Association of Antidepressant Medication Use During Pregnancy With Intellectual Disability in Offspring

Abstract

Importance: Maternal antidepressant medication use during pregnancy has previously been associated with adverse outcomes in offspring, but to our knowledge, the association with intellectual disability (ID) has not been investigated.

Objectives: To examine the association of maternal antidepressant medication use during pregnancy with ID in offspring and investigate the importance of parental mental illness for such an association.

Design, setting, and participants: A population-based cohort study of 179 007 children born from January 1, 2006, through December 31, 2007, with complete parental information from national registers who were followed up from birth throughout 2014.

Main outcomes and measures: We estimated relative risks (RRs) and 95% CIs of ID in children exposed during pregnancy to any antidepressant medication or specifically to selective serotonin reuptake inhibitor (SSRI) antidepressants, all other non-SSRI antidepressants, or other nonantidepressant psychotropic medications. Analyses were adjusted for potential confounders. In addition to full population analyses, we used a subsample to compare mothers who used antidepressants during pregnancy with mothers who had at least one diagnosis of depression or anxiety before childbirth but did not use antidepressants during pregnancy.

Results: Of the 179 007 children included in the study (mean [SD] age at end of follow-up, 7.9 [0.6] years; 92 133 [51.5%] male and 86 874 [48.5%] female), ID was diagnosed in 37 children (0.9%) exposed to antidepressants and in 819 children (0.5%) unexposed to antidepressants. With adjustment for potential confounders, the RR of ID after antidepressant exposure was estimated at 1.33 (95% CI, 0.90-1.98) in the full population sample and 1.64 (95% CI, 0.95-2.83) in the subsample of women with depression. Results from analyses of SSRI antidepressants, non-SSRI antidepressants, and nonantidepressant psychotropic medications and analyses in the clinically relevant subsample did not deviate from the full-sample results.

Conclusions and relevance: The unadjusted RR of ID was increased in offspring born to mothers treated with antidepressants during pregnancy. After adjustment for confounding factors, however, the current study did not find evidence of an association between ID and maternal antidepressant medication use during pregnancy. Instead, the association may be attributable to a mechanism integral to other factors, such as parental age and mother's psychiatric disorder.

Figure 1.. Relative Risks (RRs) of Intellectual Disability Attributable to Exposure to Any Antidepressant During Pregnancy

The full sample consists of 179 007 children born during 2006 and 2007, of whom 873 had been diagnosed with intellectual disability and 3982 were born to a mother with antidepressant treatment during pregnancy. The figure presents the RRs (95% CIs) of intellectual disability among children of mothers with at least 2 dispensations of antidepressant drugs that overlapped the pregnancy compared with unexposed children. There was a clinically relevant subsample of 8021 children, of whom 69 had been diagnosed with intellectual disability and 2372 were born to a mother with antidepressant treatment during pregnancy. All mothers, both medicated and nonmedicated, had at least 1 diagnosis of depression or an anxiety disorder before childbirth (eTable 4 in the Supplement). Therefore, the offspring of mothers with medication use during pregnancy is compared with the offspring of mothers who may share similar underlying factors. ^aAnalyses not adjusted for covariates. ^bAnalyses adjusted for birth date, maternal and paternal age, the father's psychotropic medication use that overlapped the pregnancy, and maternal and paternal educational levels at childbirth. ^cAnalyses adjusted for the factors listed in footnote b and for any maternal diagnosis of depression before childbirth (yes/no) (see eTable 4 in the Supplement for specific diagnosis codes). ^dAnalyses adjusted for the factors listed in footnote b and for maternal or paternal diagnoses before childbirth of specific psychiatric disorder subgroups (yes/no), including depression, anxiety disorders, substance use disorder, bipolar disorder, compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intellectual disability, schizophrenia, and other psychiatric diagnosis (see eTable 4 in the Supplement for specific diagnosis codes).

Figure 2.. Relative Risks (RRs) of Intellectual Disability Among Offspring of Mothers Treated With Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants, Non-SSRI Antidepressants, or Nonantidepressant Psychotropic Drugs

The sample consists of 179 007 children born during 2006 and 2007, of whom 873 had been diagnosed with intellectual disability. There were 3178 children born to mothers treated with SSRIs during pregnancy, 804 children born to mothers treated with non-SSRI antidepressants during pregnancy, and 1626 children born to mothers treated with nonantidepressant psychotropic medications during pregnancy. The figure presents RRs (95% CIs) of intellectual disability among children of mothers with at least 2 dispensations of antidepressants or other psychotropic medications that overlapped the pregnancy compared with unexposed children. ^aAnalyses not adjusted for covariates. ^bAnalyses adjusted for birth date, maternal and paternal age, the father's psychotropic medication use that overlapped the pregnancy, and maternal and paternal educational levels at childbirth. ^cAnalyses adjusted for the factors listed in footnote b and for any maternal diagnosis of depression before childbirth (yes/no) (see eTable 4 in the Supplement for specific diagnosis codes). ^dAnalyses adjusted for the factors listed in footnote b and for maternal and paternal diagnoses before childbirth of specific psychiatric disorder subgroups (yes/no), including depression, anxiety disorders, substance use disorder, bipolar disorder, compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intellectual disability, schizophrenia, and other psychiatric diagnosis (see eTable 4 in the Supplement for specific diagnosis codes).