010 (accessed on 23 July 2013).
- Divakar, U.; Sathish, T.; Soljak, M.; Bajpai, R.; Dunleavy, G.; Visvalingam, N.; Nazeha, N.; Soh, C.K.; Christopoulos, G.; Car, J. Prevalence of Vitamin D Deficiency and Its Associated Work-Related Factors among Indoor Workers in a Multi-Ethnic Southeast Asian Country. Int. J. Environ. Res. Public Health 2019, 17, 164. [Google Scholar] [CrossRef] [Scilit]
- Cashman, K.D.; Dowling, K.G.; Skrabakova, Z.; Gonzalez-Gross, M.; Valtuena, J.; De Henauw, S.; Moreno, L.; Damsgaard, C.T.; Michaelsen, K.F.; Molgaard, C.; et al. Vitamin D deficiency in Europe: Pandemic? Am. J. Clin. Nutr. 2016, 103, 1033–1044. [Google Scholar] [CrossRef] [Scilit]
- Şengenç, E.; Kıykım, E.; Saltik, S. Vitamin D levels in children and adolescents with autism. J. Int. Med. Res. 2020, 48, 300060520934638. [Google Scholar] [CrossRef] [Scilit]
- Arastoo, A.A.; Khojastehkia, H.; Rahimi, Z.; Khafaie, M.A.; Hosseini, S.A.; Mansouri, M.T.; Yosefyshad, S.; Abshirini, M.; Karimimalekabadi, N.; Cheraghi, M. Evaluation of serum 25-Hydroxy vitamin D levels in children with autism Spectrum disorder. Ital. J. Pediatr. 2018, 44, 150. [Google Scholar] [CrossRef] [Scilit]
- Bener, A.; Khattab, A.O.; Bhugra, D.; Hoffmann, G.F. Iron and vitamin D levels among autism spectrum disorders children. Ann. Afr. Med. 2017, 16, 186–191. [Google Scholar] [CrossRef] [Scilit]
- Dosman, C.F.; Drmic, I.E.; Brian, J.A.; Senthilselvan, A.; Harford, M.; Smith, R.; Roberts, S.W. Ferritin as an indicator of suspected iron deficiency in children with autism spectrum disorder: Prevalence of low serum ferritin concentration. Dev. Med. Child Neurol. 2006, 48, 1008–1009. [Google Scholar] [CrossRef] [Scilit]
- Chiong, T.X.B.; Tan, M.L.N.; Lim, T.S.H.; Quak, S.H.; Aw, M.M. Selective Feeding-An Under-Recognised Contributor to Picky Eating. Nutrients 2024, 16, 3608. [Google Scholar] [CrossRef] [Scilit]
- Kittana, M.; Ahmadani, A.; Williams, K.E.; Attlee, A. Nutritional Status and Feeding Behavior of Children with Autism Spectrum Disorder in the Middle East and North Africa Region: A Systematic Review. Nutrients 2023, 15, 711. [Google Scholar] [CrossRef] [Scilit]
- Malhi, P.; Venkatesh, L.; Bharti, B.; Singhi, P. Feeding Problems and Nutrient Intake in Children with and without Autism: A Comparative Study. Indian J. Pediatr. 2017, 84, 283–288. [Google Scholar] [CrossRef] [Scilit]
- Lim, T.S.H.; Wong, C.Y.; Lin, C.; Phua, Q.Q.; Tok, A.E.S.; Cheng, A.S.M.; Chan, Y.H.; Aw, M.M. Diet, growth, nutritional status and predictors of severity of feeding difficulties in autistic children with co-occurring pediatric feeding disorder. Early Hum. Dev. 2024, 199, 106137. [Google Scholar] [CrossRef] [Scilit]
| Total N = 241 | |
|---|---|
| Age, years | |
| Mean (sd) | 4.21 (2.25) |
| Median (25th Percentile–75th Percentile) | 4.00 (2.38 to 6.00) |
| Gender, n (%) | |
| Male | 191 (79.3%) |
| Female | 50 (20.7%) |
| Race, n (%) | N = 191 |
| Chinese | 123 (64.4%) |
| Malay | 23 (12.0%) |
| Indian | 20 (10.5%) |
| Others | 25 (13.1%) |
| Category | N (%) |
|---|---|
| Vitamin D (Total N = 222) | |
| Deficient | 10 (4.5%) |
| Insufficient | 71 (32%) |
| Sufficient | 140 (63.1%) |
| Toxicity | 1 (0.5) |
| Iron (Total N = 236) | |
| Iron deficiency | 89/236 (37.7%) |
| Iron deficiency anaemia | 19/122 (15.6%) |
| Presence of Vitamin D | Unadjusted | Adjusted | ||||
|---|---|---|---|---|---|---|
| Insufficiency/ Deficiency (n = 81) | Sufficient/ Toxic (n = 141) | OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
| Age (months) | ||||||
| Mean (SD) | 58.3 (27.9) | 46.7 (24.8) | 1.02 (1.01 to 1.03) | 0.002 | 1.04 (1.03 to 1.06) | <0.001 |
