The Atopic March - updated: Leading to Autism and ADHD in some children?

 

I was thinking yesterday about the link between eczema (atopic dermatitis) and autism following a comment regarding a therapy I must have mentioned long ago (l-histidine with zinc). The therapy did work well for this child.

This then brought me back to one of my pet subjects, which is the minimization of the risk of future autism. I did write a section in my book on this subject, but it remains a work-in-progress. My elder son wants to avoid autism in his future children. If there are simple, safe, inexpensive steps that can be taken, that also provide broader health benefits then it would be crazy not to take them.

This brings me to the subject of the so-called atopic march. I have updated it to include its effects on the brain, increasing the risk of autism and ADHD and also suggest that in fact there may be slightly different atopic journeys, rather than a singular march with the same start and end points.

 

The atopic march

The traditional "atopic march" describes the progression from atopic dermatitis (eczema) in infancy to food allergies, asthma and allergic rhinitis later in childhood. While this framework has been useful for decades, it may be too simplistic.

Perhaps there is not one atopic march, but several.

Recent years have seen an explosion of research into the gut microbiome, immune development, mast cells and neurodevelopment. Numerous studies continue to investigate probiotics as a treatment for eczema, allergies and even autism. However, there is a recurring problem: many of these studies are performed in children who may already be too old to receive the maximum benefit.

The first few months of life appear to be a critical developmental window. During this period, the gut microbiome, immune system and brain are all developing simultaneously. Alterations during this time may have lifelong consequences.

One particularly intriguing study from Finland was originally designed to investigate eczema prevention. What makes this study especially interesting is that the intervention began before many people would even think about treating the microbiome. Mothers received the probiotic Lactobacillus rhamnosus GG during the final 2–4 weeks of pregnancy. After birth, the infants received the probiotic for only the first six months of life.

A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial

Remarkably, this relatively brief intervention, lasting just a few months around the time of birth, was followed by measurable differences many years later.

In other words, the researchers were not treating eczema, ADHD or autism. They were attempting to influence the earliest stages of microbiome development. This timing is important because the infant microbiome is initially seeded by microbes acquired from the mother during birth, breastfeeding and close maternal contact. By giving the probiotic to both mother and infant, the researchers may have been influencing the microbial ecosystem at the very moment it was being established.

Years later, when the children were followed into adolescence, the researchers found not only a reduction in eczema but also a surprising reduction in diagnoses of ADHD and Asperger syndrome. If the finding proves to be real, it would suggest that a six-month intervention during infancy may have influenced developmental trajectories more than a decade later. The study was small and requires replication, but the findings were striking. 

Group	Children	ADHD or Asperger syndrome by age 13	Percentage
Probiotic (LGG)	40	0	0%
Placebo	35	6	17%

One reason the Finnish study has not been easily replicated is the sheer difficulty of performing such research. To repeat the study properly, researchers would need to recruit women during pregnancy, administer the intervention before birth, continue treatment during infancy, and then follow the children for 10–15 years while carefully tracking neurodevelopmental outcomes. Such studies are expensive, logistically challenging and suffer from inevitable participant drop-out over time. Furthermore, because probiotics are inexpensive and cannot easily be patented, there is limited commercial incentive to fund a trial that may take more than a decade to produce results. As a consequence, many probiotic studies focus on older children and adults where results can be obtained within months rather than years, even though the greatest biological impact may occur during the earliest stages of development.

At the same time, other observations point in a similar direction:

• Early pet exposure reduces the risk of eczema.
• Children raised on farms have lower rates of allergic disease.
• Early probiotic use can reduce the risk of atopic dermatitis.
• Food allergies are increasingly viewed as part of the atopic march.
• Autism and ADHD are associated with higher rates of allergic disease in many studies.

The common denominator may be early-life immune and microbiome development.

The protective effects of pets and farm exposure are often discussed in the context of the hygiene hypothesis, although the modern interpretation is really a microbial exposure hypothesis. Children growing up around animals are exposed to a much greater diversity of microorganisms. Rather than overwhelming the immune system, these microbial exposures appear to help educate and calibrate it. Studies of children raised on traditional farms consistently show lower rates of eczema, asthma and allergic disease. The immune system evolved in a world rich in microbial exposures, and it may require those signals to develop normally.

