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Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children
Hilary K Brown1, Joel G Ray2, Andrew S Wilton3
1Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada3Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Insights
This study found no significant association between prenatal exposure to serotonergic antidepressants and autism spectrum disorder in children. Previous observations may be explained by confounding factors, not a direct causal link.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Pharmacoepidemiology
Background:
- Previous studies suggested a potential link between maternal antidepressant use during pregnancy and increased risk of autism spectrum disorder (ASD) in children.
- However, these associations may have been influenced by confounding factors, necessitating further investigation.
Purpose of the Study:
- To investigate the association between in utero exposure to serotonergic antidepressants and the subsequent diagnosis of autism spectrum disorder in children.
- To address potential confounding factors through advanced statistical methods.
Main Methods:
- A retrospective cohort study utilizing health administrative data from Ontario, Canada (2002-2010).
- Maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) was defined by prescription records.
- Children were followed until age 2 years for ASD diagnosis, with analyses adjusted using inverse probability of treatment weighting and sibling comparisons.
Main Results:
- The study included 35,906 singleton births, with 7.9% exposed to serotonergic antidepressants during pregnancy.
- Initial analysis showed a higher incidence of ASD in exposed children, but this association was not significant after adjusting for confounding factors using high-dimensional propensity scores.
- Comparison with unexposed siblings also yielded a non-significant association.
Conclusions:
- In utero exposure to serotonergic antidepressants was not associated with an increased risk of autism spectrum disorder in children born to mothers with public drug coverage in Ontario.
- The previously observed association may be attributable to unmeasured confounding factors rather than a direct causal relationship.
Importance:
Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded.
Objective:
To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder.
Design, Setting, And Participants:
Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014.
Exposures:
Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery.
Main Outcomes And Measures:
Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings.
Results:
There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children were compared with unexposed siblings (incidence of autism spectrum disorder was 3.40 per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR, 1.60 [95% CI, 0.69-3.74]).
Conclusions And Relevance:
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.
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