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      Gestational vitamin D deficiency and autism spectrum disorder

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          Abstract

          Background

          There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.

          Aims

          To determine the association between gestational vitamin D status and ASD.

          Method

          Based on a birth cohort ( n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).

          Results

          Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.

          Conclusions

          Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.

          Declaration of interest

          None.

          Copyright and usage

          © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

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          Most cited references26

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          The Changing Epidemiology of Autism Spectrum Disorders

          Kristen Lyall, Lisa A Croen, Julie T. Daniels … (2017)
          Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts. Genetic and environmental factors contribute to ASD etiology, which remains incompletely understood. Research on ASD epidemiology has made significant advances in the past decade. Current prevalence is estimated to be at least 1.5% in developed countries, with recent increases primarily among those without comorbid intellectual disability. Genetic studies have identified a number of rare de novo mutations and gained footing in the areas of polygenic risk, epigenetics, and gene-by-environment interaction. Epidemiologic investigations focused on nongenetic factors have established advanced parental age and preterm birth as ASD risk factors, indicated that prenatal exposure to air pollution and short interpregnancy interval are potential risk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals. We discuss future challenges and goals for ASD epidemiology as well as public health implications.
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            Estimating the population attributable risk for multiple risk factors using case-control data.

            P. Bruzzi, S Green, D Byar … (1985)
            A straightforward and unified approach is presented for the calculation of the population attributable risk per cent (etiologic fraction) in the general multivariate setting, with emphasis on using data from case-control studies. The summary attributable risk for multiple factors can be estimated, with or without adjustment for other (confounding) risk factors. The relation of this approach to procedures in the literature is discussed. Given values of the relative risks for various combinations of factors, all that is required is the distribution of these factors among the cases only. The required information can often be estimated solely from case-control data, and in some situations relative risk estimates from one population can be applied to calculation of attributable risk for another population. The authors emphasize the benefits to be obtained from logistic regression models, so that risks need not be estimated separately in a large number of strata, some of which may contain inadequate numbers of individuals. This approach allows incorporation of important interactions between factors, but does not require that all possible interactions be included. The approach is illustrated with data on four risk factors from a pair-matched case-control study of participants in a multicenter breast cancer screening project.
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              Autism Spectrum Disorders in the Stockholm Youth Cohort: Design, Prevalence and Validity

              Selma Idring, Dheeraj Rai, Henrik Dal … (2012)
              Objective Reports of rising prevalence of autism spectrum disorders (ASD), along with their profound personal and societal burden, emphasize the need of methodologically sound studies to explore their causes and consequences. We here present the design of a large intergenerational resource for ASD research, along with population-based prevalence estimates of ASD and their diagnostic validity. Method The Stockholm Youth Cohort is a record-linkage study comprising all individuals aged 0–17 years, ever resident in Stockholm County in 2001–2007 (N = 589,114). ASD cases (N = 5,100) were identified using a multisource approach, involving registers covering all pathways to ASD diagnosis and care, and categorized according to co-morbid intellectual disability. Prospectively recorded information on potential determinants and consequences of ASD were retrieved from national and regional health and administrative registers. Case ascertainment was validated through case-note review, and cross validation with co-existing cases in a national twin study. Results The 2007 year prevalence of ASD in all children and young people was 11.5 per 1,000 (95% confidence interval 11.2–11.8), with a co-morbid intellectual disability recorded in 42.6% (41.0–44.2) of cases. We found 96.0% (92.0–98.4) of reviewed case-notes being consistent with a diagnosis of ASD, and confirmed ASD in 85.2% (66.2–95.8) of affected twins. Conclusions Findings from this contemporary study accords with recently reported prevalence estimates from Western countries at around 1%, based on valid case ascertainment. The Stockholm Youth Cohort, in light of the availability of extensive information from Sweden's registers, constitutes an important resource for ASD research. On-going work, including collection of biological samples, will enrich the study further.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BJPsych Open
                Journal ID (iso-abbrev): BJPsych Open
                Journal ID (publisher-id): bjporcpsych
                Journal ID (hwp): bjporcpsych
                Title: BJPsych Open
                Publisher: The Royal College of Psychiatrists
                ISSN (Electronic): 2056-4724
                Publication date (Electronic): 10 April 2017
                Publication date Collection: March 2017
                Volume: 3
                Issue: 2
                Pages: 85-90
                Affiliations
                [1] Anna A. E. Vinkhuyzen, PhD, Queensland Brain Institute, The University of Queensland, St Lucia, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia
                [2] Darryl W. Eyles, PhD, Queensland Brain Institute, The University of Queensland, St Lucia, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Australia
                [3] Thomas H. J. Burne, PhD, Queensland Brain Institute, The University of Queensland, St Lucia, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Australia
                [4] Laura M. E. Blanken, MD, MSc, The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [5] Claudia J. Kruithof, MSc, The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [6] Frank Verhulst, MD, PhD, Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [7] Tonya White, MD, PhD, Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [8] Vincent W. Jaddoe, MD, PhD, The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands
                [9] Henning Tiemeier, MD, PhD, Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [10] John J. McGrath, MD, PhD, Queensland Brain Institute, The University of Queensland, St Lucia, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Australia
                Author notes
                Correspondence: John J. McGrath, Queensland Brain Institute, The University of Queensland, St Lucia QLD 4072, Australia. Email: j.mcgrath@ 123456uq.edu.au
                Article
                Publisher ID: bjporcpsych004077
                DOI: 10.1192/bjpo.bp.116.004077
                PMC ID: 5385921
                PubMed ID: 28446959
                SO-VID: c5c62011-28f9-4dd5-9630-d487234fa53b
                Copyright © © 2017 The Royal College of Psychiatrists
                License:

                This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 21 October 2016
                Date revision received : 24 January 2017
                Date accepted : 12 March 2017
                Categories
                Subject: Paper

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