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Friday, 30 August 2019

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). 

                                                               



18 comments:

  1. Hi Peter, so many factors contributed to my son's autism: he was born by c-section, I had gestational diabetes and also my mutated gen MTHFR homocygous caused me trombophilia.
    Now,he is doing excellent with Clemastine,it makes such a big difference when he takes it. Could be added MS in my husband's family and PD to the list?
    Valentina

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    1. Valentina, I am glad that your son responds well to Clemastine. Can you give details of the effect you observe and the dosage you use. Also, have you observed what happens when you do not give Clemastine for a few days?

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    2. Peter, when he takes it, he stabilizes. He is better connected, so to speak. His executive functiones improve day by day, these have been the hardest thing to improve. His English teacher told me he has improved creative thinking and language production. I don't dare to stop it for a few days.He is taking clamist,1.34 mg a day.
      Valentina

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    3. Clemastine seems to be a winner for my son too. Over the last 3 months while using 1mg twice a say, he has gotten out of a plateau he had ay speech therapy and his ability to regulate his behaviors and stop himself has improved noticeably. Furthermore, he is far exceeding my expectations at swimming classes and he is doing far better at independently crossing the street. I am still there with him, but have had to prompt him less to look both ways and stop if a vehicle is approaching and not walk until that vehicle is stopped. He is still a very long way from crossing the street safely without my assistance, but he has made progress in areas which might suggest his brain is better connected in that manner.

      His core autism symptoms are still there but if I were to have given him some form of IQ test before and after this summer, I would be very surprised if there were not significant improvements.

      On another note, there really should be some sort of testing application for regular parents so that they can independently verify if progress has been made for any particular intervention rsther than relying on experts, whose professionalism you cannot question yourself unless you have a tool to objectively monitor progress in your child. There is just no good way to know if a new therapy whether it be a drug, diet, speech/occupational or a particular school is helping or hurting as most parents almost have to go on the faith preached by the medical professionals that treat their children. This scenario always is ripe for abuse and incompetence by erudite doctors and other autism professionals on the one hand, as well as vulnerable to impatient parents who expect instant miracles for their little angel on the other.

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    4. Tyler, that is great to hear. It would seem based on the feedback in this blog that a significant percentage of children with autism do respond to Clemastine, a safe and inexpensive re=purposed H1 antihistamine. It will be in my next Polypill update.

      It is extremely difficult to measure/quantify responses, I think IQ would be one potential measure, but situational awareness is one critical life skill that is very hard to measure.

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    5. Hi Valentina and Tyler,

      Just wanted to say great news and congratulations to you both!

      It's great to hear that you're both seeing improvements.

      AJ

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  2. Hi Peter! I am looking at autism and c-sections from the opposite end. (Pregnancy outcomes in women with autism: a nationwide population-based cohort study./ https://europepmc.org/abstract/MED/30555264) I was undiagnosed with autism when I was pregnant (at 36). I was healthy prior to getting pregnant. My pregnancy was uneventful except for pre-eclampsia in the third trimester. I carried to full-term... went into labor 2-3 days after reaching my due date. After getting to the hospital, then problems began. I couldn't dilate beyond 3-4 cm. I stayed that way for almost 48 hours despite many interventions to get my labor to progress. Finally, the doctor decided to do an emergency c-section. I was so happy. I now think that my daughter's health was/and is impacted in a negative way by not having her go through the birth canal.... She has struggled to overcome infections... and at 20 years of age, I still worry about her immune system.

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    1. Siverseas, your study is from the same University in Sweden. It is interesting.

      "Women with autism in our study had a 1.3-fold risk of preeclampsia in our main analyses. In the sensitivity analyses, the risk was not significantly increased for primiparous women; nevertheless, biparous women with autism had a 2.3-fold risk for preeclampsia. Preeclampsia is considered to be caused by an exaggerated systemic inflammatory response. Thus, it is possible that an altered immune response in individuals with autism contributed to the higher prevalence of preeclampsia.

      Studies have proposed preeclampsia, labor induction, and SGA (small for gestational age) as risk factors for autism in offspring. Since autism is a highly inherited disease with only partial penetrance, it is possible that preeclampsia, labor induction, and SGA are signs of overlapping inheritance."

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  3. Peter,plolactin in males is likked with health problems, however, according to lifescience, men with levels of prolactin that were lower than average, although still within the normal range, were more likely to generally fell unhealthier.
    This statement, together with my attempt to explain my son's pharmacogenetic profile, blood test results and behavioural indicators, prompted me to find research data of positive association between PRL serum levels and white matter volume which support the role of PRL promoting myelin repair.
    Petra

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    1. Petra, it has been shown that the increase in Prolactin levels as a result of pregnancy causes women with Multiple Sclerosis to experience improved remyelination.

      Both low and high prolactin in men can interfere with male hormones.

      If the pituitary gland is not working properly, low prolactin can be the result.

      The problem with hormones is that they have multiple functions and are interrelated, so if change the level of one you can expect many other changes.

      If you think your son has a low level of Prolactin best to ask an endocrinologist if it is clinically significant.

