Early life environmental factors associated with autism spectrum disorder symptoms in children at age 2 years: A birth cohort study

Autism ◽  
2022 ◽  
pp. 136236132110682
Author(s):  
Cindy Pham ◽  
Christos Symeonides ◽  
Martin O’Hely ◽  
Peter D Sly ◽  
Luke D Knibbs ◽  
...  

Mounting evidence finds that early life environmental factors increased the probability of autism spectrum disorder. We estimated prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93; 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status; maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress; prenatal alcohol; environmental air pollutant exposures, including particulate matter < 2.5 µm at birth, child secondhand tobacco smoke exposure at 12 months, dampness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression, and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways. Lay abstract Mounting evidence indicates the contribution of early life environmental factors in autism spectrum disorder. We aim to report the prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93; 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status; maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress; maternal lifestyle factors, such as prenatal alcohol and environmental air pollutant exposures, including particulate matter < 2.5 μm at birth, child secondhand tobacco smoke at 12 months, dampness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways.

2019 ◽  
Author(s):  
Celia Rasga ◽  
João Xavier Santos ◽  
Ana Leonie Lopes ◽  
Ana Rita Marques ◽  
Joana Vilela ◽  
...  

ABSTRACTBackgroundAutism Spectrum Disorder (ASD) is a pervasive and clinically heterogeneous neurodevelopmental disorder characterized by deficits in social communication and interaction skills, and repetitive and stereotyped behaviours. It is known that ASD has a strong genetics component, but heritability estimates of 50-80% suggest that modifiable non-genetic factors may play an important role in the onset of the disorder. Recently, pre-, peri and post-natal exposure to a variety of environmental factors has been implicated in ASD. Yet, the comprehensive assessment of environmental exposures in this pathology, using large population datasets, is still lacking. The objective of this study was to pilot an environmental exposure assessment tool in Portugal.MethodsTo examine environmental exposures in a population of Portuguese children with ASD, we translated, adapted and piloted the Early Life Exposure Assessment Tool (ELEAT). The ELEAT was originally developed to assess environmental factors in studies of neurodevelopmental disorders. It is a questionnaire filled by mothers of children with ASD, enquiring about Demographic Information, Maternal Conditions/Medical Interventions, Breastfeeding and Child Diet, Maternal Diet, Supplements, Lifestyle, Home and Environment, Environment, Occupation and Exposures. The ELEAT gathers information about environmental exposure along key phases for early neurodevelopment, from 3 months prior to conception, pregnancy, labor and delivery to the first year of life of the child. Two focus groups were realized, one with mothers of typically-developing children and another with mothers of children with ASD, in order to discuss the mothers opinion regarding the tool comprehensiveness and relevance.ResultsThe large majority of mothers were sure about their answers for all modules, with a small fraction of the group reporting difficulties for the Occupations/Exposures module. Most mothers considered the ELEAT to be a little too long, but generally found that the instructions were clear and, most importantly, agreed that the questions were important.ConclusionsIntegration of the pilot feedback will allow us to enhance the tool and optimize its usage in Portuguese-speaking communities, improving its capacity to assemble accurate environmental data from diverse cultural settings, and to be extended to larger population datasets. Combined with genetic and clinical data, the ELEAT will contribute to the identification of modifiable lifestyle and environmental risk factors for ASD. Such evidence may eventually provide the opportunity for disease prevention or reduced severity by mitigating exposure when genetic susceptibility is identified early in life.


2020 ◽  
Vol 14 (2) ◽  
pp. 170-174
Author(s):  
Koichi Kawada ◽  
Nobuyuki Kuramoto ◽  
Seisuke Mimori

: Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristina Cheroni ◽  
Nicolò Caporale ◽  
Giuseppe Testa

Abstract The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals’ genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment.


2020 ◽  
Vol 174 (7) ◽  
pp. 690 ◽  
Author(s):  
Karen Frankel Heffler ◽  
Danielle M. Sienko ◽  
Keshab Subedi ◽  
Kathleen A. McCann ◽  
David S. Bennett

Autism ◽  
2017 ◽  
Vol 22 (3) ◽  
pp. 377-384 ◽  
Author(s):  
For-Wey Lung ◽  
Tung-Liang Chiang ◽  
Shio-Jean Lin ◽  
Meng-Chih Lee ◽  
Bih-Ching Shu

The use of assisted reproduction technology has increased over the last two decades. Autism spectrum disorders and assisted reproduction technology share many risk factors. However, previous studies on the association between autism spectrum disorders and assisted reproduction technology have shown inconsistent results. The purpose of this study was to investigate the association between assisted reproduction technology and autism spectrum disorder diagnosis in a national birth cohort database. Furthermore, the results from the assisted reproduction technology and autism spectrum disorder propensity score matching exact matched datasets were compared. For this study, the 6- and 66-month Taiwan Birth Cohort Study datasets were used (N = 20,095). In all, 744 families were propensity score matching exact matched and selected as the assisted reproduction technology sample (ratio of assisted reproduction technology to controls: 1:2) and 415 families as the autism spectrum disorder sample (ratio of autism spectrum disorder to controls: 1:4). Using a national birth cohort dataset, controlling for the confounding factors of assisted reproduction technology conception and autism spectrum disorder diagnosis, both assisted reproduction technology and autism spectrum disorder propensity score matching matched datasets showed the same results of no association between assisted reproduction technology and autism spectrum disorder. Further study on the detailed information regarding the processes and methods of assisted reproduction technology may provide us with more information on the association between assisted reproduction technology and autism spectrum disorder.


2019 ◽  
Vol 25 (10) ◽  
pp. 2556-2566 ◽  
Author(s):  
John P. Hegarty ◽  
Luiz F. L. Pegoraro ◽  
Laura C. Lazzeroni ◽  
Mira M. Raman ◽  
Joachim F. Hallmayer ◽  
...  

Abstract Atypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6–15 years) were recruited to participate in this study. T1-weighted MRIs (n = 164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.


2017 ◽  
Vol 15 (03) ◽  
pp. 099-104
Author(s):  
Takeo Kubota

AbstractThe number of children with autism spectrum disorder (ASD) has increased in many countries over the past 10 years. Genetic studies have revealed that ASD is caused by mutations in the genes coding proteins related to neuronal function. However, such genetic abnormalities cannot underlie the increase in this disorder since mutations do not accumulate among children in the short-term. Epigenetics is a mechanism that is involved in gene regulation not by changing DNA sequence (mutations) but by changing the chemical modifications of DNA and histone proteins. Current studies suggest that mental stress and other forms of environmental stress in early life alter the epigenetic status of genes and change the neuronal gene function, resulting in persistent behavioral abnormalities. Therefore, it can be speculated that the current increase in the prevalence of ASD is partially caused by epigenetic changes in the brains of children induced by some recent socio-environmental conditions. However, epigenetic changes are reversible. Indeed, it has been demonstrated that some drugs for mental disorders reverse the altered epigenetic state and recover the expression of neuronal genes. It has also been demonstrated that offering an appropriate nurturing environment in early life reverses the altered epigenetic state and recovers the neurological gene function in mouse models of ASD. Therefore, from the epigenetic point of view, early medical and educational interventions may be important for children with ASD.


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