Specificity of Early Childhood Hyperphagia Profiles in Neurogenetic Conditions.

Hyperphagia is highly penetrant in Prader-Willi syndrome (PWS) and has increasingly been reported in other neurogenetic conditions (NGC). The Hyperphagia Questionnaire (HQ) was completed by caregivers of 4-8-year-olds with PWS (n = 17), Angelman syndrome (AS; n = 22), Williams syndrome (WS; n = 25), or low-risk controls (LRC; n = 35). All NGC groups were significantly elevated in HQ Total and Behavior scores compared to LRC. Only AS and WS were significantly elevated in the Drive domain, and only PWS in the Severity domain. After controlling for externalizing behavior, HQ Total scores were higher for PWS relative to other groups. Hyperphagic symptoms may not differentiate PWS from other NGCs in early childhood. However, hyperphagic phenotypes may be most severe in PWS. Further investigation of these profiles may inform etiology and syndrome-specific treatments.

COVID-19 and Food-Related Outcomes in Children with Autism Spectrum Disorder: Disparities by Income and Food Security Status.

BACKGROUND: Limited research suggests increased adverse behavioral outcomes, such as distractibility and hyperactivity, among children with autism spectrum disorder (ASD) as a result of coronavirus 2019 (COVID-19); however, little is known about how the pandemic has impacted food-related behaviors among children with ASD. OBJECTIVE: This study characterizes the impact of the pandemic on access to preferred foods and eating behaviors among children with ASD. METHODS: Caregiver proxies (n = 200) participated in a cross-sectional, online survey investigating the impact of COVID-19 on reported food and eating behaviors of children, ages 2-17 y. Logistic regression models were used to assess the magnitude of association of a change in the child's eating behaviors and in food availability, overall and by household income and food security status. RESULTS: A majority of respondents reported a moderate-to-large impact on their child's eating behaviors (57%) since the onset of COVID-19, and 65% reported unavailability of their child's preferred foods. Increased risk of a moderate-to-large impact on children's eating behaviors was associated with shelter regulations compared with no regulations (OR: 2.30; 95% CI: 1.12, 4.72), food insecurity compared with security status (OR: 2.60; 95% CI: 1.45, 4.67), and household income of <$50,000 compared with ≥$100,000 (OR: 2.33; 95% CI: 1.02, 5.29). The pandemic also amplified the risk of food unavailability by household food security status (food insecure vs. secure; OR: 4.13; 95% CI: 2.12, 7.69) and across income levels (<$50,000 vs. ≥$100,000; OR: 3.48; 95% CI: 1.42, 8.55; and $50,000 to <$100,000 vs. ≥$100,000; OR: 4.00; 95% CI: 1.71, 9.34). Reported frequencies of consumption of meat, seafood, vegetables, and 100% fruit juice significantly decreased among the children post-onset of COVID-19, while frequency of consumption of sweets increased. CONCLUSIONS: A large proportion of caregivers reported substantial COVID-19 impacts on food availability and eating behaviors of children with ASD, especially among low-resource dyads. This study highlights the added burden of existing disparities due to the pandemic on children living with ASD.

COVID-19 and behaviors in children with autism spectrum disorder: Disparities by income and food security status.

