Science

Takoua Boukhris, MSc;
Odile Sheehy, MSc;
Laurent Mottron, MD, PhD;
Anick Bérard, PhD

Antidepressants (ADs) are widely used during gestation for the treatment of depression. In the United States, the prevalence of AD use during pregnancy increased from 5.7% in 1999 to 13.3% in 20031; in Canada, 4.5% of pregnant women reported using ADs between 2001 and 2006.2 How- ever, there is continued confusion regarding the appropriate use of ADs during this critical period. Gestational exposure to ADs has been associated with an increased risk of spontaneous abortion,3 major congenital malformations,4 prematurity,5,6 low birth weight,5 ,6 neonatal withdrawal,7 and pregnancy- induced hypertension.8 Discontinuation of ADs during pregnancy in women with severe depression was associated with relapse in some studies.9 Nevertheless, up to 20% of women who continue to use ADs during pregnancy remain depressed,10 suggesting a lack of efficacy in some pregnant women.
Autism spectrum disorder (ASD) is a neurodevelopmental syndrome detected in early childhood and characterized by alterations in communication, language, and social interaction and by particular patterns of interests and behaviors.11 The estimated prevalence of ASD has increased from 0.04% in 1966 to approximately 1% today12 in the United States. Although this increase is explained mainly by widening diagnostic criteria, improved detection, and the recoding of intellectual disability in ASD,13 environmental risk factors may also play a role. Accordingly, any factor that modifies spontaneous mutation rates (eg, parental age14) or affects synaptic plasticity (eg, exposure to valproic acid during pregnancy15), including in utero exposure to medications,16 may result in neurodevelopmental alterations included in the autistic phenotype. Although the causes of ASD remain unknown, both genetic and environmental factors are probably involved,16 and several risk factors, such as particular genetic variants,17 de novo mutations,18 maternal disease,19 and maternal history of psychiatric disorders,20 already have been linked with ASD. Few studies have investigated the effect of AD use during pregnancy on the risk of ASD in children.21-24 Although some investigators have found an increased risk of ASD with antenatal AD use,22,24 others have suggested there is no statistically significant association.21,23 However, studies thus far have potential limitations, such as lack of adequate adjustment for maternal psychiatric illnesses and genetic predispositions for ASD. In addition, to our knowledge, no study had sufficient power to investigate the risk of ASD for each class of ADs. Given projections that depression will be the second leading cause of death by 2020,25 ADs are likely to remain widely used, including during pregnancy. Therefore, a better understanding of the long- term neurodevelopmental effects of ADs on children when used during gestation is a public health priority. We used province- wide administrative, hospital, and clinical registers in Québec to investigate the association between AD use during pregnancy and the risk of ASD, taking into account classes of ADs, trimester of use, and maternal psychiatric conditions.