Taking antidepressants during the second or third trimester of pregnancy may increase the risk of having a child with autism spectrum disorder, according to a study of Canadian mothers and children published Monday in JAMA Pediatrics.
But scientists not involved in the research say the results are hard to interpret and don't settle the long-running debate about whether expectant mothers with depression should take antidepressants.
"This study doesn't answer the question," says Bryan King, program director of the autism center at Seattle Children's Hospital and a professor of psychiatry and behavioral sciences at the University of Washington. "My biggest concern is that it will be over-interpreted," says King, who wrote an editorial that accompanied the study.
"It kind of leaves you more confused," says Alan Brown, a professor of psychiatry and epidemiology at Columbia University who studies risk factors for autism. "Mothers shouldn't get super worried about it," he says.
One reason it's confusing is that there's strong evidence that mothers with depression are more likely than other women to have a child with autism, whether or not they take antidepressants during pregnancy. King and Brown say that makes it very hard to disentangle the effects of depression itself from those of the drugs used to treat it.
Earlier this year, a study of several thousand U.S. children found that prenatal antidepressant exposure did not increase the risk of autism spectrum disorder. In 2013, a study of nearly 670,000 Danish children also found no association between prenatal exposure to antidepressant medication and autism spectrum disorder.
But a 2013 study of more than 4,400 Swedish children concluded that in utero exposure did increase the risk that a child would develop autism. And a 2011 study of about 300 children with autism in California concluded that antidepressants "may modestly increase the risk" of an autism spectrum disorder.
The Canadian study looked at more than 145,000 children born in Quebec from 1998 to 2009. It found that children whose mothers took antidepressants during the second or third trimester of pregnancy were 87 percent more likely to be diagnosed with autism spectrum disorder.
The study tried to account for depression's effect on risk by identifying mothers with a history of psychiatric disorders. It also compared mothers who stopped taking antidepressants during the first trimester with mothers who continued taking the medications.
Those steps allowed the team to conclude that the 87 percent increase was "above and beyond" the risk posed by depression itself, says Anick Berard, the study's senior author and an epidemiologist and biostatistician at the University of Montreal. Berard has done other studies that linked antidepressants to birth defects and has worked as a consultant for plaintiffs who are suing companies that make antidepressants.
Other scientists aren't so sure that Berard's study truly shows a risk associated with antidepressant use. Mothers who kept taking antidepressants may have had more severe depression, they say. Also, they say, the increase in risk was so small that it might have been a chance finding.
An 87 percent increase "sounds very concerning," King says. But the figure is based on just 31 children who developed autism after being exposed to antidepressants. And many of these children would have developed autism anyway, he says.
The absolute risk numbers are small, Berard says. But she says a secondary analysis showed that the risk was highest for women who took drugs called SSRIs, which affect serotonin levels. And serotonin plays an important role in brain development, she says. The number of women using only other types of antidepressants was very small, so it was impossible to draw conclusions about their safety.
"We have to be vigilant even if the risk is small," Berard says. "Maybe we should rethink our treatment process."
King responds that untreated depression can result in poor nutrition, sleep problems and stress, all of which can affect the health of a developing fetus. So pregnant women who are concerned about taking antidepressants should consult with their doctor before taking any action, he says.
Better information about the risks of antidepressants and other factors may emerge from a large, ongoing study of children born in Finland, says Brown, who is the study's principal investigator. Those results may be available in the next few years.