In 2016, a team of Danish researchers published a study that showed people taking the drug fluconazole during pregnancy had a higher risk of spontaneous abortion. That finding made health agencies like the Food and Drug Administration (FDA) sit up and take notice. Fluconazole is one of the most common prescription medications used to treat yeast infections—which pregnant women are particularly likely to develop.

In Canada, the Drug Safety and Effectiveness Network turned to Anick Bérard, research chair on medications, pregnancy, and lactation at the University of Montreal, and asked her to take an additional look at the drug.

Her team found that women who took the antifungal medication during the first trimester of pregnancy, at both low and high doses, were more likely to have a pregnancy loss, in a study published this week of 320,868 spontaneous abortions. The results are consistent with the findings of the Danish research, says Berard—but even though they showed an increased risk, they’re actually reassuring. “The risk is small,” she says.

Adding more data onto the Danish study helps build a fuller picture of the risks associated with fluconazole, says Vanessa Paquette, a clinical pharmacy specialist at BC Women’s Hospital and Health Centre, who published a commentary on the study. That’s important, because observational studies are the only way to study drugs in pregnant women—randomized trials testing a drug during pregnancy aren’t ethical, and the best way to get better information is by following more people.

It also means, Paquette says, that doctors can’t say that the drug caused a pregnancy loss. “You can never say there’s a cause and effect, and don’t want to scare people,” she says. “If you take fluconazole, and have a miscarriage, no one would say that was the cause.”

The study identified women within the Quebec Pregnancy Cohort who were prescribed both low and high doses of fluconazole early in their pregnancy. Doctors were already aware that high doses of fluconazole were associated with an increased likelihood of birth defects, and that relationship has been identified in animal studies, as well. However, less is known about how lower doses affect pregnancy, Berard says. “Given the majority of women with yeast infections in pregnancy will take low doses, we wanted to know the risk associated,” she says.

The analysis showed an increased risk for spontaneous abortion at both dosages. The researchers also looked at major birth defects and stillbirths—they found no association between the drug and stillbirths, and found that a high dose of the drug was associated with a small increase in risk for certain birth defects.

However, says Berard, the risk for spontaneous abortion in the first trimester is already around 6 percent. A low dose of fluconazole doubles the risk, based on the study findings, and a high dose triples that risk—but that still means the risk is relatively low. “Even if you take a high dose, and have three times more risk, you still, at worst case, will have around an 80 percent chance of not having a spontaneous abortion,” she says.

There are also alternative treatments available for yeast infections, notes Paquette. The first-line treatment is usually a topical, over the counter cream, which usually can take care of the problem—and they’re just as effective as an oral antifungal. If those don’t work, it’s often because the treatment wasn’t used for long enough. “In pregnancy, it’s not recommended to use the one or two or three day treatments, studies show you should use the seven day treatments,” she says. “Any time there is a failure in therapy, [the solution is] not as simple [as] just using the oral option.” You must ask whether the therapy was used correctly and if the diagnosis was correct, she says, before turning to fluconazole.

If situations emerge where fluconazole became an important option, Paquette says, physicians would have a conversation about the potential risk. “I’d say, it’s unclear if the risk exists but an association has been seen, and it’s very small,” she says.

Berard says that the findings do not mean that people who are pregnant should never take the drug, she says. “It’s always a risk-benefit analysis. Our study did not look at the benefits of fluconazole, or the risk of not treating yeast infections,” she says. “It’s a decision that’s made with all the evidence between the physician and the woman.”

And though the risk exists, it’s important to treat yeast infections, which are uncomfortable and reduce quality of life, Berard says. “We tend to forget that pregnant women do get sick, and need to be treated.”