Viktorin A, Uher R, Kolevzon A, Reichenberg A, Levine SZ, Sandin S. Association of Antidepressant Medication Use During Pregnancy With Intellectual Disability in Offspring. JAMA Psychiatry. 2017 Jul 12. doi:10.1001/jamapsychiatry.2017.1727. [Epub ahead of print]
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.
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.
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.
A team of researchers from the Icahn School of Medicine at Mount Sinai, in New York City, found that intellectual disability (ID) was diagnosed in 37 children (0.9%) who had been exposed to antidepressants vs 819 (0.5%) who had not been exposed.
Although there was a higher estimate of relative risk (RR) for intellectual disability, once confounding factors such as parental age and psychiatric history were accounted for, the risk was no longer deemed statistically significant.
"The take-home message to clinicians from our study is that although there is an association between antidepressant use in pregnancy — especially SSRIs [selective serotonin reuptake inhibitors] —and intellectual disability in offspring, it is probably not due to the medication," study author Abraham Reichenberg, PhD, professor of psychiatry, Icahn School of Medicine, told Medscape Medical News.
"Based on results of this study, the association is due to other characteristics in parents that we know are related to intellectual disability, including history of psychiatric disorders, older age of mothers or fathers, and psychiatric disorders in the mother before pregnancy," he said…
Conventional medications used in pregnancy, including certain antiepileptic and mood stabilizing medications, "have been associated with poor cognitive development and lower IQ in exposed offspring," the authors write.
Antidepressants in general and SSRIs in particular are increasingly being used by pregnant women. These agents, which pass the placenta, have been implicated in abnormalities of offspring in animal models and in some human observational studies…
Of the cohort, 3982 children (2.2%) were born to mothers with two or more dispensations of antidepressant medication that overlapped the pregnancy; 172,646 children (96.4%) were born to mothers who had no antidepressant medication dispensations that overlapped the pregnancy. The unadjusted RR of ID in exposed children was estimated at 1.97 (95% confidence interval [CI], 1.42 - 2.74)…
"We observed a higher RR of ID among offspring born to mothers treated with antidepressants during pregnancy (0.9% of children affected), compared with offspring of mothers not treated with antidepressants during pregnancy (0.5% of children affected) before adjustment for confounding factors.
"However, with incremental adjustment for maternal and paternal confounding factors, this association was gradually attenuated to a statistically nonsignificant RR estimated at 1.33 (95% CI, 0.90 - 1.98)," the researchers write.
They note several study limitations. The use of registry data captured only the number of medications prescribed and collected; it did not capture adherence to these medications.
"The evidence we have so far regarding autism and intellectual disability in mothers who used antidepressants during pregnancy is that the medications per se are not what increase the risk but rather it is what the mother may carry genetically or other confounding factors that may increase the risk. And even the increased risk is very small," said Dr Reichenberg.