Up to 40% of children in the “failed” phase 3 bumetanide trial were actually responders, according to AI reanalysis of the data – Treating autism in the real world

 

In some parts of the world even the words “treating autism” can still get you into trouble and some people have to go to quite extreme lengths to get their child’s developmental trajectory back on track.

I did note that in the US big changes have been made to their Interagency Autism Coordinating Committee (IACC) that coordinates all efforts within the Department of Health and Human Services (HHS) concerning autism. Now it includes some readers of this blog. Will this make a difference?

https://iacc.hhs.gov/ 

 

Over in France, the Bumetanide researchers Ben-Ari, Lemonnier and pals published their AI driven reanalysis of the “failed” phase 3 autism trial. They found that using AI they could actually predict who did actually respond; and many did. Nonetheless this large trial of all-jumbled-together kids with an autism diagnosis showed that overall bumetanide was no better than a placebo. Sounds strange to you? This is a common theme in autism trials because they do not narrow down a specific type of autism that they are trying to treat.

Over where I am, I keep getting positive reports of success. Some people are lucky and find that much of what works for my son works for theirs. There is a lot in this blog about other types of autism.

Why autism remains untreatable?

Autism is not simple to treat. Autism has no biological definition and measurement scales are all likely not fit for purpose. What would treatment success even mean?

From the perspective of severe autism with apparent ID (the old “Classic autism”) the biggest issues are to do with the slow rate of acquiring new skills. There are very well established tools to measure the skillset of such kids, such as  ABLLS (Assessment of Basic Language and Learning Skills). There are also non-verbal IQ tests. 

For young kids with classic autism you want them to add these basic skills ASAP, so that they can move on with their lives. In our case Bumetanide was the key to unlock new skill addition.

This is not what the phase 3 bumetanide trial was trying to measure.

Indeed one of the recurring comments from parents and teachers is the child has become more “present.” How do you quantify something like that?

For most children with autism in 2026, they do not have a problem with skill acquisition, they are a bit quirky, nervous, resistant to change, stim a bit, do not make friends. It is a very different condition. These issues are very real and genuinely concern some parents, but they are very different problems.

The modern cookie-cutter, protocol-driven, approach does work for most of medicine. But it will never work on an ill-defined category like autism. It actually becomes ridiculous when you look at all the varied types of autism. Even people with cerebral palsy or Down syndrome can be given an “autism” diagnosis on top, but they are completely different biological conditions.

Where to from here?

What does Ben-Ari do now?

Start again with another phase 3 trial? Paid for by who?  Will Servier come back and fund the second attempt?

In the meantime the clock keeps ticking.

I read Ben-Ari’s initial study and made my n=1 trial in 2012. My trial met its primary endpoint (Peter satisfied) and therapy started.

Academic performance went from complete basket-case to passing his high school public IGCSE exams a decade later.

Now it is 2026 and therapy still continues. No side effects,  heart ultrasound (echocardiogram) all normal.

Crazy world.

40% “disabled” at Stanford

I was surprised to read that almost 40% of undergraduates at Stanford University are claiming disability, to get extra time in exams. It does tell you a lot about the current generation of 20 year olds.

I would give them an E on their final diploma (I passed but needed Extra time). It is perfectly reasonable for a small number of clever students to need extra time, they might have a physical disability with their hands, be deaf, or blind, or dyslexic. It is perfectly reasonable to give some people extra time, but 40%?

It really is not fair on the remaining 60%. Maybe just give everyone an extra hour, those that finish early just leave early. They could get E on their results, for “I work fast and finish Early - hire me!"

What is annoying is the trivialization of the word disability.

40% of Stanford undergrads receive disability accommodations—but it’s become a college-wide phenomenon as Gen Z try to succeed in the current climate

So many people claim a disability like autism that theme parks in the US and Europe have had to roll back their privileged access schemes.

When I visited Charlotte International airport a while back and had to stand in a very long line for the passport control, I was amazed to see a never-ending procession of people appearing in wheelchairs to skip the queue. I have never seen this in Europe, but I suppose it will eventually come.

 

Back to those 40% in the Bumetanide trial.

New Analysis of the Bumetanide Phase 3 Trials: Were Responders Hidden in a “Failed” Study?