| Race | ||||||
| Malay | 9 (14.5%) | 12 (10.2%) | 2.33 (0.72 to 7.52) | 0.255 | 5.0 (1.6 to 15.9) | 0.007 |
| Indian | 15 (24.2%) | 4 (3.4%) | 11.6 (2.8 to 49.1) | <0.001 | 20.9 (4.7 to 92.0) | <0.001 |
| Other Races | 9 (14.5%) | 12 (10.2%) | 2.33 (0.72 to 7.52) | 0.255 | 3.2 (1.01 to 10.4) | 0.048 |
| Chinese | 29 (46.8%) | 90 (76.3%) | 1 | 1 | ||
| Gender | ||||||
| Male | 63 (77.8%) | 113 (80.1%) | 0.87 (0.45 to 1.69) | 0.676 | 1.52 (0.55 to 4.25) | 0.422 |
| Female | 18 (22.2%) | 28 (19.9%) | 1 | 1 | ||
| Eating Habit | ||||||
| Picky Eater | 26 (44.8%) | 54 (48.6%) | 0.86 (0.45 to 1.62) | 0.637 | 0.48 (0.21 to 1.08) | 0.075 |
| Non-Picky Eater | 32 (55.2%) | 57 (51.4%) | 1 | 1 | ||
| Iron Deficiency | Unadjusted | Adjusted | ||||
|---|---|---|---|---|---|---|
| Yes (n = 89) | No (n = 147) | OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
| Age (months) | 0.809 | 0.212 | ||||
| Median (Min–Max) | 54 (8–114) | 44 (6–126) | 1.00 (0.99 to 1.01) | 0.99 (0.98 to 1.01) | ||
| Race | ||||||
| Malay | 12 (15.2%) | 11 (10.2%) | 1.91 (0.64 to 5.72) | 0.474 | 1.87 (0.73 to 4.78) | 0.194 |
| Indian | 10 (12.7%) | 9 (8.3%) | 1.94 (0.59 to 6.39) | 0.543 | 1.59 (0.52 to 4.90) | 0.420 |
| Other Races | 13 (16.5%) | 11 (10.2%) | 2.07 (0.70 to 6.09) | 0.321 | 1.95 (0.76 to 5.03) | 0.168 |
| Chinese | 44 (55.7%) | 77 (71.3%) | 1 | 1 | ||
| Gender | ||||||
| Male | 69 (77.5%) | 119 (81.0%) | 0.81 (0.43 to 1.55) | 0.94 (0.42 to 2.10) | ||
| Female | 20 (22.5%) | 28 (19.0%) | 1 | 1 | ||
| Eating Habit | ||||||
| Picky Eater | 38 (50.7%) | 49 (47.1%) | 1.15 (0.64 to 2.09) | 1.17 (0.62 to 2.23) | ||
| Non-Picky Eater | 37 (49.3%) | 55 (52.9%) | 1 | 1 | ||
| Iron Deficiency Anaemia | Unadjusted | Adjusted | ||||
|---|---|---|---|---|---|---|
| Yes (n = 19) | No (n = 103) | OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
| Age (months) | ||||||
| Median (Min–Max) | 70 (18–95) | 44 (12–114) | 1.03 (1.01 to 1.05) | 1.03 (1.01 to 1.06) | ||
| Race | ||||||
| Malay | 1 (5.3%) | 17 (16.5%) | 0.47 (0.03 to 6.47) | 1 | 0.40 (0.04 to 3.66) | 0.418 |
| Indian | 4 (21.1%) | 10 (9.7%) | 3.20 (0.60 to 17.11) | 0.290 | 3.16 (0.69 to 14.45) | 0.139 |
| Other Races | 6 (31.6%) | 12 (11.7%) | 4 (0.90 to 17.85) | 0.080 | 2.02 (0.48 to 8.42) | 0.337 |
| Chinese | 8 (42.1%) | 64 (62.1%) | 1 | 1 | ||
| Gender | ||||||
| Male | 13 (68.4%) | 86 (83.5%) | 0.43 (0.14 to 1.29) | 0.130 | 0.47 (0.13 to 1.64) | 0.235 |
| Female | 6 (31.6%) | 17 (16.5%) | 1 | 1 | ||
| Eating Habit | ||||||
| Picky Eater | 9 (50.0%) | 41 (45.1%) | 1.22 (0.44 to 3.36) | 0.701 | 0.67 (0.20 to 2.30) | 0.528 |
| Non-Picky Eater | 9 (50.0%) | 50 (54.9%) | 1 | 1 | ||
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Koh, M.Y.; Lee, A.J.W.; Wong, H.C.; Aishworiya, R. Occurrence and Correlates of Vitamin D and Iron Deficiency in Children with Autism Spectrum Disorder. Nutrients 2025, 17, 2738. https://doi.org/10.3390/nu17172738
Koh MY, Lee AJW, Wong HC, Aishworiya R. Occurrence and Correlates of Vitamin D and Iron Deficiency in Children with Autism Spectrum Disorder. Nutrients. 2025; 17(17):2738. https://doi.org/10.3390/nu17172738
Chicago/Turabian StyleKoh, Magdalena Yvonne, Audrey J. W. Lee, Hung Chew Wong, and Ramkumar Aishworiya. 2025. "Occurrence and Correlates of Vitamin D and Iron Deficiency in Children with Autism Spectrum Disorder" Nutrients 17, no. 17: 2738. https://doi.org/10.3390/nu17172738
APA StyleKoh, M. Y., Lee, A. J. W., Wong, H. C., & Aishworiya, R. (2025). Occurrence and Correlates of Vitamin D and Iron Deficiency in Children with Autism Spectrum Disorder. Nutrients, 17(17), 2738. https://doi.org/10.3390/nu17172738

