The Risks Of Taking Antidepressants While Pregnant

Looking at how antidepressants may relate to or cause birth defects is a complicated picture: there are lots of types of antidepressant and even more birth defect categories, for one. And the outcome seems to depend on when the antidepressants are taken. We're building up a picture, but bits of it are still contradictory or require more study.

A major study published in 2015 in the British Medical Journal, looking at nearly 28,000 mothers in the U.S. over 12 years and first-trimester antidepressant use, found that there were links between taking the SSRI paroxetine and five birth defects (anencephaly, atrial septal defects, right ventricular outflow tract obstruction defects, gastroschisis, and omphalocele). The antidepressant fluoxetine, often marketed as Prozac, was also found to be potentially linked to right ventricular outflow tract obstruction defects and craniosynostosis. For other types of antidepressants, like citalopram, they issued the all-clear.

But the story doesn't end there. A study that came out this month (also in the BMJ, funnily enough) looked at a cohort of nearly 19,000 pregnant Quebec women in their first trimesters, and wasn't nearly as comforting about citalopram, or antidepressants in general. Their data showed that, compared to women who weren't taking antidepressants, the statistical risk of birth defects ranged across the gamut of the drugs. Paroxetine featured once again, but tricyclic antidepressants also increased the risk of birth defects around the face and the digestive system, the SNRI venlafaxine increased respiratory problems, and citalopram carried risks of musculoskeletal and skull growth problems.

The main problem they're targeting, apparently, is serotonin and how it's used in pregnancy. "Serotonin," the scientists behind the 2017 study explain, "is essential for healthy fetal development," and numerous experiments have shown that maternal serotonin plays a big role in how a baby's brain, heart, and other organs evolve. Antidepressants that interfere with serotonin re-uptake might have an impact on fetal development, but we're not completely sure of what exactly happens, or why different kinds seem to target different types of defects.

The data on this one is seriously contradictory. There are two different camps: one that insists the science indicates there's a definitive link between autism in children and antidepressant use in pregnancy, and another that finds things a lot less conclusive. It's an issue confused by the fact that "antidepressants cause autism" headlines can take up a lot of energy, so let's look at the science.

It's not a case of earlier science being refuted by new studies: the two perspectives are occurring at the same time. Two big recent studies in 2014 and 2015, for example, show a link between antidepressant use in pregnancy and autism diagnoses in children later, and the 2015 one has the interesting caveat that it only focussed on antidepressant use in the 2nd and 3rd trimesters, which are hugely important for human brain development. Other studies, though, argue that the link may be down to women's depression itself, not the antidepressants.

One in 2016 for example, showed that the risk of autism in children seems to be higher in women who were having treatment for serious depression, and antidepressants weren't the relevant factor. Another in 2013 analyzed the mental health of the mothers, the children, and their siblings, and found that mental health diagnoses seemed to be the issue. So is it all about depression in mothers, are antidepressants just a symptom rather than a cause, or does taking them in pregnancy also make autism risk worse? We're still working on it.

In 2016, Finnish scientists found that, when studying a cohort of nearly 25,000 women, their use of antidepressants during pregnancy (SSRIs, specifically) raised the risk of their newborns having a longer umbilical cord. The scientists think this may be down to "the tendency of SSRI antidepressants to induce increased fetal movement in the uterus, which may in turn lead to lengthening of the umbilical cord."

Not such a big deal, right? Well, not so much. Longer umbilical cords, the scientists point out, aren't just a risk to the fetus's health from wrapping around their necks; they're also associated with poor fetal circulation and brain imaging issues. A 2012 study also found that abnormally long cords increase the risk of cord prolapse, fetal distress and labor issues. In general, not a great outcome.

When it comes to the interaction between a mother's mental health, her antidepressant use during pregnancy, and the mental health of the resulting kids, there's some pioneering work explaining how the relationship might be a pretty complex one. And yes, antidepressants do seem to have a role to play.

A 2015 study from Norway, for instance, found that while maternal depression did seem to create a stronger possibility of anxiety in kids at three years old, those who'd been exposed to antidepressants in the womb were even more likely to be anxious. And 2016 data from Finland looked at depression in adolescents, and found that antidepressant use in pregnancy did in fact cause a greater spike in depression symptoms than just having mothers who were depressed and unmedicated while pregnant. Mom's mental health, in other words, definitely seems to impact the mental problems of her offspring, but antidepressants during pregnancy may exacerbate the issue.

This is based on one of the biggest studies of pregnancy around: a whopping 3.8 million women's data, examined in 2015 by the Journal of the American Medical Association. Persistent pulmonary hypertension of the newborn, or PPHN as it's called, is a hugely problematic birth defect that has a pretty high fatality rate, and the data of the 2015 study found that, while it's still very rare, using antidepressants late in pregnancy seemed to create a slight uptick in its likelihood. The rate of PPHN in babies who'd had no exposure to antidepressants of any kind was 20.8 per 10,000. In babies who'd been exposed to SSRIs, it was 31.5 infants, while non-SSRIs created a rate of 29.1 infants. That's still a minuscule risk, but it was elevated enough for the scientists to warn about it.

Worries about the impact of antidepressant use on the actual birth of babies date back a while. A study back in 2010, for instance, used the famous Quebec Pregnancy Register (which has been the basis for a bunch of these studies) and found that 5.5 percent of the women who'd had a miscarriage had taken antidepressants in their pregnancy. SSRIs, SNRIs, and combined antidepressants showed slight upticks, but the real problems were paroxetine, venlafaxine, or combining several ones at once.

We're accumulating new data based on specific patterns of antidepressant use. A study from 2015, for example, found that taking antidepressants in the final trimester virtually doubled the risk of severe blood loss in women postpartum, while British research released in 2016 found a link between antidepressant use in the first trimester and a small, but significant, increase in the risk of stillbirths. And 2016 research in the International Journal Of Epidemiology discovered that babies who'd been exposed to antidepressants for two or more trimesters were more likely to be born prematurely and to have a lower birth weight, something the researchers concluded couldn't be explained by genetics or other factors. Unfortunately, if you take this science in bulk, it looks as if there's not a "safe" time or way to take antidepressants while a baby's gestating.