• The panic du jour: Antidepressants and autism

    I’m getting lots of tweets, emails, tests, etc. “Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children

    Importance  The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression.

    Objective  To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression.

    Design, Setting, and Participants  We conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145 456 singleton full-term infants born alive and whose mothers were covered by the Régie de l’assurance maladie du Québec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015.

    Exposures  Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes.

    Main Outcomes and Measures  Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95% CIs.

    Researchers used a big database of pregnancies and children from 1998-2009 in Quebec. There were more than 145,000 full-term infants in the cohort. They then looked at whether a mother’s use of antidepressants in pregnancy was associated with a later diagnosis of autism in their children. Exposure to antidepressants was defined as having at least one prescription filled during pregnancy or at a time that would overlap with pregnancy. They controlled for a host of mom’s variables, including sociodemographic characteristics, and history of psychiatric and chronic physical conditions. They controlled for baby things as well.

    They found that, after adjusting for confounders including maternal psychiatric conditions, that the use of antidepressants during the second and/or third trimester was associated with an increased risk (Hazard ratio 1.87) of a child later being diagnosed with autism. Cue the scary headlines.

    Now, let’s break this down.

    In the entire cohort of 145,456 kids, 0.7% of them had ASD. That’s actually on the low side. Of course, some of the kids in the cohort were still too young to be reliably diagnosed. Moreover, they excluded any prematurely born kids from this analysis, and premies are at an increased risk of autism.

    Let’s talk numbers first, though. Of the 145,456 kids born into this cohort, only 4724 were exposed to antidepressants. The other 140,732 were not. Of the 4724 exposed to antidepressants, 46 developed an ASD and 4678 did not. Of course, 1008 kids who were not exposed to an antidepressant were diagnosed with an ASD, too.

    Antidepressants in the first trimester were not found to be significantly related to the risk of an ASD, though. Of those 46 kids, only 31 were exposed to an antidepressant in the second or third trimester.

    In other words, the headline finding is a comparison between the kids who were never exposed to antidepressants and got ASD (1008/145,456) versus the kids who were exposed to antidepressants in the second or third trimester and got ASD (31/2532). Those calculate to 0.7% and 1.2%. The adjusted relative risk increase was 87% when taking into account person-years. The absolute increase is 0.5%. If you accept this at face value, the NNH is therefore about 200. The vast majority of kids who were exposed to antidepressents in the second and/or third trimester did not develop an ASD.

    Further, only SSRIs were shown to be related when looking at classes of drugs individually. They all do have different mechanisms after all. There were 22 kids exposed to SSRIs in the second and/or third trimester who developed ASD (out of the 145,456 kids).

    The point of laying out these numbers is to show you that this isn’t a problem of epidemic proportions. At the end of the day, this study hinges on a small number of children. That doesn’t mean the findings aren’t robust or that they aren’t real. But you have to place things in context. The mothers are theoretically getting a benefit from these drugs, or they wouldn’t be on them. Those benefits need to be weighed against risks.

    And anyone who says that “any risk is too big when it comes to a child” needs to answer for cars.

    We also need to consider this finding in context. There have been a number of studies in this area. This study showed an association between maternal use of SSRIs and a lower risk for preterm birth and many adverse outcomes. Depression in moms in general has been shown to be associated with low birth weight, preterm birth, and being small for gestational age. This case-control study found antidepressant use wasn’t linked to ASD, but that it might be to ADHD.

    I didn’t tout any of those studies as truth when they were published any more than I would this one. It’s a data point, and we should adjust our priors accordingly.

    Finally, there are limitations to this work. They did adjust for the presence of depression in mothers, but not necessarily the severity. It’s possible that the most severe cases were treated with antidepressants, and that’s what’s related to ASD in kids, not the drugs. It’s possible that mothers presceibed antidepressants are more plugged into the health system, and their kids were more likely to get a diagnosis of ASD than those whose mothers aren’t as plugged in. It’s possible that just filling a prescription is not a great marker for actual antidepressant use in pregnancy. It’s possible the premies might have made a difference if they were included. It’s possible something else is at play that we are all missing.

    Here’s the tl;dr: This was a statistically significant finding, but from a relatively small group of children regardless of the size of the entire cohort. It’s only significant for SSRIs and in the second and/or third trimester, which is 22 kids total. The absolute risk increase was only 0.5%. There are limitations to the study, and other studies have found different results. My take home would be that this deserves more work and attention, and that any potential harms from the antidepressants should be weighed against the known benefits for these pregnant moms. They should discuss that with their physicians.


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