This brings us to an important point. The infant microbiome does not arise spontaneously. Much of it originates from the mother. During birth, breastfeeding and close maternal contact, microbes are transferred from mother to child. These pioneer organisms help establish the infant gut microbiome and play a critical role in training the developing immune system. In many ways, the microbiome acts as one of the earliest teachers of the immune system, helping it learn the difference between harmless substances and genuine threats.

This process of immune calibration appears to occur very early in life. Once established, the microbiome becomes increasingly stable and resistant to change. This may explain why probiotics often show their greatest effects when administered during pregnancy or infancy, while studies in older children and adults frequently produce much smaller results. By the time many interventions are attempted, the window during which the microbiome is shaping immune development may already be closing.

Perhaps the most remarkable aspect of the Finnish study is not the probiotic itself, but the timing. The intervention was completed by six months of age, yet the outcomes were measured at 13 years of age. This is precisely what one would expect if the microbiome plays a role in calibrating the developing immune system during a narrow critical window early in life.

Mast cells may also deserve greater attention. They play important roles in eczema, food allergies, asthma and anaphylaxis, but they are also found in the gut and nervous system. Some researchers have proposed that abnormal mast-cell activity could contribute to neurodevelopmental symptoms in susceptible individuals.

Another clue that early immune modulation may alter the trajectory of the atopic march comes from studies of ketotifen, an antihistamine and mast-cell stabilizer. In one notable study of infants with atopic dermatitis, children receiving ketotifen were significantly less likely to develop asthma during the follow-up period. The researchers also reported improvements in the severity of atopic dermatitis. These findings suggest that, at least in some children, modifying mast-cell activity and allergic inflammation early in life may alter the subsequent progression of allergic disease.

Prevention strategies for asthma — secondary prevention

If the classical atopic march can be interrupted before eczema progresses to asthma, it raises a broader question. Could other early interventions—such as probiotics, microbial exposure from pets and farm environments, or targeted immune modulation—also alter developmental trajectories extending beyond allergy and into neurodevelopment in susceptible children?

This raises an interesting possibility. For a subgroup of children, the atopic march may not end with asthma and hay fever. Instead, immune dysregulation, microbiome alterations and barrier dysfunction could also influence neurodevelopment, increasing the risk of ADHD or autism.

The proposed sequence might look something like this:

Microbiome disturbance / barrier dysfunction → Eczema → Food allergy → Mast-cell activation → ADHD / Autism susceptibility

or perhaps

Microbiome disturbance → Food allergy → Eczema → Neurodevelopmental effects

In other words, there may be multiple entry points and multiple destinations.

Importantly, this hypothesis does not suggest that eczema causes autism, nor that most children with eczema will develop autism. Rather, it suggests that some children may share an underlying biological pathway affecting the skin, gut, immune system and brain.

If this hypothesis contains even a grain of truth, it has profound implications. It would mean that interventions aimed at modifying the microbiome or immune system may be most effective during infancy, before symptoms of autism or ADHD are apparent. By the time a child is diagnosed at age 3, 5 or 10, the critical developmental window may already have passed.

The irony is that we continue to perform large numbers of probiotic studies in older children and adults, where effects are often modest. The greatest opportunity may lie much earlier, during the period when the microbiome and immune system are still being assembled.

The challenge for researchers is to identify which children belong to this subgroup before the window of opportunity closes.

The classical atopic march has evolved over time. Perhaps the next evolution will be to recognize that, in some children, the journey extends beyond allergies and into neurodevelopment.

  

Conclusion

 In the Finnish study, the intervention was actually in both the mother and the infant:

• Mothers took Lactobacillus rhamnosus GG during the final 2–4 weeks of pregnancy.
• After birth, the infants received the probiotic until 6 months of age.

It would be very easy to implement this.

Dog and farm animal exposure (pregnant mother and later the baby) might be more difficult for some, but easy for others.

NAC during pregnancy is another simple one. It was also show very effective in reducing miscarriages and increasing the “take-home baby rate.”

We also saw Prof Ramaekers using folinic acid during pregnancy where future parents test positive for folate receptor antibodies. This requires the future parents taking the FRAT test.

In older children and adults probiotics can have a benefit, but the dramatic effect only occurs when given prior to the immune system being (mis)calibrated. In the older age-group it appears that you need something more potent – FMT works in some cases. 

The Finnish study only refers to level 1 autism (then called Asperger's syndrome).

