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Cortical responses before 6 months of life associate with later autism.

ABSTRACT: Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

SUBMITTER: Lloyd-Fox S

PROVIDER: S-EPMC5900943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) have 2-3 times increased healthcare utilization and annual costs once diagnosed, but little is known about their utilization patterns early in life. Quantifying their early health system utilization could uncover condition-specific health trajectories to facilitate earlier detection and intervention. Patients born 10/1/2006-10/1/2016 with ≥ 2 well-child visits within the Duke University Health System before age 1 were grouped as ASD, ADHD, ASD + ADHD, or No Diagnosis using retrospective billing codes. An additional comparison group was defined by later upper respiratory infection diagnosis. Adjusted odds ratios (AOR) for hospital admissions, procedures, emergency department (ED) visits, and outpatient clinic encounters before age 1 were compared between groups via logistic regression models. Length of hospital encounters were compared between groups via Mann-Whitney U test. In total, 29,929 patients met study criteria (ASD N = 343; ADHD N = 1175; ASD + ADHD N = 140). ASD was associated with increased procedures (AOR = 1.5, p < 0.001), including intubation and ventilation (AOR = 2.4, p < 0.001); and outpatient specialty care, including physical therapy (AOR = 3.5, p < 0.001) and ophthalmology (AOR = 3.1, p < 0.001). ADHD was associated with increased procedures (AOR = 1.41, p < 0.001), including blood transfusion (AOR = 4.7, p < 0.001); hospital admission (AOR = 1.60, p < 0.001); and ED visits (AOR = 1.58, p < 0.001). Median length of stay was increased after birth in ASD (+ 6.5 h, p < 0.001) and ADHD (+ 3.8 h, p < 0.001), and after non-birth admission in ADHD (+ 1.1 d, p < 0.001) and ASD + ADHD (+ 2.4 d, p = 0.003). Each condition was associated with increased health system utilization and distinctive patterns of utilization before age 1. Recognizing these patterns may contribute to earlier detection and intervention.

Project description:Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand.To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood.Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data.A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months.The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior.Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale?=?111; performance?=?108; verbal?=?111) and unexposed siblings (scores: full scale?=?111; performance?=?107; verbal?=?111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale?=?-0.2 (95% CI, -2.6 to 2.9); performance?=?0.5 (95% CI, -2.7 to 3.7); and verbal?=?-0.5 (95% CI, -3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior.Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

Project description:BackgroundCanonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed.MethodsVocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome.ResultsNo diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression.LimitationsSmall numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds.ConclusionsLower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

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Cortical responses before 6 months of life associate with later autism.

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