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]
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.
____________________________________________________________________________
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.
http://www.medscape.com/viewarticle/883012#vp_3
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