South African health professional groups have added their voices to the global outcry against the Trump administration urging pregnant women against using paracetamol (or acetaminophen as it is known in the US), claiming – without definitive evidence – that it is linked to autism, writes MedicalBrief.
President Donald Trump and his health officials warned that acetaminophen, the active ingredient in Tylenol and more than 600 other medications, should be avoided in early pregnancy except in cases of high fever – a sharp pivot in public health guidance which has caused alarm worldwide.
Respected global medical associations, like the World Health Organisation and the American College of Obstetricians and Gynaecologists, and experts have slammed the move, saying the evidence shows that acetaminophen is safe to use during pregnancy.
In South Africa, the South African Society of Obstetricians and Gynaecologists, the Society of Obstetric Medicine South Africa and the SA Society for Ultrasound in Obstetrics and Gynaecology issued a joint statement yesterday, saying they had “carefully reviewed the available evidence, drawing on large cohort studies, systematic reviews, sibling-controlled analyses, and authoritative international assessments”.
They said, in agreement with position statements from several international bodies, there is no evidence that taking paracetamol in pregnancy at recommended therapeutic doses causes autism in children.
The WHO, in its statement on Tuesday, said “neither the painkiller Tylenol nor vaccines have been shown to cause autism”. It added that medical groups have long cited paracetamol as among the safest painkillers to take during pregnancy, reports The Witness.
Treatment recommended
In his announcement, Trump also highlighted leucovorin, a form of vitamin B and a drug used to treat the side effects of certain cancer medications, as a potential autism treatment, The Washington Post reports.
Early trials involving small groups of children have shown encouraging gains in speech, and although researchers emphasise the need for larger studies, the administration said the FDA would move to formally acknowledge the drug’s potential use in autism treatment and ask states to monitor and study its use.
Some expressed concerns that the warnings could prompt pregnant women to avoid Tylenol even when sick, or could push parents to try leucovorin without proper medical oversight and limited understanding of its effectiveness or long-term risks.
What alarms many in the scientific community is the politicised rush to present these drugs as solutions, bypassing the slow, careful work that research demands. They warn that drawing broad conclusions from incomplete evidence isn’t just premature but reckless. And it risks undermining the public trust that is the foundation of public health.
However, the FDA’s notice offered a more measured take on the possibility of a connection between the drug and autism. It noted that a causal link has not been established, but in the “spirit of patient safety and prudent medicine” it urged clinicians to consider minimising its use during pregnancy for routine low-grade fevers.
Kenvue, the company that makes Tylenol, said in a statement that research shows the medication does not cause autism: “The facts are that more than a decade of rigorous research, endorsed by leading medical professionals and global health regulators, confirms there is no credible evidence linking acetaminophen to autism.”
Conflicting evidence
Research into a potential link between Tylenol and autism has produced some conflicting findings. The largest study to date – a 2024 analysis published in JAMA that tracked siblings across Sweden – found no evidence of a connection.
Yet a comprehensive review released this August (in the journal Environmental Health), which pooled all existing studies, did uncover a link. Its authors cautioned that it was too soon to conclude that the medication causes autism, but they did recommend what they called a “precautionary” approach to taking the drug.
“Patients who need fever or pain reduction during pregnancy should take the lowest effective dose of acetaminophen, for the shortest possible duration,” said Andrea Baccarelli, one of the authors and a Professor of Environmental Health at the Harvard TH Chan School of Public Health, in a statement.
Genetic and familial – SA experts
However, the South African experts said that while some early observational studies suggested a small association between prenatal paracetamol exposure and ASD, these analyses were particularly vulnerable to confounding by genetic, familial and environmental factors, and in many cases, relied on self-reported exposure data of limited reliability.
"By contrast, more robust study designs, especially sibling-control analyses, show no increased risk of ASD. The large Swedish population-based study, for example, demonstrated that when shared familial factors were accounted for, the association between paracetamol use and ASD disappeared.
"Comprehensive systematic reviews and meta-analyses confirm this conclusion: once unmeasured confounding is considered, there is no meaningful increase in ASD risk. Together, the evidence strongly suggests that earlier reported associations were explained by confounding rather than a causal effect of paracetamol."
The organisations said it was equally important to consider the consequences of leaving maternal symptoms untreated. "Fever in pregnancy is not benign; it has been associated with miscarriage, congenital malformations including neural tube defects and cardiac defects, preterm delivery and intrauterine foetal demise."