I imagine if you could repeat this study and also include all the common issues like

• Dyslexia
• Dyscalculia
• Developmental language disorder
• Dyspraxia (developmental coordination disorder)
• Learning disabilities generally
• Level 2 and 3 autism

you would see some shocking results. 

You would not have 0% incidence of each disorder in the probiotic group, but I bet you would see a substantial reduction.

The de-diagnosis of autism begins? And calcium channel blockers considered for ADHD, which type of ADHD and which blocker?

Stockholm – an autism diagnosis hotspot according to the psychologist Sebastian Lundström

Nordic countries often lead the way and after apparently over-diagnosing autism and ADHD they are now eager to de-diagnose it.

I received an article from the British Medical Journal which drew my attention.

Autism and ADHD de-diagnosing services could be rolled out in Sweden—should the US and UK follow suit?

Swedish authorities are considering requests for “de-diagnosis services” for autism and attention deficit/hyperactivity disorder (ADHD) from a new patient group: adults who no longer want their diagnosis.

The proposals come against the backdrop of an ongoing study on around 100 patients, all of whom joined the trial with the hope of getting their diagnostic labels removed. It could see de-diagnosis services rolled out in several of Sweden’s clinics in a matter of months, the study authors told The BMJ.

While “de-diagnosis” is gaining traction in Sweden, clinicians and patient groups who spoke to The BMJ were divided as to whether similar services should be set up in the UK or the US.

What is a de-diagnosis service?

The psychologist Sebastian Lundström, one of the study’s researchers, told The BMJ that his work on this new patient group was prompted by “the sheer number of people with these diagnoses who now are turning into adult age and being told that they can’t join the military services [or] the draft.”

Historically, Swedish citizens with an ADHD or autism diagnosis have been barred from joining the military or working as train drivers without a specific doctor’s note. They must also provide a medical certificate when applying for a driving licence.

At the Preventing Overdiagnosis Conference in Oxford earlier this month, Lundström said that diagnoses had been “assigned by well meaning clinicians” to an increasing number of Swedish children in recent years but that the label could often be “sticky.”

 

Preventing Overdiagnosis Conference in Oxford

In September 2025 there was a conference about overdiagnosis across a wide range of conditions, it was not just about autism and ADHD.

https://www.cebm.ox.ac.uk/preventing-overdiagnosis

But, it did have presentations like:

THE TIDAL WAVE OF ADHD AND AUTISM: INSIGHTS FROM PATIENTS, PROFESSIONALS AND PUBLIC HEALTH

 

Sebastian Lundström’s presentation is available on YouTube. It is very interesting for anyone interested in the skyrocketing level of autism diagnosis.

I have mentioned previously that since in schools in many Western countries more than 20% of kids are now seen as having special educational needs, do not be surprised if autism/ADHD rates eventually hit 20%.  ADHD does look like autism-lite to me and the genetic studies also back this up. So, expect that autism/ADHD reaches 20% of boys.

Now look at Stockholm.

It turns out that in Stockholm 5.9% of teenage boys now have an autism diagnosis and 15% have an ADHD diagnosis. Some will have both.

 

 

Here is the full video for those who think this must be a mistake, or that doctors in Stockholm have gone insane.

 

Now, much to psychiatrists' surprise, adult Swedes are coming forward and trying to delete their autism/ADHD diagnosis from their records. Being Sweden, everything is recorded centrally. In the first 100 cases that were re-evaluated 90% were found to have no symptoms of autism/ADHD. In the video Professor Lundström gives the reasons for the misdiagnosis. It ranges from the parents insisting to have one, to the doctor giving one so that the child can access extra help at school. In many European countries the diagnosis qualifies the child/parents for various social security payments.

There are some downsides in Sweden to be an adult with an autism/ADHD diagnosis. It can affect employment, driving, or securing insurance.

The subject of ADHD leads to the second half of this post. Here we reconnect with the theme of treatable ion channel dysfunctions that have become somewhat a hallmark of this blog.

  

Calcium channel blockers now considered for ADHD treatment

 Blood pressure drug could be a safer alternative for treating ADHD symptoms, finds study

Repurposing amlodipine, a commonly used blood pressure medicine, could help manage attention-deficit/ hyperactivity disorder (ADHD) symptoms, according to an international study involving the University of Surrey.

