Abstract
We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks’ pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean. The offspring of 406 women completed the Autism-Spectrum Quotient in early adulthood. Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales. However, offspring of mothers with low 25(OH)-vitamin D concentrations (<49 nmol/L) were at increased risk for ‘high’ scores (≥2SD above mean) on the Attention Switching subscale (odds ratio: 5.46, 95 % confidence interval: 1.29, 23.05). The involvement of maternal vitamin D during pregnancy in autism requires continued investigation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: American Psychiatric Press.
Atif, F., Sayeed, I., Ishrat, T., & Stein, D. G. (2009). Progesterone with vitamin D affords better neuroprotection against excitotoxicity in cultured cortical neurons than progesterone alone. Molecular Medicine, 15, 328–336.
Baron-Cohen, S., Wheelwright, S., Skinner, R., Martin, J., & Clubley, E. (2001). The Autism-Spectrum Quotient (AQ): Evidence from Asperger Syndrome/high-functioning autism, males and females, scientists and mathematicians. Journal of Autism and Developmental Disorders, 31(1), 5–17.
Brown, J., Bianco, J. I., McGrath, J. J., & Eyles, D. W. (2003). 1, 25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neuroscience Letters, 343(2), 139–143.
Camargo, C. A., Rifas-Shiman, S. L., Litonjua, A. A., Rich-Edwards, J. W., Weiss, S. T., Gold, D. R., et al. (2007). Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. The American Journal of Clinical Nutrition, 85(3), 788–795.
Cannell, J. J. (2008). Autism and vitamin D. Medical Hypotheses, 70(4), 750–759.
Cekic, M., Sayeed, I., & Stein, D. G. (2009). Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease. Frontiers in Neuroendocrinology, 30, 158–172.
Corder, E. H., Guess, H. A., Hulka, B. S., Friedman, G. D., Sadler, M., Vollmer, R. T., et al. (1993). Vitamin D and prostate cancer: A prediagnostic study with stored sera. Cancer Epidemiology, Biomarkers and Prevention, 2(5), 467–472.
Eyles, D., Brown, J., Mackay-Sim, A., McGrath, J., & Feron, F. (2003). Vitamin D3 and brain development. Neuroscience, 118(3), 641–653.
Gale, C. R., Robinson, S. M., Harvey, N. C., Javaid, M. K., Jiang, B., Martyn, C. N., et al. (2008). Maternal vitamin D status during pregnancy and child outcomes. European Journal of Clinical Nutrition, 62(1), 68–77.
Garcion, E., Wion-Barbot, N., & Montero-Menei, C. N. (2002). New clues about vitamin D functions in the nervous system. Trends in Endocrinology and Metabolism, 13, 100–105.
Gardener, H., Spiegelman, D., & Buka, S. L. (2009). Prenatal risk factors for autism: Comprehensive meta-analysis. British Journal of Psychiatry, 195(1), 7–14.
Happé, F., & Ronald, A. (2008). The ‘fractionable autism triad’: A review of evidence from behavioural, genetic, cognitive and neural research. Neuropsychology Review, 18(4), 287–304.
Holick, M. F. (1987). Photosynthesis of vitamin D in the skin: Effect of environmental and life-style variables. Federation Proceedings, 46, 1876–1882.
Holick, M. F. (2007). Vitamin D deficiency. New England Journal of Medicine, 357(3), 266–281.
Javaid, M. K., Crozier, S. R., Harvey, N. C., Gale, C. R., Dennison, E. M., Boucher, B. J., et al. (2006). Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: A longitudinal study. Lancet, 367(9504), 36–43.
Kolevzon, A., Weiser, M., Gross, R., Lubin, G., Knobler, H., Schmeidler, J., et al. (2006). Effects of season of birth on autism spectrum disorders: Fact or fiction? American Journal of Psychiatry, 163, 1288–1290.
Landau, E. C., Cicchetti, D. V., Klin, A., & Volkmar, F. R. (1999). Season of birth in autism: A fiction revisited. Journal of Autism and Developmental Disorders, 29(5), 385–393.
Levis, S., Gomez, A., Jimenez, C., Veras, L., Ma, F., Lai, S., et al. (2005). Vitamin D deficiency and seasonal variation in an adult South Florida population. Journal of Clinical Endocrinology and Metabolism, 90(3), 1557–1562.
Lundström, S., Chang, Z., Rastam, M., Gillberg, C., Larsson, H., Anckarsater, H., et al. (2012). Autism Spectrum Disorders and autistic-like traits: Similar etiology in the extreme end and the normal variation. Archives of General Psychiatry, 69(1), 46–52.
