Using acetaminophen during pregnancy is not associated with an increased risk of autism or ADHD in children, according to a major study of health records.
Researchers from the Hong Kong Hospital Authority evaluated more than 120,000 children across two decades of electronic medical data, finding no link between prenatal exposure to the common pain reliever and neurodevelopmental diagnoses.
The research team warned that pregnant women who skip acetaminophen to treat fever or severe pain risk developing serious complications such as birth defects, preterm labor, and miscarriage, or being driven toward unsafe alternative medications.
In contrast, a separate study from Denmark published in Human Reproduction Open found that infant girls whose mothers used acetaminophen during pregnancy had smaller ovaries, smaller uteruses, fewer ovarian follicles, and lower levels of reproductive hormones.
Researchers from Copenhagen University Hospital emphasized that mothers should not be alarmed by the findings, as the study established statistical associations rather than direct causation, though long-term follow-up is needed to evaluate potential impacts on future fertility.
Acetaminophen, widely sold under brand names such as Tylenol and known as paracetamol in Europe, is the active drug in common over-the-counter cold, flu, and pain relievers. It remains the primary pain reliever and fever reducer recommended during pregnancy because alternatives such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, as well as opioids, carry well-documented risks including birth defects.
The drug has drawn controversy in recent years following claims that maternal use could increase the risk of offspring developing neurodevelopmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder (ADHD).
Hong Kong study on autism and ADHD risks
In the Chinese study published in JAMA Internal Medicine, researchers analyzed electronic health records to identify pregnancies where mothers received an acetaminophen prescription, creating a cohort of mother-child pairs between January 2001 and December 2023. Although acetaminophen is usually sold over the counter, higher doses may only be accessible with a prescription.
To evaluate autism outcomes, the researchers tracked 124,333 children with an average age of nine years, split nearly evenly between males and females. Within this group, investigators identified 3,445 autism diagnoses, representing a rate of 2.8 percent.
For the ADHD analysis, the team examined data from 97,285 children with an average age of seven years, also split evenly between males and females. A total of 5,168 children in this group were diagnosed with ADHD, yielding a rate of 5.3 percent.
The analysis revealed no association between prenatal acetaminophen use and autism or ADHD. The findings remained consistent regardless of whether the drug was taken during a specific trimester or used at different frequencies, such as intermittently or daily. Advanced maternal age, defined as pregnancy in women over 35, also did not play a role in the results.
Women prescribed acetaminophen during pregnancy were more likely to be older, to have pre-existing conditions such as psychiatric disorders, and to present with common medical indicators for use, including infection, fever, or chronic pain, when compared to mothers who were not prescribed the drug.
"Paracetamol remains a safe and essential analgesic [pain reliever] and antipyretic [fever reducer] during pregnancy, whereas alternatives, such as NSAIDs and opioids carry well-documented risks," the researchers from the Hong Kong Hospital Authority wrote.
The authors added: "Unwarranted reluctance to use paracetamol could lead to undertreatment of pain and fever, or the use of more harmful alternatives, both posing risks to the pregnancy and developing fetus." They noted that mothers should evaluate their acetaminophen use under their doctor's guidance.
Surge in US autism and ADHD cases
The findings arrive as neurodevelopmental diagnoses continue to rise sharply in the United States, where one in 31 children now has autism, compared to one in 150 in the early 2000s. Experts are still unraveling the specific causes behind the increase, speculating that it may stem from heightened public awareness and expanded screening, as well as potential environmental concerns.
ADHD diagnoses are also on the rise among American children and adults. The latest figures from the Centers for Disease Control and Prevention (CDC) indicate that seven million US children were diagnosed with the neurodevelopmental disorder in 2022, up from six million in 2016.
Recent Yale University data shows that between 2021 and 2024, first-time ADHD diagnoses surged 61 percent in adults aged 30 to 44 and rose 64 percent in adults between 45 and 64 years old.
Danish findings on female reproductive organs
In the second study, researchers from Copenhagen University Hospital evaluated 685 pregnant women with no pre-existing conditions who enrolled during their first trimester, along with 302 of their infant daughters. Participants visited the testing facility three times during the study: during the first trimester, during the third trimester, and for a screening when the babies were three months old.
This three-month screening takes place around the time infants experience mini-puberty, a temporary surge of reproductive hormones caused by the reproductive system awakening, which usually settles within several months or up to one to two years. Infant girls experience high levels of follicle-stimulating hormone (FSH) and estradiol, an estrogen hormone, both of which control egg development, regulate the menstrual cycle, and drive ovulation.
Pregnant women in the study completed questionnaires every two weeks detailing their use of analgesic medications such as acetaminophen. Infant girls received ultrasound scans to evaluate the size of their reproductive organs, alongside blood tests to measure hormone levels.
Researchers also examined a separate group of 1,210 girls who were followed from infancy to adolescence and whose mothers reported acetaminophen use during their third trimester.
The team found that three-month-old infant girls exposed to acetaminophen in utero had an average of 40 percent smaller ovarian volume, 13 percent smaller uterine volume, and 23 percent fewer ovarian follicles. Those exposed in the first trimester also had lower levels of Anti-Müllerian hormone, which serves as a marker for ovarian function.
In the group of older girls, those exposed to acetaminophen in the womb were more likely to have smaller uteruses at puberty and smaller ovaries in their teenage years.
Potential implications for female fertility
"Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging," said Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark.
"Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort," Dr Fischer said.
However, she cautioned that women who used acetaminophen in pregnancy "should not be alarmed by our findings," noting that the study found statistical associations rather than direct causation, and that individual outcomes remain unclear.
"Importantly, our study does not evaluate whether [acetaminophen] causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause," she added.
"Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life," Dr Fischer said.
