Is Acetaminophen the cause of Autism?
- mfulk78
- Oct 13
- 11 min read
Review Part III - after the Attia Podcast
After completing the interview with Dr. William Parker and now listening to Peter Attia's analysis, let us look again at this question. I repeat that the initial question has not changed for me. The first and most fundamental question to ask is this: What is the true value of acetaminophen in health compared with the potential risk if the associated findings are indeed correct?
My response to this question has been altered by the analysis so far.
I love this from Dr. Attia: "Some people might be wondering, why did you just take so long to explain all this to us? Why don’t you just give us the answer? I just want the sound bite, man
Peter’s reply, “If you just want sound bites, you’re never going to learn.”
Honestly, if you just want sound bites, this isn’t the podcast for you. But if you actually want to be able to learn to think for yourself, then that’s what we’re here to do. And that’s the reason we killed ourselves over the past week to put together the most thorough gathering of all the data we could find and the most intense night-weekend analysis possible. "
I agree! I believe that the science and data are key. So here goes - round three!
Disclaimer: I do not have the statistical analysis abilities of either Dr. Attia or Dr. Parker.
The contention: Dr. Parker and colleagues believe that Autism can be accounted for to the tune of 94.5% by the use of acetaminophen and critical timepoints in a child's life when oxidative stress levels are high. This is believed to be mostly peri and post natal in timing. For me, after listening to him for over an hour and now Dr. Attia, I still fall into the category of "there is enough smoke here in the data that acetaminophen is a potential serious risk factor for autism" in certain at risk groups. Yet, I still believe that the bulk risk is prenatally induced and immunometabolic in nature.
However, I would not recommend using acetaminophen during pregnancy or the first 2 years of life until better data says that it is truly safe and or the risk of an issue necessitates use. This risk reward benefit analysis still slants towards risk significantly in my opinion.
So, is acetaminophen the cause of ASD?
Let us look at Dr. Attia's points about the acetaminophen equals autism story.
Let us start with the primary statement: Peter emphasizes, “I want people to understand that the strength of these associations is very small and in many cases vanishes altogether when you apply some rigorous statistical corrections that look at the most important variables that we should be considering here, which is genetic and environmental.” (Peter Attia)
· For minor aches and pains, maybe it’s best to just err on the side of caution and skip the acetaminophen (I agree)
· Whereas when the pain becomes really a nuisance and it might interfere with you doing things that are otherwise going to help you provide the best environment for your fetus then judicious use of acetaminophen can help (with the oversight of your physician) (This I disagree with unless the need is very very strong for use)
· For maternal fever, the balance is clearly leaning towards the use of acetaminophen (Peter Attia) (I Disagree - Limited data at best)
Let us first look at fever and pregnancy. During the first trimester of pregnancy, febrile infections in a mother raises the risk of neurodevelopmental disorders by an odds ratio of 1.24. "We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case–control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation ." (Antoun et. al. 2024)
From another paper: "The available literature supported an increased risk of adverse offspring health in association with fever during pregnancy. The strongest evidence was available for neural tube defects, congenital heart defects, and oral clefts, in which meta-analyses suggested between a 1.5- and nearly 3-fold increased risk with fever exposure in the first trimester. We did not find strong evidence of a dose–response relationship, but there was some evidence that antipyretic medications may have a protective effect when used in relation to febrile episodes." (Dreier et. al. 2014) Fever and ASD was shown to occur in the second trimester by Hornig et. al. in 2018.
There are other studies listed below that support the fever in pregnancy = not good for baby in the first 3 months of pregnancy. However, that is in no way a statement for fever is the issue and or that acetaminophen use equals a good and or protective thing during these events. The virus and or bacterial illness itself and the maternal response to it, is likely the greatest risk factor for the child in a mother that is immunometabolically unhealthy, i.e. obese, diabetic or with metabolic syndrome. I think of the data around Covid and human deaths during the pandemic. The people that died had immunometabolic issues that underlie the entire disease morbidity and mortality burden: metabolic syndrome and ASCVD. Thus, I think that these same issues in a pregnancy state, would be the reasons for a negative outcome on balance - not fever or acetaminophen use - these are likely proxies for immune activation. (After reviewing Dr. Parker's work, the acetaminophen side of the argument may be greater than I think and Dr. Attia negates.)
Significant maternal viral illness, such as COVID-19 or influenza during pregnancy, dramatically increases disease risk in certain populations. (Edlow et. al. 2023) In my review of the literature, maternal viral infections without accompanying fever have not been consistently associated with an increased risk of autism spectrum disorder (ASD). Current research remains mixed and evolving. Evidence suggests that elevated risk appears primarily in cases of severe infections requiring hospitalization or when infection is coupled with fever or elevated inflammatory markers. This pattern points to the maternal immune response, especially a robust, fever-related inflammatory reaction, rather than the infection itself as the more likely contributor to fetal neurodevelopmental risk. In other words, the severity of the illness with fever frequency and or hospitalization as the risk assessment marker dictates ASD risk. This begs the question of whether fever is the concern or again a marker of the inflammatory cytokine mileu? I think that the latter is more important.
