RT Journal Article
SR Electronic
T1 Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: a population-based cohort study
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e016368
DO 10.1136/bmjopen-2017-016368
VO 7
IS 12
A1 Fen Yang
A1 Jianping Chen
A1 Mao-Hua Miao
A1 Wei Yuan
A1 Lin Li
A1 Hong Liang
A1 Vera Ehrenstein
A1 Jiong Li
YR 2017
UL http://bmjopen.bmj.com/content/7/12/e016368.abstract
AB 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.