Similarly, severe or persistent pain, if not treated, can have a significant impact on maternal mental health, with clear consequences for both mother and foetus, they said.
"Against this backdrop, paracetamol remains the safest and most effective first-line treatment for pain and fever in pregnancy, as no alternative agent has a superior safety profile. At standard therapeutic doses (500 mg-1 000 mg up to four times daily, to a maximum of 4 g in 24 hours), paracetamol is not associated with an increased risk of adverse pregnancy or child health outcomes," the experts said.
They added that clinical practice should not change. Paracetamol remains an essential, safe, and effective treatment for fever and pain in pregnancy, and pregnant women should not be denied appropriate care because of unsubstantiated claims.
The statement was issued by Dr Jarrod Zamparini – President: Society of Obstetric Medicine South Africa, Dr Samantha Budhram: President South African Society of Ultrasound in Obstetrics and Gynaecology, and Professor Ismail Bhorat: President South African Society of Obstetricians and Gynaecologists.
WHO confirms no link
WHO spokesman Tarik Jasarevic acknowledged that there had been some “observational studies that have suggested a possible association between prenatal exposure to acetaminophen and autism, but the evidence remains inconsistent.”
But, he said, observational studies had “found no such relationship”, The Witness reports.
“If the link between acetaminophen and autism were strong, it would likely have been consistently observed across multiple studies,” he said, warning against “drawing casual conclusions”.
Brainchild of duo
The autism initiative is a shared brainchild of Trump and Health Secretary Robert F Kennedy Jr, with both men long voicing concerns about the rise of autism diagnoses in the country and often invoking debunked claims that the condition is linked to vaccines.
In April, Kennedy pledged that his team would know by September “what has caused the autism epidemic” and work “to eliminate those exposures”, sparking scepticism from researchers and former officials, who said a five-month timeline was unrealistic, given that decades of careful study have not produced definitive answers.
On the announcement by the FDA that it was taking initial steps to try to approve leucovorin as a treatment option for some people with autism, Professor Helen Tager-Flusberg, Department of Psychological & Brain Sciences at Boston University and an autism expert, noted that women are already told to take folic acid before conception and during pregnancy because it reduces the chances of certain birth defects, advice that possibly could help lower autism risk as well.
She cautioned that while leucovorin is sold for other health conditions and already used by some families in hopes of helping autism, only a few small, first-step studies have been done so far.
“Is this something worth pursuing? Yes, it is in potentially a subset of individuals,” she said. “But there needs to be a large, very rigorous study to prove if it really works.”
What is leucovorin?
The government’s recommendations that leucovorin can treat speech-related difficulties sometimes experienced by children with autism seems to stem from a theory that low levels of folate in the brain can lead to a condition called cerebral folate deficiency, write Professor of Natural Sciences at Australia’s Macquarie University Nial Wheate and Pharmacist/PhD candidate Jasmine Lee of Sydney University, in The Conversation.
Leucovorin is a form of folic acid, a B vitamin our bodies usually get from foods like legumes, citrus fruits and fortified grains.
The medication is most often used in cancer treatment, typically with the chemotherapy drug fluorouracil, which stops cancer cells from making DNA and dividing. Leucovorin enhances the effects of fluorouracil.
Leucovorin is also used to reduce the toxic side effects of methotrexate, another chemotherapy drug.
Methotrexate works by blocking the body’s use of folate, which healthy cells need to make DNA. Leucovorin provides an active form of folate that healthy cells can use to make DNA, thereby “rescuing” them while methotrexate continues to target cancer cells.
Because methotrexate is also used to treat the skin condition psoriasis, leucovorin can also be used as a rescue agent during treatment for this autoimmune condition.
Importance of folate
Because folate is essential for making DNA and other genetic material, it’s especially important during pregnancy. Insufficient folate is linked to the development of spina bifida, and for this reason, women are advised to take folic acid supplements before conception and during early pregnancy.
Folate is also important for supporting the production of red blood cells and overall brain function.
Children with cerebral folate deficiency don’t usually display symptoms for the first two years. Then they show signs of speech difficulties, seizures and intellectual disability.
As the signs of autism are similar and it usually presents at around the same age, some people have proposed a link between cerebral folate deficiency and autism.
Gathering the evidence
Can giving children folate, in the form of leucovorin, help them to function better with autism?
