A new study of more than two million births found that children whose mothers were prescribed acetaminophen, best known by the brand name Tylenol, during pregnancy were slightly more likely to be diagnosed with attention-deficit/hyperactivity disorder (ADHD) or autism — but the link disappeared when researchers compared those children with their siblings.
The study is one of the largest investigations to examine whether prenatal exposure to acetaminophen is connected to neurodevelopmental conditions.
With the new study, “The take-home message seems to be that there is not an association between acetaminophen exposure and autism or ADHD risk, at least when appropriately controlling for other factors,” says Jeremy M. Veenstra-VanderWeele, MD, a professor and autism researcher at Columbia University Irving Medical Center in New York City, who was not involved in the study.
Comparing Tylenol Exposure Between Siblings
For the new study, researchers analyzed national health records from nearly 2.1 million births in Taiwan between 2004 and 2015.
Close to half the children (48 percent) were born to mothers who had at least two prescriptions for acetaminophen during pregnancy. Among all the children:
- 23,557 were diagnosed with autism (1 percent, or 1 in 100 children)
- 116,387 were diagnosed with ADHD (6 percent, or 6 in 100 children)
Children whose mothers used Tylenol during pregnancy had about a 12 percent higher relative risk of ADHD and a roughly 6 percent higher relative risk of autism compared with children who weren’t exposed.
The study also found that higher prescription frequency or higher average daily doses were associated with somewhat higher risks.
But those patterns changed when the researchers compared siblings, which allowed the investigators to better account for factors that families share — such as genetics, education, family income, and aspects of the home environment, including environmental exposures.
This analysis compared siblings born to the same parents but with different levels of prenatal exposure to acetaminophen.
“Any shared underlying risk factors between the siblings will be controlled for in the study design, which is a strength,” says coauthor Zeyan Liew, PhD, MPH, an associate professor of epidemiology at the Yale School of Public Health in New Haven, Connecticut.
When the researchers compared siblings, the link between fetal Tylenol exposure and both ADHD and autism disappeared.
The authors say one limitation of the study is that it relied on prescription records, which may not capture all acetaminophen use — particularly if patients obtained the medication over the counter.
A Puzzling Pattern in the Sibling Data
When researchers looked more closely at the sibling comparisons, they noticed an unexpected pattern.
If only the older sibling had been exposed to acetaminophen during pregnancy, the risk of ADHD or autism appeared higher. But when only the younger sibling had been exposed, the risk appeared lower. For the sibling design to work as intended, researchers would expect results to remain relatively consistent regardless of which sibling was exposed, says Dr. Liew.
This pattern suggests that other factors may be influencing the results, something unmeasured that researchers can’t pin down, he says.
Dr. Veenstra-VanderWeele says this finding shouldn’t be over-interpreted.
This comparison was not the focus of the analysis, and there isn’t an obvious interpretation of what this means. It could relate to other exposures that differ in the population, for example viruses circulating at any given time, he says.
“The overall findings stand, that there is not a clinically meaningful association” between fetal exposure to Tylenol and ADHD or autism, says Veenstra-VanderWeele.
Why Studying Medication Use During Pregnancy Is Challenging
It’s difficult to reach definitive conclusions from studies that examine medication use during pregnancy because researchers cannot randomly assign treatments. In any kind of medical study, it’s unethical to randomly assign some participants to a treatment that may cause harm.
In these scenarios, researchers rely on observational data, which in this case means that the reason women took Tylenol in the first place may be linked to other factors that also affect outcomes. For example, Tylenol is commonly used during pregnancy to treat fever, infection, or pain, which may themselves influence fetal development.
Untreated Fever and Pain Pose Real Risks to Pregnant Women and Unborn Children
Experts agree the findings should not change current pregnancy best practices.
“The bottom line is that these data, while interesting, would not change the current recommendation on Tylenol use in pregnancy,” says Cynthia Gyamfi-Bannerman, MD, a professor of maternal-fetal medicine in the obstetrics and gynecology department at UC San Diego Health Sciences and past president of the Society for Maternal-Fetal Medicine.
“If anything, they suggest that use of Tylenol remains safe,” says Dr. Cynthia Gyamfi-Bannerman, who was not involved in the study.