On SAGE Insight: Prenatal and perinatal risk factors and the clinical implications on autism spectrum disorder

From Autism

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Autism spectrum disorder (ASD) is a multi-factorial neurodevelopmental disorder that afflicts approximately 1 in 68 children in the United States and 1 in 100 children in Taiwan.  The development of ASD is associated with a sophisticated collection, both genetic and environmental variables. Prenatal and perinatal factors may increase the risk of autism spectrum disorder. However, little is known about whether unaffected siblings of probands with autism spectrum disorder also share the phenomenon and whether the prenatal/perinatal factors are related to the clinical severity of autistic symptoms.

In this study, researches hypothesized that the prenatal/perinatal factors might be associated with the severity of ASD core symptoms. They first adopted an unaffected sibling design to compare the rates of prenatal/perinatal factors for probands with ASD and their unaffected siblings, relative to that of typically developing controls (TDC). They further tested the relationship between the total number of the prenatal/perinatal factors and the severity of autistic symptoms using several instruments developed for ASD research. There were 323 probands with ASD recruited from the Department of Psychiatry of two medical centers from Northern Taiwan.

As one of few studies examining the prenatal/perinatal factors for ASD using a sibling design and correlating these factors with ASD core symptoms, this study presents the following findings. First, similar to probands with ASD, unaffected siblings had higher frequencies of prenatal/perinatal factors than TDC. Second, probands with ASD had higher total numbers of prenatal/perinatal factors than unaffected siblings. Third, in ASD probands, the total number of prenatal/perinatal factors was associated with overall symptom severity, as well as specific symptoms such as stereotyped behaviors. The novel finding that the number of prenatal/perinatal events in probands was associated with the severity of overall autistic symptoms and stereotyped behaviors is of particular interest. This “dose effect” of prenatal/perinatal events is compatible with a previous finding that the optimality scores were associated with symptom numbers in autism (suggesting a relationship between the extent of environmental adversities and the severity of clinical symptoms. Whether and how the accumulation of factors relate to the clinical expression of ASD warrants further investigation. This article demonstrated that prenatal/perinatal factors occurred more frequently in both ASD probands and their unaffected siblings.

Abstract

Prenatal and perinatal factors may increase the risk of autism spectrum disorder. However, little is known about whether unaffected siblings of probands with autism spectrum disorder also share the phenomenon and whether the prenatal/perinatal factors are related to the clinical severity of autistic symptoms. We compared the frequency of prenatal and perinatal factors among 323 probands with autism spectrum disorder (mean age ± standard deviation, 10.7 ± 3.5 years; males, 91.0%), 257 unaffected siblings (11.7 ± 4.5; 42.8%), and 1504 typically developing controls (8.9 ± 1.6 years; 53.1%); and investigated their effects on the severity of autistic symptoms. We found that probands with autism spectrum disorder and their unaffected siblings had more prenatal/perinatal events than typically developing controls with higher numbers of prenatal/perinatal factors in probands than in unaffected siblings. The prenatal/perinatal events were associated with greater stereotyped behaviors, social-emotional problems, socio-communication deficits, and overall severity. We also found that six prenatal/perinatal factors (i.e. preeclampsia, polyhydramnios, oligoamnios, placenta previa, umbilical cord knot, and gestational diabetes) were associated with the severity of autistic symptoms, particularly stereotyped behaviors and socio-communication deficits. Our findings suggest that prenatal and perinatal factors may potentially moderate the clinical expression of autism spectrum disorder. The underlying mechanism warrants further research.

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Article details

Prenatal and perinatal risk factors and the clinical implications on autism spectrum disorder
Yi-Ling Chien, Miao-Chun Chou, Wen-Jiun Chou,  Yu-Yu Wu, Wen-Che Tsai, Yen-Nan Chiu and Susan Shur-Fen Gau
First Published June 28, 2018 Research Article
DOI: 10.1177/1362361318772813
Autism

     
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