Marini, F., Bartoccini, E., Cascianelli, G., Voccoli, V., Baviglia, M. G., Magni, M. V., et al. (2010). Effect of 1α, 25-dihydroxyvitamin D3 in embryonic hippocampal cells. Hippocampus, 20(6), 696–705.
Morley, R., Carlin, J. B., Pasco, J. A., & Wark, J. D. (2006). Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. Journal of Clinical Endocrinology and Metabolism, 91(3), 906–912.
Neveu, I., Naveilhan, P., Jehan, F., Baudet, C., Wion, D., De Luca, H. F., et al. (1994). 1, 25-Dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells. Molecular Brain Research, 24(1–4), 70–76.
Newnham, J. P., Evans, S. F., Michael, C. A., Stanley, F. J., & Landau, L. I. (1993). Effects of frequent ultrasound during pregnancy: A randomized controlled trial. Lancet, 342(8876), 887–891.
Nomura, A. M. Y., Stemmermann, G. N., Lee, J., Kolonel, L. N., Chen, T. C., Turner, A., et al. (1998). Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Cancer Causes and Control, 9(4), 425–432.
O’Loan, J., Eyles, D. W., Kesby, J., Ko, P., McGrath, J. J., & Burne, T. H. J. (2007). Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology, 32(3), 227–234.
Ozonoff, S., Young, G. S., Carter, A., Messinger, D., Yirmiya, N., Zwaigenbaum, L., et al. (2011). Recurrence risk for autism spectrum disorders: A baby siblings research consortium study. Pediatrics, 128(3), e488–e495.
Rice, D., & Barone, S. (2000). Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. Environmental Health Perspectives, 108, 511–533.
Robinson, E. B., Koenen, K. C., McCormick, M. C., Munir, K., Hallett, V., Happé, F., et al. (2011). Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5 %, 2.5 %, and 1 %). Archives of General Psychiatry, 68(11), 1113–1121.
Whitehouse, A. J. O., Hickey, M., Stanley, F. J., Newnham, J. P., & Pennell, C. E. (2011). A preliminary study of fetal head circumference growth in Autism Spectrum Disorder. Journal of Autism and Developmental Disorders, 41, 122–129.
Whitehouse, A. J. O., Holt, B. J., Serralha, M., Holt, P. G., Kusel, M. M. H., & Hart, P. H. (2012). Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics, 129(3), 485–493.
Wilkinson, R. J., Llewelyn, M., Toossi, Z., Patel, P., Pasvol, G., Lalvani, A., et al. (2000). Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: A case-control study. The Lancet, 355(9204), 618–621.
Wion, D., Macgrogan, D., Neveu, I., Jehan, F., Houlgatte, R., & Brachet, P. (1991). 1, 25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. Journal of Neuroscience Research, 28(1), 110–114.
Wolke, D., Waylen, A., Samara, M., Steer, C., Goodman, R., Ford, T., et al. (2009). Selective drop-out in longitudinal studies and non-biased prediction of behaviour disorders. The British Journal of Psychiatry, 195(3), 249–256.
Zosky, G. R., Berry, L. J., Elliot, J. G., James, A. L., Gorman, S., & Hart, P. H. (2011). Vitamin D deficiency causes deficits in lung function and alters lung structure. American Journal of Respiratory and Critical Care Medicine, 183(10), 1336–1343.
Acknowledgments
The authors would like to acknowledge the National Health and Medical Research Council (NHMRC) for their long term contribution to funding the study over the last 20 years. Core Management of the Raine study has been funded by the University of Western Australia (UWA), Curtin University, the UWA Faculty of Medicine, Dentistry and Health Sciences, the Raine Medical Research Foundation, the Telethon Institute for Child Health Research, and the Women’s and Infants Research Foundation. AJOW is funded by a Career Development Fellowship from the NHMRC (#1004065). This study was partly funded by NHMRC Project Grant #1003424. These funders had no further role in study design, analysis, data interpretation or manuscript writing and submission. The authors are extremely grateful to all of the families who took part in this study and the whole Raine Study team, which includes the Cohort Manager, Data Manager and data collection team.
Author information
Authors and Affiliations
Corresponding author
Additional information
Prue H. Hart and Merci M. H. Kusel contributed equally to this work.
Rights and permissions
About this article
Cite this article
Whitehouse, A.J.O., Holt, B.J., Serralha, M. et al. Maternal Vitamin D Levels and the Autism Phenotype Among Offspring. J Autism Dev Disord 43, 1495–1504 (2013). https://doi.org/10.1007/s10803-012-1676-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10803-012-1676-8