1. In a large nationwide Swedish cohort study, preterm and early-term births were associated with a significantly increased risk of developing autism spectrum disorder (ASD) in males and females.
2. The increased risk of ASD was independent of genetic and environmental factors.
Evidence level: 2 (good)
Study Rundown: ASD is prevalent in the general population but causative factors have not yet been fully elucidated. A population-level study using Swedish birth registry data from 4 million individuals sought to explore the relationship between gestational age and ASD as well as the role of sex, and genetic and environmental factors. Those born preterm and at early-term had a significantly increased risk of developing ASD. These results were largely unchanged after accounting for genetic or environmental factors. The risk for autism was highest in the extremely preterm group (6.1%). The strength of this study lies in its large sample size, allowing sufficient statistical power for analyses. However, being a single-nation study, the results may not be generalizable to other ethnic backgrounds. Overall, these findings can assist physicians and parents in understanding the neurodevelopmental risks associated with preterm and early term birth.
In-depth [retrospective cohort]: This is a national cohort study in Sweden analyzing data from 4,061,795 individuals between 1973-2013. The primary variable of interest was gestational age. Multiple covariates were considered including sex, birth year, birth order, maternal BMI, preeclampsia. ASD was diagnosed in 1.4% of the cohort (n=58,404). Relative to full-term birth, the adjusted prevalence ratios (PR) of ASD in those born preterm or early term were 1.40 (95% CI, 1.36-1.45) and 1.12 (1.10-1.14) respectively (p<0.001 for both). Females born preterm had a higher relative risk of ASD than males (PR: 1.53 vs. 1.35). Co-sibling analyses was performed to investigate the impact of shared genetic and environmental factors on ASD risk and led to a slight decline in that risk, from 1.40 (1.36-1.45) to 1.32 (1.29-1.36). Due to being largely independent of covariates and familial factors, these findings suggest a potential causal connection between preterm or early term birth and ASD.
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