 

Here is the full study

 

Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records

ADHD is a chronic neurodevelopmental disorder that significantly affects life outcomes, and current treatments often have adverse side effects, high abuse potential, and a 25% non-response rate, highlighting the need for new therapeutics. This study investigates amlodipine, an L-type calcium channel blocker, as a potential foundation for developing a novel ADHD treatment by integrating findings from animal models and human genetic data. Amlodipine reduced hyperactivity in SHR rats and decreased both hyperactivity and impulsivity in adgrl3.1−/− zebrafish. It also crosses the blood-brain barrier, reducing telencephalic activation. Crucially, Mendelian Randomization analysis linked ADHD to genetic variations in L-type calcium channel subunits (α1-C; CACNA1C, β1; CACNB1, α2δ3; CACNA2D3) targeted by amlodipine, while polygenic risk score analysis showed symptom mitigation in individuals with high ADHD genetic liability. With its well-tolerated profile and efficacy across species, supported by genetic evidence, amlodipine shows potential to be refined and developed into a novel treatment for ADHD.

 

This is not an entirely new finding, but prior research shows that crossing the blood barrier is a key factor. Drugs like Verapamil win over Amlodipine.

 

Brain-penetrant calcium channel blockers are associated with a reduced incidence of neuropsychiatric disorders 

Calcium channel blockers (CCBs) differ in their ability to penetrate into the brain. Pharmacoepidemiological studies suggest that CCBs as a class may have beneficial effects on the risks and outcomes of some psychiatric and neurological disorders. It is plausible but unknown whether this effect relates to their brain penetrance. To address this, we used the TriNetX electronic health records network to identify people prescribed a brain-penetrant CCB (BP-CCB), or those given amlodipine, a CCB with low brain penetrability. We created cohorts of patients who, prior to first CCB exposure, either had to have, or could not have had, a recorded ICD-10 diagnosis in any of the following categories: psychotic disorder; affective disorder (including bipolar disorder and major depressive disorder); anxiety disorder; substance use disorder; sleep disorder; delirium; dementia, or movement disorder. Cohort pairs were propensity score matched for age, sex, race, blood pressure, body mass index, and a range of other variables. The outcomes were the incidence of these disorders measured over a two-year exposure period. Matched cohort sizes ranged from 17,896 to 49,987. In people with no prior history of psychiatric or neurodegenerative disorder, there was a significantly lower incidence of most disorders with BP-CCBs compared to amlodipine, with risk ratios ranging from 0.64 to 0.88 and an overall risk ratio of 0.88, i.e. a risk reduction of 12%. In people who did have a prior psychiatric or neurodegenerative diagnosis, differences were much smaller, but again showed lower risks for several disorders with BP-CCBs compared to amlodipine. The differences were somewhat more marked in women and in people less than 60 years old. Results were similar when comparing BP-CCBs with verapamil and diltiazem. We also compared BP-CCBs with angiotensin receptor blockers, and found an overall risk ratio of 0.94 in favour of BP-CCBs, but with differential effects across disorders including a higher risk of psychotic disorder and dementia, but a lower risk for anxiety and sleep disorders. In some analyses, there was evidence of residual confounding even after the extensive matching, in that negative control outcomes showed a reduced incidence with BP-CCBs relative to the comparator cohort. In summary, CCBs that readily penetrate the brain are associated with a lower incidence of neuropsychiatric disorders, especially first diagnoses, compared to CCBs which do not. This may reflect their blockade of neuronal voltage-gated calcium channels. The findings encourage repurposing trials using existing BP-CCBs, and suggest that novel BP-CCBs with enhanced and more selective central actions might have greater therapeutic potential for psychiatric and neurodegenerative disorders.

  

Conclusion

I do not think de-diagnosis of autism/ADHD will catch on in the UK or US. Few countries have a centralized register of who has autism/ADHD and in general there are few downsides to adults holding a diagnosis, unlike in Sweden. If it affected your rights to drive a car and what you pay for insurance, there would be a long queue for de-diagnosis.

In the Swedish military conscription/assessment medical guidelines, autism spectrum disorders are listed among psychiatric/neurological conditions that can lead to exemption from service. Some patriotic young Swedes with autism/ADHD actually want to serve.

As conscription may return to other less patriotic European countries, you can expect an additional demand for adult autism diagnosis to avoid the draft!

When it comes to calcium channels, I think all bases have already been well covered in this blog.

