Pregnancy exposure to SSRIs and offspring autism risk: debate continues

"It remains unclear whether the association between first trimester SSRI [selective serotonin reuptake inhibitor] exposure and child autism that was present in the case-control studies even after adjustment for MMI [maternal mental illness] is a true association or a product of residual confounding."

So said the results of the systematic review and meta-analysis undertaken by Hilary Brown and colleagues [1] looking at a potentially important association between pregnancy use of a class of medicines typically used as antidepressants (albeit with some caveats [2]) and risk of offspring autism. This topic has previously received some airtime on this blog (see here and see here) and specifically, how maternal mental health - as per the question 'why were mothers taking SSRIs during pregancy?' - might be a rather large confounding variable affecting any possible correlation.

Unfortunately even with the Brown paper, the debates will continue as to whether the SSRI-offspring autism correlation is a 'true' correlation or not. Based on the results of 6 studies - "4 case-control studies and 2 cohort studies" - where MMI was adjusted for/restricted to, authors reported some interesting trends. So in their meta-analysis of the data where results from case-control studies were adjusted for a potential impact from MMI, researchers observed that "first trimester exposure remained statistically significant." In "MMI-restricted analyses" covering the same study type, the collected studies did not show any connection between pregnancy SSRI use and offspring autism during either the first trimester or 'any time during pregnancy'. Similar results were found in the cohort studies included in the Brown paper (although both first trimester and 'any point during pregnancy' SSRI use both showed significant correlations to offspring autism in adjusted studies). I might also add that the Brown meta-analysis on this topic is not the only recent addition to the peer-reviewed literature [3]; indeed, there are several [4] others.

"Future studies require robust measurement of MMI prior to and during pregnancy" said Brown et al. I would agree with this sentiment added to the caveat that we may never truly know whether there is a definitive connection between pregnancy SSRI use and offspring autism risk on the basis of observational studies alone. Yes, I know it is unethical to withhold treatment such as SSRIs when clinically indicated even during pregnancy and so investigations utilising this kind of 'interventionist' study design are not likely to be undertaken anytime soon. But it does strike me that we could do quite a bit more modelling any potential effects (or not) in animal studies for example, as per some investigations with fish a while back (see here) as a start.

And finally, although it is not my place to give clinical or medical advice on this blog, I should point out that much like investigations on another medicine prescribed during pregnancy potentially linked to offspring outcomes (see here), SSRIs are not generally given willy-nilly to pregnant women; there are very valid reasons for managing mum's psychiatric health particularly during pregnancy. If anyone is in doubt, please consult your doctor (and not just Dr Google).

To close, before 'fake news' there was The Day Today (and they did it oh so well)...

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[1] Brown HK. et al. The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. J Clin Psychiatry. 2017 Jan;78(1):e48-e58.

[2] Jakobsen JC. et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017; 17: 58.

[3] Kaplan YC. et al. Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. Reprod Toxicol. 2016 Dec;66:31-43.

[4] Kobayashi T. et al. Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reprod Toxicol. 2016 Oct;65:170-178.

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Brown HK, Hussain-Shamsy N, Lunsky Y, Dennis CE, & Vigod SN (2017). The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. The Journal of clinical psychiatry, 78 (1) PMID: 28129495