Autism Spectrum Disorders in Survivors of Extreme Prematurity

Department of Neurology and Neurosurgery, School of Physical and Occupational Therapy, McGill University, 2300 Tupper Street, Montreal, Quebec, H3H 1P3, Canada.
Clinics in perinatology (Impact Factor: 2.44). 12/2009; 36(4):791-805, vi. DOI: 10.1016/j.clp.2009.07.010
Source: PubMed


Recent studies in survivors of extreme prematurity point to an increased prevalence of a previously underrecognized atypical social-behavioral profile strongly suggestive of an autism spectrum disorder. Prospective studies that incorporate early autism screening and autism diagnostic testing are needed to better delineate the sensitivity and specificity of early signs of autism in ex-premature children. Advances in neonatal MRI techniques capable of quantitative structural and functional measurements will also provide important insights into the effects of prematurity itself, and prematurity-related brain injury on the genesis of autism spectrum disorders in this population. Available evidence linking prematurity and autism spectrum disorders is reviewed in this article.

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    • "Indeed, among children born weighing < 2000 g, the prevalence of autism spectrum disorder is 5%—a value approximately five times higher than that seen in the general population (Pinto- Martin et al., 2011). It has been argued, however, that the " autistic phenotype " of preterm children represents a milder form of the disorder seen in full-term children (Indredavik, Vik, Skranes, & Brubakk, 2008) and reflects the effects of brain injuries and altered neurodevelopment associated with very premature birth (Johnson & Marlow, 2011; Limperopoulos, 2009). In particular, Movsas et al. (2013) have shown that in low-birth-weight children the risk of screening positive for, or being diagnosed with, an autism spectrum disorder is related to white matter injury but not to isolated germinal matrix/intraventricular hemorrhage (another common type of brain injury affecting premature infants; Volpe, 1995). "
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    ABSTRACT: Biological motion perception can be assessed using a variety of tasks. In the present study, 8- to 11-year-old children born prematurely at very low birth weight (<1500 g) and matched, full-term controls completed tasks that required the extraction of local motion cues, the ability to perceptually group these cues to extract information about body structure, and the ability to carry out higher order processes required for action recognition and person identification. Preterm children exhibited difficulties in all 4 aspects of biological motion perception. However, intercorrelations between test scores were weak in both full-term and preterm children-a finding that supports the view that these processes are relatively independent. Preterm children also displayed more autistic-like traits than full-term peers. In preterm (but not full-term) children, these traits were negatively correlated with performance in the task requiring structure-from-motion processing, r(30) = -.36, p < .05), but positively correlated with the ability to extract identity, r(30) = .45, p < .05). These findings extend previous reports of vulnerability in systems involved in processing dynamic cues in preterm children and suggest that a core deficit in social perception/cognition may contribute to the development of the social and behavioral difficulties even in members of this population who are functioning within the normal range intellectually. The results could inform the development of screening, diagnostic, and intervention tools.
    Child Neuropsychology 08/2014; 21(5):1-26. DOI:10.1080/09297049.2014.945407 · 2.42 Impact Factor
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    • "Of great concern is the fact that these children are also at substantially elevated risk of screening positive for (Kuban et al., 2009; Limperopoulos et al., 2008; Moore, Johnson, Hennessy, & Marlow, 2012), and being diagnosed with (Johnson et al., 2010; Pinto-Martin et al., 2011), an autism spectrum disorder (ASD). The 'autistic phenotype' of preterm children, however , is thought to represent a milder form of the disorder than that seen in full-term children (Indredavik, Vik, Skranes, & Brubakk, 2008), and to arise from a different causative pathway – one that is nongenetic and stems from brain injuries and altered neurodevelopment associated with very premature birth (Johnson & Marlow, 2011; Limperopoulos, 2009). It is important for researchers, clinicians, and educators to understand the core deficits that underlie the social difficulties, and other 'autistic-like' symptoms, displayed by certain preterm children. "
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    ABSTRACT: Research has shown that children born very prematurely are at substantially elevated risk for social and behavioral difficulties similar to those seen in full-term children with autism spectrum disorders (ASDs; e.g., Johnson et al., The Journal of Pediatrics,, 156, 519). To gain insight into core deficits that may underlie these difficulties, in this study, we assessed the social perceptual skills of 8- to 11-year-old children born at very low birthweight (VLBW) (<1,500 g) and age-matched, full-term controls, using the Child and Adolescent Social Perception Measure (Magill-Evans et al., Journal of Nonverbal Behaviour, , 19, 151). We also assessed social and behavioral outcomes with two parent-report measures used in ASD screening. Children in the preterm group had normal range estimated verbal IQ. However, we found that they were impaired in their ability to use nonverbal cues from moving faces and bodies, and situational cues, to correctly identify the emotions of characters depicted in videotaped social interactions. Their performance on this task was related to the number of 'autistic-like' traits they displayed. This research highlights links between social perceptual deficits and poor social and behavioral outcomes in children born very prematurely. The results also suggest that even those who have escaped major intellectual/language problems are at risk for social and behavioral problems that can be of clinical concern.
    Journal of Child Psychology and Psychiatry 02/2014; 55(9). DOI:10.1111/jcpp.12210 · 6.46 Impact Factor
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    • "Infants born between 32 and 36 weeks account for a significant increase in the rate of prematurity in the recent years [22] and are also at risk for neurologic injury [23-26]. Studies evaluating neurobehavioral outcomes following preterm birth reveal a “preterm behavioral phenotype” characterized by inattention, anxiety and social interaction difficulties, and learning difficulties [27,28]. "
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    ABSTRACT: Background Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by varying deficits in social interactions, communication, and learning, as well as stereotypic behaviors. Despite the significant increase in ASD, there are few if any clues for its pathogenesis, hampering early detection or treatment. Premature babies are also more vulnerable to infections and inflammation leading to neurodevelopmental problems and higher risk of developing ASD. Many autism “susceptibility” genes have been identified, but “environmental” factors appear to play a significant role. Increasing evidence suggests that there are different ASD endophenotypes. Discussion We review relevant literature suggesting in utero inflammation can lead to preterm labor, while insufficient development of the gut-blood–brain barriers could permit exposure to potential neurotoxins. This risk apparently may increase in parents with “allergic” or autoimmune problems during gestation, or if they had been exposed to stressors. The presence of circulating auto-antibodies against fetal brain proteins in mothers is associated with higher risk of autism and suggests disruption of the blood–brain-barrier (BBB). A number of papers have reported increased brain expression or cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines, especially TNF, which is preformed in mast cells. Recent evidence also indicates increased serum levels of the pro-inflammatory mast cell trigger neurotensin (NT), and of extracellular mitochondrial DNA (mtDNA), which is immunogenic. Gene mutations of phosphatase and tensin homolog (PTEN), the negative regulator of the mammalian target of rapamycin (mTOR), have been linked to higher risk of autism, but also to increased proliferation and function of mast cells. Summary Premature birth and susceptibility genes may make infants more vulnerable to allergic, environmental, infectious, or stress-related triggers that could stimulate mast cell release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in an endophenotype of ASD patients.
    BMC Pediatrics 07/2012; 12(1):89. DOI:10.1186/1471-2431-12-89 · 1.93 Impact Factor
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