      You can have just one of the eight hormones produced at a low level and this is called selective hypopituitarism. Best to discuss the lab results with an endocrinologist

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    2. Peter, thank you, you are absolutely right as you put it down.

      My son has less than half the upper normal male limit and I am confused as the pituitary gland is part of the fight or flight response and he is supposed to produce more prolactin due to constant stress.

      Petra

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  4. I accidentally stumbled over two different studies mentioning a drug called Guanabenz, which I had not heard about before.

    The first one caught my eye because I was looking for further ways to enhance ATF4 (a gene important for antioxidant defense, amino acid metabolism, glucose homeostasis, memory, behavior…):

    Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864566/

    “We tested the hypothesis that guanabenz, by inhibiting GADD34 and consequently increasing eIF2α phosphorylation and elevating ATF4, would improve survival in models of PD by up-regulating parkin.
    [..]
    We further demonstrated that guanabenz attenuates 6-hydroxydopamine induced cell death of differentiated PC12 cells and primary ventral midbrain dopaminergic neurons in culture, and of dopaminergic neurons in the substantia nigra of mice.
    [..]
    Furthermore, if either ATF4 or parkin is silenced, then the protective effect of guanabenz is lost.”


    The other study fell into my lap when I googled for myelin-related articles:

    Regulation of PERK–eIF2α signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes
    https://www.nature.com/articles/ncomms12185

    “Tuberous sclerosis complex-1 or 2 mutations cause white matter abnormalities, including myelin deficits in the CNS
    [..]
    data suggest that Tsc1-mTOR [sustained activation] signalling elevates ER stress response and apoptotic pathways in addition to inhibition of the myelination program
    []
    Treatment with guanabenz [..] rescues oligodendrocyte cell death and myelination defects in Tsc1-mutant mice.”
    []
    We find that elevation of p-eIF2α-mediated adaptive responses by guanabenz protects OLs from apoptosis and maintains the balance between stress remediation and cell death in Tsc1 mutants."

    [I also found this interesting quote when matching symptoms with molecular mechanisms:]
    “This suggests that constitutive activation of mTOR signalling impedes the differentiation of all oligodendrocyte lineage cells, whereas deletion of mTOR mainly impacts spinal cord myelination.”
    -------------------------------

    Sustained activation of the UPR is implicated in several relevant diseases like Alzheimer's, Huntington's, Creutzfeldt–Jakob, ALS and diabetes, so why not autism too?

    /Ling

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    1. Hi Ling, I am interested in Guanabenz but it was discontinua ted or retired from the market in many countries.Who knows why.
      Valentina

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    2. Hi Ling!

      Hope all is well.

      Ling, my research had led me to ER stress as a potential contributor in ASD a couple of years ago, and I found a potential treatment for ER stress in TUDCA.

      TUDCA has some very interesting properties. If, down the road, any objective testing reveals that it would help in my specific case, I would consider using it.

      It's sold as a supplement, so is readily available.

      I hope this is helpful Ling, and if you hadn't run into TUDCA before, try Pubmeding it, I think you will be fascinated by what it can do, especially if you're interested in UPR / ER Stress.

      AJ

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    3. Thanks AJ!
      No I haven't looked at TUDCA before, hardly recognize the name of it. I'm very much into the ER stress / unfolded protein response right now, so this will be some good reading.

      Did I mention how much I value your input? :-)

      /Ling

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    4. Hi Ling!

      Thank you for the kind words :-)

      You know the same goes for me. Between the two of us, I think we may represent a big part of PubMed searches.

      As far as TUDCA, it's a fascinating molecule in terms of ER stress and the good news is, it's easily accessible as a supplement.

      I believe it also crosses the BBB, so a really good option for those whose issues arise from ER Stress.

      If you find any interesting items about it, please share as I hadn't looked TUDCA up in years. I've kept it in my back pocket should ER Stress turn out to be a factor for my daughter.

      Hope all is well with you and the family!

      AJ

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  5. Peter,

    Please could you tell me if my childs opposite reaction to melatonin is an indicator that he may be a responder to bumetanide?? I have tried him on varying doses from .75mg to 2 mg and it makes him more restless.

    Just wondered if melatonin has an effect on gaba. I would assume it does but is regularly prescribed for autistic children but doesnt seem effective for my child.

    Would be greatful for any insight you might have.

    Many thanks

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  6. Just came across some new and interesting Alzheimer's research concerning ghrelin and had a thought about how it may connect to autism:

    Press Release:

    https://www.sciencedaily.com/releases/2019/09/190903173401.htm

    Paper:

    https://stm.sciencemag.org/content/11/505/eaav6278

    In effect, the researchers found that beta-amyloid binds and inhibits the ghrelin receptor in the hippocampus, thereby triggering what the researchers called "ghrelin resistance". This receptor works with dopamine D1 receptors to enable proper synaptic plasticity in the hippocampus.

    Here is a study showing low ghrelin levels in autistic boys:

    https://www.ncbi.nlm.nih.gov/pubmed/25257829

    Low ghrelin levels of course are not the same thing as "ghrelin resistance", but the outcome could be similar in that a lack of or at least low levels of ghrelin could be causing D1 receptor dysfunction in the hippocampus, thereby decreasing synaptic plasticity and impeding learning.

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