Studies Question Association Between Autism and Antidepressant Use During Pregnancy

A previously described association between exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants in the first-trimester of pregnancy and a heightened risk for autism was not found in two recent large-population studies.

Both studies used sophisticated statistical methods to account for multiple confounding conditions, with one finding that the antidepressants were associated instead with a small increased risk of preterm birth.

Brian D'Onofrio, PhD, Department of Psychological and Brain Sciences, Indiana University, Bloomington (pictured), and colleagues attributed the apparent increased risk of autism in these children to other factors.

"These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both account for the population-wide associations between first-trimester antidepressant exposure and these outcomes," D'Onofrio and colleagues remarked.

Simone Vigod, MD, Women's College Hospital, Toronto, Ontario, Canada and colleagues, authors of the concurrently published, separate study, came to a similar conclusion. They suggested that the presence of a mood disorder in the mother rather than her antidepressant treatment is a more likely risk factor.

In an editorial accompanying the two studies, Tim Oberlander MD, Division of Developmental Pediatrics, Department of Pediatrics, University of British Columbia, Vancouver, Canada and Lonnie Zwaigenbaum, MD, Department of Pediatrics, University of Alberta, Edmonton, Canada described the difficulty in disentangling the confounders from causal factors.

"Because both antidepressant exposure and maternal depression are closely intertwined, it is essential to distinguish whether prenatal exposure increases the risk of autism spectrum disorder, or whether the link is due to a shared relationship with maternal depression," they indicated.

D'Onofrio and colleagues accessed several registries in Sweden to obtain records for 1,580,629 infants of 943,776 mothers, and to track their progress through 15 years of age. They compared the 6.98% of the children who had first-trimester exposure to any antidepressant, of which 82% were SSRIs, to the 4.78% not exposed.

D'Onofrio and colleagues reported that after adjusting for pregnancy, maternal and paternal traits, the first-trimester antidepressant exposure was associated with a small increased risk of preterm birth, but not with gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder (ADHD). Vigod and colleagues examined records of approximately 36,000 births and similarly found after accounting for other factors that there was no statistical difference in risk of autism spectrum disorder between the 7.9 % exposed to antidepressants and those without exposure.

Oberlander and Zwigenbaum point out that SSRIs have been the suspected causal factor because their effects on serotonin were postulated to shape neurotropic signals during developmentally sensitive periods. An alternative possibility, however, which is made more likely by the findings of these two large retrospective cohort studies, is that the antidepressants are markers for the depressive illness, and it is that maternal stress that can influence early brain development.

"Identifying how maternal mood and related genetic and environmental factors shape developmental risk is needed," Oberlander and Zwigenbaum indicate, "moving away from a focus on antidepressant medications alone and toward whether some mothers and their children might actually benefit from prenatal maternal antidepressant treatment."

The study by D'Onofrio and colleagues and the study by Vigod and colleagues examining the putative association of antidepressant use in pregnancy with risk for autism were published in the April 18 issue of JAMA.