1. Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children
Hilary K. Brown, PhD; Joel G. Ray, MD, MSc, FRCPC; Andrew S. Wilton, MSc; Yona Lunsky, PhD, CPsych; Tara Gomes, MHSc; Simone N. Vigod, MD, MSc, FRCPC
JAMA. 2017
Date:2017/08/22
Presenter: Wen Ching Lan

2. Depression is one of the most common complications during pregnancy, affecting 1 in every 10 women.
In a study of 15 health insurance plans in the United States, 6% of pregnant women had taken selective serotonin reuptake inhibitor (SSRI) antidepressants.
Animal studies suggest that in utero exposure to SSRIs could lead to dysfunctional serotonin signaling and loss of serotonin terminals in exposed fetuses, resulting in the autism phenotype.

3. AIM
To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder.

4. Methods Data Sources and Study Cohort Retrospective cohort study
Health administrative data from Ontario, Canada
The data were analyzed at the Institute for Clinical Evaluative Sciences.
Births were identified using the MOMBABY database

5. We considered singleton children born in Ontario hospitals between April 1, 2002, and March 31, 2010, whose mothers were between the ages of 16 and 50 years.
Date of conception was estimated using the delivery date and gestational age at birth.
Excluded:
1.children born to non-Ontario residents
2.without a valid health card number (<1%)
3.those who died before the age of 2 years.

6. Methods Exposure Status
Serotonergic antidepressant exposure during pregnancy was defined as 2 or more consecutive prescriptions for an SSRI or selective norepinephrine reuptake inhibitor medication filled between conception and delivery .
The unexposed group : no serotonergic antidepressants prescribed during pregnancy or within 90 days prior to conception.

7. Methods Outcome followed up to March 31, 2014.
It was defined as 2 or more outpatient diagnoses by either a pediatrician or psychiatrist.
Follow-up was to a minimum age of 4 years and a maximum age of 10 years.

8. Methods
Covariates
maternal age, parity, neighborhood income quintile, rural residence, medical and psychiatric diagnoses……
high-dimensional propensity score (HDPS)
hospital, emergency department diagnoses and procedures, outpatient fee codes and diagnoses , and prescription drug claims.

9. Methods Main and Other Analyses
Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs using a robust sandwich-type estimator.
Sibling analysis
Recent user analysis

10. Methods Sensitivity Analyses
We conducted a sensitivity analysis matching 1:1 on the HDPS to test the robustness of the findings in an analysis that retained the original size of the exposed group.
outcome risk among children of women prescribed serotonergic antidepressants 90 to 365 days prior to but not during pregnancy was compared with risk among children in the unexposed group.
SAS version 9.2

11. included 35 906 singleton children
There were deliveries to women covered under the public prescription drug plan.
excluded
1501 deliveries to women who filled only 1 prescription for a serotonergic antidepressant during pregnancy.
2210 deliveries to women who filled a prescription within the 90 days prior to pregnancy.
included singleton children
mean gestational age of 38.7 weeks;
(50.4%) were male.
Mothers were a mean age of 26.7 years
2837 (7.9%) were serotonergic
antidepressant users during pregnancy.

12. Results

16. Discussion
Children exposed to serotonergic antidepressants were at higher risk for autism spectrum disorder compared with unexposed children prior to confounder adjustment.
Furthermore, among children whose mothers were prescribed antidepressants shortly before but not during pregnancy, outcome risk was as high compared with unexposed children as it was for exposed children.

17. Discussion Limitations
It was limited to women in Ontario’s publicly funded drug plan.
If prescriptions were filled but not used, creating a bias toward the null.
The outcome definition was restricted in outpatient data to diagnoses made by a pediatrician or a psychiatrist to improve specificity.
There were no data on paternity or postnatal environment characteristics.

18. Conclusions
In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child.
Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.

19. Thank you for listening