Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder.

BACKGROUND: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. METHODS: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. RESULTS: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). CONCLUSIONS: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development.

Breastfeeding patterns in infants are associated with a later diagnosis of autism Spectrum disorder.

Breastfeeding is associated with medical and developmental benefits. This study aimed to assess associations between nutritional patterns in the first year of life and the likelihood of autism spectrum disorder (ASD). 270 children diagnosed with ASD (cases) and 500 neurotypical children (controls) matched to cases by sex, ethnicity, and birth date (± 3 months) were included in this retrospective case-control study. Both groups were ascertained from children born between 2014 and 2017 whose development/nutrition were monitored at mother-child health clinics in southern Israel. Conditional logistic regression was used to determine the independent association of nutritional patterns with ASD while adjusting for socio-demographic and clinical characteristics. Both exclusive and partial breastfeeding modes were associated with decreased odds of ASD diagnosis (aOR = 0.221, 95%CI = 0.136-0.360; aOR = 0.494, 95%CI = 0.328-0.743, respectively). A breastfeeding duration of >12 months was associated with lower ASD odds (aOR = 0.418, 95%CI = 0.204-0.855), while the introduction of solids after 6 months of age was associated with higher ASD odds than the introduction of solids at 6 months (aOR = 2.455, 95%CI = 1.116-4.201). These findings suggest that a longer period of exclusive breastfeeding is associated with a subsequent reduced likelihood of ASD diagnosis, thus reiterating the importance of proper post-natal nutrition for infant neurodevelopment.

Adherence to treatment and parents' perspective about effectiveness of melatonin in children with autism spectrum disorder and sleep disturbances.

OBJECTIVE: Melatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking. METHODS: In this retrospective cohort study, we assessed the adherence to melatonin treatment and parents' perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence. RESULTS: Melatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036-0.565; and aHR = 0.195, 95%CI = 0.047-0.806, respectively). CONCLUSIONS: Based on parents' report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.