http://www.nytimes.com/2016/09/25/opinion/sunday/the-trouble-with-tylenol-and-pregnancy.html 2016-09-24 21:18:59 The Trouble With Tylenol and Pregnancy The drug appears to increase the risk of asthma or developmental problems in children. === If you’re a pregnant woman and have a But evidence has accumulated that, when taken during pregnancy, acetaminophen may increase the risk that children will develop The odd thing about acetaminophen is that even after decades of widespread use, no one knows precisely how it blunts pain. But it has earned a reputation for strange side effects. Experiments indicate that it impedes people’s ability to empathize. It The prevalence of asthma doubled between 1980 and 2000. At the same time, worries over Reye’s syndrome, a rare complication in children who take aspirin, led to a rise in the popularity of acetaminophen. On the basis of this circumstantial — and rather weak — evidence, 16 years ago, scientists at King’s College London proposed a link between rising acetaminophen use and the so-called asthma epidemic. Their reasoning was that acetaminophen depleted the body’s native antioxidant, called glutathione, spurring inflammation of the lungs. Numerous studies followed showing an association with asthma, but they often relied on mothers’ potentially unreliable memories of what they took, or simply compared one group — mothers of asthmatic children, say — to a control group, a suboptimal study design. Recently, however, much stronger studies showing a link have emerged. Then, in August, Of course, some familial trait may push people to reach for acetaminophen, and this quality, as opposed to the drug itself, may explain the increased risks. But that doesn’t seem to be the case. A mother’s use Still, the authors are the first to note that perhaps they missed something. They don’t always know how much of the drug women take, or why they’re taking it. And there are reasons to think that the infections whose symptoms women might be treating with the pain reliever could themselves increase the risk of asthma and developmental problems. And yet these and some previous studies controlled for infections, and the association remained. Not all of the research has confirmed the relationship. But at this point, the number of strong studies that do find a link are hard to overlook, and are unnerving. Moreover, there’s evidence that the drug interacts more strongly with certain genotypes. Some of us carry gene variants that naturally alter the activity of the antioxidant glutathione, reducing its ability to detoxify. A Petra Arck, a professor of fetal-maternal medicine at the University Medical Center Hamburg-Eppendorf, and colleagues gave the pain reliever to pregnant mice, and found it stressed the liver, altered the placenta and increased the pups’ vulnerability to wheezing. During pregnancy, the immune system must tolerate the fetus, which is half foreign, while also retaining enough firepower to fend off pathogens. Professor Arck argues that the drug can interfere with this balancing act. But two other mouse studies found no such effect on asthma or behavior. A major difference is the amount of acetaminophen given to the animals. Professor Arck used a big dose. The other two studies used less. Antonio Saad, a researcher at the University of Texas Medical Branch at Galveston whose own study failed to produce A.D.H.D.-like symptoms in mice, thinks that Professor Arck used an unrealistically high amount. But the dose was intentional, Professor Arck told me. Acetaminophen is in hundreds of medications, making it easy for pregnant women to take too much. Professor Arck thinks some women overdose without knowing it. Last year, the Food and Drug Administration reviewed evidence on acetaminophen and developmental outcomes and deemed it “inconclusive.” That was before the more recent studies appeared. When I asked, an F.D.A. spokeswoman told me that the F.D.A. was “actively reviewing” the new research. A spokeswoman for Johnson & Johnson, the maker of Tylenol, said the company wasn’t aware of evidence showing a “causal link” between prenatal use and later problems, but recommended discussing risks and benefits with a doctor. The greater problem is that the kind of study that would definitively answer the prenatal acetaminophen question — a trial on pregnant women — is unlikely to happen, because such studies are generally considered unethical. This leaves mothers-to-be awash in uncertainty when contemplating a drug that’s widely recommended. So what to do? No one I spoke with proposed they avoid acetaminophen outright. There’s nothing else to take. And untreated fever during pregnancy can have severe consequences, premature birth among them. Instead, experts suggested that women use the minimum amount possible. Augusto Litonjua, a pulmonologist at Harvard Medical School who follows the research, noted that if women found themselves taking lots of acetaminophen, maybe they should consider non-pharmacological approaches to pain management, like The broader takeaway, said Evie Stergiakouli, lead author on the JAMA study, is that just because acetaminophen is easy to acquire doesn’t mean it’s not a drug, and that it doesn’t have potential side effects.