Utilisation d’antidépresseurs durant la grossesse et le risque du spectre du trouble autistique et du trouble du déficit d’attention avec ou sans hyperactivité chez l’enfant

Depression is a prevalent psychiatric illness in women of childbearing age, affecting up to 20% of women. Pregnancy is a critical period for the onset or recurrence of symptoms of depression, with prevalence in pregnant women ranging from 7% to 15%. It has been shown that depression during pregnancy is associated with several adverse outcomes for the woman, including pre-eclampsia, postpartum depression, and alcohol and tobacco use. On the other hand, prenatal depression can lead to adverse outcomes for the unborn child, including prematurity (OR =3.3, 95% confidence interval [95% CI] 1.2-9.2), low birth weight (adjusted OR =1.71, 95% CI 1.12-2.62)[1], and birth defects (adjusted OR =1.82, 95% CI 1.01-3.29)[2]. Antidepressants are one of the options for the treatment of depression during pregnancy. These drugs are widely used by pregnant women, with an estimated prevalence of up to 13%. However, there is inconsistent evidence on the safety of antidepressants during gestation. In addition, studies assessing the risk of neurodevelopmental disorders, specifically Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) in children associated with taking antidepressants during pregnancy are limited and conflicting. As a result, a research program was developed using the Québec Pregnancy Cohort (QPC) to investigate: 1) In the first part of this thesis, the risk of ASD associated with the use of antidepressants during pregnancy. To achieve our goals, a review was first conducted to review and synthesize existing data regarding this research question. It seems generally that most existing studies tend to detect an association between antidepressant use during pregnancy and increased risk of ASD. However, uncertainty remains around whether antidepressant use during pregnancy independentltly increases the risk for ASD in the child. 2) Secondly, given the methodological limitations of previous studies, we further conducted a cohort study including singleton full-term children to quantify the association between antidepressant exposure during pregnancy and the risk of ASD, taking into account the trimester of exposure and several potentially confounding factors. The absolute risk was 0.7%. The results suggestted a statistically significant increased risk of ASD associated with antidepressant exposure during the 2nd/3rd trimesters of pregnancy (HR=1.87, 95% CI 1.15-3.04). In addition, we observed that the use of selective serotonin reuptake inhibitors (SSRIs) during the 2nd/3rd trimesters of pregnancy was significantly associated with more than a 2-fold increased risk of ASD. However, a potential confusion bias is not completely excluded. 3) In the third part of this thesis project, we were interested in evaluating the risk of ADHD associated with the use of antidepressants during pregnancy. Thus, a cohort study was conducted.  The absolute risk was 3.1%. Our results suggestted an increased risk of ADHD associated with exposure to antidepressants during the 2nd/3rd trimesters of pregnancy, more specifically tricyclics (HR=1.3, 95% CI 1.0-3.1), even after controlling for several confounding variables, including maternal depression/anxiety, and ADHD. However, potential residual confounding by severity is not fully ruled out. ADHD affects about 5.0% to 7.9% of children. There is limited data on the prevalence of drug use for the treatment of ADHD. Although studies in the literature have reported an increase in the prevalence of use of ADHD medications among children over time, few updated data exist for the Canadian population. In addition, no study has investigated questions with regards to characteristics of ADHD drug dosage and class switching, as well as the determinants of the use of such drugs for children with ADHD. Therefore, in the second part of this thesis project, we conducted a longitudinal cohort study to answer all these questions using data from QPC between 1998 and 2015. It has been found that the prevalence of use of ADHD medications increases significantly over time, with a higher prevalence for boys. In addition, our results showed that ADHD medications were used predominantly (96.7%) according to the Canadian/Québec guidelines for the evaluation and treatment of ADHD. We further found that 20.4% of children had at least one switch from one class of ADHD medications to another. Several factors associated with the use of ADHD medications have been identified, including the use of anti-depressants by children before being diagnosed with ADHD (OR adjusted=3.06, 95% CI 2.21-4.22), the sex of the child, maternal ADHD   and others psychic disorders.

Keyphrases: Antidepressants, Autism spectrum disorder, Attention deficit disorder with or without hyperactivity, Québec pregnancy cohort, Cohort, Prevalence and determinants of use, Review