I know of several different calcium and other channel blockers being used by readers, the latest being Journavx/suzetrigine, a new one approved in 2025, which blocks Nav1.8. Nicardipine is more likely to block Nav1.8 in the brain. Journavx was developed specifically to have poor CNS penetration to avoid central side effects. It targets acute pain situations where short-term opioid use would normally be considered. It all depends which Nav1.8 channels you want to block. But, if the blood brain barrier is impaired (as we know it is in certain types of autism) then more of the drug will enter the brain than expected.

An impaired blood brain barrier would also help Amlodipine to cross.

 

Regular readers of this blog will already know that calcium channels are dysfunctional across a wide range of disorders from bipolar, schizophrenia, autism, intellectual disability to epilepsy.

I was nonetheless surprised that a university in the United Kingdom would propose repurposing Amlodipine (an L type calcium channel blocker) to treat ADHD. Even if they are mistaken, at least they are showing signs of curiosity!

There is no single perfect calcium channel blocker for the brain.

If you want to target Cav1.2 you have a great option in Verapamil, because it is relatively selective for this channel and it crosses the blood brain barrier easily.

If you want to target Cav1.2 and Cav1.3 then Amlodipine appears the best drug, but it does not cross the blood brain barrier as well as Verapamil.

I think the ADHD researchers should start with Cav1.2, because we know 100% it can be blocked in the brain using Verapamil. Then compare the result with taking Amlodipine.

 

Pleiotropic Association of CACNA1C Variants With Neuropsychiatric Disorders

 

From this blog we know that both verapamil and amlodipine can be safely used in autism. A small number of people do have side effects and discontinue, but most do not have issues.

The effect of the two drugs overlap but are not identical. This matches what we know about what channels they block. Verapamil also has other effects:

·        Verapamil partially blocks Cav1.3

·        Verapamil partially blocks T-type channels (Cav3.1–3.3) particularly at higher doses.

·        Verapamil partially blocks potassium Kv channels.

The big advantage of Amlodipine is that it has a long half-life, so you take it once a day.

Verapamil needs to be taken 3 times a day, or in the extended release version.

I did look on Reddit and plenty of people with ADHD were commenting that taking Amlodipine for high blood pressure had not improved their ADHD symptoms.

Note that ADHD is another umbrella diagnosis and there will be many sub-types. For some people Amlodipine might well help. For some people ADHD is just a consequence of being glued to a smartphone all day, every day, for years on end. Guess what, 60% of adults with ADHD report chronic sleep problems.

The over liberal diagnosis of autism in Stockholm does look crazy. Maybe it is the Greta effect?

It is as if Stockholm has developed a new version of the old “Stockholm syndrome” — an emotional loyalty to the very diagnostic culture now being questioned. When 90% of adults seeking de-diagnosis are found not to have autism or ADHD, it suggests that what began as a well-meaning effort to help children may have trapped an entire system in its own narrative. Fancy that.

 

(The term “Stockholm syndrome” comes from a 1973 bank robbery in Stockholm, when hostages ended up sympathising with their captors — a classic case of misplaced loyalty.)

 

From Conception to Early Childhood: Managing pain, fever, and neurodevelopmental risk. Time to apply some common sense? Time for NAC?

 

Donald Trump recently reignited debate about Tylenol (paracetamol/acetaminophen) in pregnancy. His comments drew attention to research linking prenatal use to higher rates of autism and ADHD.

A large review of 46 studies, including work from Harvard, found consistent associations between paracetamol in pregnancy and neurodevelopmental risks. The FDA now advises caution: use the lowest dose for the shortest time.

 

Tylenol in pregnancy linked to higher autism risk, Harvard scientists report

Researchers reviewing 46 studies found evidence linking prenatal acetaminophen (Tylenol) exposure with higher risks of autism and ADHD. The FDA has since urged caution, echoing scientists’ advice that the drug be used only at the lowest effective dose and shortest duration. While important for managing fever and pain in pregnancy, prolonged use may pose risks to fetal development. Experts stress careful medical oversight and further investigation.

 Why the concern?

• Paracetamol depletes glutathione (GSH), the body’s main antioxidant.
• This raises oxidative stress in both mother and fetus.
• The fetus has weak antioxidant defences, so damage may occur during critical brain development.

But here is the dilemma: the fever, pain, or inflammation that drives a mother to take paracetamol is itself risky. We have long known from maternal immune activation models that fever and cytokine surges in pregnancy can disturb fetal brain development and cause autism or schizophrenia. There is also evidence linking maternal immune activation to ADHD in the offspring.

