Antidepressants taken in pregnancy don’t cause autism

Women who take a common type of antidepressant during pregnancy are not more likely to have a child with autism, according to a new study from Denmark.

But children did have a higher than usual risk when their mothers took the drugs - known as selective serotonin reuptake inhibitors (SSRIs) - for depression or anxiety before becoming pregnant.

That suggests a possible link between a mother’s preexisting mental health issues and the developmental disorder that hinders social and communication skills.

“Our interpretation is that women with indications for SSRI use differ from women who do not use SSRIs because of these indications (depression, anxiety), and some of these differences are somehow related to an increased risk of having children who develop autism,” Dr. Anders Hviid said. He led the study at the Statens Serum Institute in Copenhagen.

“Whether these differences are genetic, social or something completely different is speculation at this point,” Hviid said.

The findings, combined with a separate analysis of the same database published last month in the journal Clinical Epidemiology, suggest people looking for a link between autism and SSRIs need to look elsewhere, Dr. Mark Zylka said.

Antidepressants taken in preGnancy don't cause auTism Zylka, from the University of North Carolina at Chapel Hill School of Medicine, has studied autism but was not involved in the analyses.

“There’s been a big question in the literature about whether these drugs affect brain development in any way and cause autism,” he told Reuters Health. That’s important because of how many people take antidepressants, including pregnant women.

A much smaller study conducted in Northern California and published in 2011 suggested SSRI use during pregnancy is tied to a two-fold higher risk of autism.

For the new study, published in the New England Journal of Medicine, the researchers used data on 626,875 babies born in Denmark in 1996 to 2005.

They recorded which mothers had taken a SSRI like Prozac, Zoloft or Paxil before or during pregnancy, based on a nationwide registry of prescription drugs.

Of the 3,892 children found to have an autism spectrum disorder, 52 had mothers who took one of those drugs while pregnant.

Antidepressants taken in preGnancy don't cause auTism The researchers calculated the risk of autism was 20 percent higher among children whose mothers took an SSRI during pregnancy. But the difference was so small among the small number of women involved that it could have been a coincidence.

Children whose mothers once used SSRIs but stopped at least a few months before becoming pregnant were 46 percent more likely to have autism than other children. That finding was not likely to be a coincidence.

Because taking SSRIs during pregnancy didn’t seem to cause autism, other factors may explain the higher rate among children whose mothers used the drugs before becoming pregnant, Hviid told Reuters Health in an email.

“At this point I do not think that this potential association (SSRI and autism) should feature prominently when evaluating the risks and benefits of SSRI use in pregnancy,” he said.

“People who are taking these drugs prior to pregnancy often have some underlying psychiatric condition, and what they did find in the study was that having some psychiatric disorder does increase the risk of autism,” Zylka said.

A study published last year showed children who had a parent or sibling with schizophrenia had an almost three times higher risk of developing autism (see Reuters Health story of July 5, 2012 here:

Similarly, in the new study, women who had been diagnosed with schizophrenia before delivery were three and a half times more likely to have a child with autism.

“The numbers are remarkably consistent,” Zylka said.

The study also showed taking mood stabilizers or antipsychotics during pregnancy was linked to an increased risk of autism among children, he noted. That gives researchers “ammunition” for where to look in the future, Zylka said.

SOURCE: New England Journal of Medicine, online December 18, 2013


Use of Selective Serotonin Reuptake Inhibitors during Pregnancy and Risk of Autism

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used in the treatment of depression and anxiety disorders. Currently, SSRIs appear to provide the best balance between efficacy and safety and are the preferred first-line treatment. Depression is common during pregnancy, and given the risks of untreated depression to mother and fetus pharmacologic treatment is warranted, often with SSRIs. However, SSRIs cross the placenta, and a number of safety concerns have been raised. These include concerns about birth defects, adverse obstetrical and neonatal outcomes, and effects on cognitive and behavioral development in childhood.

Recently, autism spectrum disorders have been linked to maternal use of SSRIs during pregnancy. In a case–control study involving 298 children with autism spectrum disorders, the use of SSRIs by the mother during pregnancy was shown to be associated with a risk of autism spectrum disorder that was increased by a factor of 2. A causal association is plausible. Increased blood levels of the neurotransmitter serotonin have been observed in persons with autism spectrum disorders. Furthermore, this neurotransmitter appears to play an important role in early brain development, and manipulation of serotonin homeostasis can alter neuroanatomical and neurophysiological development and produce enduring behavioral changes in animal models. However, more research - including large observational studies involving humans - is needed to address a potential association. Using data from the Danish health registries, we conducted a nationwide cohort study of SSRI use during pregnancy and the risk of autism spectrum disorders in the offspring.


We did not detect a significant association between maternal use of SSRIs during pregnancy and autism spectrum disorder in the offspring. On the basis of the upper boundary of the confidence interval, our study could not rule out a relative risk up to 1.61, and therefore the association warrants further study. (Funded by the Danish Health and Medicines Authority.)

Anders Hviid, Dr.Med.Sci., Mads Melbye, M.D., Dr.Med.Sci., and Björn Pasternak, M.D., Ph.D.
N Engl J Med 2013; 369:2406-2415December 19, 2013DOI: 10.1056/NEJMoa1301449

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