BACKGROUND: Research on the impact of the COVID-19 pandemic on behaviors of children with autism spectrum disorder (ASD) is lacking. AIMS: This study investigates the relationship between COVID-19 and behaviors of children with ASD living in the United States. METHODS AND PROCEDURES: Parents and caregivers (n = 200) across the United States, as proxies for children 2-17 years of age with ASD, participated in an online survey querying changes in overall behavior and 15 specific behaviors during the COVID-19 pandemic. Logistic regression was used to assess the association of a moderate-to-large impact on the child's overall behavior with household income level and food security status. OUTCOMES AND RESULTS: A majority of respondents reported a moderate-to-large impact on the child's overall behavior (74 %) due to COVID-19. Several specific behaviors were also affected. Stratifying by income level and food security status revealed disparities in the impact on overall behavior and most specific behaviors. Compared to a household income ≥$100 K, an income <$50 K was associated with an increased risk of moderate-to-large impact on the child's overall behavior (odds ratio (OR): 4.07, 95 % CI: 1.60, 10.38). Food insecurity also significantly impacted this risk, even after adjusting for potential confounding factors (OR: 3.31, 95 % CI: 1.13, 9.66). CONCLUSIONS AND IMPLICATIONS: Our findings show a large proportion of caregivers reporting moderate-to-large changes post-COVID-19 in the behaviors of U.S. children with ASD, particularly in families with low income and/or food insecurity. This study highlights the effects of existing disparities on children with ASD and their families during this unprecedented time.

Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder.

BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI - 0.46, 0.88 and 0.10; 95% CI - 0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d - 0.96; 95% CI - 1.73, - 0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p < 0.001). There were significant changes with SF compared to PL in biomarkers of glutathione redox status, mitochondrial respiration, inflammatory markers and heat shock proteins. Clinical laboratory studies confirmed product safety. SF was very well tolerated and side effects of treatment, none serious, included rare insomnia, irritability and intolerance of the taste and smell. LIMITATIONS: The sample size was limited to 45 children with ASD and we did not impute missing data. We were unable to document significant changes in clinical assessments during clinical visits in those taking SF compared to PL. The clinical results were confounded by placebo effects during the open-label phase. CONCLUSIONS: SF led to small yet non-statistically significant changes in the total and all subscale scores of the primary outcome measure, while for secondary outcome measures, caregivers' assessments of children taking SF showed statistically significant improvements compared to those taking PL on the ABC but not the SRS-2. Clinical effects of SF were less notable in children compared to our previous trial of a SF-rich preparation in young men with ASD. Several of the effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (NCT02561481) on September 28, 2015. Funding was provided by the U.S. Department of Defense.

Trends in Nutrient- and Non-Nutrient-Containing Dietary Supplement Use among US Children from 1999 to 2016.

OBJECTIVES: To characterize dietary supplement use among US children, including product type, motivations, user characteristics, and trends over time with a primary focus on non-vitamin/non-mineral dietary supplements (NVNM). STUDY DESIGN: Overall, NVNM, and vitamin and/or mineral dietary supplement only (VM-only) use; motivations for use; and trends in use over time were examined in children (≤19 years of age) using the National Health and Nutrition Examination Survey 1999-2016 data (n = 42 510). RESULTS: Between 1999 and 2016, overall dietary supplement and VM-only dietary supplement use among all children remained relatively stable at ∼30%; yet, NVNM dietary supplement use increased from 2.9% to 6.4%, mainly due to increased use of omega-3 polyunsaturated fatty acids. NVNM use was greater in boys than in girls (3.9% vs 3.3%), and greater in older children than in younger children (Ptrend < .0001), the opposite of what was observed with VM-only dietary supplement use. Although both user groups shared 2 primary motivations, both motivations were reported by a significantly greater percent of vitamin and/or mineral dietary supplement users vs NVNM users: to maintain health (38.7% vs 23.1%) and to improve health (33.1% vs 22.6%). NVNM users were much more likely to use dietary supplement for relaxation, stress, and sleep; for mental health; and for colon and bowel health. CONCLUSIONS: Although the prevalence of any dietary supplement and VM-only dietary supplement use among US children has both remained stable, the prevalence of NVNM use has increased substantially over time. Yet, NVNM use remains relatively low overall. NVNM use exhibited different patterns by sex, age, and motivations when compared with vitamin and/or mineral dietary supplement use. Despite increasing NVNM use, high-quality evidence supporting their use is lacking, especially in children.

Maternal Dyslipidemia, Plasma Branched-Chain Amino Acids, and the Risk of Child Autism Spectrum Disorder: Evidence of Sex Difference.

