Cynthia A. Molloy

Elevated cytokine levels in children with autism spectrum disorder

UNLABELLED This study compared production of IL-2, IFN-gamma, IL-4, IL-13, IL-5 and IL-10 in peripheral blood mononuclear cells from 20 children with autism spectrum disorder to those from matched controls. Levels of all Th2 cytokines were significantly higher in cases after incubation in media alone, but the IFN-gamma/IL-13 ratio was not significantly different between cases and controls. Cases had significantly higher IL-13/IL-10 and IFN-gamma/IL-10 than controls. CONCLUSION Children with ASD had increased activation of both Th2 and Th1 arms of the adaptive immune response, with a Th2 predominance, and without the compensatory increase in the regulatory cytokine IL-10.

Prevalence of Chronic Gastrointestinal Symptoms in Children with Autism and Autistic Spectrum Disorders

The purpose of this study was to estimate the prevalence of chronic gastrointestinal symptoms in a general population of children with autism or autistic spectrum disorder (ASD). The study site was a clinic specializing in ASD in a large pediatric medical center serving a 10 county area in the midwestern USA. In a sample of 137 children, age 24-96 months, classified as having autism or ASD by the Autism Diagnostic Observation Schedule-Generic, 24 percent had a history of at least one chronic gastrointestinal symptom. The most common symptom was diarrhea, which occurred in 17 percent. There was no association between chronic gastrointestinal symptoms and a history of developmental regression. The potential phenotypic association between autism and gastrointestinal symptoms is discussed.

Elevated levels of growth‐related hormones in autism and autism spectrum disorder

Objective  Children with autism are known to have larger head circumferences; whether they are above average in height and weight is less clear. Moreover, little is known about growth‐related hormone levels in children with autism. We investigated whether children with autism were taller and heavier, and whether they had higher levels of growth‐related hormones than control children did.

Nutrient Intake From Food in Children With Autism

OBJECTIVE The impact of abnormal feeding behaviors reported for children with autism spectrum disorders (ASDs) on their nutritional status is unknown. We compared nutrient intake from food consumed by children with and without ASD and examined nutrient deficiency and excess. METHODS Prospective 3-day food records and BMI for children (2–11 years) with ASD participating in the Autism Treatment Network (Arkansas, Cincinnati, Colorado, Pittsburgh, and Rochester) were compared with both the National Health and Nutrition Examination Survey data and a matched subset based on age, gender, family income, and race/ethnicity (N = 252 analyzed food records). RESULTS Children with ASD and matched controls consumed similar amounts of nutrients from food. Only children with ASD aged 4 to 8 years consumed significantly less energy, vitamins A and C, and the mineral Zn; and those 9 to 11 years consumed less phosphorous. A greater percentage of children with ASD met recommendations for vitamins K and E. Few children in either group met the recommended intakes for fiber, choline, calcium, vitamin D, vitamin K, and potassium. Specific age groups consumed excessive amounts of sodium, folate, manganese, zinc, vitamin A (retinol), selenium, and copper. No differences were observed in nutritional sufficiency of children given restricted diets. Children aged 2 to 5 years with ASD had more overweight and obesity, and children 5 to 11 years had more underweight. CONCLUSIONS Children with ASD, like other children in America, consume less than the recommended amounts of certain nutrients from food. Primary care for all children should include nutritional surveillance and attention to BMI.

Use of the Autism Diagnostic Observation Schedule (ADOS) in a clinical setting

The aim of this study was to examine the Autism Diagnostic Observation Schedule (ADOS) as it is commonly used in clinical practice. ADOS classifications were compared to final diagnoses given by a multidisciplinary team to 584 children referred for evaluation for possible autism spectrum disorder (ASD) at the Cincinnati Children’s Hospital Medical Center. A total of 177 children were evaluated with a Module 1 (87 No Words), 198 with a Module 2 (90 < 5 years) and 209 with a Module 3. Of these, 142 (26%) were diagnosed with autism, 185 (32%) with non-autism ASD, and 257 (44%) with non-spectrum disorders. Sensitivities were moderate to high on both original and revised algorithms, while specificities were substantially lower than those previously reported. This difference is likely attributable to the composition of the sample that included many children with a broad array of developmental and behavioral disorders. The clinical impression of the team member who administered the ADOS was critical to the accuracy of the overall diagnosis. Using numeric scores alone resulted in misclassification from false positive results. The study highlights the importance of the qualitative interactions of the ADOS activities as well as the score in diagnostic decision making.

Plasma 25(OH)D concentration in children with autism spectrum disorder

Autism spectrum disorders (ASD) are a class of neurodevelopmental disorders characterized by impairments in communication and social reciprocity, and by the presence of restricted and repetitive interests and behaviors.1 The prevalence of ASD is currently estimated to be 6.7 per 1000 school-age children in the United States,2 making ASD and co-occurring conditions an important public health issue. 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.

Iron Status in Children With Autism Spectrum Disorder

BACKGROUND AND OBJECTIVES Children with autism spectrum disorders (ASDs) often have food selectivity and restricted diets, putting them at risk for nutritional deficiencies. Previous studies have demonstrated a high prevalence of iron deficiency (ID) in children with ASDs living in Wales, Canada, and Turkey. The objectives of this study were to determine the prevalence of ID and the adequacy of iron intake in children with ASD in the United States. METHODS Participants (age 2–11 years recruited from the Autism Treatment Network Diet and Nutrition Study) completed a 3-day diet record (n = 368) and had laboratory measures of serum ferritin (SF), complete blood count, iron, total iron binding capacity, and transferrin saturation (TS) (n = 222). RESULTS Of the 222 participants with laboratory data, 18 (8%) had SF <12 µg/L and 2 (1%) had ID defined by both low SF and TS (3 children with low SF had missing TS data). One subject had iron deficiency anemia. Fewer than 2% of subjects had iron intake below the estimated average requirement. CONCLUSIONS Although the determination of iron status is complex, these data do not support previous reports that children with ASD are at greater risk for ID than the general population; however, 8% percent of the sample did demonstrate low SF despite <2% of the sample demonstrating iron intake below the estimated average requirement. The prevalence of low SF may be an underestimate, because SF is an acute phase reactant and the study included no measure of inflammation.

Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders

Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4-8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohens D 0.51-0.66, P>0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner-Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r=0.23, P=0.039), chronologic age (r=0.35, P=0.001), and skeletal age (r=0.42, P<0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children.