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

3. Association Between Antidepressant Use in Pregnancy and ASD1
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),
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.

4. “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.

5. > 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.

6. > 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.

7. 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),

8. 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),
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.

9. 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.

10. 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),

11. 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.

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

13. 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.

14. Next Presentation Treating Depression in Pregnancy: Conclusions