Developmental vitamin D and autism spectrum disorders: findings from the Stockholm Youth Cohort

Brian K Lee,Renee M Gardner,Pauline Ko,Cecilia Magnusson,John J Mcgrath,Darryl W Eyles,David Kvaskoff,Christina Dalman,Craig J Newschaffer,Håkan Karlsson

doi:10.1038/s41380-019-0578-y

Abstract

Animal studies indicate that early life vitamin D is crucial for proper neurodevelopment. Few studies have examined whether maternal and neonatal vitamin D concentrations influence risk of autism spectrum disorders (ASD). Participants were sampled from the Stockholm Youth Cohort, a register-based cohort in Sweden. Concentrations of total 25-hydroxyvitamin D (25OHD) were assessed from maternal and neonatal biosamples using a highly sensitive liquid chromatography tandem mass spectrometry method. The maternal sample consisted of 449 ASD cases and 574 controls, the neonatal sample: 1399 ASD cases and 1607 controls; and the paired maternal-neonatal sample: 340 ASD cases and 426 controls. Maternal 25OHD was not associated with child ASD in the overall sample. However, in Nordic-born mothers, maternal 25OHD insufficiency (25 − <50 nmol/L) at ~11 weeks gestation was associated with 1.58 times higher odds of ASD (95% CI: 1.00, 2.49) as compared with 25OHD sufficiency (≥50 nmol/L). Neonatal 25OHD < 25 nmol/L was associated with 1.33 times higher odds of ASD (95% CI: 1.02, 1.75) as compared with 25OHD ≥ 50 nmol/L. Sibling-matched control analyses indicated these associations were not likely due to familial confounding. Children with both maternal 25OHD and neonatal 25OHD below the median had 1.75 (95% CI: 1.08, 2.86) times the odds of ASD compared with children with maternal and neonatal 25OHD both below the median. Our results are consistent with an increasing body of evidence suggesting that vitamin D concentrations in early life may be associated with increased risk of neurodevelopmental disorders including ASD.

Highlights

Supplementary information The online version of this article contains supplementary material, which is available to authorized users.2 A.J
Life nutrition is critical for proper neurodevelopment [1] and the paradigm may extend to autism spectrum disorders (ASD) as well [2]
Because of prior reported associations of early life 25OHD with intellectual function, we explored whether associations were different for ASD subtyped by presence or absence of cooccurring intellectual disability (ID)

Summary

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Recent epidemiological studies have provided evidence that lower concentrations of gestational 25-hydroxyvitamin D (25OHD) may be correlated with increased risk of ASD phenotypes. In the Generation R study in the Netherlands, lower mid-gestation and cord blood 25OHD concentrations were associated with more abnormal scores on the Social Responsiveness Scale, a measure of an ASD-related phenotype [18]. There is evidence suggesting that early life 25OHD may be associated with ASD case status, findings have been mixed. In the Generation R study ( based on 68 cases), mid-gestation vitamin D deficiency was associated with 2.4 times higher risk of ASD [21]. We examine the associations of maternal and neonatal 25OHD and later risk of ASD in a Swedish population-based sample. Because of prior reported associations of early life 25OHD with intellectual function, we explored whether associations were different for ASD subtyped by presence or absence of cooccurring intellectual disability (ID)

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Compliance with ethical standards