Also, is the Pope a Catholic, and do brown bears poop in the woods?
25 August 2025
When I wrote The ADHD scam three years ago, a vigorous debate was underway in the research community regarding the involvement of paracetamol/acetaminophen in the skyrocketing incidence of (so-called) ADHD, autism and other neurodevelopmental disorders. In that post, I cited an article published in Nature Reviews Endocrinology in September 2021, which rang the alarm bell on use of paracetamol during pregnancy:
“A review of 25 years of research in humans, animals and in vitro on the prenatal use of paracetamol (known in the US as acetaminophen), concluded that the children of mothers who took this over-the-counter drug whilst pregnant with them were more likely to be diagnosed with ADHD and autism, and to have a lower IQ. Girls whose mothers took paracetamol during their pregnancy were also found to have a higher risk of language delays and early onset of puberty, whilst boys showed indicators of disturbed masculinisation including a higher risk of undescended testicles (cryptorchidism) and reduced anogenital distance.”
The ADHD scam
This review received strenuous pushback, with multiple responses pointing out that the research literature on prenatal use of paracetamol and neurodevelopmental disorders is plagued with methodological weaknesses. Chief among these is confounding by indication – that is, the conditions for which pregnant women take paracetamol may be what is adversely affecting their babies’ neurodevelopment, rather than the paracetamol itself. Fever and migraine, for example, are common conditions for which people take paracetamol, and both are associated with adverse effects on foetal neurological development.
The authors of the review responded to these critiques with an acknowledgment that there were indeed significant gaps in the research literature. But they insisted that extrapolation from animal research justifies a precautionary approach – that is, avoiding any use of paracetamol during pregnancy unless strictly necessary, and limiting necessary use to the smallest effective dose for the shortest possible duration – until those gaps in the research are filled in.
This is, of course, how science is supposed to work: researchers publish a study, others working in the field pore over their work, pointing out its flaws and proposing alternative explanations for the observed phenomena, and the researchers who published the study – along with others working in the field – take this criticism on board in order to design a more robust study to test their hypothesis.
Well, that more robust study has now been published, in BMC Environmental Health, with Ann Bauer, who was first author of the 2021 Nature Review Endocrinology paper, on the research team. And it confirms that children whose mothers used paracetamol whilst pregnant with them are at higher risk of neurodevelopmental disorders including autism and ADHD. Most importantly, the highest-quality studies are more likely to show an association between prenatal paracetamol use and impaired neurodevelopment.
Convincing evidence of harm from prenatal paracetamol use
The research team analysed the findings of 46 observational studies (20 focused on ADHD, 8 on autism spectrum disorder [ASD] and 18 on other neurodevelopmental disorders), involving a total of over 100 000 participants, using the Navigation Guide Systematic Review methodology. The Navigation Guide was designed specifically for synthesising and evaluating environmental health research. It provides a framework for researchers to assess and rate each study’s risk of bias, such as selective reporting of the outcomes, recall bias, incomplete data and confounding, including confounding by indication, as well as the quality of the studies, both individually and collectively, and the overall strength of the evidence.
These 46 studies controlled for known confounding factors including “maternal age, maternal illness, maternal use of medications other than acetaminophen, maternal intelligence, parental education levels, socioeconomic status, maternal drinking, maternal smoking, maternal drug use, genetic confounding, confounding due to indication (i.e., clinical reason for taking the medication), and other risk factors for NDDs [neurodevelopmental disorders] including child birth weight, child gestational age as well as some others”. In other words, every effort was made to ensure that any observed relationship between maternal paracetamol use and adverse neurodevelopmental outcomes was actually attributable to the paracetamol use, and not some other variable.
So, what did they find? Of those 46 studies of prenatal paracetamol use and neurodevelopmental outcomes, 27 reported positive associations (i.e. children whose mothers took paracetamol during pregnancy were more likely to have a neurodevelopmental disorder), 9 found no significant link, and 4 reported negative associations (i.e. that children were less likely to have a neurodevelopmental disorder if their mother used paracetamol whilst pregnant with them). Overall,
“Our Navigation Guide-based evaluation of the existing literature showed a strong, consistent association between prenatal acetaminophen exposure and ADHD/ASD/other NDDs. These studies were controlled for multiple potential confounders that might have plausibly explained the associations, yet the associations persisted. After directly controlling for confounders or employing sophisticated study designs such as using negative control exposure periods (e.g., comparing acetaminophen use before/after vs. during pregnancy, comparing associations with the use of other pain relievers), and/or propensity score matching to determine whether unmeasured and residual sources of confounding might drive these associations, the associations persisted.”
