A recent paper (Boukhris et al., 2015) raised once again the concern that women who take antidepressants during pregnancy are at increased risk for giving birth to a child who will be diagnosed with Autism Spectrum Disorder. This is not a new finding – a series of papers in recent years have reported similar results (e.g., Rai et al 2013; Sørensen et al., 2013), including those that focused on one particular class of antidepressant, namely the selective serotonin reuptake inhibitors (Croen et al., 2011; Gidaya et al 2014).

Boukhris and colleagues (2015) “conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145,456 singleton full-term infants . . . were included.” Children with ASD were identified by the presence of a health care claim listing any of diagnosis codes associated with an autism spectrum condition.

The analysis corrected for maternal sociodemographic characteristics, history of maternal psychiatric and chronic physical conditions, and infant characteristics as potential confounding variables. The authors reported that “use of during the second and/or third trimester is associated with an 87% increased risk of ASD, even after taking into account potential confounders; no association was observed between use of ADs during the first trimester and the risk of ASD” but they noted that “increased risk was observed with the use of SSRIs only, as well as the use of more than 1 class of , during the second and/or third trimester.”

However, an editorial (King, 2016) published in the same issue as the Boukhris paper raised several methodological questions about the study, further noting that “untreated maternal depression is associated with a host of other complications . . . a recent study . . . suggested that selective serotonin reuptake inhibitors actually reduced several deleterious reproductive outcomes . . .”

Furthermore, research findings on the question of antidepressant use and ASD have not been consistent. A new paper (Castro et al., 2016) based on data from a substantial sample in New England failed to find a relationship, replicating the results of an earlier study (Hviid et al., 2013). Castro and colleagues reported results based on a sample of 1,245 children with ASD, compared to a sample of 3,405 control children, all drawn from a database of electronic health records of hospitals in the Boston area. ASD diagnosis was based on the presence in the record of an ICD code for a pervasive developmental disorder.

Castro and colleagues found that use of antidepressants during pregnancy was not associated with a significant increase in risk for ASD. They noted that a woman’s use of antidepressants before pregnancy, and participation in psychotherapy, were associated with a significant increase in ASD risk, indicating that “the requirement for maternal antidepressant treatment, rather than the medication itself, may be associated with risk for neurodevelopmental disorders in offspring.” In other words, the culprit in terms of increased risk for bearing a child with ASD may be maternal depression itself, rather than the treatment for that depression.

This mixed record of research findings will, perhaps, do little to allay the fears of women anticipating childbirth, or to relieve the sense of guilt of the mothers of children with ASD who took antidepressants during pregnancy. However, there is reasonable doubt about the role that antidepressant medications play in the etiology of autism, such that, at this point, it would be irresponsible to counsel a woman who experiences significant depression to abandon an effective pharmacological treatment if she is pregnant or anticipates becoming pregnant, particularly in light of the fact that the biological effects of serious depression may be more dangerous to the child than medication (Bock et al., 2015).

The fact is that antidepressant treatment during pregnancy is only one of a wide range of potential “causes” of ASD that have been proposed, with supporting data, in recent years; examples include prenatal exposure to endocrine disrupting chemicals (Kalfa et al., 2015), gestational diabetes mellitus (Xiang et al., 2015), birth by Caesarean section (Curran et al., 2014), maternal infection during pregnancy (Atladottir et al., 2010), and any number of unique genetic differences (Betancur, 2011). Continued investigation of how depression and its treatment relate to ASD is certainly indicated, but the state of the science at this point does not justify clinical guidance.

As long as one is living, risk is inevitable; and a decision to bring a child into the world brings with it the “risk” of considerable joy, along with a risk for a whole range of sources of pain. To those mothers of children with ASD who experience a burden of guilt, worrying that their perfectly justified treatment for depression caused their child’s disability, one can only say that the evidence does not warrant such worry; most autism arises from some other source.

References

Atladottir, H. O., Thorsen, P., Ostergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010). Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 40(12), 1423-1430. doi:10.1007/s10803-010-1006-y

Betancur, C. (2011). Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting. Brain Research, 1380, 42-77. doi:10.1016/j.brainres.2010.11.078

Bock, J., Wainstock, T., Braun, K., & Segal, M. (2015). Stress in utero: Prenatal programming of brain plasticity and cognition. Biological Psychiatry, 78(5), 315-326. doi:10.1016/j.biopsych.2015.02.036

Boukhris, T., Sheehy, O., Mottron, L., & Berard, A. (2016). Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatrics, 170(2), 117-124. doi:10.1001/jamapediatrics.2015.3356

Castro, V. M., Kong, S. W., Clements, C. C., Brady, R., Kaimal, A. J., Doyle, A. E., . . . Perlis, R. H. (2016). Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: A replication study. Translational Psychiatry, 6, e708. doi:10.1038/tp.2015.190

Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Hendrick, V. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorders. Archives of General Psychiatry, 68(11), 1104-1112. doi:10.1001/archgenpsychiatry.2011.73

Curran, E. A., O’Neill, S. M., Cryan, J. F., Kenny, L. C., Dinan, T. G., Khashan, A. S., & Kearney, P. M. (2015). Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 56(5), 500-508. doi:10.1111/jcpp.12351

Gidaya, N. B., Lee, B. K., Burstyn, I., Yudell, M., Mortensen, E. L., & Newschaffer, C. J. (2014). In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder. Journal of Autism and Developmental Disorders, 44(10), 2558-2567. doi:10.1007/s10803-014-2128-4

Hviid, A., Melbye, M., & Pasternak, B. (2013). Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. The New England Journal of Medicine, 369(25), 2406-2415. doi:10.1056/NEJMoa1301449

Kalfa, N., Paris, F., Philibert, P., Orsini, M., Broussous, S., Fauconnet-Servant, N., . . . Sultan, C. (2015). Is hypospadias associated with prenatal exposure to endocrine disruptors? A french collaborative controlled study of a cohort of 300 consecutive children without genetic defect. European Urology, 68(6), 1023-1030. doi:10.1016/j.eururo.2015.05.008

King, B. H. (2016). Assessing risk of autism spectrum disorder in children after antidepressant use during pregnancy. JAMA Pediatrics, 170(2), 111-112. doi:10.1001/jamapediatrics.2015.3493

Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013). Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: Population based case-control study. BMJ (Clinical Research Ed.), 346, f2059. doi:10.1136/bmj.f2059

Sorensen, M. J., Gronborg, T. K., Christensen, J., Parner, E. T., Vestergaard, M., Schendel, D., & Pedersen, L. H. (2013). Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clinical Epidemiology, 5, 449-459. doi:10.2147/CLEP.S53009

Xiang, A. H., Wang, X., Martinez, M. P., Walthall, J. C., Curry, E. S., Page, K., . . . Getahun, D. (2015). Association of maternal diabetes with autism in offspring. Jama, 313(14), 1425-1434. doi:10.1001/jama.2015.2707