In contrast to the well-observed associations between obesity, diabetes, and autism spectrum disorder (ASD), the roles of maternal dyslipidemia and sex disparity in ASD have not been well-studied. We examined the joint associations of maternal plasma cholesterols, branched-chain amino acids (BCAAs) and child sex on child ASD risk. We analyzed data from 756 mother-infant pairs (86 ASD) from the Boston Birth Cohort. Maternal plasma cholesterols and BCAAs were measured in samples collected 24-72 h postpartum. We found that in this urban, low-income prospective birth cohort, low maternal high-density lipoprotein cholesterol (HDL-C), above-median maternal plasma BCAA concentrations, and male sex additively or synergistically increased risk of ASD. Additional studies are necessary to confirm our findings.

Maternal Obesity/Diabetes, Plasma Branched-Chain Amino Acids, and Autism Spectrum Disorder Risk in Urban Low-Income Children: Evidence of Sex Difference.

Maternal metabolic conditions are known risk factors for child autism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of child ASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72 hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019, 12: 1562-1573. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study investigated whether maternal obesity/diabetes and maternal circulating branched-chain amino acids (BCAAs) can jointly affect child ASD risk and whether the associations differ by child's sex. We found that the risk of ASD was greater among mothers with obesity/diabetes who also had elevated concentrations of BCAAs and that this risk was even greater for male children. These findings provide new evidence on fetal origins of ASD and sex difference and warrant additional investigation.

A Strategy to Deliver Precise Oral Doses of the Glucosinolates or Isothiocyanates from Moringa oleifera Leaves for Use in Clinical Studies.

The tropical tree Moringa oleifera produces high yields of protein-rich leaf biomass, is widely used as a food source, contains an abundance of phytochemicals, and thus has great potential for chronic disease prevention and perhaps, treatment. We have developed and characterized standardized ways of preparing aqueous "teas" from moringa leaves to deliver precisely calibrated levels of phytochemicals for use in clinical trials. These phytochemicals, especially the glucosinolate glucomoringin and the isothiocyanate moringin, produced from it following hydrolysis by the enzyme myrosinase, provide potent anti-inflammatory and cytoprotective indirect antioxidant activity. The taste of both hot and cold teas is palatable without the need for flavor masking. These teas can be easily and reproducibly prepared in underserved tropical regions of the world where moringa is cultivated. Isothiocyanate yield from a cold extraction was rapid and essentially complete after 30 min and its anti-inflammatory potential is comparable to that of equimolar purified moringin. A preparation similar to this may be safe to consume with respect to its bacterial titer even after 48 h without refrigeration. Thus, facile delivery of moringa tea to both adults and children for clinical evaluation of their effects on such conditions as autism, diabetes, and hypertension, is now possible.

Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis.

Crucifers and related vegetables and supplements for neurologic disorders: what is the evidence?

PURPOSE OF REVIEW: Neurologic disorders have varied pathophysiology, yet many of them appear to have core molecular pathways that are aberrant. We review the evidence that a dietary component may have utility in ameliorating or preventing at least some of them. RECENT FINDINGS: The weight of evidence supporting prescriptive dietary recommendations to promote or enhance healthspan has been building for decades. Cruciferous vegetables are a key part of the arsenal of nutrition-based approaches for reducing the burden of chronic disease. Much new evidence suggests that neurological disorders are among the potential targets for this approach. This evidence includes at least nine clinical studies of neurodevelopmental conditions like autism spectrum disorder and schizophrenia, and there are a great many studies in animal model systems, of neurodegenerative disorders like Alzheimer's and Parkinson's diseases. This review highlights the most bioactive and most well-studied compounds from crucifers - the isothiocyanates, in particular sulforaphane. SUMMARY: There is great promise for the regular use of cruciferous vegetables or supplements containing standardized levels of bioactives in the treatment and prevention of neurologic disorders. Many clinical and animal studies are underway, and the evidence is building to support this strategy.