And crucially,
“Higher-quality studies were more likely to show positive associations.”
Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology
The most dangerous time to take paracetamol
While not all studies provided detailed information on the timing of maternal paracetamol exposure and neurodevelopmental outcomes, those that did found that the second and third trimesters were the riskiest times to pop a Panadol. This contrasts with classic teratogens (drugs that induce birth defects) such as thalidomide, which are most damaging if taken during the first trimester, when organs are being formed.
Like all the other organs, the basic structure of the brain takes shape in the first trimester. But it’s during the second and third trimesters that the brain is ‘wired up’ for the multitude of functions it will need to perform after birth. And studies conducted in animals show that when a pregnant female is administered paracetamol, the drug freely crosses the placenta and within an hour, has attained similar concentrations in foetal circulation as in maternal circulation. Paracetamol is then broken down into toxic metabolites that cause oxidative damage to the rapidly-developing brain, as well as altering endocrine, prostaglandin and endocannabinoid pathways that are involved in the development of the animal’s nervous system. Importantly, these same pathways are integral to the development of the human nervous system. As the authors point out, it’s hard to argue that we wouldn’t see the neurodevelopmental deficits observed in the offspring of pregnant animals who were deliberately exposed to paracetamol, in human children who were exposed via their mother’s use of the drug.
Mechanisms of harm
When I think about paracetamol toxicity, the first thing that springs to mind is its adverse effects on the liver and kidneys, which render it the most common cause of drug overdose in Australia, responsible for over 95 000 hospitalisations (including almost 23 000 intentional overdoses) and 200 deaths in the decade from 2007-2017. But paracetamol is also an endocrine disruptor – that is, a chemical that interferes with the body’s complex and intricately interwoven hormonal system. And that’s a hugely big deal for foetal development:
“During prenatal development, the endocrine system plays a crucial role in brain development, as it regulates the production and activity of hormones that are essential for healthy neurological development. Disruptions to the endocrine system, such as exposure to endocrine-disrupting chemicals, can interfere with the activity of these hormones and potentially lead to permanent structural and functional alterations in the developing brain. Acetaminophen is an endocrine disruptor that directly perturbs hormone-dependent processes, affects neurodevelopment and reproductive disorders, and might alter steroidogenesis in the placenta and induce placental damage. In vivo, in vitro, and ex vivo studies show that acetaminophen directly perturbs hormone-dependent processes [87,88,89] that are implicated in the development of NDDs [90].”
Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology
Furthermore, paracetamol has epigenetic effects, meaning that it alters the activity of genes – including genes that sculpt brain development – without changing the DNA sequence of those genes:
“During prenatal development, the epigenome undergoes dynamic changes that regulate gene expression, contributing to brain development [91]. Alterations in the epigenome can alter neural networks critical for normal brain function [93], resulting in abnormal gene expression that may contribute to NDDs [94]. Prenatal acetaminophen use is associated with DNA methylation changes in fetal tissues and the placenta, including at loci vital for neurodevelopment [95]. Similar results have been shown in children diagnosed with ADHD exposed to prenatal acetaminophen, with one study suggesting DNA methylation changes in genes involved in oxidative stress, neural transmission, and olfactory sensory pathways [97]. Prenatal acetaminophen exposure of human embryonic stem cells during neuronal differentiation has been shown to induce alterations in transcriptional and epigenetic regulation in early brain development [71], consistent with gene expression changes seen in the brains and placentas of acetaminophen developmentally exposed rodents [99]. A recent human study evaluating RNA sequencing changes from maternal acetaminophen exposure found placental upregulation of immune system pathways in females and downregulation of oxidative phosphorylation in both sexes [17], aligning with earlier transcriptomic results from acetaminophen-exposed mice [99]. Several studies have linked elevated immune response during pregnancy with offspring neurodevelopmental disorders [101]. Additionally, oxidative phosphorylation deficiencies have been associated with adverse neurodevelopmental trajectories [102].”
Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology
In summary, the mechanisms via which prenatal exposure to paracetamol can harm a baby’s neurodevelopmental trajectory include:
- Oxidative damage to the brain
- Disruption to endocrine development
- Altered prostaglandin pathways
- Altered endocannabinoid pathways
- Altered sensory development
- Upregulated immune activity, manifesting as an excessive inflammatory response
- Disrupted brain energy metabolism
Long-time readers might remember the research that I discussed in The surprising – and disturbing – effects of paracetamol on your mind. In a nutshell, adult volunteers who took even a single dose of paracetamol experienced reduced sensitivity to the pain of social rejection, diminished perceptions of risk when contemplating potentially dangerous behaviour, blunted emotional responses to existential threat, as well as to both positive and negative stimuli, and reduced empathy for both the painful and joyful experiences of other people.
Hmmm, does any of this remind you of the excessive risk-taking behaviour of children with (so-called) ADHD, or the difficulties with interpretation of, and appropriate responses to, the emotions of other people which affect children with autism? Is it possible that at least some of these kids are suffering from paracetamol-induced brain damage?
Individual differences
Given that well over half of pregnant women worldwide are estimated to use paracetamol, you might wonder why we don’t see an even higher rate of neurodevelopmental disorders. The answer is that there is significant individual variation in genes involved in every facet of paracetamol’s impact on neurodevelopment – from the genes that govern the way it is metabolised, to those that influence antioxidant defences, to those that shape the endocannabinoid and prostaglandin systems. Just as some people are gifted with genes that protect them against cardiovascular disease even while they eat enough junk food to sink a battleship and drink enough booze to refloat it, some people hit the genetic jackpot when it comes to paracetamol metabolism… and conversely, others draw an unlucky hand.
The problem is, pregnant women don’t have any way of knowing how badly their babies might be affected by their use of paracetamol, until it’s too late for some of them. And that makes the endorsement of paracetamol by doctors’ organisations particularly disturbing:
“Associations such as the American College of Obstetricians and Gynecology have reassured patients that acetaminophen is safe to take during pregnancy [7]. Thus, acetaminophen has become the first-line medication for fever and pain during pregnancy. It has been estimated that > 60% of women use acetaminophen during pregnancy for headaches and other pain, or fever, with ~ 20% of pregnant women using acetaminophen for > 20 days [8].”
Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology
So, to protect your unborn baby from harm, you should avoid unwashed fruit, sprouts, salad bars, soft cheeses, high-mercury fish and alcohol whilst pregnant, but paracetamol is totally fine. While you’re at it, take an mRNA COVID jab. What could possibly go wrong?
What’s the alternative to paracetamol?
The authors of the study suggest that in the case of fever in pregnant women, physical cooling methods should be considered instead of paracetamol, and that when it is used, “judicious acetaminophen use—lowest effective dose, shortest duration—under medical guidance, tailored to individual risk–benefit assessments” should be the rule. But in my opinion, these suggestions don’t go nearly far enough.
I will be the first to acknowledge – having been through the experience twice, with both my kids going well past their (supposed) due date – that pregnancy is bloody uncomfortable, especially in its final stages. And in many cases, that discomfort crosses the line into out-and-out pain.
But when over half of pregnant women are taking paracetamol at some point, and one fifth are using paracetamol for three weeks or more out of their nine-month gestation, we have serious questions to ask ourselves. Why are they in so much pain? What dietary, lifestyle and postural factors are at play? Did they enter pregnancy already overweight and undermuscled, such that their bodies struggle to adapt to the physical demands of carrying around an extra 10-15 kg of baby weight? Are they working in jobs that are physically and/or psychologically incompatible with healthy pregnancy? Do they need instruction in non-pharmaceutical methods of pain management, whether that be various forms of physical therapy, or mindfulness practices… or both? In a nutshell, how can we improve pregnant women’s lives, so that they’re not reaching for that pack of Panadol? Shouldn’t real feminists be more focused on solving this dilemma, than on getting more women into the C-suite of psychopathic corporations?
Finally, neurodevelopmental disorders impose almost incalculable costs on the children who have them, their families, and the communities in which they live. The paper discussed in this post presents strong evidence that the use of paracetamol during pregnancy is contributing to their skyrocketing incidence. The two most common diagnoses of people accessing Australia’s National Disability Insurance Scheme (NDIS) – which has been described as a “‘black hole’ [that] threatens to disable Australia’s economy” – are autism and other developmental delays. And yet, nary a mention has been made of this paper, or any other publication that discusses potential causes of autism, ADHD and other neurodevelopmental disorders, by the individuals tasked with administering the bloated bureaucratic behemoth of the NDIS. Their silence speaks volumes.
