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Background:  This study aimed to explore the main effects of environmental risk factors as well as their interaction effects with miRNA on the risk of autism spectrum disorder (ASD).   Methods:  One hundred fifty-nine ASD children (ASD group) and 159 healthy children (control group), aged 2–6 years, were included in this study. ASD diagnoses were based on DSM-5 criteria. The extensive medical and demographic characterization of the two groups were recorded. MicroRNAs (miRNAs) in serum were detected by qRT-PCR.   Results:  Compared with the control group, the ASD group had significantly higher rates of maternal stress during pregnancy ( p  < 0.001), maternal drinking during pregnancy ( p  = 0.006), threatened abortion ( p  = 0.011), pregnancy-induced hypertension ( p  = 0.032), gestational diabetes ( p  = 0.039), maternal anemia during pregnancy ( p  < 0.001), umbilical cord knot ( p  < 0.001), neonatal jaundice ( p  < 0.001), family psychiatric history ( p  = 0.001), and much lower birth weight ( p  = 0.012). Furthermore, the ASD group had much lower expression levels of hsa-miR-181b-5p ( p  < 0.001) and hsa-miR-320a ( p  < 0.001) and significantly higher levels of hsa-miR-19b-3p ( p  < 0.001). The interactions of hsa-miR-320a and maternal stress during pregnancy (OR = 39.42,  p  < 0.001), hsa-miR-19b-3p and neonatal jaundice (OR = 2.44,  p  < 0.001), and hsa-miR-181b-5p and family psychiatric history (OR = 8.65,  p  = 0.001) could increase ASD risk.   Conclusions:  The dysregulation of hsa-miR-181b-5p, hsa-miR-320a, and hsa-miR-19b-3p could interact with environmental factors, such as maternal stress during pregnancy, neonatal jaundice, and family psychiatric history, to impact the risk of ASD.

Impact of MicroRNAs in Interaction With Environmental Factors on Autism Spectrum Disorder: An Exploratory Pilot Study