The Association between Autism Spectrum Disorder and Precocious Puberty: Considering Effect Modification by Sex and Neuropsychiatric Comorbidities

Abstract

Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two medical conditions and effect modification by sex and neuropsychiatric comorbidities in a nationwide population. To compare the risk of precocious puberty between ASD and non-ASD cases, we conducted a Cox regression analysis using ASD as the exposure and time to precocious puberty as the outcome. We adjusted for sex, attention-deficit/hyperactivity disorder (ADHD), tic disorder, obsessive–compulsive disorder (OCD), anxiety disorder, intellectual disability, and epilepsy. We performed a moderation analysis to examine the potential moderating effects of sex and comorbidities. Patients with ASD were prone to have precocious puberty, with an adjusted hazard ratio (aHR) of 1.80 (95% CI: 1.61–2.01). For effect modification, sex, specifically females, moderated the association between ASD and precocious puberty, with a relative excess risk due to interaction (RERI) of 7.35 (95% CI 4.90–9.80). No significant effect modification was found for any of the comorbidities within the scope of additive effect modification. We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders. Girls with ASD are at a particularly higher risk of developing precocious puberty.