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Maternal Vitamin D Levels During Pregnancy and Offspring Autism Spectrum Disorder

  • Author Footnotes
    1 AS and SU contributed equally to this work.
    Andre Sourander
    Correspondence
    Address correspondence to Andre Sourander, M.D., Ph.D.
    Footnotes
    1 AS and SU contributed equally to this work.
    Affiliations
    Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland

    INVEST (Inequalities, Interventions and a New Welfare State) Research Flagship, University of Turku, Turku, Finland

    Department of Child Psychiatry, Turku University Hospital, Turku, Finland

    New York State Psychiatric Institute, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York
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  • Author Footnotes
    1 AS and SU contributed equally to this work.
    Subina Upadhyaya
    Footnotes
    1 AS and SU contributed equally to this work.
    Affiliations
    Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland
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  • Heljä-Marja Surcel
    Affiliations
    Faculty of Medicine, University of Oulu, Oulu, Finland

    Biobank Borealis of Northern Finland, Oulu, Finland
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  • Susanna Hinkka-Yli-Salomäki
    Affiliations
    Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland
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  • Keely Cheslack-Postava
    Affiliations
    New York State Psychiatric Institute, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York
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  • Sanju Silwal
    Affiliations
    Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland
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  • Minna Sucksdorff
    Affiliations
    Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland

    Department of Pediatrics, Turku University Hospital, Turku, Finland
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  • Ian W. McKeague
    Affiliations
    Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York
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  • Alan S. Brown
    Affiliations
    New York State Psychiatric Institute, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York

    Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York
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  • Author Footnotes
    1 AS and SU contributed equally to this work.

      Abstract

      Background

      Findings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent.

      Methods

      The association between maternal 25(OH)D levels during pregnancy and offspring ASD was examined using data from a nationwide population-based register with a nested case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015; cases were matched with an equal number of controls. Maternal 25(OH)D levels during pregnancy were measured using quantitative immunoassay from maternal sera collected during the first and early second trimesters and archived in the national biobank of the Finnish Maternity Cohort. Conditional logistic regression examined the association between maternal 25(OH)D levels and offspring ASD.

      Results

      In the adjusted model, there was a significant association between increasing log-transformed maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.62–0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03–1.79, p = .02) and 20–39 (aOR 1.31, 95% CI 1.01–1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15–1.81, p = .001) and insufficient (30–49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95% CI 1.04–1.52, p = .01) compared with sufficient levels.

      Conclusions

      This finding has implications for understanding the role of maternal vitamin D during fetal brain development and increased risk of ASD.

      Keywords

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