Autism in Norway: The 7-fold increase in Autism linked to Maternal Migration

 

The Olso to Bergen line is one of Europe’s most beautiful railways

 

I did have another sense of déjà vu, when I read about the big spike in autism in one city in Norway.  Norway is a very expensive country, but well worth a visit.  We enjoyed it.  One of Monty’s former 1:1 assistants emigrated to Norway to work in their excellently funded special needs therapy system.  

A decade ago, there was a peak in media interest in Somali autism clusters in Sweden, Minneapolis and San Diego. Refugees had been taken to live in far away lands, with very different environmental conditions.  They soon started to produce children with a very high incidence of autism. This was a surprise to all the academics and a shock to the parents.   The Somali-Swedes even started calling it the Swedish disease, because they had never encountered such children before in Somalia.

 

Swedish study dissects autism risk in immigrants

Swedish migration: Only specific groups of immigrants — those from low-income countries and those who migrated near or during pregnancy — have an increased risk of autism, suggests a new study.

 

The Swedish Disease (Link to the old blog post)

 

A few hundred posts later after my one on the “Swedish disease”, it really is absolutely no surprise that the Norwegians have experienced the same phenomenon. 

 

Risk of autism seven times higher in Norwegian children with immigrant mothers

A study was conducted after health professionals started noticing a concerning pattern.

Researchers concluded in a recent Norwegian study that children of foreign-born mothers have a far higher risk of being diagnosed with autism. The study included 142 children aged 2-6 years old with an autism diagnosis in Sør-Trøndelag in mid-Norway.

The risk of autism in these children was just over seven times higher if the children were born of immigrant mothers.

The over-representation of this population indicates that the mothers' immigrant backgrounds may impact the development of autism, the researchers behind the study write in an article in Tidsskriftet, the journal of the Norwegian Medical Association. 

 

The actual research paper:

 

Autism spectrum disorder in preschool children in Sør-Trøndelag 2016–19

BACKGROUND

Autism spectrum disorder (ASD) is an umbrella term covering a range of conditions characterised by challenges with social interaction, restricted interests and repetitive behaviours. The prevalence of ASD has increased significantly in recent years, and there is a clinical impression of a preponderance of cases among young children whose mothers were not born in Norway.

MATERIAL AND METHOD

The study included 142 children aged 2 to 6 years who were diagnosed with autism in the county of Sør-Trøndelag, Norway in the period 2016–2019. The following information was collected: age at onset of symptoms and diagnosis, primary diagnosis, ADOS-2 (Autism Diagnostic Observation Schedule) scores, whether the child was born in Norway and the mother's country of birth.

RESULTS

Children of mothers born outside of Norway had a 7.7 times higher risk of being diagnosed with autism than children of Norwegian-born mothers, with an annual incidence of 0.74 % and 0.10 % respectively. These children were diagnosed earlier, at an average age (standard deviation) of 41.9 (11.8) and 51.8 (18.1) months respectively (95 % CI 4.7 to 15.2); a p-value of <0.001 for the difference. They also had a higher ADOS score, with an average (standard deviation) of 19.0 (6.2) and 15.3 (7.1) respectively.

INTERPRETATION

The preponderance of autism diagnoses may be an indication that the mothers' country of origin has an impact on the development of the condition. This has implications for adaptions to the assessment and follow-up of this patient group.

MAIN FINDINGS

The incidence of autism spectrum disorder was higher among children of migrant mothers than children of Norwegian-born mothers.

Children of migrant mothers were younger at the time of diagnosis and had more severe symptoms than children of Norwegian-born mothers. 

Clinical impressions suggest an overrepresentation of autism spectrum disorder (ASD) among young children of migrant mothers and that the severity of ASD is greater in this group. This impression is supported by an official Norwegian report from 2020, where data from the Norwegian Patient Registry suggests an increased risk of autism in young children with a minority background (1).

 

 

Age at symptoms onset in preschool children with autism spectrum disorder in Sør-Trøndelag 2016–19 divided into six-month intervals (n = 133). The difference in reported symptom onset between the two groups is not statistically significant.

 

Country of origin for mothers of preschool children diagnosed with ASD in Sør-Trøndelag 2016–19 (N = 142).

  

The study included 142 children in Sør-Trøndelag diagnosed with ASD in the period 2016–19 (Table 1). Parents of 80 of the children (56 %) reported their first concern about symptoms between 12–24 months of age (Figure 1). The difference in age at symptom onset between children of migrant mothers and children of Norwegian-born mothers was not statistically significant.

 Our findings suggest that the mother's migration background is associated with an increased risk of ASD in preschool children, as well as more severe symptoms and a younger age at diagnosis. The findings suggest that the mother's migration background may influence the development of ASD.

