Using acetaminophen during pregnancy is not linked to autism or ADHD, though it may lead to fertility issues in the future, a pair of studies suggests.
Acetaminophen, the active ingredient in Tylenol, is the only over-the-counter pain and fever reliever recommended for pregnant women, as alternatives such as ibuprofen have been associated with birth defects.
However, the drug has drawn controversy in the past several years over claims that it may increase the risk of children being born with neurodevelopmental disorders such as autism.
In a new analysis of two decades’ worth of health records from more than 120,000 children, researchers disputed these claims. The team found exposure to acetaminophen, called paracetamol in Europe, in pregnancy was not associated with an increased risk of having an autism diagnosis.
Additionally, data from another 100,000 children showed no increased risk of an ADHD diagnosis in children born to mothers who used acetaminophen while pregnant.
The researchers warned that mothers skipping acetaminophen to treat a fever or severe pain could drive them to use unsafe alternatives or develop complications such as birth defects, preterm labor and miscarriage.
In contrast, however, a second study out of Denmark found that girls whose mothers took acetaminophen while pregnant had smaller ovaries, uteruses, ovarian follicles and lower levels of reproductive hormones as infants.
The team noted these changes could lead to fertility issues later in life, though they cautioned mothers ‘should not be alarmed’ and should discuss acetaminophen use with their doctor.
A pair of studies found that while acetaminophen was not associated with autism or ADHD, it may increase the risk of fertility issues in offspring later in life (stock image)
The pair of studies come as one in 31 US children now have autism, up from one in 150 in the early 2000s.
Experts are still unraveling the specific causes of the increase in cases, though they have speculated it may be due to increased awareness and screening, as well as potential environmental concerns.
ADHD is also on the rise in the US in both children and adults. The latest Centers for Disease Control and Prevention figures suggest seven million American children were diagnosed with the neurodevelopmental disorder in 2022, up from six million in 2016.
Recent Yale University data also shows that between 2021 and 2024, first-time ADHD diagnoses surged 61 percent in adults ages 30 to 44 and 64 percent in adults between ages 45 and 64.
In the Chinese study, published in JAMA Internal Medicine, researchers looked at electronic health records to identify pregnancies in which the mother received an acetaminophen prescription and then created a group of mother-child pairs from January 2001 through December 2023.
Acetaminophen is usually sold over the counter, but higher doses may only be accessible with a prescription.
The team looked at 124,333 children, split nearly evenly between males and females, and evaluated them for autism diagnoses. Children were nine years old on average. There were 3,445 autism diagnoses in this group, a rate of 2.8 percent.
The ADHD analysis included 97,285 children who were seven years old on average and split evenly between males and females. Among this group were 5,168 ADHD diagnoses, a rate of 5.3 percent.
Women who took acetaminophen during pregnancy were more likely to be older, have pre-existing conditions such as psychiatric disorders and more common indicators for use such as infection, fever or chronic pain compared to those who were not prescribed the drug.
Acetaminophen is the active drug in Tylenol and other common over-the-counter cold, flu and pain relievers. It is the only recommended pain and fever reliever for pregnant women
Researchers found no association between prenatal acetaminophen use and autism or ADHD. There was also no difference in taking the drug in a specific trimester or at different frequencies, such as intermittently or daily. Advanced maternal age, pregnancy in women over 35, also did not play a role.
‘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 Hong Kong Hospital Authority, wrote.
‘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.’
The authors also noted mothers should evaluate their acetaminophen use with their doctor’s guidance.
In the second study, published in the journal Human Reproduction Open, researchers from Copenhagen University Hospital evaluated 685 pregnant women with no pre-existing conditions who were enrolled during their first trimester, along with 302 infant daughters.
Participants visited the testing facility three times during the study: during the first trimester, third trimester and a screening when the babies were three months old.
This is around the time infants experience mini-puberty, a surge of reproductive hormones caused by the reproductive system temporarily awakening. This usually settles within several months or up to one to two years.
Infant girls experience high levels of follicle-stimulating hormone (FSH) and estradiol (estrogen), both of which control egg development, regulate the menstrual cycle and drive ovulation.
Pregnant women in the study completed questionnaires every two weeks about their use of analgesic medications such as acetaminophen. Infant girls were given an ultrasound scan to evaluate the size of their reproductive organs and blood tests to measure hormone levels.
Researchers also looked at 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 the drug 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 teen years.
‘Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging,’ Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark, said.
‘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.’
However, she cautioned that women who have used acetaminophen in pregnancy ‘should not be alarmed by our findings,’ as the study found associations rather than direct causation, and outcomes for individual women and children are 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 said.
‘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.’