Approximately one-quarter to one-third of participants fit validated clinical profiles in which bumetanide showed statistically significant benefit on SRS-2, despite the overall trial being negative. The abstract itself says up to 40%.

Treating autism with Bumetanide: Identification of responders using Q-Finder machine learning algorithm

Bumetanide, a specific NKCC1 co-transporter inhibitor, restores deficient GABAergic inhibition implicated in various brain disorders, including Autism Spectrum Disorders (ASD). In keeping with this mechanism, nine successful phase 2 clinical trials, conducted by seven independent teams using an identical protocol, have shown significant improvements in ASD symptoms among individuals treated with Bumetanide. Despite these promising results, two large phase 3 clinical trials (over 400 children recruited in approximately 50 centers and covering age groups 2–6 and 7–17 years) failed with no significant difference between patients treated by placebo or Bumetanide. This failure may stem from the substantial heterogeneity of ASD symptom profiles across the study population, potentially diluting the overall observed treatment effect. To address this, we reanalyzed the phase 3 data using Q-Finder, a supervised machine learning algorithm, aiming to identify subgroups of patients who responded to the treatment. This analysis was based on clinical parameters collected at the baseline of trial and used the same standard endpoints and success criteria defined in the original phase 3 protocol. It enabled the identification of responder subgroups showing a statistically significant difference between placebo and Bumetanide treatment arms. We report detailed descriptions and statistical evaluations of these subgroups. The discovered responder subgroups, representing up to 40% of participants, were cross validated between the two study populations. These findings suggest that meaningful treatment responses can be uncovered within negative phase 3 trials, highlighting the limitations of a one-size-fits-all approach for heterogeneous conditions such as ASD. Machine learning appears to be a promising tool to support this precision medicine strategy.

The 2026 reanalysis published in Translational Psychiatry revisited the large Phase 3 bumetanide trials that previously failed to meet their primary endpoint.

The original Phase 3 trials included more than 400 children (ages 2–17) and found no significant overall difference between bumetanide and placebo on the primary outcome measure (CARS2).

This new study asked a different question:

Instead of “Did bumetanide work for everyone?”, could it have worked for specific subgroups that were diluted in the overall average?

To explore this, the authors used a supervised machine-learning algorithm (Q-Finder) to identify baseline clinical profiles associated with treatment response.

What They Found

The original overall result remains negative

Across the entire population:

• No significant benefit on the primary endpoint (CARS2).
• No meaningful average effect.

So the trial still officially failed.

Subgroups showing benefit were identified

When the data were stratified by symptom profiles at baseline, several subgroups showed:

• Statistically significant improvement on the SRS-2 (Social Responsiveness Scale)
• Treatment effects of roughly 12–17 points in validated groups
• Coverage of about 25–36% of participants in the largest responder profiles

Importantly, these findings were cross-validated between the younger and older trial cohorts.

A Consistent Feature of Responders

Across validated subgroups, one feature repeatedly appeared:

Mildly abnormal “adaptation to environmental changes” on CARS2

This domain reflects:

• Difficulty with transitions
• Rigidity around routines
• Stress with change

Responders were typically:

• Clearly autistic (often moderate–severe social symptoms)
• With repetitive behaviours
• But not globally or profoundly impaired across all domains

Interestingly, IQ did not emerge as a defining predictor of response.

Primary Endpoint vs Secondary Endpoint

A key nuance:

• No validated responder subgroups were found using the primary endpoint (CARS2).
• Validated subgroups were found using the secondary endpoint (SRS-2).

From a regulatory standpoint, this matters: trials are judged on their primary endpoint.

From a scientific standpoint, it suggests:

SRS-2 may have been more sensitive to the type of change bumetanide produces.

What This Means

This reanalysis does not prove bumetanide works broadly in autism.

It does suggest:

• Autism is highly heterogeneous.
• A one-size-fits-all trial design may dilute effects.
• A biologically or symptom-stratified approach may be necessary.
• Around one-quarter to one-third of participants may represent a responder subtype.

However, these findings are post hoc and exploratory.

To confirm them, a new trial would need to:

• Prospectively enroll only the identified responder phenotype.
• Use appropriate primary endpoints.
• Replicate the treatment effect.

