Relationship Between Neonatal Vitamin D at Birth and Risk of Autism Spectrum Disorders: the NBSIB Study

Abstract

Previous studies suggested that lower vitamin D might be a risk factor for autism spectrum disorders (ASDs). The aim of this study was to estimate the prevalence of ASDs in 3-year-old Chinese children and to examine the association between neonatal vitamin D status and risk of ASDs. We conducted a study of live births who had taken part in expanded newborn screening (NBS), with outpatient follow-up when the children 3-year old. The children were confirmed for ASDs in outpatient by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was defined by the intelligence quotient (IQ < 80) for all the participants. The study design included a 1:4 case to control design. The concentration of 25-hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from neonatal dried blood samples. A total of 310 children were diagnosed as having ASDs; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level was significantly lower in children with ASD as compared to controls (p < 0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile: 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5; 95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1 to 3.3; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk relationship was more prominent when the data were assessed in deciles. This model predicted the lowest relative risk of ID in the 72rd percentile (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was significantly associated with the risk of ASDs and intellectual disability. The nature of those relationships was nonlinear. © 2017 American Society for Bone and Mineral Research.

The mTOR Signaling Pathway Activity and Vitamin D Availability Control the Expression of Most Autism Predisposition Genes

“…Thus, vitamin D deficiency has become a major world pandemic [29] and might result in abnormal mTOR activation by itself and increased expressivity of the gene mutations whose transcription is regulated by vitamin D worsened autistic phenotype. The findings that higher concentrations of perinatal/neonatal 25(OH)D3 are associated with a lower risk of ASD additionally support this assumption [32][33][34][35].…”

Newborn vitamin D levels in relation to autism spectrum disorders and intellectual disability: A case–control study in california

“…Interestingly there was no association with 25(OH)D deficiency in cord blood, despite a higher proportion of deficiency, or examining 25(OH)D continuously. A larger study from China [Wu et al, ] also reported increased risk of ASD with 25(OH)D3 deficiency, with some suggestion of a nonlinear pattern with continuous levels. Median (or mean) 25(OH)D levels were lower in these studies compared to ours, perhaps contributing to differences in findings, e.g., 32–60 nmol/L (in control samples where specified) vs. 84 nmol/L in our study.…”

“…Several studies examining the association between vitamin D and ASD were published after Cannell's hypothesis; however, many examined surrogates of vitamin D status, such as latitude or season, or measured vitamin D levels after ASD diagnosis, so are likely to reflect current lifestyle [Du et al, ; Fernell et al, ; Humble et al, ; Meguid, Hashish, Anwar, & Sidhom, ; Molloy, Kalkwarf, Manning‐Courtney, Mills, & Hediger, ; Mostafa & Al‐Ayadhi, ]. Only recently have vitamin D levels (typically as total 25‐hydroxyvitamin D, e.g., 25(OH)D) been measured prenatally or perinatally, a critical period for brain development; two small studies found lower 25(OH)D levels among ASD cases compared with controls but did not adjust for many other factors [Chen, Xin, Wei, Zhang, & Xiao, ; Fernell et al, ], as did a larger study from China [Wu et al, ] that also reported increased ASD risk with neonatal vitamin D deficiency in a thoroughly matched analysis. Other studies with measured perinatal 25(OH)D levels have examined related neurobehavioral metrics, with several finding adverse outcomes associated with lower vitamin D levels [Darling et al, ; Hanieh et al, ; Morales et al, ; Vinkhuyzen et al, ; Whitehouse et al, ].…”

Vitamin D Deficiency During Pregnancy and Autism Spectrum Disorders Development

“…Finally, the degree of VD deficiency was positively associated with ASD severity as defined by scores on the Childhood Autism Rating Scale (CARS). Wu et al (71) examined the associations between neonatal vitamin D status, the expression of maternal VD deficiency, and the risk of ASD development in the first three years after birth. A total of 310 ASD cases and 1,240 controls were studied.…”