Gestational vitamin D deficiency and autism spectrum disorder

Abstract

BackgroundThere 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.AimsTo determine the association between gestational vitamin D status and ASD.MethodBased 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).ResultsIndividuals 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.ConclusionsMid-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 interestNone.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.

Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

“…A much larger ( n = 4,229) cohort study showed an association between vitamin D deficiency measured at mid‐gestation and in cord blood and autism‐related traits [Vinkhuyzen et al, ], but the association with cord blood vitamin D deficiency appeared to be driven primarily by those who had deficiencies at both time points. Similarly, in the same cohort ( n = 4,334), vitamin D deficiency in cord blood was not associated with ASD diagnosis, while low maternal mid‐gestation 25(OH)D was associated [Vinkhuyzen et al, ]. Taken together, these studies and a study that found low maternal first trimester 25(OH)D was associated with higher risk for ASD diagnosis [Chen et al, ], suggest that there may be a critical period for gestational vitamin D and ASD earlier in pregnancy, that was not well‐measured in this study.…”

“…Animal studies show long‐lasting neurodevelopmental effects of transient vitamin D deficiency during gestation leading to autism‐relevant structural and functional changes in the brain and behaviors of the offspring [Eyles et al, ; Eyles et al, ; Grecksch, Ruthrich, Höllt, & Becker, ; Levenson & Figueiroa, ]. Several studies have recently found associations between gestational vitamin D status and ASD diagnosis [Chen, Xin, Wei, Zhang, & Xiao, ; Fernell et al, ; Vinkhuyzen et al, ] and autism‐related traits [Vinkhuyzen et al, ], but findings have been inconsistent, and the number of children diagnosed with ASD has been relatively small and did not allow for investigation of effect modification by race and sex. There is biological potential for heterogeneous effects across sex given that sex hormones like estrogen and testosterone have very different effects on calcitriol's metabolism [Cannell, ], and males are more prone to vitamin D deficiency [Tonnesen, Hovind, Jensen, & Schwarz, ].…”

The neurobiology of BRD1 implicates sex-biased dysregulation of nuclear receptor signaling in mental disorders

“…has been implicated with both psychotic and affective disorders [16][17][18][19][20][21][22] and since it acts as an epigenetic regulator during neurodevelopment, it has the potential to integrate intrinsic and environmental signals into the shaping of the maturing brain. Here, we demonstrate that 74 and autism spectrum disorder 75,76 ), and genome wide association of loci harboring the RXRG in bipolar disorder 77 and attention deficit hyperactivity disorder 77 , LXRA in autism spectrum disorder 78 , and NR4A2 in major depressive disorder 79 . Gene set and pathway analyses of GWAS data in major depressive disorder and bipolar disorder additionally reveal enrichment of genes implicated with thyroid hormone and retinoic acid signaling 60 as well as genes containing RAR/RXR consensus sequences 79 .…”

Maternal and Foetal Health Implications of Vitamin D Status during Pregnancy

“…Accordingly, Vinkhuyzen et al [81] also showed an association between both mid-gestational and neonatal vitamin D deficiency [25(OH)D concentration less than 25 nmol/L] with autism-related traits at 6 years of age in a large Dutch population-based birth cohort. Moreover, mid-gestation vitamin D deficiency was associated with a higher risk of being diagnosed with clinical ASD [82]. DOI: 10.1159/000487370 In summary, the current evidence indicates that prenatal vitamin D status may impact the risk of ADHD symptoms and ASD later in life; however, the evidence for other neurobehavioral problems is still inconsistent.…”