So, what is the solution? Pair paracetamol with NAC.

Why NAC?

• NAC (N-acetylcysteine) is a precursor to glutathione.
• It’s used worldwide in emergency rooms to save lives after paracetamol/ acetaminophen overdose.
• In pregnancy, NAC has been shown to reduce miscarriage risk by 50%,

N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss

• Increased pregnancy continuation: Women receiving NAC and folic acid were 2.9 times more likely to continue their pregnancies beyond 20 weeks compared to those receiving folic acid alone
• Higher take-home baby rate: The NAC group had a 1.98 times higher rate of delivering a live baby.
• These findings suggest that NAC, an antioxidant, may help mitigate oxidative stress, a factor implicated in pregnancy loss.

  

A combined Paracetamol/acetaminophen + NAC pill would:

• Prevent liver toxicity,
• Buffer oxidative stress in the fetus,
• Eliminate the overdose suicide risk that haunts current paracetamol use.

So far, no company has produced it. Perhaps the “rotten egg” smell of NAC is a barrier—but solid sustained-release tablets avoid this.

 

Why Paracetamol/acetaminophen use is problematic in under 5s

Paracetamol depletes glutathione (GSH), the body’s primary antioxidant, increasing oxidative stress. A fetus with some genetic predispositions might already be in a state of oxidative stress, as might the mother

Paracetamol is mainly metabolized in the liver. A small fraction is metabolized into NAPQI — a reactive toxic metabolite. Glutathione (GSH) neutralizes NAPQI by forming a harmless conjugate.

If GSH stores are low (or paracetamol is taken in high doses), NAPQI accumulates, causing liver toxicity and GSH is exhausted raising oxidative stress.

Acute oxidative stress can be very damaging to developing brains. The risk after 5 years old fades away, other than in those who have already exhibited a profound metabolic/mitochondrial condition.

Why Oxidative Stress Rises in Pregnancy

Placental development: Early pregnancy is low-oxygen; as blood flow increases, oxygen surges and generates reactive oxygen species (ROS).

High metabolic demand: The mother and placenta require much more energy, leading to increased mitochondrial ROS.

Immune adaptations: Pregnancy involves a shift in maternal immunity, with inflammatory cytokines contributing to oxidative stress.

Fetal growth: Rapid cell division and organ development naturally produce oxidative byproducts, while the fetus’s antioxidant defenses are immature.

Limited antioxidant reserves: Maternal antioxidants (glutathione, vitamins C & E, enzymes) are partly depleted as pregnancy progresses.

 

Compounding Risk Factors

Polycystic Ovary Syndrome (PCOS): Associated with high androgens, insulin resistance, and chronic inflammation. These increase oxidative stress and are linked to higher autism risk in offspring.

Gestational Diabetes: Maternal hyperglycemia and insulin resistance increase ROS, damage the placenta, and expose the fetus to oxidative and metabolic stress.

Other amplifiers: Obesity, infection, fever, or poor nutrition further elevate oxidative stress.

 

How Oxidative Stress Affects the Fetus

Neurodevelopmental disruption: ROS can damage neural stem cells, impair migration, and disturb synapse formation.

Epigenetic reprogramming: Oxidative stress alters DNA methylation and gene expression, shaping long-term brain function.

Immune activation: Inflammatory cytokines cross the placenta and disturb fetal brain development.

Mitochondrial dysfunction: ROS damage fetal mitochondria, reducing energy for developing neurons.

Neurotransmitter imbalance: Antioxidant depletion disrupts glutamate/GABA balance and monoamine systems.

 

Consequences for the Unborn Child

Most pregnancies manage oxidative stress without harm, thanks to maternal–fetal antioxidant defences.

When oxidative stress overwhelms these defences—especially in mothers with PCOS, GDM, or infections—the risk of complications rises:

Preterm birth, growth restriction, or preeclampsia

Higher vulnerability to neurodevelopmental disorders, including autism spectrum disorder (ASD) and ADHD.

Genetic predispositions in antioxidant or mitochondrial pathways may make some fetuses especially sensitive to these oxidative challenges.

