Maternal Antidepressant Use During Pregnancy and Autism Risk
Maternal Antidepressant Use During Pregnancy and Autism Risk
Objective. To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.
Design. Population based nested case-control study.
Setting. Stockholm County, Sweden, 2001-07.
Participants. 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43,277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16,845 controls with data on maternal antidepressant use nested within a cohort (n=589,114) of young people aged 0-17 years.
Main Outcome Measure. A diagnosis of autism spectrum disorder, with or without intellectual disability.
Exposures. Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.
Results. A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.
Conclusions. In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
The estimated prevalence of autism spectrum disorders in the United States has dramatically increased from fewer than 5 in 10,000 children in the 1980s to 1 in 88 in 2008. Similar increases have been reported in much of the Western world. Better recognition and more inclusive diagnostic criteria for autism spectrum disorders may explain this rising prevalence, but a real increase in incidence has not been ruled out. Relatively little is known about the causes of autism spectrum disorders and both genetic and environmental factors are implicated. The identification of modifiable environmental risk factors may aid in the primary prevention of some cases.
A recently reported association between use of selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and autism spectrum disorders in offspring has raised the possibility of discovering one such modifiable causal factor. There is increasing interest in the role of the serotonergic system in the pathophysiology of autism, and prenatal exposure to serotonergic agents is a biologically plausible pathway. SSRIs have increasingly been used in the treatment of depression during pregnancy since the 1990s, mirroring the secular rise in the observed prevalence of autism spectrum disorders.
However, an association between SSRI use during pregnancy and autism may not imply a causal relation. An alternative explanation is confounding by indication—the possibility that maternal depression is responsible for the associations observed between SSRIs and autism spectrum disorders in offspring. Although the relation between parental depression and risk of autism spectrum disorders is often assumed to be well established and has a genetic origin, the supporting evidence is relatively weak. Two recent meta-analyses were inconclusive and reported a lack of studies with psychiatric diagnosis of parents before the birth of the child.
In a large population based study in Sweden, we investigated whether maternal or paternal depression identified before the birth of the child is associated with autism spectrum disorders in offspring; whether maternal antidepressant use during pregnancy is associated with autism spectrum disorder in offspring, and, if so, whether this explains any associations between maternal depression and autism; whether any associations between antidepressants and autism are unique to SSRIs or also evident for other antidepressants; and whether all the above associations are similar in offspring with autism with and without comorbid intellectual disability.
Abstract and Introduction
Abstract
Objective. To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.
Design. Population based nested case-control study.
Setting. Stockholm County, Sweden, 2001-07.
Participants. 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43,277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16,845 controls with data on maternal antidepressant use nested within a cohort (n=589,114) of young people aged 0-17 years.
Main Outcome Measure. A diagnosis of autism spectrum disorder, with or without intellectual disability.
Exposures. Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.
Results. A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.
Conclusions. In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
Introduction
The estimated prevalence of autism spectrum disorders in the United States has dramatically increased from fewer than 5 in 10,000 children in the 1980s to 1 in 88 in 2008. Similar increases have been reported in much of the Western world. Better recognition and more inclusive diagnostic criteria for autism spectrum disorders may explain this rising prevalence, but a real increase in incidence has not been ruled out. Relatively little is known about the causes of autism spectrum disorders and both genetic and environmental factors are implicated. The identification of modifiable environmental risk factors may aid in the primary prevention of some cases.
A recently reported association between use of selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and autism spectrum disorders in offspring has raised the possibility of discovering one such modifiable causal factor. There is increasing interest in the role of the serotonergic system in the pathophysiology of autism, and prenatal exposure to serotonergic agents is a biologically plausible pathway. SSRIs have increasingly been used in the treatment of depression during pregnancy since the 1990s, mirroring the secular rise in the observed prevalence of autism spectrum disorders.
However, an association between SSRI use during pregnancy and autism may not imply a causal relation. An alternative explanation is confounding by indication—the possibility that maternal depression is responsible for the associations observed between SSRIs and autism spectrum disorders in offspring. Although the relation between parental depression and risk of autism spectrum disorders is often assumed to be well established and has a genetic origin, the supporting evidence is relatively weak. Two recent meta-analyses were inconclusive and reported a lack of studies with psychiatric diagnosis of parents before the birth of the child.
In a large population based study in Sweden, we investigated whether maternal or paternal depression identified before the birth of the child is associated with autism spectrum disorders in offspring; whether maternal antidepressant use during pregnancy is associated with autism spectrum disorder in offspring, and, if so, whether this explains any associations between maternal depression and autism; whether any associations between antidepressants and autism are unique to SSRIs or also evident for other antidepressants; and whether all the above associations are similar in offspring with autism with and without comorbid intellectual disability.
Source...