Abstract
Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50−1.54 for ASD; 0.97, 95% confidence interval 0.53−1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.
Highlights
As in our prior report, greater maternal age was associated with increased autism spectrum disorder (ASD) risk, while younger maternal age was associated with increased attention-deficit hyperactivity disorder (ADHD) risk
We examined ASD and ADHD risk associated with antidepressant exposure before and during pregnancy (Table 2)
In an effort to clarify the risk for neurodevelopmental disorders associated with prenatal antidepressant exposure, we applied a novel methodology to identify a new and independent cohort of ASD cases, another of ADHD cases, and matched cohorts of healthy control children
Summary
In a previous EHR study in a large health system, we did not detect elevated autism risk after controlling for aspects of maternal psychopathology.[6] elevated ADHD risk—without clear mechanistic explanation—was detected and not fully explained by maternal psychiatric illness. The decision to expose a developing fetus to any medication is a difficult one for parents and clinicians; such a decision may be even more fraught in case of depression and related disorders, where the potential benefits of treatment are still misunderstood by the lay press[7] and clinicians despite evidence that treatment discontinuation increases depressive recurrence risk substantially.[8] we extended our methods to allow matching of children and mothers across different health systems without exposing identifying information, and applied this approach to identify another large, independent cohort of children with ASD and ADHD and matched controls for a replication study
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