Pregnancy naturally involves a controlled increase in oxidative stress, but when combined with maternal conditions like PCOS, gestational diabetes, or acute infections, the oxidative burden can exceed protective capacity. This imbalance may impair placental function and fetal brain development, increasing the risk of adverse outcomes, including autism. 

 

Pregnancy: Choosing safer options for pain and fever

• Paracetamol → Remains the best option if pain relief is absolutely needed, but should be paired with NAC.
• NSAIDs (ibuprofen, mefenamic acid) → Unsafe in later pregnancy due to fetal kidney damage and premature closure of the ductus arteriosus. Premature closure of the ductus arteriosus is a serious condition that occurs when the fetal blood vessel connecting the pulmonary artery to the aorta closes before birth. Do not use NSAIDs!
• NAC supplementation → Low-cost, safe, and evidence-backed for reducing oxidative stress.

 

Infancy and Early Childhood

• Paracetamol
• Licensed from birth.
• Effective for pain and fever, but still depletes glutathione.
• In at-risk infants (metabolic or mitochondrial issues), consider pairing with NAC.
• NSAIDs (ibuprofen, Ponstan)
• Suitable from 3–6 months (depending on guidelines).
• Do not deplete glutathione, making them safer for oxidative stress.
• Hydration matters to protect kidneys.

 

Vaccinations, Fever, and Oxidative Stress

Vaccines work by briefly activating the immune system. This triggers a short burst of oxidative stress—far smaller than that caused by actual infections.

• Healthy children clear this easily.
• At-risk children (mitochondrial disease, metabolic errors, weak antioxidant systems) may struggle, leading to fatigue, regression-like symptoms, or metabolic instability.

Medication choices around vaccines

• NSAIDs → Good for post-vaccine fever. Avoid routine pre-dosing to prevent dampening immunity, unless the child is in the at-risk group.
• Paracetamol → Pre-vaccine dosing can reduce antibody production and reduce GSH. Post vaccine should be paired with NAC.
• Montelukast → Anti-inflammatory, theoretically helpful in at-risk children, but not tested in trials, but is used at metabolic/mitochondrial clinics treating children.
• NAC → Biologically plausible support for antioxidant status, though not studied formally in this setting.

Mainstream pediatrics avoids routine prophylactic anti-inflammatories, but some specialists (e.g., Dr. Kelley, Johns Hopkins) do use them selectively in fragile children. Using paracetamol without NAC is a bad idea.

 

Metabolic Decompensation: The Hidden Risk

Some children with mitochondrial or metabolic disorders cannot handle stress from fever or illness. This can trigger:

• Energy failure (low ATP)
• Accumulation of toxic metabolites (lactate, ammonia)
• Seizures or regression

In developing brains, these crises can leave permanent autism-like features and/or intellectual disability. These symptoms are secondary to brain injury. Prevention is key:

• Hydration, glucose support
• Early fever control
• Antioxidant support (NAC, vitamins C & E)

 

Key Takeaways

• Pregnancy: If pain relief is needed, paracetamol + NAC is safer than paracetamol alone. Avoid NSAIDs.
• Infancy: Paracetamol is widely used, but NSAIDs are safer from 3 months onward when oxidative stress is a concern.
• Vaccination: Vaccines prevent far greater oxidative stress from infections. At-risk children may benefit from antioxidant or anti-inflammatory support, but this should be individualized.
• Metabolic decompensation: Recognize and prevent crises in vulnerable children—this reduces risk of secondary neurodevelopmental injury.

 

Conclusion

Paracetamol has been trusted for decades, but its link with oxidative stress and neurodevelopmental risk is becoming harder to ignore. A Paracetamol + NAC pill makes both medical and common sense—safer for mothers, safer for children, and suicide-proof.

Until then, thoughtful use of NAC, NSAIDs, and tailored fever management could make a real difference in protecting brain development from conception through early childhood.

 

My original draft post was rather long, so here is the “optional” part 2, for any avid readers out there!

 

 

Part 2: Vaccines, Oxidative Stress, and Children at Risk

Why some kids may react differently — and what parents and clinicians can do

Vaccines are one of the greatest public health achievements, protecting children from infections that would otherwise cause significant illness, hospitalization, or death. But for children with mitochondrial disorders, metabolic diseases, or weak antioxidant systems, even routine vaccination can temporarily stress the body.

