The use of paracetamol during pregnancy is not linked to autism ADHDeven though it may lead to it fertility problems in the future, a few studies suggest.
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 linked to birth defects.
However, the medicine does has sparked controversy in recent years over claims that it could increase the risk of children being born with neurodevelopmental disorders such as autism.
In a new analysis of two decades of health records from more than 120,000 children, researchers disputed these claims. The team found that exposure to paracetamol, called acetaminophen in Europe, during pregnancy was not associated with an increased risk of a diagnosis of autism.
In addition, data from a further 100,000 children showed no increased risk of an ADHD diagnosis in children born to mothers who took paracetamol during pregnancy.
The researchers warned that mothers who skip acetaminophen to treat fever or severe pain could prompt them to use unsafe alternatives or develop complications such as birth defects, premature labor and miscarriage.
In contrast, a second study from Denmark found that girls whose mothers took acetaminophen while pregnant had smaller ovaries, uteruses, ovarian follicles and lower levels of reproductive hormones as babies.
The team noted that these changes could lead to fertility problems later in life, although they warned mothers ‘not to be alarmed’ and should discuss the use of paracetamol with their doctor.
A few studies have found that while acetaminophen has not been linked to autism or ADHD, it may increase the risk of fertility problems in offspring later in life (stock image)
These two studies come as one in 31 American children now has autism, up from one in 150 in the early 2000s.
Experts are still unraveling the specific causes of the increase in cases, although they speculate that it may be due to increased awareness and screening, as well as potential environmental problems.
ADHD is also on the rise in the US, in both children and adults. The latest figures from the Center for Disease Control and Prevention show that seven million American children were diagnosed with the neurodevelopmental disorder in 2022, up from six million in 2016.
Recently Data from Yale University also shows that between 2021 and 2024, for the first time, rates of ADHD increased by 61 percent in adults aged 30 to 44 and by 64 percent in adults aged 45 to 64.
From the Chinese study, published in JAMA Internal Medicineresearchers looked at electronic medical records to identify pregnancies in which the mother received a prescription for acetaminophen and then created a group of mother-infant pairs from January 2001 through December 2023.
Paracetamol is usually sold without a prescription, but higher doses may only be available with a prescription.
The team looked at 124,333 children, almost evenly split between men and women, and assessed them for autism diagnoses. The children were on average nine years old. There were 3,445 autism diagnoses in this group, a rate of 2.8 percent.
The ADHD analysis included 97,285 children who were on average seven years old and were evenly split between males and females. There were 5,168 ADHD diagnoses among this group, a rate of 5.3 percent.
Women who used acetaminophen during pregnancy were likely to be older, have pre-existing conditions such as psychiatric disorders, and more common indicators of use such as infection, fever, or chronic pain, compared with 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 link between prenatal paracetamol use and autism or ADHD. There was also no difference between taking the drug in a specific trimester or at different frequencies, such as intermittently or daily. Higher maternal age and pregnancy in women over 35 years also did not play a role.
‘Paracetamol remains a safe and essential painkiller [pain reliever] and antipyretic [fever reducer] during pregnancy, while alternatives, such as NSAIDs and opioids, carry well-documented risks,” the Hong Kong Hospital Authority researchers wrote.
‘Unfounded reluctance to use paracetamol may lead to under-treatment of pain and fever, or to the use of more harmful alternatives, both of which carry risks for pregnancy and fetal development.’
The authors also noted that mothers should evaluate their use of acetaminophen under the guidance of their doctor.
In the second study, published in the journal Human reproduction openedresearchers from Copenhagen University Hospital evaluated 685 pregnant women without pre-existing conditions enrolled during their first trimester, along with 302 young daughters.
Participants visited the testing facility three times during the study: during the first trimester, the third trimester, and a screening when the babies were three months old.
This is around the time babies experience mini-puberty, a surge of reproductive hormones caused by the reproductive system temporarily waking up. This usually settles within a few months or a maximum of one to two years.
Baby girls experience high levels of follicle-stimulating hormone (FSH) and estradiol (estrogen), both of which control egg development, regulate the menstrual cycle, and stimulate ovulation.
Pregnant women in the study completed questionnaires every two weeks about their use of pain-relieving medications such as paracetamol. Baby girls were given an ultrasound to assess 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 childhood to adolescence and whose mothers reported acetaminophen use during their third trimester.
The team found that three-month-old baby girls exposed to the drug in the womb had, on average, 40 percent less ovarian volume, 13 percent smaller uterine volume and 23 percent fewer ovarian follicles. Those exposed in the first trimester also had lower levels of the anti-Müllerian hormone, which serves as a marker of ovarian function.
In the group of older girls, those exposed to acetaminophen in utero were more likely to have smaller uteruses at puberty and smaller ovaries in their teens.
‘Animal studies have shown that reduced ovarian follicle formation can lead to reduced fertility and earlier reproductive aging,’ says Dr Margit Bistrup Fischer, lead author of the study and postdoctoral researcher at 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.’
However, she cautioned that women who have taken paracetamol during pregnancy ‘should not be alarmed by our findings’, as the study found associations rather than direct causation, and the outcomes for individual women and children are unclear.
‘It is important that our research 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.’