After reviewing many papers on this topic, I found one by Egorova et. al. that I will significantly discuss now for context of this entire discussion. This is going to feel like an aside and in some ways it is. However, it will all tie together at the end.
Influenza: Erogova article- Here are my takeaways: Pregnancy transforms the immune landscape. What once was a robust defense system becomes a carefully modulated network designed to protect two lives at once. This immune shift, while necessary for tolerance of the fetus, renders the mother more susceptible to severe infections like influenza. Epidemiologic data show that infection in early gestation carries increased risks for neural tube defects, congenital heart disease, and preterm birth. Severe maternal illness such as that seen during the 2009 H1N1 pandemic further amplifies risks for preterm delivery, low birth weight, and infant mortality. Yet, intriguingly, the influenza virus rarely crosses the placenta. The fetus is not infected directly. The question then becomes how does a transient respiratory illness in the mother alter the destiny of the developing brain?
Animal models give us clues. When pregnant mice encounter influenza, their offspring exhibit changes in brain architecture and later behavior even without evidence of viral RNA in the fetal brain. The mechanism points toward previously discussed topic, maternal immune activation: a surge of cytokines, particularly IL-6, IL-1β, and TNF-α, altering the intrauterine environment. Fever itself, essentially an inflammatory signal, appears to influence neural patterning. This neuroimmune crosstalk may rewrite the genetic script within the placenta, modifying transcriptional programs that guide brain development. Such reprogramming could predispose offspring to later neuropsychiatric conditions like ADHD or autism spectrum disorders, especially when coupled with genetic susceptibility.
The convergence of maternal inflammation and fetal genotype is where complexity deepens. Animal data support this synergy, mice with certain inflammatory gene variants show exaggerated neurobehavioral responses after prenatal immune activation. It’s the perfect storm: genes primed for vulnerability, and an environment that flips the switch. Very much like that is posited by Dr. Parker peri and post -nataly.
Another subtle factor emerges, our therapeutic responses. Analgesics and antipyretics, while comforting for the febrile mother, may alter immune tone and fetal brain signaling. Most studies examining neurodevelopmental outcomes fail to adjust for medication use, making it difficult to disentangle the effects of virus, fever, and drug. Yet, fever alone has been independently linked with higher risk of ASD and ADHD.
Research now points to three overlapping possibilities:
1. Direct viral invasion: plausible in animals but rare in humans.
2. Cytokine-mediated disruption: inflammatory messengers reshape brain development.
3. Autoimmune cross-reactivity: maternal antibodies may mistakenly target fetal neural structures, a mechanism seen in post-streptococcal OCD and Tourette’s.(Egorova et. al. 2025)
The emerging message is not one of fear, but of awareness. Maternal infection, even without direct viral exposure, can act as a developmental signal. It whispers into the womb through heat, cytokines, and metabolic intermediates. It can alter how genes are read, how synapses form, and how behavior manifests decades later.
Pregnancy represents an exquisite dialogue between mother and child one that can be disrupted by inflammatory noise. Preventing influenza through vaccination, reducing the severity of infection, and minimizing uncontrolled inflammation during pregnancy remain key acts of protection for two intertwined immune systems.
In the broader lens of functional medicine, this story reinforces an enduring principle: the environment in which life begins shapes the health trajectory for life itself. Whether the trigger is viral, chemical, or emotional, the maternal milieu writes the opening chapters of a child’s biological story.
(Egorova et. al. 2025) See below for more from this excellent article.
How about Dr. Attia's contention #3? Does treating maternal fever with acetaminophen have an effect on ASD in offspring? "Adjustment for acetaminophen use in our study and the Hornig study did not alter findings." (Croen et. al. 2021) (Hornig et. al. 2018) There is zero robust (one study CHARGE Zerbo et. al. 2012) evidence that treating the fever with antipyretics alleviates the neurodevelopmental disorder (NDD) changes. Thus, I fall on the side of what is the benefit of a potential toxic drug unless the circumstances are extenuating.
Fever also has been implicated in ASD etiology in a few studies, such as prolonged fevers during pregnancy (Atladottir et al., 2012), untreated fevers in the first and second trimester (Zerbo et al., 2013), and fever in the second trimester (Hornig et al., 2017) or third trimester (Brucato et al., 2017). However, these studies could not separate the effects of fever itself from those of a specific infectious organism on the developing brain. (Croen et al., 2018)
Maternal infection without fever is NOT associated with increased NDD risk. Again, this to me is a statement of disease severity and less about fever in and of itself. Fever to me is a marker of viral illness severity driving immune cytokine release, especially IL6 which is a known driver of ASD/NDD in the womb. Fever itself may play a role in pathogenesis of ASD but reducing it with medicine remains questionable at best.
