(249) Use of Selective Serotonin Reuptake Inhibitors During Pregnancy and The Risk of Child's Neurodevelopmental Disorders

Publication Number: 580

Background: Maternal use of selective serotonin reuptake inhibitors (SSRIs) is common, estimated at 8% in the US. Although the risks to infants from antennal exposure appear to be small, clear quantitative data is missing. Studies have found that higher risk of autistic spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) was associated with maternal exposure to antidepressants during and prior-to pregnancy, as well as with paternal exposure, indicating that there may be residual confounding factors.

Objectives: We aimed to estimate the effects of SSRIs and maternal depression on the child’s risk of ASD and ADHD, using data from electronic health records.

Methods: We used primary care electronic health records of mothers and their children from IMRD-UK (incorporating data from THIN, a Cegedim database). The cohort included 141,974 children of 115,453 mothers, born between 2000-2018. We applied large-scale propensity score matching that included all demographic and clinical covariates (conditions, drugs, observations and procedures) and estimated the hazard ratio (HR) of ASD and ADHD diagnosed at ages 3-10 years using Cox proportional hazards model. We compared the following groups: (1) mothers with history of depression that were either exposed to SSRIs or unexposed to any antidepressant during pregnancy; (2) mothers that used SSRIs before conception and were either exposed or unexposed during pregnancy; (3) mothers unexposed during pregnancy with or without history of depression. To adjust for unmeasured confounding bias, we applied empirical calibration using unrelated health outcomes as negative controls and synthetic positive controls.

Results: The mean follow-up time of the children was 7.1±4.7 years. The prevalence of ASD and ADHD in the cohort were 1.2% and 0.7%, respectively. In patients unexposed to antidepressants during pregnancy (N=133,630), history of depression was associated with an increased risk of ASD (HR 1.30 [1.07,1.59], P=0.01) and ADHD (HR1.32 [1.01,1.74],P=0.04) in the child. In patients with history of depression before pregnancy (N=32,029), children with maternal exposure to SSRIs during pregnancy were at higher risk of ASD (HR 1.52 [1.07,2.53], P=0.02), but not of ADHD (HR 0.97 [0.55,1.67], P=0.93). In patients with pre-conception SSRI use (N=11,980), exposure during pregnancy was associated with increased risk of ASD (HR1.49 [1.03,2.38], P=0.05) and statistically insignificant increased risk of ADHD (HR1.36 [0.84,2.38], P=0.25).

Conclusions: Both maternal depression and SSRI exposure seem to contribute to the increased risk of ASD in the child. However, as the condition and the treatment are tightly coupled, further analysis is required to address possible confounding factors, such as the severity of depression.