Association Between Assisted Reproductive Technology and Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) comprises neurodevelopmental conditions characterized by difficulties in social communication and interaction, together with restricted and repetitive behaviours. Assisted reproductive technology (ART) includes methods used to achieve pregnancy when natural conception is difficult or impossible, and its use has increased markedly in developed countries. Previous studies have suggested a possible association between ART and neurodevelopmental disorders, including ASD, but findings remain inconclusive. The aim of this study was to systematically evaluate the association between ART and ASD by reviewing large population-based cohort studies and performing a meta-analysis. Eligible studies were peer-reviewed cohort studies published in reputable journals, examined ART as the exposure and ASD as the outcome, included more than 500,000 births, provided effect estimates or sufficient data for their calculation, and adjusted for comparable confounders, including maternal age, paternal age, parity, and sociodemographic factors. Five cohort studies, encompassing over 12 million births, met the inclusion criteria. Using a random-effects model, the pooled analysis yielded a hazard risk ratio of 1.26 (95% CI 1.08–1.49), indicating a statistically significant association, although between-study heterogeneity was substantial (I 2  = 74%). These findings suggest a modest association that may be shaped substantially by underlying subfertility and specific procedures rather than ART exposure alone.