For me, the preponderance of the data says that we need to focus on maternal immunometabolic health first as opposed to a binary decision of acetaminophen versus none for fever. I prefer the idea that we reduce all controllable a priori risk for infectious disease morbidity (think Covid) in the pregnancy period. This would in effect:
· reduce the baseline inflammatory burden that causes a larger cytokine response to any given infection beyond what is necessary
· allow the use of all medicines with known toxic risk to occur very sparingly (this is a known - immunometabolically healthy people use dramatically less medicine per capita)
· reduce perinatal birth complications and preterm births which are known risk factors for ASD (see previous newsletters for deep dives here)
Back to Dr. Parker and his work:
In my current view, the relationship between acetaminophen use and neurodevelopmental outcomes remains largely associative, though an argument for conditional causation is emerging. Women who frequently require antipyretics or analgesics often share a background of immunometabolic dysregulation, a physiology already burdened by oxidative stress and impaired detoxification. Under these conditions, the body struggles to efficiently metabolize acetaminophen, leading to bioaccumulation of NAPQI, its toxic intermediate.
Acetaminophen is cleared through three primary pathways: glucuronidation, sulfation, and oxidation. In neonates, glucuronidation is immature. In children with autism spectrum disorders, evidence suggests that sulfation capacity is impaired, forcing reliance on oxidative metabolism for clearance. (Clarke et al., 2022) Other studies, however, challenge this view, noting that glucuronidation may also be compromised in children with ASD, particularly when exposed to endocrine-disrupting chemicals.(Cook et al., 2017)
Taken together, if there exists a genetic or epigenetic predisposition toward weakened acetaminophen metabolism, especially in the context of oxidative stress, then a plausible mechanism of harm emerges for the neonate or fetus exposed in utero. Regardless of these nuances, one fact remains: acetaminophen is not benign. It places a measurable strain on glutathione reserves, heightening oxidative stress and slowing the clearance of other toxins. This perpetuates an inflammatory loop, symptoms recur, prompting repeated dosing, all while the root cause remains untouched.
The deeper question, then, is why acetaminophen is needed in the first place. Is the mother inflamed from a poor diet, chronic stress, environmental toxins, infection, circadian disruption, or nutrient depletion? These upstream drivers define the immunometabolic terrain. Go upstream and assess them.
In the end, acetaminophen use during pregnancy may serve more as a proxy marker for maternal metabolic health than a singular cause of harm. Yet its intrinsic effects, glutathione depletion, oxidative load, and potential epigenetic signaling, may amplify risk in vulnerable infants, especially when genetic fragility already exists.
I repeat: personally, I neither use nor recommend acetaminophen except in rare, medically justified cases. My concern rests on two well-documented mechanisms: glutathione depletion and potential epigenetic alterations in gene expression. Occasional, isolated use during pregnancy is likely safe, but repeated or chronic exposure, especially in pregnancy and young children, raises concern. Fever itself is not an enemy; it is part of the body’s intelligent defense system, mobilizing immunity and inhibiting viral replication. For moderate fevers (100–102°F), I generally recommend observation, hydration, and rest, no medication unless clinically indicated. When temperatures climb above 103°F, simple physical cooling measures like cool compresses can effectively bring relief without disrupting the immune response. Pregnancy febrile episodes remain the domain of obstetrics and I will defer to them here.
In a country where autism spectrum disorder now affects roughly 1 in 30 children, prudence demands that we minimize every avoidable risk within our reach. This is not a mutational genetic reality where a population increases the volume of a disease exponentially over 5 decades without major environmental epigenetic triggers. And, I am sorry, but the bulk of new ASD cases are not based on better diagnostic skills and or changes in classifications. I wholeheartedly disagree with Dr. Attia who notes: "The analyses that have looked and attempted to assess this directly report that the expanded criteria account for 40 to 60% of the increase, and furthermore, increased awareness accounts for 20 to 30% of the increase in diagnoses". (PeterAttia) I have yet to meet a general practicing pediatrician who does not believe that ASD is skyrocketing in incidence. I have yet to meet a general pediatrician that believes that the bulk of new ASD cases are due to expanded criteria and increased awareness. There is a massive disconnect between the clinic and the research institutions. 80-90% genetic heritability with epigenetics as the incidence variable makes sense, not awareness and criteria.
The Clinical Takeaway - the bullet point after all that!
After careful review of the current evidence and drawing on decades of clinical experience, my conclusion is clear: acetaminophen provides little compelling justification for use. The potential link to autism spectrum disorder, while not definitively causal, combined with its limited demonstrated benefit for fever management and the possibility of fetal or infant neurological disruption, argues strongly for prudence and restraint in its use during pregnancy and early childhood. I now counsel expectant parents to avoid acetaminophen unless an extenuating medical need exists, and always in discussion with their healthcare provider. The greater concern for me lies in the reality that the robustness of the viral illness is the big issue at hand and that is absolutely driven by a priori maternal immunometabolic health.
Avoiding acetaminophen removes a variable that could be contributing to the ongoing autism question, a variable that is easy to control. In truth, if acetaminophen use in pregnancy and early childhood (unless absolutely necessary) was halted for even two to four years, we might finally gain clarity on whether the connection is associative or causative.
That is an experiment I would fully support.
I think that I am done with this topic!
Dr. M
Above image from Jones et. al. 2024 in Life
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