The Association Between Preterm Birth and the Risk of Autism Spectrum Disorder: A Systematic Review

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex etiology involving genetic and environmental factors. Preterm birth, a significant global health issue, has been frequently identified as a potential risk factor, but a comprehensive synthesis of the evidence is needed. This systematic review aimed to evaluate and synthesize the current evidence on the association between preterm birth and the risk of ASD. The review was conducted following the PRISMA guidelines. A systematic search of PubMed, Web of Science, SCOPUS, and Science Direct was performed. Two independent reviewers screened titles, abstracts, and full-text articles. Observational studies investigating the association between preterm birth and ASD were included. Data were extracted using a standardized form, and the risk of bias was assessed using the Newcastle-Ottawa Scale. Results demonstrated a significant association between preterm birth and an increased risk of ASD, characterized by a strong dose-response relationship where risk escalates with decreasing gestational age. For instance, one large cohort study reported adjusted prevalence rate of 3.72 for boys born extremely preterm. This association was largely independent of shared genetic and environmental factors, as shown in co-sibling analyses. Studies reported alarmingly high ASD prevalence rates, up to 20.8%, in very preterm cohorts. Preterm birth is a major, independent risk factor for ASD, with a clear inverse relationship between gestational age and risk. The findings underscore the critical need for systematic developmental surveillance and early ASD screening in preterm populations. Future research should focus on elucidating the underlying neurobiological mechanisms to inform targeted interventions.

Affiliated Institutions

• Maternity and Children's Hospital SA
• University of Tabuk SA
• King Khaled Hospital SA
• Umm al-Qura University SA
• Northern Border University SA
• Ibn Sina National College for Medical Studies SA

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