Acetaminophen & Autism - what does the data say?
On April Fool’s Day in 1961, thalidomide was approved for sale in Canada as a treatment for morning sickness in pregnant women. Within less than a year, it was withdrawn from the market as alarming evidence of severe birth defects began to emerge. Among the most devastating effects was phocomelia — a condition in which babies were born with absent or severely shortened, often flipper-like limbs. In addition to limb malformations, other serious abnormalities were reported, including facial and cranial deformities, as well as defects in internal organs.
South of the border, a battle over thalidomide’s approval unfolded — but it was never authorized in the United States, thanks to the steadfast opposition of US Food and Drug Administration (FDA) reviewer Frances Kelsey, MD, PhD. Her ongoing concerns about the drug’s safety were ultimately validated when reports from Europe linked thalidomide use during pregnancy to a surge in births of severely deformed infants. This public health crisis prompted the passage of the Kefauver-Harris Amendment, which significantly strengthened drug regulation in the US by requiring manufacturers to provide robust evidence of safety, including results from animal testing, before receiving marketing approval. Tragically, although thalidomide was never officially approved in the US, it was nonetheless distributed widely through loosely regulated clinical trials — exposing thousands of patients, including pregnant women, to its devastating effects.
For better or worse, a real-world experiment is now underway. Many women contemplating pregnancy — who may not have been previously aware of this ongoing debate — will now be informed. This heightened awareness is likely to lead to a decline in acetaminophen use during pregnancy. Whether this shift will result in a corresponding change in the incidence of NDDs remains to be seen. In any case, more comprehensive studies are currently underway or being planned, and they should offer more definitive answers to this important question.
For clinicians, this issue can no longer be avoided in patient discussions. Healthcare providers should be transparent about the current state of evidence. While research has yet to reach a definitive conclusion, it would be premature to offer blanket reassurance about the safety of this drug during pregnancy. Patients deserve to know that uncertainty remains, and that ongoing studies may shift our understanding. Presenting the available information honestly allows patients to make informed choices, even in the face of incomplete data.
Stephen A. Hoption Cann, PhD, is a clinical professor and epidemiologist in the School of Population and Public Health at the University of British Columbia in Vancouver. His research focuses on adverse drug effects and infectious disease management.