How Vaccines Trigger Oxidative Stress

• Vaccination works by activating the immune system, prompting cytokine release, mild inflammation, and reactive oxygen species (ROS) production.
• In healthy children, this burst is short-lived. Antioxidant defences like glutathione, superoxide dismutase, and dietary vitamins C & E neutralize ROS quickly.
• In children with mitochondrial or metabolic vulnerabilities, baseline ROS is already elevated, and antioxidant defences may be limited. A small extra load from vaccination can feel disproportionately stressful.

 

Why Some Children React Differently

Mitochondrial Disorders

• Mitochondria produce ATP and ROS. Dysfunction means higher baseline oxidative stress and lower energy reserves.
• A vaccine-induced oxidative spike can linger longer, leading to fatigue, metabolic stress, or regression-like symptoms.

Metabolic Disorders

• Children with amino acid, fatty acid, or urea cycle defects have limited antioxidant capacity.
• ROS accumulation may overwhelm defences, causing secondary mitochondrial stress or toxic metabolite build-up.

Genetic Variants

• Some children carry variants that reduce glutathione production or antioxidant enzyme activity (e.g., GSTM1/GSTT1 deletions, MTHFR variants, impaired SOD/catalase).
• Even minor oxidative challenges can temporarily disturb synapse formation, neurotransmitter balance, and myelination in the developing brain.

 

Medications Around Vaccination

NSAIDs

• Symptom-driven use for fever or pain post-vaccine is generally safe.
• Routine prophylactic use is usually avoided because it can reduce antibody responses, but specialists consider this is likely minimal

Paracetamol

• Pre-vaccine dosing can modestly blunt antibody formation in some vaccines and is unwise because it reduces GSH just before it will be needed most.
• Post-vaccine, symptom-driven use is often considered safe, but is unwise due to the ruction in GSH when needed most
• High-risk children should always avoid paracetamol unless paired with NAC to protect glutathione and limit oxidative stress.

NAC (N-acetylcysteine)

• Biologically plausible support for antioxidant status in at-risk children.
• Safely used during pregnancy and by babies
• Not yet studied in formal vaccine trials, but safe and used in clinical settings for other oxidative stress conditions.

Montelukast

• Anti-inflammatory, may reduce oxidative stress, but not proven for vaccine prophylaxis.
• Used by children at vaccination time when already prescribed it for asthma/allergic disease.

 

Managing Vaccination in At-Risk Children

1.     Ensure good hydration, feeding, and metabolic stability before vaccination.

2.     Monitor closely for post-vaccine fever, fatigue, or regression-like symptoms.

3.     Have supportive measures ready:

o    NAC or other antioxidant support

o    Symptom-driven NSAIDs

o    Avoid paracetamol unless paired with NAC

o    Quick access to a specialist if metabolic stress occurs

 

Takeaways for Parents and Clinicians

• Vaccines do cause a small, transient oxidative stress, but it is far less than the oxidative burden from infections.
• Children with mitochondrial or metabolic vulnerabilities may need extra care before and after vaccination.
• NAC, hydration, symptom-driven NSAIDs, and careful monitoring can reduce risk without compromising immunity.
• Always coordinate with a metabolic or mitochondrial specialist when planning vaccination for high-risk children.

By understanding oxidative stress, supporting antioxidant defences, and tailoring care, parents and clinicians can protect both immunity and neurodevelopment.

Since most parents, in reality, do not have access a mitochondrial specialist it pays to do your homework in advance. All the needed resources are in plain view.

You do wonder why nobody makes a combined Paracetamol/acetaminophen + NAC pill.

Such a pill is perfect for pregnant women.

Nobody would be able to commit suicide with this pill. This pill blocks the harmful effect on the liver that ultimately can lead to death.

NAC does smell of rotten eggs. One argument against such a pill is that it would stink and pregnant women are often feeling nausea. If the pill is solid (like NAC Sustain) there is no smell of rotten eggs. So you certainly can have a combined pill.

Personally, I would ban all liquid formulations of Paracetamol, other than for babies under 3 months. Many countries have long used exclusively Ibuprofen or Ponstan for children. Once a child is 5 years old the potential for paracetamol to do neurodevelopmental harm should have faded.

You can give babies NAC, it is sold in a liquid form for this purpose. NAC acts as a mucolytic, meaning it thins mucus in the airways.

How common is Metabolic Decompensation as a cause of severe autism? We know it exists, but I think we will never know how common it is. Hannah Poling is the best-known example. Evidence of an inconvenient truth.