Why This Matters for Autism Research

The study reflects a broader shift toward precision medicine:

• Rather than asking “Does this drug work for autism?”
• The better question may be:

“Which subtype of autism does it work for?”

Machine learning may help identify these subgroups, but prospective validation is essential.

The original Phase 3 trial remains negative at the population level.

This reanalysis suggests that meaningful responses may have been present in specific clinical subgroups — particularly children with:

• Mild adaptation abnormalities
• Repetitive behaviours
• Significant social impairment

Whether this represents a reproducible biological subtype remains to be tested in future trials.

Conclusion

In Rett syndrome a very expensive new drug called Trofinitide was approved, even though reports suggest it is only really effective in about 20% of these girls. I was really surprised.  It costs $300,000 to $900,00 a year depending on the girl’s weight.

It looks very odd that the large bumetanide failed, even though 25-40% were actually responders. By the way, my son’s bumetanide therapy has cost about $80 a year, for the last 13 years.

It does not fill you with great confidence.

I recently saw an article saying that “paracetamol/ acetaminophen does not, after all, increase the incidence of autism.” Well theoretically it should be harmful, by depleting glutathione, which is why it should be taken with NAC. We also know that NAC taken during pregnancy can significantly reduce the risk of miscarriage and this has been studied in a clinical trial.

N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss

A controlled clinical trial studied N-acetylcysteine (NAC) in 168 pregnant women with a history of recurrent unexplained miscarriage. Women received either folic acid alone or folic acid plus NAC at 600 mg per day. In the NAC group, 52% of pregnancies continued beyond 20 weeks, compared with 27% in the control group. The take-home baby rate was 47% in the NAC group, compared with 21% in the control group. This represents more than a doubling of the live birth rate. NAC works by restoring glutathione, the cell’s main antioxidant, protecting placental and fetal tissue from oxidative stress. Oxidative stress is known to impair placental function and contribute to pregnancy loss. NAC was well tolerated, with no significant safety concerns reported. These results suggest that correcting oxidative stress can directly improve pregnancy outcomes in a defined high-risk group. This study illustrates how targeting a specific biological mechanism can dramatically change developmental outcomes.

If a professionally-managed autism trial cannot detect the 25-40% who responded to some extent, do you believe a study that effectively says nobody gets autism from pre-natal acetaminophen. Not even 1%? All you likely need to do is pair it with NAC to make the risk 0%.

For decades doctors refused to believe regressive autism existed. Once people started videoing their toddlers, it became impossible to doubt that some actually had developed speech and then lost it. Parents were not imagining it. It was just an inconvenient truth, and still is.

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.

 

Cesarian Delivery and Autism – another inconvenient truth?

Brasil is the C-section capital of the world, with rates in the public sector of 35–45%, and 80–90% in the private sector.

A recent study from the Karolinska Institute in Sweden, analysing 61 previous studies, has again shown a connection between birth by Cesarian Section and an increased risk of autism or indeed ADHD. 

C-sections account for just 16% of births in Sweden, but 32% in North America.

This of course prompted a reaction to reassure future mothers that they have nothing to fear, from experts in obstetrics who of course know nothing about the etiology of autism.  Mothers should be reassured, but trashing the study helps nobody.  Instead of a 1% risk of non-trivial autism, it rises to 1.3%. You still have more than a 98% chance of having a neurotypical child, all other factors being equal.  Without a medically necessary C-section, death is a real possibility.

It was a couple of years ago that the Karolinska Institute highlighted the fact that those with severe autism currently have a life expectancy of under 40 years.  Another inconvenient truth.

Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring 

Question  Is birth by cesarean delivery associated with an increased risk of neurodevelopmental and psychiatric disorders in the offspring compared with birth by vaginal delivery?

Findings  In this systematic review and meta-analysis of 61 studies comprising more than 20 million deliveries, birth by cesarean delivery was significantly associated with autism spectrum disorder and attention-deficit/hyperactivity disorder.

Meaning  The findings suggest that understanding the potential mechanisms behind these associations is important, especially given the increase in cesarean delivery rates for nonmedical reasons.

Abstract

Importance  Birth by cesarean delivery is increasing globally, particularly cesarean deliveries without medical indication. Children born via cesarean delivery may have an increased risk of negative health outcomes, but the evidence for psychiatric disorders is incomplete. 

