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Infantile spasms (IS) is an age-specific epileptic syndrome. ACTH has been the standard treatment for IS and a large and impressive body of experience has documented the efficacy of ACTH for IS. However, the mechanism of ACTH therapy is still unclear. Using case-control study we found that there was a statistically significant difference in the prenatal stress level among mothers of infants in the three groups. Prenatal stress exposure in children can trigger infantile spasms on the basis of leading causes of symptomatic epilepsy, such as brain dysplasia and inherited metabolic disease. The two may act in combination to cause the occurrence of infantile spasms. (2) It has been shown that the expression of ACTH binding sites on human adrenocortical cells is upregulated after exposure of the cells to ACTH. ACTH not only increases the transcriptional rate of MC2R message but also prolongs the MC2R mRNA half-life According to our results, the TCCT haplotype has not only protective effect on IS, but also has high responses to ACTH treatment. These results based on our in-vitro system may advance understanding of mechanisms of ACTH in IS treatment.