TORONTO -- Taking antidepressants during pregnancy -- especially the class that includes Prozac, Zoloft and Celexa -- appears to raise the risk of autism spectrum disorder in children, a study suggests.
The study by the University of Montreal found that taking antidepressants of any kind while pregnant somewhat boosts the risk that a child will be diagnosed with ASD by age seven.
But the risk doubles with drugs known as selective serotonin re-uptake inhibitors, or SSRIs, when they are taken during the second and third trimesters -- the critical period for fetal brain development, the researchers say.
"It is biologically plausible that antidepressants (could be) causing autism if used at the time of brain development in the womb, as serotonin is involved in numerous pre- and postnatal developmental processes, including ... the creation of links between brain cells," said Anick Berard, a pharmacy professor at the university and principal investigator of the study.
"Some classes of antidepressants work by inhibiting serotonin, which will have a negative impact on the ability of the brain to fully develop and adapt in-utero."
Autism spectrum disorder, which includes a number of separate diagnoses like autism and Asperger's syndrome, impairs a child's ability to communicate and interact with others. It may include repetitive behaviours as well as an intense focus on a narrow range of interests and activities.
SSRIs are the most commonly prescribed antidepressants, with an estimated six to 10 per cent of pregnant women being treated for depression with the drugs.
Berard said the findings do not prove the drugs are among the causes of the neurodevelopmental disorder in children -- although some previous studies also pointed to the drugs as a possible culprit.
"We don't know all the causes of autism," she said. "Certainly there could be a very strong genetic predisposition and probably something environmental, meaning medications and lifestyle and so forth."
Some doctors argue that leaving depression untreated can be more dangerous for pregnant women and their unborn babies, and say the benefits of antidepressants may outweigh their potential harms.
But Berard said that, as with the general population, most pregnant women have mild to moderate depression, which can be alleviated by other means. Exercise, psychotherapy and light therapy can all have benefits, she said.
"When it comes to depression in pregnancy, I'm not saying don't treat, but think of other options," she advised doctors. "And obviously follow them carefully during their pregnancy, as you would for hypertension or diabetes."
The study, published Monday in the journal JAMA Pediatrics, analyzed the health records of almost 145,500 Quebec children, of whom 1,054 were diagnosed with autism spectrum disorder, between 1998 and 2009.
Among 2,532 infants born to mothers who took antidepressants in the last two trimesters of pregnancy, 31 children were diagnosed with ASD; 22 of the babies' mothers had been taking an SSRI.
In absolute terms, SSRI use appears to be associated with a doubling in the incidence of ASD, from one per cent of children to about two per cent, said Berard.
Put another way, seven in 1,000 children without antidepressant exposure were diagnosed with ASD, compared to about 12 in 1,000 with mid- to late-pregnancy antidepressant exposure, said Barbara Mintzes, a pharmacology expert at the University of Sydney who was not involved in the study. The researchers found no increased ASD risks with first-trimester use.
The study adds to an existing body of research suggesting a link between antidepressant use and a higher risk of autism, said Mintzes, formerly of the University of British Columbia.
"There are a number of reasons to be cautious about SSRI use in pregnancy, including increased risks of miscarriage and pre-term births, and, with late pregnancy exposures, increased rates of persistent pulmonary hypertension of the newborn, and of a newborn withdrawal syndrome that sometimes leads to the need for neonatal intensive care," she said by email.
"There is also no reliable evidence showing that antidepressant use in pregnancy leads to better health for the baby. If a woman is pregnant and wants to stop taking her antidepressant, however, it's important that she comes off by gradually lowering the dose, and that she gets help from a health professional in working out a schedule to taper down the dose."
In an editorial accompanying the study, Dr. Bryan King of the department of psychiatry and behavioural sciences at the University of Washington said other studies have shown that taking SSRIs during pregnancy reduced the risk of late pre-term birth, very early pre-term birth and C-sections, compared to pregnant women not taking the drugs.
Untreated depression may also increase prenatal stress, which was linked in one study to potentially lifelong effects on brain plasticity and cognition in children, he added.
"It makes no more sense to suggest that (antidepressants) should always be avoided than to say they should never be stopped," writes King.
However, Berard said pregnant women taking a medication to treat depression, or women who plan to become pregnant, should discuss both the risks and benefits of antidepressants with their doctors.
"This study is not there to scare them," she said, adding that researchers want women to know the risks before they decide whether to continue taking the drugs.