Previous studies support our findings of an increased risk for ASD in children of migrant mothers (9–11, 22).

We found a higher mean ADOS score in children of migrant mothers compared with children of Norwegian-born mothers. This group was also younger at the time of diagnosis. A plausible explanation could be that these children were identified and examined at an earlier age because they had more severe symptoms. An Australian study (12) found that children of mothers who migrated from low-income countries were younger at the time of diagnosis and had an increased risk of intellectual disability. Our findings may indicate greater severity of the disorder in children of migrant mothers. The association between higher ADOS scores and early age of diagnosis was shown in both groups. This indicates that young children with clear signs of developmental disorder are identified and evaluated early, regardless of the mother's country of origin. 

A Swedish study (10) found that the mother's migration background increased the risk for ASD independent of the migration background of the father. A Finnish study (11) found no increased risk of ASD among children where only the father had a migrant background.

CONCLUSION AND IMPLICATIONS

This study supports the clinical impression that ASD is overrepresented among children of migrant mothers. The incidence of ASD was 7.7 times higher in children of migrant mothers than children of Norwegian-born mothers. Our findings also suggest that children with ASD of migrant mothers are younger at the time of diagnosis and have more severe symptoms.

   

It’s the Immune system, forget Vitamin D

One explanation for those Somali autism clusters a decade ago was vitamin D; researchers thought that the pregnant mothers in Sweden were short of sunshine.   But what about the big Somali autism cluster in very sunny San Diego? 

The immune system adapts very slowly to its environment and gets used to living along side a wide family of bacteria from the environment.

Adults will struggle to adapt to changes in their bacterial environment.  Consider a Western backpacker travelling around India on the cheap, he is going to get sick, or just lose a lot of weight.  I chose the latter when I did this.  If you want to lose weight, take a budget trip to India.  Visit Scandinavia and you will not get sick, but it will lighten your wallet. 

For the fetus created in Somalia, it is the lack of exposure to the expected bacteria in Sweden or Norway that upsets the immune system. It ends up over-reacting and damaging itself.  

  

Conclusion 

Migration from very poor countries to very rich ones, while pregnant, risks seriously disrupting development of the immune system of the fetus and its vital calibration process.  The result may be autism or other neurological conditions.  In Norway a 7-fold increase in autism has been found; they did not measure the impact on related, but less troubling disorders like ADHD and dyslexia.

Not only is there 7x more autism, but it is more severe autism, with a higher score on the ADOS scale.

Clearly many people do not get advance knowledge of when they might become a refugee.  Very poor countries have very high birth rates and so young females are quite likely to be pregnant at any given time.

We know that any kind of severe stress also increases the incidence of autism.  Examples in the research include extreme weather events like hurricanes. Wars, fleeing from home, journeying overland in harsh conditions will be very stressful.

We can use this data to further the wider understanding of how the immune system is a factor in the increase in autism prevalence worldwide. We can then consider modifying the immune system to protect the future fetus from autism and indeed pure auto-immune conditions (asthma, eczema, IBS etc).  The simple way to do this is to add back exposure to bacteria that your grand parents and great grand parents would have been exposed to.  In particular, this means exposure to domesticated animals, even just cats and dogs.

We were recently in Pelion, Greece and over there you cannot avoid contact with animals.  Cats and dogs are roaming freely in cafes and restaurants, mainly outside but not exclusively.  Several times a day you will brush up against some four-legged new friend.  Are auto-immune diseases less prevalent in Greece?  What do you think?

Ideally you would be exposed to cows, horses, sheep, goats etc.  Take a hike through the countryside or visit a farm.  Don’t try and sterilize your shoes afterwards.

This kind of animal contact is nowadays uncomfortable to many people, but over tens of thousands of years your immune system has been trained to expect it.

Another take home message is that nobody is reading all this autism research and putting the pieces together; you have to do it for yourself.

 

Preventing Auto-Immune Disease and some Autism

Today’s post is another one filling in some gaps in this blog.

I think it is common sense to say that preventing a problem from developing is much wiser than trying to solve it later on.  This is a recurring issue in both life and medicine.

In the research we now see preventative measures developed to reduce the risk of cancer, we also see how some interventions are only effective when started very early.

In the case of autism we have seen than often it is caused by a myriad of factors that by themselves might have been harmless but when taken together are the multiples hits that caused the brain to develop differently.

Much research looks individually at these factors that increase the risk of autism.  In the wider media much disdain is directed to these findings as if each factor is THE cause of autism and how can so many things cause autism.  But by understanding these factors you can then set about countering them.

I did create my simplified schematic to explain classic autism a while back.  It is not perfect but it does illustrate much of what is going on.

