Association entre l'utilisation d'antidépresseurs sérotonergiques pendant la grossesse et le trouble du spectre de l'autisme chez les enfants

Aperçu: G.M.

Les observations antérieures d'un risque plus élevé de troubles du spectre de l'autisme chez les enfants avec une exposition aux antidépresseurs sérotonergiques pendant la grossesse peuvent avoir été confondues. L'étude propose d'évaluer l'association entre l'exposition aux antidépresseurs sérotonergiques pendant la grossesse et le trouble du spectre de l'autisme de l'enfant.

Il y avait 35906 naissances isolées à un âge gestationnel moyen de 38,7 semaines (50,4% étaient des hommes, l'âge maternel moyen était de 26,7 ans et la durée moyenne de suivi était de 4,95 ans). Parmi les 2837 grossesses (7,9%) exposées aux antidépresseurs, 2,0% (IC à 95%, 1,6% -2,6%) des enfants ont été diagnostiqués avec un trouble du spectre de l'autisme. L'incidence du trouble du spectre de l'autisme était de 4,51 pour 1000 ans-personne parmi les enfants exposés aux antidépresseurs contre 2,03 pour 1000 personnes chez les enfants non exposés. 

Chez les enfants nés de mères ayant un régime public de délivrance de médicaments en Ontario, au Canada, l'exposition aux antidépresseurs sérotonergiques chez l'utérus contre l'absence d'exposition n'a pas été associée au trouble du spectre de l'autisme chez l'enfant. Bien qu'une relation causale ne puisse pas être exclue, l'association précédemment observée s'explique par d'autres facteurs. 

JAMA. 2017 Apr 18;317(15):1544-1552. doi: 10.1001/jama.2017.3415.

Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children

Brown HK¹, Ray JG², Wilton AS³, Lunsky Y⁴, Gomes T⁵, Vigod SN¹.

Author information

1

Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada3Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.

2

Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada4Department of Obstetrics and Gynaecology, St Michael's Hospital, Toronto, Ontario, Canada5Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

3

Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.

4

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada3Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada6Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

5

Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada7Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

Abstract

Importance:

Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded.

Objective:

To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder.

Design, Setting, and Participants:

Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014.

Exposures:

Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery.

Main Outcomes and Measures:

Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings.

Results:

There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children were compared with unexposed siblings (incidence of autism spectrum disorder was 3.40 per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR, 1.60 [95% CI, 0.69-3.74]).

Conclusions and Relevance:

In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.

PMID: 28418480 

DOI: 10.1001/jama.2017.3415