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Reviewing the Literature: SSRIs in Pregnancy and Association with Autism Vivien Burt, MD, PhD The Women’s Life Center Resnick Neuropsychiatric Hospital at UCLA

Association Between Antidepressant Use in Pregnancy and ASD 1 Only with SSRIs Confounding by indication With SSRIs + other antidepressants 2 Only with SSRIs 3 3 Case-control studies Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Hendrick, V. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorders. Archives of general psychiatry, 68(11), 1104-1112. Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013). Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. Bmj, 346, f2059. Harrington, R. A., Lee, L. C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2014). Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics, peds-2013.

“SSRI Use During Pregnancy Linked to Autism and Developmental Delay in Boys” Science News; April 15, 2014 Harrington, R. A., Lee, L. C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2014). Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics, peds-2013.

> Half a million children ~ 9,000 prenatal exposures to SSRIs Danish Registry Study Risk of autism 2% with SSRIs 1.5% without SSRIs Sørensen, M. J., Grønborg, T. K., Christensen, J., Parner, E. T., Vestergaard, M., Schendel, D., & Pedersen, L. H. (2013). Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clinical epidemiology, 5, 449.

> Half a million children ~ 9,000 prenatal exposures to SSRIs Prenatal affective disorders Danish Registry Study Risk of autism No significant association between ASD and SSRIs Sørensen, M. J., Grønborg, T. K., Christensen, J., Parner, E. T., Vestergaard, M., Schendel, D., & Pedersen, L. H. (2013). Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clinical epidemiology, 5, 449.

Revisiting Autism Cohort study If any risk: confounding by indication Maternal depression No risk of ASD Cohort study Hviid, A., Melbye, M., & Pasternak, B. (2013). Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism.  New England Journal of Medicine, 369(25), 2406-2415.

Problems with Studies on SSRIs in Pregnancy and Autism Association No randomized controlled studies of antidepressants in pregnancy Residual confounds, such as: Genetic Behavioral Environmental Some studies cover the same population.  Some studies arrive at conclusions not explainable by their own data. Studies do not always arrive at the same conclusions.  Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Hendrick, V. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorders. Archives of general psychiatry, 68(11), 1104-1112. Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013). Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. Bmj, 346, f2059.

Meta-analysis 4 Case-control studies Cohort study No risk for ASD with first trimester SSRIs Association between first trimester SSRIs and ASD Brown, H. K., Hussain-Shamsy, N., Lunsky, Y., Dennis, C. E., & Vigod, S. N. (2017). The association between antenatal exposure to selective serotonin reuptake inhibitors and autism: a systematic review and meta-analysis.

Swedish Population Registry Accounted for: Family Timing of exposure Results Paternal factors Swedish Population Registry First trimester exposure to antidepressants not associated with risk for ASD Sujan, A. C., Rickert, M. E., Öberg, A. S., Quinn, P. D., Hernández-Díaz, S., Almqvist, C., ... & D’Onofrio, B. M. (2017). Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. Jama, 317(15), 1553-1562.

Summary: Meta-Analysis of Prenatal Antidepressants and the Risk of Autism  Exposure to antidepressants in pregnancy is associated with a significantly increased risk of ASD. Findings diminished in magnitude and significance when adjusted for confounding variables. Antidepressants are associated with an increased risk of ASD even in preconception periods.  Andrade, C. (2017). Antidepressant Exposure During Pregnancy and Risk of Autism in the Offspring, 1: Meta-Review of Meta-Analyses.

Discuss ASD risk with patients. It’s understandable that women are concerned. Case-control studies may identify associations but overestimate the magnitude of risk.

Key Points Although some studies suggest an increased risk for ASD with prenatal exposure to antidepressants, when confounders by indication are addressed, this risk is reduced and often nonexistent. Treating maternal mental illness is important to address women’s psychiatric suffering and to reduce the risk for impairment and negative offspring outcomes.

Next Presentation Treating Depression in Pregnancy: Conclusions