I do get occasional questions about reducing the risk of autism.  For example, Monty now aged 13 with ASD, has a big brother and he wants to know.  Our reader, Kritika from India, has also raised this issue.  If you have autism in your family you may well decide you would like to minimize the risk of more cases.

In practical terms, you cannot change your genes or those inherited epigenetic markers.  Maybe this will change in future.  But there are things you can do.

We know that oxidative stress is a driver of much disease including autism.  This can be minimized by lifestyle changes and indeed with a little pharmacological help.

I was interested to see a study that used NAC to treat mothers who suffer unexplained pregnancy loss, the antioxidant showed a “significant increase in the take-home baby rate”.  I was really just looking for safety information.

N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss 

Pregnancy could be associated with a state of oxidative stress that could initiate and propagate a cascade of changes that may lead to pregnancy wastage. This process of oxidative stress may be suppressed by the antioxidant effect of N-acetyl cysteine (NAC). The current study aimed to evaluate the effect of NAC therapy in patients diagnosed with unexplained recurrent pregnancy loss (RPL). The study was a prospective controlled study performed in the Women's Health Centre, Assiut University, Egypt. A group of 80 patients with history of recurrent unexplained pregnancy loss were treated with NAC 0.6 g + folic acid 500 microg/day and compared with an aged-matched group of 86 patients treated with folic acid 500 microg/day alone. NAC + folic acid compared with folic acid alone caused a significantly increased rate of continuation of a living pregnancy up to and beyond 20 weeks [P < 0.002, relative risk (RR) 2.9, 95% confidence interval (CI) 1.5-5.6]. NAC + folic acid was associated with a significant increase in the take-home baby rate as compared with folic acid alone (P < 0.047, RR 1.98, 95% CI 1.3-4.0). In conclusion, NAC is a well-tolerated drug that could be a potentially effective treatment in patients with unexplained RPL.

This then made be recall a US fertility clinic, that our reader Roger once mentioned in a comment.

http://www.preventmiscarriage.com/

http://www.preventautism.com/

“At Braverman Reproductive Immunology, we believe Autism Spectrum Disorder (ASD) and various pregnancy and infertility complications (listed below) appear to have the same cause. In fact, we have found that a large number of patients who present to our center with the below complications already have a child with ASD.

This discovery started us on the journey to see if ASD itself could be prevented while treating other associated conditions. We believe treatment for these common issues will not only prevent the pregnancy complications listed below, but may also prevent ASD in the group of patients that have already had a child with ASD.”

Dr Braverman does not mention oxidative stress, but perhaps he should.

So step one would be to reduce oxidative stress during pregnancy, via lifestyle changes and taking antioxidants.

Step two would be to avoid inflammation, Dr Braverman refers to the link to auto-immune disease and miscarriage/autism.

We know that maternal inflammation is one of the easiest ways to cause autism in mouse models (the MIA model - Maternal Immune Activation).

  

We have some research to show that the risk of auto-immune disease can indeed be reduced and indeed that the risk of progression from minor to more major auto-immune disease can also be minimized.

We even have a tiny study showing that immuno-modulatory therapy using a probiotic during pregnancy can reduce incidence of ADHD and autism. For me ADHD is just a case of autism-lite.

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

Background:

Recent experimental evidence suggests that gut microbiota may alter function within the nervous system providing new insight on the mechanism of neuropsychiatric disorders.

Methods:

Seventy-five infants who were randomized to receive Lactobacillus rhamnosus GG (ATCC 53103) or placebo during the first 6 mo of life were followed-up for 13 y. Gut microbiota was assessed at the age of 3 wk, 3, 6, 12, 18, 24 mo, and 13 y using fluorescein in situ hybridization (FISH) and qPCR, and indirectly by determining the blood group secretor type at the age of 13 y. The diagnoses of attention deficit hyperactivity disorder (ADHD) and Asperger syndrome (AS) by a child neurologist or psychiatrist were based on ICD-10 diagnostic criteria.

Results:

At the age of 13 y, ADHD or AS was diagnosed in 6/35 (17.1%) children in the placebo and none in the probiotic group (P = 0.008). The mean (SD) numbers of Bifidobacterium species bacteria in feces during the first 6 mo of life was lower in affected children 8.26 (1.24) log cells/g than in healthy children 9.12 (0.64) log cells/g; P = 0.03.

Conclusion:

Probiotic supplementation early in life may reduce the risk of neuropsychiatric disorder development later in childhood possible by mechanisms not limited to gut microbiota composition.

The issue, as with NAC during pregnancy, is whether immuno-modulatory therapy is safe.

The study on ADHD and autism was actually a study looking at whether a certain probiotic if given during pregnancy could reduce eczema later on in the child.

