April 18, 2017

expert reaction to review and meta analysis on use of antidepressants before and during pregnancy and autism spectrum disorders

Publishing in JAMA Pediatrics, researchers conducted a systematic review and meta-analysis of studies that examined the association between autism spectrum disorders (ASD) and fetal exposure to antidepressants.

Dr Irene Petersen, Reader in Epidemiology and Statistics at UCL, said:

“The authors seem to jump to conclusions based on their analysis of case-control studies despite the fact that their cohort analysis provides no evidence to support their findings.

“There has for some time been a great interest in the exposure on antidepressants in pregnancy and the risk of autism spectrum disorder (ASD).  However, it is a tricky subject to study as with observational data we often cannot separate the effects of drug treatment from other risk factors such as maternal illnesses. The findings from this systematic review by Mezzacappa and colleagues clearly demonstrates these difficulties.

“On one hand, Mezzacappa and colleagues summarise the findings from six case-control studies and conclude that there is a significant association between prenatal antidepressant exposure and ASD (Odds Ratios: 1.81 (95%CI 1.49-2.20)) On the other hand they find no significant associations (hazard ratio, 1.26; 95%CI, 0.91-1.7) when they summarise the findings from two cohort studies. Ironically, the findings in both analyses seems to be driven by studies from the same Danish population registries, but with conflicting results.(1,2)  Interestingly, Mezzacappa and colleagues also find an elevated risk of ASD in children of women who have been treated with antidepressants before pregnancy (OR 1.77; 95%CI, 1.49-2.09).

“The findings from this review suggest that antidepressant treatment may be a ‘marker’ of women who may have an elevated risk of giving birth to a child with ASD. However, I would be very cautious about reaching a conclusion that antidepressants treatment in pregnancy itself is causing autism. With the existing evidence, we still cannot exclude the possibility that it is maternal illnesses linked to ASD – and not the antidepressants.”

1.  Hviid A, Melbye M, Pasternak B. Use of Selective Serotonin Reuptake Inhibitors during Pregnancy and Risk of Autism. N Engl J Med. 2013 Dec 19;369(25):2406–15.
2.  Gidaya NB, Lee BK, Burstyn I, Yudell M, Mortensen EL, Newschaffer CJ. In Utero Exposure to Selective Serotonin Reuptake Inhibitors and Risk for Autism Spectrum Disorder. J Autism Dev Disord. 2014 Oct;44(10):2558–67.
3.  Sørensen MJ, Grønborg TK, Christensen J, Parner ET, Vestergaard M, Schendel D, et al. Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clin Epidemiol. 2013;5:449–59.

* ‘Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure’ by Antonia Mezzacappa et al. will be published in JAMA Pediatrics at 4pm UK time on Monday 17 April, which is also when the embargo will lift. 

Declared interests

None declared