Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: a population-based cohort study

Objective: The present study aimed to examine the association between paternal selective serotonin reuptake inhibitor (SSRI) use before conception and the risk of autism spectrum disorder (ASD) in offspring.

Design: A population-based cohort study.

Methods: We conducted a cohort study of 669 922 children born from 1998 to 2008, with follow-up throughout 2013. Based on Danish national registers, we linked information on paternal use of SSRIs, ASD diagnosed in children and a range of potential confounders. The children whose fathers used SSRIs during the last 3 months prior to conception were identified as the exposed. Cox regression model was used to estimate the HR for ASD in children.

Results: Compared with unexposed children, the exposed had a 1.62-fold higher risk of ASD (95% CI 1.33 to 1.96) and the risk attenuated after adjusting for potential confounders, especially fathers' psychiatric conditions (HR=1.43, 95% CI 1.18 to 1.74). When extending the exposure window to 1 year before conception, the increased risk persisted in children of fathers using SSRIs only from the last year until the last 3 months prior to conception (HR=1.54, 95% CI 1.21 to 1.94) but not in children of fathers using SSRIs only during the last 3 months prior to conception (HR=1.17, 95% CI 0.75 to 1.82). We also performed stratified analyses according to paternal history of affective disorders and observed no increased ASD risk among children whose father had affective disorders. Besides, the sibling analysis showed that the ASD risk did not increase among exposed children compared with their unexposed siblings.

Conclusions: The mildly increased risk of ASD in the offspring associated with paternal SSRI use before conception may be attributable to paternal underlying psychiatric indications related to SSRI use or other unmeasured confounding factors.