fetal autism

The biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies...

OBJECTIVES: Due to the crucial role of polyamines during fetal growth and development, we aimed to determine the effect of prenatal administration of agmatine, an endogenous active metabolite of arginine, and a nutritional supplement, on autistic-like behaviors, oxidative-anti-oxidative profile, and histopathological changes of the prefrontal cortex (PFC) and CA1 area of the hippocampus in valproic acid (VPA) model of autism in male rats. MATERIALS AND METHODS: VPA was injected intraperitoneally on embryonic days (ED) 12...

There is evidence in the literature that youth with intellectual/developmental disabilities (IDD) experience mental health issues to a greater extent compared to youth without IDD. In addition, transition from pediatric to adult services may be a period of increased anxiety and mental health problems for these youth. This study used a retrospective cohort design using population level administrative health data to compare mental health diagnoses between youth with IDD and youth without IDD; particularly examining the period when youth transition from pediatric health services to adult health services...

Autism spectrum disorder (ASD) is a widespread neurodevelopmental disorder with unknown etiology. Dysfunction of several brain areas including the prefrontal cortex (PFC), hippocampus, and cerebellum is involved in cognitive and behavioral deficits associated with ASD. Several studies have reported a reduction in the number of parvalbumin-immunoreactive (PV+ ) neurons in brain areas of ASD patients and animal models such as a shank mutant mouse model and rodents receiving fetal valproic acid (VPA) administration...

Gestational exposure to the anticonvulsant drug valproic acid (VPA) is associated with congenital malformations and neurodevelopmental disorders through its action as a histone deacetylase inhibitor. VPA can elicit placental toxicity and affect placental growth and development. The objective of this study was to evaluate the impact of maternal exposure to VPA on the mouse placenta following exposure on gestational day (GD) 13 since previous studies have shown that mice exposed at this time during gestation give birth to offspring with an autism spectrum disorder-like phenotype...

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that involves functional and structural defects in selective central nervous system (CNS) regions, harming the individual capability to process and respond to external stimuli, including impaired verbal and non-verbal communications. Etiological causes of ASD have not been fully clarified; however, prenatal activation of the innate immune system by external stimuli might infiltrate peripheral immune cells into the fetal CNS and activate cytokine secretion by microglia and astrocytes...

There is an increased incidence of autism among the children of women who take the anti-epileptic, mood-stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration to the pregnant dam revealed that VPA rapidly and significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed...

BACKGROUND: Chromosomal-microarray-analysis (CMA) may reveal susceptibility-loci (SL) of varied penetrance for autism-spectrum-disorder (ASD) and other neurodevelopmental conditions. Attitudes of women/parents to disclosure of SL during pregnancy are understudied. METHODS: A multiple-choice questionnaire was distributed to postpartum women. Data were collected on women's interest to receive prenatal genetic information with various levels of penetrance. RESULTS: Women's (n = 941) disclosure choices were dependent on the magnitude of risk: approximately 70% supported disclosure of either full or 40% penetrance, 53% supported disclosure at a 20% risk threshold, and 40% supported disclosure at 10% or less...

Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts...

BACKGROUND: Preterm birth is often associated with chorioamnionitis and leads to increased risk of neurodevelopmental disorders, such as autism. Preterm birth can lead to cerebellar underdevelopment, but the mechanisms of disrupted cerebellar development in preterm infants are not well understood. The cerebellum is consistently affected in people with autism spectrum disorders, showing reduction of Purkinje cells, decreased cerebellar grey matter, and altered connectivity. METHODS: Preterm rhesus macaque fetuses were exposed to intra-amniotic LPS (1 mg, E...

Autism, also known as an autism spectrum disorder, is a complex neurodevelopmental disorder usually diagnosed in the first three years of a child's life. A range of symptoms characterizes it and can be diagnosed at any age, including adolescence and adulthood. However, early diagnosis is crucial for effective management, prognosis, and care. Unfortunately, there are no established fetal, prenatal, or newborn screening programs for autism, making early detection difficult. This review aims to shed light on the early detection of autism prenatally, natally, and early in life, during a stage we call as "pre-autism" when typical symptoms are not yet apparent...

Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood-brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis...

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition with unknown etiology. Both genetic and environmental factors have been associated with ASD. Environmental exposures during the prenatal period may play an important role in ASD development. This narrative review critically examines the evidence for a relationship between maternal thyroid dysfunction during pregnancy and ASD in the child. Summary: Studies that assessed the associations of hypothyroidism, hyperthyroidism, hypothyroxinemia, thyroid hormone concentrations, or autoimmune thyroid disease with ASD outcomes were included...

Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1, a component of the BRG1-associated factor (BAF) chromatin remodeling complex, as a candidate congenital hydrocephalus (CH) gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, CH-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo...

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts...

Inflammation during pregnancy may occur due to various factors. This condition, in which maternal immune system activation occurs, can affect fetal brain development and be related to neurodevelopmental diseases. MIA interacts with the fetus's brain development through maternal antibodies, cytokines, chemokines, and microglial cells. Antibodies are associated with the development of the nervous system by two mechanisms: direct binding to brain inflammatory factors and binding to brain antigens. Cytokines and chemokines have an active presence in inflammatory processes...

Children from old fathers carry an increased risk for autism spectrum (ASD) and other neurodevelopmental disorders, which may at least partially be mediated by paternal age effects on the sperm epigenome. The brain enriched guanylate kinase associated (BEGAIN) protein is involved in protein-protein interactions at and transmission across synapses. Since several epigenome-wide methylation screens reported a paternal age effect on sperm BEGAIN methylation, here we confirmed a significant negative correlation between BEGAIN promoter methylation and paternal age, using more sensitive bisulfite pyrosequencing and a larger number of sperm samples...

IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH). OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH. DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023...

BACKGROUND: Autism spectrum disorder (ASD) has been associated with intrauterine growth restriction (IUGR), but the underlying mechanisms are unclear. RESULTS: We found that the IUGR rat model induced by prenatal caffeine exposure (PCE) showed ASD-like symptoms, accompanied by altered gut microbiota and reduced production of indole 3-propionic acid (IPA), a microbiota-specific metabolite and a ligand of aryl hydrocarbon receptor (AHR). IUGR children also had a reduced serum IPA level consistent with the animal model...

BACKGROUND: Nutritional status and maternal feeding during the perinatal and postnatal periods can program the offspring to develop long-term health alterations. Epidemiologic studies have demonstrated an association between maternal obesity and intellectual disability/cognitive deficits like autism spectrum disorders (ASDs) in offspring. Experimental findings have consistently been indicating that maternal supplementation with methyl donors, attenuated the social alterations and repetitive behavior in offspring...