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When U.S. Chairwoman Donald ruff and wellness secretarial assistant henry martyn robert F. Kennedy Jr. Promoted unsupported warnings last fall about acetaminophen use in pregnancy, Canadian doctors began fielding worried questions from patients and colleagues about whether the common pain and fever medication was safe.
A new practice paper in this week's CMAJ says the latest, highest-quality evidence is reassuring for pregnant people who need acetaminophen, also known as paracetamol and sold under the brand name Tylenol, when it is used as directed.
The episode is a high-profile example of why so-called null findings — studies that find no link or no difference — matter. Often known as the "file drawer problem," these findings can sit unpublished or overlooked because they may seem like scientific dead ends. But doctors and researchers say they can help patients make safer decisions, counter health misinformation and prevent unnecessary changes in care.
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Dr. Jonathan Zipursky, an internist at Sunnybrook Health Sciences Centre in Toronto and one of the CMAJ paper's authors, said the paper was prompted by the U.S. Messaging last fall.
"We found that there were a lot of questions we were getting clinically also from colleagues about its safety with pregnancy and a lot of mixed messaging to patients," Zipursky said.
"We wanted to write a paper to provide guidance to clinicians in Canada and elsewhere about our interpretation of the data and how we would approach speaking to patients and their families about the use of acetaminophen for treatment of pain and fever in pregnancy."
The best-designed studies have typically found no association between acetaminophen use in pregnancy and a child's risk of neurodevelopmental disorders such as autism.
Trump's messaging on acetaminophen "created an unnecessary public health crisis around what women can take safely during pregnancy," said Dr. Kamran Abbasi, editor-in-chief of the British Medical Journal.
"The research that refutes that frankly false statement does not get the same amplification or the same publicity that disinformation did, so I think it's a big problem, unfortunately," Abbasi said. "We need politicians to be more responsible."
Some studies have suggested taking acetaminophen in pregnancy may be associated with autism spectrum disorder or ADHD in children. But Abbasi said that association disappears in sibling-pair studies, which compare siblings from the same family and are better designed to reduce bias from genetics, environment and other factors.
He said the problem is not just acetaminophen. In medicine, early positive findings often get attention before later null findings emerge. If only positive signals shape medical practice, health systems can waste money and patients can be harmed, he said.
Viktor Ahlqvist, a postdoctoral researcher at the Karolinska Institute in Stockholm, said null findings are one way to counter medical hype.
"The medical field really suffered from this problem that we had a lot of initial hype about something which then couldn't be replicated," said Ahlqvist, an epidemiologist who conducted a large investigation into acetaminophen use during pregnancy and children's risk of autism, ADHD and intellectual disability.
Ahlqvist said if research journals, pharmaceutical companies and news media were more open to null findings, then money would not be wasted and progress delayed.
Parents, autism advocates and researchers push back on Trump's Tylenol claims
The Swedish sibling study on acetaminophen has now been supported by findings in Taiwan and Japan, which obstetricians say adds reassurance about using the pain reliever in pregnancy when medically indicated.
Ahlqvist said stronger effects are easier to spot quickly, while subtle or absent effects take more work to confirm. He compared it to noticing a black stripe on a green wall versus trying to tell apart two nearly identical shades of green.
"I could probably spot it if I scrutinized it very heavily under a light, but the bigger the difference, the easier it is to spot. And that's the same in science and the same in statistics," he said.
Dr. Arun Sundaram, a neuro-ophthalmologist at Sunnybrook, said another useful null finding came from research into whether hormonal contraceptives are safe for women with idiopathic intracranial hypertension, or IIH.
The disorder causes increased pressure around the brain and can lead to chronic headaches and vision problems. Left untreated, it can cause irreversible vision loss.
Sundaram and his co-authors reviewed the medical literature and found no association between taking hormonal birth control and IIH.
Some physicians may avoid prescribing hormonal contraceptives out of concern they could worsen the condition, Sundaram said, "leading to unwanted sufferings for the patients with gynecological problems like PCOS, painful and excessive menstruation and lack of contraception."
The null finding means doctors can be more comfortable continuing contraceptives for those patients, he said.
Abbasi said the lesson extends beyond acetaminophen: patients, doctors and drug companies can all become invested in a promising treatment. But rigorous testing sometimes shows the idea does not hold up — and those null findings need to be heard, too.
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