  

We also have the studied effect of having a pet dog at home.

House dust exposure mediates gut microbiome Lactobacillus enrichmentand airway immune defense against allergens and virus infection

 

Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched for Lactobacillus johnsonii, which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.

One of my views is that by early treatment of autism you may indeed reduce the risk of epilepsy.  The key here is “reduce the risk”, it does not mean there is no risk.  There are likely hundreds of causes of epilepsy, but if you can reduce the incidence by 30+% that would look like a big success to me.

I recall another study that looked at treating people with eczema to see if you could reduce the chance of progression to asthma.  Using Ketotifen the trial showed that it was indeed possible.

Prevention of asthma by ketotifen in infants with atopic dermatitis. 

To evaluate the prophylactic effect of ketotifen against the onset of asthma we selected 121 infants with atopic dermatitis, without any history suggestive of asthma (cough and/or wheezing). Sixty-one children received ketotifen twice daily. Those who weighed less than 14 kg received 0.8 mg; 14 kg or more, 1.2 mg. Sixty children, a placebo syrup indistinguishable from the active syrup. Both groups were followed for 1 year, with bimonthly evaluations. The criteria for onset of asthma were two different episodes of wheezing treated with bronchodilator drugs. Both groups were comparable regarding age, sex, weight, onset, and duration of atopic dermatitis and age at the onset of asthma. During the 1 year study, asthma was observed in eight children of the ketotifen group (13.1%) and in 25 children of the placebo group (41.6%) (P less than .001). Side effects were negligible and routine laboratory tests disclosed no significant alterations. Ketotifen is a very useful drug for prevention of asthma in children with atopic dermatitis and total IgE more than 50 IU/mL.

Somali Autism Clusters

This then takes me back to that issue I looked at long ago, which was the reason for the Somali immigrants to Sweden and US having so many children with autism.  This even got termed the Swedish Disease by the migrants, they claimed to have never seen autism back home in Somalia.

Then we have the hygiene hypothesis which in effect says that, within limits, a little dirt is good for you.

Hormonal Dysfunction

We know that gestational diabetes increases the risk of autism and we also known that the mother being hypothyroid increases the risk.  In some cases the hormone dysfunction is a consequence of the auto-immune dysfunction.

We also know the female hormone progesterone is extremely neuro-protective.  The level of this hormone is supposed to rise during pregnancy.

  

In past times hormones were given to some pregnant mothers, but this went out of fashion.  Perhaps this should be revisited?

Then we have the surge of the hormone oxytocin that the baby is supposed to receive at birth.  This surge may be relevant to the GABA switch when shortly after birth this neurotransmitter is supposed to switch from excitatory to inhibitory as the neurons mature. If the baby is born by Caesarian there will be no oxytocin surge for the baby.   

Preventing Regressive Autism Secondary to Mitochondrial Disease (AMD)

It is on open secret that doctors at Johns Hopkins have identified a variant of regressive autism called Autism secondary to Mitochondrial Disease (AMD).

It remains unclear how rare this is and absolutely nobody serious is going to research this, if they ever want to receive a research grant in the future.

We saw that in people with a genetic predisposition to mitochondrial dysfunction, an immune over-reaction to an insult like multiple vaccinations can trigger mitochondrial disease.  This will present itself as autism and quite possibly severe autism in a previously unaffected child.

Those doctors treating AMD use mild immuno-suppressing drugs before any future vaccinations.

How do you minimize the chance of AMD? 

The first thing is to never use paracetamol/acetaminophen in a baby or child, particularly just after vaccination.  This drug may kill the pain but it depletes GSH the body’s main antioxidant, just when it needs it most.   Use something like Ibuprofen.

Vaccines are given in multiples so as to save time and money and I suppose improve compliance. You might expect giving them one-by-one would actually make them more effective as well minimizing any collateral damage to a small percentage of kids.

Conclusion

As I keep reminding readers, I am not a doctor, but it would be nice if a few more doctors other than Braverman took preventing autism seriously.

I would like to know if progesterone is an effective therapy in the MIA model of autism.  In this model they trigger the mother’s immune system during pregnancy which leads to offspring with autism.  What would be the effect of giving progesterone?  Would it protect the pups?

Are progesterone levels reduced in mice that will become autistic?

So I suppose I would trial NAC and progesterone in the mother mouse.

For everyone else it is case of choosing whether or not to make lifestyle changes to reduce oxidative stress.  Improving gut bacteria can be done via probiotics, eating more (slightly dirty) fruit and vegetables, having a pet dog, spending some time in the nature.  

As for vaccine risk, however small it might indeed be, there will never be a serious investigation of this, for understandable reasons.