Two recent studies showed negative effects from painkillers like acetaminophen (Tylenol) in pregnancy—even though pregnant women are given the OK to take them. So are they really safe?

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You may know that some medications aren't safe to take while pregnant, but you've probably received the green light from your doctor to take Tylenol. However, a 2016 study published in the journal Scientific Reports showed that there could be consequences from taking the drug acetaminophen (the active ingredient in Tylenol), as well another painkiller in the same class as ibuprofen (the active ingredient in Advil), during pregnancy. In addition, another study published in the International Journal of Epidemiology found that children of women who took acetaminophen while pregnant had a higher risk of asthma.

Does Acetaminophen Alter Reproductive Systems?

In the first study, researchers tested rats to see if exposing them to painkillers had any effect on their babies. The rodents were given acetaminophen or indomethacin, an NSAID (nonsteroidal anti-inflammatory drug) similar to ibuprofen. With both drugs, the rats had female babies with fewer eggs, smaller ovaries, and smaller litters themselves as adults. Male babies had a smaller number of cells that led to sperm later in life, but they bounced back to normal by adulthood. Even more concerning was that the granddaughters of the rats who were given the drugs also had smaller ovaries and reduced reproductive function. 

What could be causing the medications' impact on fertility? It has to do with the painkillers' effects on prostaglandins, hormones that regulate female reproduction, including ovulation, menstruation, and even the start of labor. These hormones can also cause pain and inflammation, so painkillers work to lower them—but, in pregnant women this may have unintended consequences to the development of their babies' reproductive systems. Specifically, the drugs may have negative effects on the fetuses' "germ cells," which grow into eggs and sperm.

Although the study was performed in rats, it may be applicable to humans—but that's still far from certain. "It's important to remember that this study was conducted in rats not humans; however, there are many similarities between the two reproductive systems," says Richard Sharpe, Ph.D., who co-led the study at the University of Edinburgh's MRC Centre for Reproductive Health in the U.K. "We now need to understand how these drugs affect a baby's reproductive development in the womb so that we can further understand their full effect."

In addition, more research is needed to see what the minimum dosage to have these negative effects would be for humans. Sharpe and his colleagues gave the rodents an acetaminophen dose higher than the equivalent in humans, but rats are less sensitive to it so the amount used may actually be comparable. The dose of indomethacin was similar to the equivalent in humans. "Assuming the rat effects would also occur in humans, we do not know how long an exposure would be necessary, though we suspect that it would be longer rather than shorter than for the rats," Sharpe says. "We see some effects of just one dose of indomethacin on fetal ovaries in rats, so we do not even know for sure what is the minimum time of exposure necessary to induce effects in rats, let alone humans."

Another issue in figuring out safety of the drugs for humans is how early in pregnancy they are taken. "It is likely that 'when' exposure occurs is as important as 'for how long,'" Sharpe says. "We suspect that exposure early in pregnancy—before 12 weeks—will be most important."

Tylenol During Pregnancy and Asthma Risk

Another study that actually did involve humans showed that the children of moms who had taken acetaminophen in pregnancy were more likely to have asthma at three and seven years old. Researchers in Europe looked at data from 114,500 children in Norway to compare those who had asthma (5.7 percent at three years old and 5.1 percent at seven) with those whose moms had taken acetaminophen during pregnancy, and found a link.

Even more important, the researchers were able to see why the moms had taken the med—for fever, pain, or the flu—and to compare to moms who had the same symptoms but didn't take the drug. By looking at the data this way, they were able to rule out the symptom itself as being a reason for the increase in asthma risk. In addition, they looked at the mothers' and fathers' acetaminophen use outside pregnancy, to confirm that it was the drugs' use during pregnancy specifically, and not any outside factors or health behaviors, that was the cause. The study authors theorize that the drug could cause an increase in "oxidative stress" (the difficulty of the body to fight off toxins) during pregnancy, which is thought to raise the risk of asthma.

Although there have been other studies that looked at acetaminophen use during pregnancy and asthma, this was the largest, and the first to compare pregnant moms' symptoms with and without the drug to the risk of childhood asthma. But, the study authors weren't able to confirm the severity of the mothers' symptoms, or how much acetaminophen the pregnant women took.

Should You Take Advil or Tylenol While Pregnant?

Advil is already not recommended in pregnancy, especially during the last trimester, because of the risk of certain birth defects and complications for delivery. Tylenol is generally considered safe in pregnancy—although the FDA did recently review its position based on other studies concerning acetaminophen's safety, and found the research "too limited" to make any recommendations against its use.

The benefits of taking any drug during pregnancy have to be weighed against the risks—being in a lot of pain during pregnancy isn't good either. The authors of both studies advise pregnant women to stick with the current recommendations for now. But, Sharpe does recommend to use the lowest possible dose for the shortest period of time, just to be on the safe side.