ABSTRACT
BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.
ABSTRACT
OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.
Subject(s)
Autism Spectrum Disorder , Folic Acid , Vitamin B 12 , Humans , Autism Spectrum Disorder/blood , Autism Spectrum Disorder/etiology , Child, Preschool , Male , Female , Folic Acid/blood , Vitamin B 12/blood , Child , Child DevelopmentABSTRACT
BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).
