Antidepressant use in second, third trimester may increase risk for autism

Use of antidepressants, particularly selective serotonin reuptake inhibitors, during the second and/or third trimester of pregnancy was associated with an increased risk for autism in offspring, even when considering maternal depression.

Perspective from Gagan Joshi, MD;

“Few studies have investigated the effect of [antidepressant] use during pregnancy on the risk of [autism spectrum disorder (ASD)] in children. Although some investigators have found an increased risk of ASD with antenatal [antidepressant] use, others have suggested there is no statistically significant association,” Takoua Boukhris, MSc, of the University of Montréal, Québec, Canada, and colleagues wrote. “However, studies thus far have potential limitations, such as lack of adequate adjustment for maternal psychiatric illnesses and genetic predispositions for ASD.”

To assess risk for ASD in children associated with antidepressant use during pregnancy, researchers conducted a register-based study of an ongoing population-based cohort with data on all pregnancies and children in Québec from January 1998 to December 2009. Analysis included 145,456 singleton full-term infants.

Overall, 3.2% of infants were exposed to antidepressants in utero; of those, 88.9% were exposed during the first trimester and 53.6% were exposed during the second and/or third trimester.

ASD was diagnosed in 1.2% of those exposed to antidepressants during the second and/or third trimester and 1% of those exposed during the first trimester.

When adjusting for all potential confounders, use of antidepressants in the second and/or third trimester was associated with an increased risk for ASD (HR = 1.87; 95% CI, 1.15-3.04). Use of antidepressants in the first trimester was not associated with an increased risk for ASD.

Use of SSRIs (HR = 2.17; 95% CI, 1.2-3.93) and use of more than one class of antidepressants (HR = 4.39; 95% CI, 1.44-13.32) during the second and/or third trimester was significantly associated with an increased risk for ASD.

In adjusted analysis of only mothers with a history of depression, use of antidepressants during the second and/or third trimester was associated with an increased risk for ASD (HR = 1.75; 95% CI, 1.03-2.97), compared with those who did not use antidepressants.

In adjusted analysis of children with ASD diagnoses confirmed by psychiatrists or neurologists, use of antidepressants during the second and/or third trimester was associated with an increased risk for ASD, but it was not statistically significant due to a reduced sample size.

“Of course, even one potentially preventable case [of ASD] is noteworthy. But this finding must also be viewed in the context of other risks. As Boukhris et al highlight, untreated maternal depression is associated with a host of other complications,” Bryan H. King, MD, MBA, of the University of Washington, Seattle, wrote in an accompanying editorial.

Untreated depression can increase prenatal stress and lead to increased corticosteroid production and release of vasoactive amines, according to King.

This may lead to reduced blood blow to the umbilical cord and increase risk for hypoxia and preterm birth and other negative psychiatric outcomes, such as anxiety, depression and hyperactivity.

“It makes no more sense to suggest that [antidepressants] should always be avoided than to say that they should never be stopped,” King wrote. “In the ongoing search for environmental contributions to the risk of ASD, in utero exposures are increasing as a focus. It is unlikely that there will be a straight line from such exposures that leads unwaveringly to ASD, and future studies should expand the neurodevelopmental outcomes examined.” – by Amanda Oldt

Disclosure: Boukhris and King report no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.

Perspective

Gagan Joshi, MD

Disclosures:

Perspective

As clinicians and researchers devoted to the understanding of both serious mood disorders and autism spectrum disorders (ASD), we support these research efforts from our Canadian colleagues that attempt to better elucidate the complex environmental etiologies of ASD, bearing in mind that the etiology of autism is the most strongly genetic of all childhood psychiatric disorders. This is particularly important with the significantly increased reported prevalence of ASD.

That said, care is needed in over-generalizing from the results of this study. We do not believe that there is yet conclusive evidence that SSRI use during the second and third trimesters of pregnancy increases the risk of ASD. Moreover, we should note that maternal depression itself has been associated with ASD and that non-SSRI antidepressants have also been implicated in its increased prevalence.

Depression during pregnancy can be serious to the health of both the mother and the fetus and these findings should not be interpreted as a reason to fail to treat it. This study might, however, suggest that until the complex environmental etiologies of ASD become clearer, the use of alternative therapeutic modalities such as psychotherapy or neurostimulation pose less risk to the fetus, and are therefore the treatments of choice for depression during pregnancy. Certainly these findings will help pregnant patients and their psychiatrists make better informed therapeutic decisions.

Scott T. Aaronson, MD

Director, Clinical Research Programs, Sheppard Pratt Health System

Desmond Kaplan, MD

Service Chief, Child and Adolescent Neuropsychiatric Unit, Sheppard Pratt Health System

Disclosures: Aaronson reports receiving research support from Neuronetics and speaking honoraria from Lundbeck, Otsuka and Takeda.

Sources/Disclosures

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Source: Boukhris T, et al. JAMA Pediatrics. 2015;doi:10.1001/jamapediatrics.2015.3356.
King BH, et al. JAMA Pediatrics. 2015;doi:10.1001/jamapediatrics.2015.3493.