الفهرس 
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Abstract
Autism spectrum disorders (ASDs) are a heterogeneous group of a complex neurodevelopmental disorders. ASD cause is still unknown and somewhat controversial. There is increasing evidence that it may be as a result of combination between genetic and environmental factors that play an essential role in early brain development (Cannell, 2010, Kinney et al., 2010, Coleman et al., 2011). One of gene-environment interaction theories proposed was the effect of vitamin D and its deficiency on the children development (Freitag et al., 2010) (Bakare et al., 2011, DeLuca et al., 2013, Neggers, 2014).
Vitamin D is a neurosteroid with an important role in cell proliferation and apoptosis, brain development and function (Holick, 2007)as well as gene regulation, (Ramagopalan et al., 2010, Harms et al., 2011, Sigmundsdottir, 2011) modulation of immune function (Hayes et al., 2003), neuroprotective properties especially against cognitive impairment and neurological conditions (Berquist et al., 2007, Anastasiou et al., 2014, Annweiler et al., 2014).
The primary objective of this study was to examine the efficacy and safety of administering high doses of vitamin D3 for treating autistic behaviour. Secondary outcomes of the study were designed to examine changes in calcium, phosphorous, alkaline phosphatase and parathyroid hormone due to vitamin D supplements that might suggest a potential mechanism of action and to find the possible correlation between the blood vitamin D status and autistic severity. As well as to determine vitamin D status of autistic children and the adequacy of their vitamin D dietary intake compared to dietary reference intake.
This study was a prospective randomized double blinded placebo controlled which included 42 autistic children and 40 healthy matched children, they were allocated to:
group 1(Vitamin D group): 22 children with mean age (7.7±2.5) , mean weight (31.2±9.1) Kgs and mean height (123.7±16.6) cm received vitamin D syrup supplied from Medical Union Pharmaceuticals (MUP) at a dose of 1000 international units (IU) for 3 months according to endocrine society guidelines followed by 1000 IU / day per 25Ibs of body weight according to vitamin D council recommendations .
group 2(Placebo group): 20 children with mean age (6.4 ± 1.9) years, mean weight (23.8 ± 8.2) Kgs and mean height (116 ± 11.8) received placebo (5% glucose syrup with identical taste and colour with vitamin D ). Dosing regimen was the same in both placebo and vitamin D group. Dosing calculation and instructions were written and explained to the study participants care provider by clinical pharmacist.
group 3: 40 healthy controls (19 boys and 34 girls) for diet and sun exposure comparison.
Results showed that no significant differences were observed between the vitamin D, placebo groups and healthy controls in baseline demographics. Autistic children had significantly lower serum levels of 25 hydroxy vitamin D (median 46.5 nmol/l) than healthy children (median 70.89 nmol/l) with P-value <0.001, with 54.7% and 28.65 % being vitamin D deficient and insufficient, respectively. While only 15% of healthy children were vitamin D deficient and 45% were vitamin D insufficient. There was no significant difference between autistic and healthy children in either duration of sun exposure (minutes per week )(P=0.559) or dietary vitamin D content (P=0.42) and by comparing these values to dietary reference intake of 600 IU,both groups had much less than recommended daily intake (P-value <0.001*) with no correlations between Dietary vitamin D intake and serum vitamin D level in both groups .Also there were no correlations between CARS and vitamin D level in autistic group.
After 3 and 6 months of vitamin D therapy there were significant improvements in clinical outcomes of CARS scores in vitamin D than in Placebo (decreasing in CARS scores indicate improvement with P=0.001 and( P<0.001 )respectively . There was significant difference overtime in vitamin D (P<0.001), with no difference in Placebo group (P=1.000).
ATEC scores of both groups were non different at baseline. While, after 3 and 6 months of therapy there was statistically significant difference between both groups (P<0.001) with significant difference overtime in vitamin D (P<0.001) than placebo (P=0.735). There were improvement in both sociability (P=0.007) and sensory (P=0.008) domains after 3 months of vitamin D therapy than placebo. While speech (P=0.022) and health (P=0.007) domains improved after 6 months of therapy.
There was significant difference between both groups regarding CARS and ATEC scores (P<0.001) after 3 and 6 months ,with no difference between percent of change from baseline to 3 months or from 3 to 6 months in both groups (P>0.05). There was no significant difference between 2 groups at baseline in patient severity. While after 3 and 6 months of therapy there was significant difference in percentage of patients in mild-moderate range in vitamin D group than in placebo group with (P <0.001) with no change in the percentage of patients in vitamin D group either after 3 or 6 months of therapy. Vitamin D therapy was generally well tolerated with no serious adverse effects reported.
The Limitation of the current study was:
• The restricted sample size which didn’t allow us to consider other dosing regimens.
• At the onset of conducting the present study there were no controlled trials assessing vitamin D as an intervention in autism which made it difficult to make prior power analysis