A review of the evidence in 2021 analysed the results of 21 studies that used leucovorin for autism or cerebral folate deficiency. Children who took the drug generally had improved autism symptoms, but the authors also said more studies were needed to confirm the findings.
Since then, a small 2024 study involved about 80 children aged two to 10 with autism. Half took a daily maximum dose of 50mg of folinic acid (similar to leucovorin), the other half took a placebo. Children given folinic acid showed more pronounced improvement than those who took the placebo.
A similar 2025 study examined the same dose of folinic acid in Chinese children with autism. Those given folinic acid had greater improvement in the social skill known as social reciprocity compared with children given placebo.
While promising, none of these trials is at the level to change medical practice. Further, larger studies are needed before doctors can make a proper recommendation.
Side effects of leucovorin are severe allergic reactions, seizures and fits, and nausea and vomiting.
Rates rising for decades
There are two main reasons for the increase in autism diagnoses. First, the definition broadened as scientists expanded their understanding of its wide range of traits and symptoms, leading to changes in the criteria doctors use to diagnose the condition and improvements in screening.
Simultaneously, parents increasingly sought a diagnosis as autism became better known and schools began offering educational services they hoped could help their children.
The state of research
Science has shown autism is mostly rooted in genetics, that several hundred genes play a role. Those genes can be inherited, even if the parent shows no signs of autism, or mutations can occur as the brain is developing and its rapidly dividing cells make mistakes.
Different combinations of genes and other factors can all affect how a foetal brain develops, including factors like the child’s father’s age, preterm birth and whether the mother had health problems during pregnancy – fevers, infections or diabetes.
Pain reliever still an option
The co-author of the study linking Tylenol to autism says the drug is still an option, reports POLITICO.
The study by epidemiologist Ann Bauer and co-authors, which was cited by Trump linking Tylenol to an increased incidence of autism, said the drug still can be used for treating maternal pain and fevers.
Bauer reviewed existing research in the paper published last month with Harvard’s Baccarelli, and researchers at the Icahn School of Medicine at Mount Sinai City and the UCLA Fielding School of Public Health, and told POLITICO that while pregnant women should be made aware that high-quality studies show a correlation between acetaminophen use and autism, Tylenol and generic versions should remain a pain relief and fever-reduction option for them.
Bauer acknowledged that autism and ADHD “are a result of a complex mixture of genetics and environmental factors”.
“Our review used this gold-standard framework for environmental health data to synthesise, evaluate and to give a rank to the studies and evaluate them for their quality.
“We found a strong and consistent association between prenatal acetaminophen use and offspring diagnoses of autism and ADHD: 27 studies from around the world reported a positive link. Nine reported no association, and four reported a protective effect. The higher-quality the studies, the stronger the link.”
(Other studies, including the 2024 Swedish study that harnessed data on 2.5m children born between 1995 and 2019, have found no correlation between acetaminophen and autism.)
Bauer said maternal fever and severe pain in pregnant women had to be treated, because of the risks they pose to the developing foetus, like neural tube defects, pre-term birth, bleeding risks, and a balanced approach was important.
“Aspirin and ibuprofen have long been contraindicated, particularly for the third trimester. We recommend judicious use tailored to the individual, rather than a broad limit.”
Women should know, she added, that the risks from acetaminophen are much greater for prolonged use for taking it a few times.
“But we have to be concerned that because of these warnings, a woman might not take it when she should, for fever or for high fever. It’s a balancing act, and it’s going to probably require more work from the physician, but women could talk to their pharmacist or their physician.”
Major autism report not ready
A report on autism led by the National Institutes of Health, which is expected to be a centrepiece of the administration’s work, has not yet been completed, with researchers expected to review several dozen hypotheses related to the condition, according to two officials who spoke on the condition of anonymity.
Meanwhile, GSK, which held a patent for a brand-name version of leucovorin before it expired, confirmed it had been asked by the administration to submit a supplemental new drug application to update the label to include an indication for the treatment of a type of folate deficiency linked to autism.
The Witness article – WHO sees no autism links to Tylenol, vaccines (Restricted access)
See more from MedicalBrief archives:
Paracetamol link to autism rears again
Kennedy to ‘reveal causes of autism’ this month
US NIH to probe cause of autism
Common painkiller in pregnancy tied to ADHD risk – US study
Paracetamol: Precautions necessary during pregnancy — Consensus Statement