One condition that may occur more often in children with ASD than in children with typical development is vitamin D deficiency. Vitamin D is a fat-soluble vitamin, long known to be important in calcium homeostasis and bone health. As evidence has accumulated that vitamin D receptors are present in a wide variety of tissues, vitamin D deficiency has been implicated in numerous disease states.³ Having ASD could potentially put a child at greater risk of vitamin D deficiency secondary to dietary restrictions or decreased exposure to sunlight. Children with ASD may limit their own diet because of sensory aversions or restricted interests. The diet may also be restricted by parents to eliminate exposure to certain dietary proteins, such as the milk protein casein, in an attempt to treat the ASD symptoms.⁴ Children with ASD may have decreased exposure to sunlight because their after-school hours are often devoted to table-based therapies, they do not commonly participate in organized outdoor sports, and their preferred leisure activities often involve video game, computer, or TV screens in an indoor setting.

We previously reported that children with ASD have decreased mean metacarpal bone cortical thickness (BCT) compared with a reference population.⁵ Based on this, our overarching hypothesis is that children with ASD are at risk of decreased bone mineral density compared with typically developing children. For this study our focus was limited to one component contributing to bone mineral density, vitamin D. The aim was to test the hypothesis that children with ASD have a lower concentration of circulating vitamin D – plasma 25(OH)D. We compared plasma concentration of 25(OH)D in Caucasian males with and without ASD and 25(OH)D concentration in males with ASD with and without a casein-free diet.

At the study visit, height and weight were measured. A body mass index (BMI) z-score was calculated based on the Centers for Disease Control and Prevention 2000 growth charts for the United States.⁷ A 20ml blood sample was drawn into a tube containing EDTA, centrifuged and stored at −70°C.

Plasma specimens were available for 71 participants and 69 controls. The nine participants on a casein-free diet were identified and plasma on all nine of these children was assayed. A subset (n=80) of the remaining participants and controls was chosen by a computer-generated table of random digits. Sampling was carried out such that there were eight participants and eight controls per age group (4, 5, 6, 7, and 8y) giving a total of 40 participants and 40 controls. A priori power calculations indicated that this sample size would provide 80% power to detect a 10% difference in 25(OH)D concentration, using a two-tailed t-test, while controlling type I error rate to 5%. The study was approved by the Institutional Review Board of Cincinnati Children’s Hospital Medical Center and parents provided informed consent for all participants.

The median 25(OH)D concentration for participants on a casein-free diet was 19.9ng/mL (range 10.8–31.0ng/mL); for participants not on a casein-free diet it was 19.6ng/mL (range 8.9–30.7ng/mL); for controls it was 17ng/mL (range 7.8–28.3ng/mL; Fig. 1).

Comparison of log_10-transformed values of 25(OH)D concentration by ANOVA did not reveal any significant group differences (p=0.4). On examination of contrasts, there were no significant differences between participants not on a casein-free diet and either controls (p=0.2) or participants on a casein-free diet (p=0.6). No group differences were observed when children receiving calcium-containing supplements (n=5) were removed (p=0.4) or those receiving any supplements (n=13) were removed (p=0.4).

Vitamin D deficiency has become a major health concern in our current society where sunblock and indoor activities have limited sun exposure for children, and dietary sources cannot make up the difference. Results of this study provide additional evidence to support that concern. We expected 25(OH)D concentrations to vary by season of enrollment since exposure to sunlight is so important for vitamin D synthesis, but this expected difference by season was not observed. This could simply be a function of sample size, since the study was not designed to detect this difference. However, this finding could also represent effective use of sunblock during warmer months, keeping the measured 25(OH)D values lower.

Children with ASD in this study were no more likely than their matched controls to have a low 25(OH)D concentration. These results must be interpreted in light of the limitations of the control group. The control children were likely to have had some degree of inflammation which could affect 25(OH)D concentration. They were, however, carefully screened and excluded for steroid use or sleep apnea that might contribute to alterations in growth patterns.

The majority of children in this cohort, participants and controls, had low concentrations of 25(OH)D. This finding should be of concern to all providers of medical care to children, but especially to those managing the care of children with ASD. These children may be at risk of additional threats to calcium homeostasis and bone health as they age. Opportunities for active weight-bearing exercise in sunlight can be limited for children with ASD. At least a quarter of children with ASD will also have chronic gastrointestinal symptoms¹⁰ that could also have an impact on calcium absorption. In addition, up to 46% of them are likely to be diagnosed with co-occurring epilepsy.¹¹ Treatment with certain antiepileptic drugs, including valproic acid, is associated with reduced bone mineral density.¹²

As children with ASD age into adulthood they will be confronted by general chronic health issues such as osteoporosis that affect any aging population. However, these additional medical problems will present greater challenges in people with ASD. We need to better understand the risks and potential preventive measures that can be taken for those individuals while they are still children.