Conclusions and Relevance  The findings suggest that cesarean delivery births are associated with an increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder, irrespective of cesarean delivery modality, compared with vaginal delivery. Future studies on the mechanisms behind these associations appear to be warranted. 

Very many things are known to slightly increase the odds of a person having autism and the more risk factors you have the more severely autistic you may be.  This ranges from maternal stress (anything from experiencing a hurricane, work stress, life trauma) to maternal/paternal age, obesity, gestational diabetes, alcohol/drug abuse, illness during pregnancy etc. This combines with whatever is in the parents’ DNA and random mutations that are bound to occur.    

A more rational reaction might be to investigate further why there might be a link and how you could counter any risk to children born by cesarian section.  You only have to read the existing research, or this blog.

There are 2 very good reasons why there should be a link between autism and C section, both have been covered in this blog.

1.     The microbiome comes from the mother. Science is only recently starting to understand the role of bacteria in health, but we know that it plays a key role in conditioning/calibrating the immune system of babies.  Once the immune system has been calibrated it is set for life.  Early exposure to bacteria is necessary and humans evolved to expect it.  If your immune system is over/under sensitive there will be consequences. Birth via C-section avoids exposure to bacteria in the birth canal, unless the newly arrived baby is “seeded” with bacteria from the mother. Mother’s milk is another key source of transferring the mother’s microbiome to the baby. 

2.     We saw that the birthing hormone Oxytocin plays a key role in triggering the “GABA switch” in new-borns. This is the process which transforms immature neurons with high chloride to mature neurons with low chloride shortly after birth.  During natural birth there is a surge in the hormone Oxytocin that is transferred to the baby, this causes the chloride transporter KCC2 to be further expressed and the “opposing” transporter NKCC1 to fade away.  In many people with severe autism their neurons remain in the immature state their entire life.  Just as you can replace the bacteria transfer lost in birth via C-section, there would be absolutely no reason why you could not replicate the surge in Oxytocin to "flip the GABA switch".

The recent study showed that elective C-sections (where the baby is in perfect health and not distressed) are associated with the elevated risk of both Autism and ASD.

Regular readers of this blog would probably be surprised if C-section did not increase autism prevalence.

The important thing is to acknowledge this likely connection and mitigate it, rather than try and fault the numerous studies that have shown the same effect.

The same of course applies to reducing the very small risk from vaccines, rather than construct new studies in a contrived way to show there is zero risk.   If you can safely and cheaply reduce the risk of a negative reaction to vaccines, why wouldn’t you?  Just follow Johns Hopkins example and give Ibuprofen or Montelukast (Singular) for a few days before and after and remember to never give Paracetamol/Acetaminophen (Tylenol) in response to fever after a vaccine. Paracetamol/ Acetaminophen reduces the body’s key antioxidant GSH just when the baby/child may need its neuroprotection most.

Some conditions are associated with preterm births, a good example is Cerebral Palsy (CP), which is twice as common in babies born very early. CP is rarely genetic and is usually considered to be caused by a complication during pregnancy, birth or shortly thereafter. I think you would find a correlation between C-sections and CP, but in this case I doubt you would find it in elective C-sections.   In other words C-sections do not “cause” CP, but they may be associated with it. The ID/MR often found in CP might be elevated by C-section and, if so, would be treatable.

Conclusion

In order to halt the rise in incidence of the disabling kinds of autism there should be steps taken to reduce some of the very many factors that are driving the increase, albeit each one sometimes by a tiny amount.

This would be a good application of all those thousands of autism research papers, many of which have shown what factors contribute to increased risk, that now sit gathering dust.

We are not at the stage of wide scale gene editing, but many simple steps can be taken today to improve future health.  This does not mean do not vaccinate, or avoid medically necessary C-sections; vaccinations and C-sections have saved millions of lives. But, why would you not want to take a good thing and make it even better?  That is what we humans tend to be good at, like the Swedes and their Volvos.

Perhaps take your C-section with a generous smear of Mum's bacteria and a shot of synthetic oxytocin?  

There will be more on Cerebral Palsy in a later post on D-NAC (Dendrimer N-Acetyl Cysteine).