Preventing Miscarriages/Autism using Progesterone? And Sex-Specific Fetal and Placental Responses to Adversity

 

Today’s post returns to the theme of reducing the incidence/severity of future autism and introduces another factor that helps explain why girls have some degree of protection from autism.

The focus today is on female hormones and progesterone in particular.

It does look like hormones can play a role in both triggering and potentially treating some autism, but it is not an area likely to be followed up on in the mainstream.

We have seen previously in this blog that some infertility experts find an association between miscarriage and autism. One US fertility doctor has a prevent miscarriages website and a prevent autism website, because his feeling is that by reducing miscarriage risk, you may also reduce autism risk. He was shocked by how many of his fertility patients have other offspring with autism.

This should really be common sense.

·        In-utero stress increases the chance of a miscarriage

·        In-utero stress increases the chance of autism

The common solution would be to reduce sources of in-utero stress.  Which sounds simpler than it is.

I have previously looked in some detail into therapies that improve outcomes in traumatic brain injury (TBI), because much damage done in a TBI from a car crash, or skiing accident, occurs after the accident, as the brain over-reacts to the trauma and this then causes irreparable damage. Both the female hormones estradiol and progesterone, if given promptly, improve the outcome in TBI.  Another highly neuroprotective drug is Atorvastatin, from my son’s Polypill therapy, which has also been shown to improve outcomes in TBI; we even know how this happens. Atorvastatin, given intravenously, can extinguish a cytokine storm. Cytokine storms even play a key role in severe Covid-19, when lungs and other organs are damaged by the over-response of the immune system.

I was pleased to see that progesterone has recently been adopted as an approved therapy to prevent miscarriages in the United Kingdom.  I am actually really surprised that they were allowed to make the necessary clinical trials.  I would have thought this would be seen as unethical and risky.

 

Progesterone recommended to prevent early miscarriage

One of those behind the Tommy's National Centre for Miscarriage Research research, Prof Arri Coomarasamy, from the University of Birmingham, said  "This is a very significant moment.  We have an intervention that works that can stop a miscarriage. This gives hope to thousands of couples throughout UK. But it's really important to appreciate that only some miscarriages can be prevented by progesterone. There are other causes for miscarriages. We still need to study them. We need to find other effective treatment. About one in four pregnancies ends in miscarriage - the vast majority in the first few months or trimester.” 

 

Progesterone could prevent 8,450 miscarriages a year, finds new research 

PRISM studied 4,153 women with early pregnancy bleeding at 48 hospitals in the UK and found there was a 5% increase in the number of babies born to those who were given progesterone who had previously had one or more miscarriages, compared to those given a placebo.

The benefit was even greater for the women who had previous ‘recurrent miscarriages’ (i.e., three or more miscarriages) – with a 15% increase in the live birth rate in the progesterone group compared to the placebo group.

 

A 5% increase does not sound much.

A 5% reduction in autism incidence probably would not be seen as statistically significant. 5% would not be a very high hurdle for an autism prevention therapy. With a package of therapies, I think you could do very much better. I would consider “good” to be at least a one third reduction in genuine cases. Of course, it would be more complex, since in reality you would be reducing severity of autism. Autism is not binary, more like shades of grey.

 

Would progesterone reduce the risk of future autism?

I do not think we will ever get the answer that question.

Preventing miscarriage is seen as much more important than preventing autism.

The evidence for immediate treatment with progesterone or atorvastatin, after a head injury, has not led to its widespread adoption.  Try explaining that one to Mrs Schumacher (wife of the Formula One racing star, who had a traumatic brain injury while skiing)

The key take away from the PRISM miscarriage study is that progesterone treatment in pregnant women is safe.  It is also inexpensive.

 

Prenatal Hormones in Autism

In a perfect world, you would study hormone levels in pregnant women and find clear associations with autism incidence in offspring. We do not live in such a world.

In the research, hormone levels are all over the place and vary from study to study.

This can be seen as good news, since the range is so wide you can very likely increase the level of certain hormones without any unintended consequences.

  

Foetal oestrogens and autism

Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood,

 

When I look at the above graph my conclusion is that the fetal estradiol (oestradiol, in UK English) level is all over the place.  It is nonsense to conclude that high levels are associated with autism. 

 

Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California

Results from this large, population-based study suggest that prenatal levels of the hormones, estriol and a gonadotropin (hCG), as well as MSAFP are associated with altered risks of having a child who later develops autism. Consistently, the risk of ASD was increased at lower levels of uE3; modelled both categorically or continuously, and examining the distribution graphically, the curve seems shifted to the left for cases. Further, the risk of ASD was increased with higher levels of MSAFP, while the associations with hCG were with both low and high levels. Although associations were modest, the fact that our results are based on levels of these prenatal markers measured during a developmentally-relevant period, and account for potential confounders, p

 

Our results suggest that continued investigation of prenatal hormones and possible mechanisms for an association with ASD is warranted. The associations we report were not of a large magnitude, which may make replication of the findings difficult in other studies that do not have access to the large numbers and unique resources we used. The 90th percentiles reflect MoMs of 1.7–2.0, which are not particularly high, but approach prenatal screening risk cut-points currently in use for other conditions (usually 2.0–2.5 MoM). The 10th percentile of uE3 is about 0.75 MoM. Measurement of additional estrogens, as well as androgens, from blood samples collected during pregnancy would be an interesting avenue for future research, if available in large enough studies. In addition, studies of endocrine-disrupting chemicals and genes involved in steroid hormone metabolism may yield further clues to a hormonal etiology for autism. Though modest increases in risk were seen in this large study, converging evidence suggests that ASD has multiple causes, and thus, identifying factors with small associated risks may help to better understand ASD and potential mechanistic pathways.

  

The Prenatal Hormone Milieu in Autism Spectrum Disorder

Though the etiology of autism spectrum disorder (ASD) remains largely unknown, recent findings suggest that hormone dysregulation within the prenatal environment, in conjunction with genetic factors, may alter fetal neurodevelopment. Early emphasis has been placed on the potential role of in utero exposure to androgens, particularly testosterone, to theorize ASD as the manifestation of an “extreme male brain.” The relationship between autism risk and obstetric conditions associated with inflammation and steroid dysregulation merits a much broader understanding of the in utero steroid environment and its potential influence on fetal neuroendocrine development. The exploration of hormone dysregulation in the prenatal environment and ASD development builds upon prior research publishing associations with obstetric conditions and ASD risk. The insight gained may be applied to the development of chronic adult metabolic diseases that share prenatal risk factors with ASD. Future research directions will also be discussed.

 

Female placentas are “superior” to male placentas.  Note the placenta has the same sex as the fetus and yes, it is a binary choice.

  

Sex-Specific Fetal and Placental Responses to Adversity

Fetal growth, development, and HPA axis programming in the setting of obstetric adversity differ by fetal sex (173–175). These sex-specific responses serve as additional mechanisms in which to consider male ASD predominance (see Figure 2). As the placenta is derived from extra-embryonic tissues, the placenta has the same sex as the fetus (178). Evidence suggests that the placentas of male and female fetuses differ in response to adverse prenatal environments through modulation of steroid pathways, placental genes, and protein synthesis (176). Placental growth and structure differ by sex, with male placentas being smaller in size but more efficient at nutrient and oxygen delivery (179, 180). Fetal growth depends upon the limited capacity of the maternal-placental interface to deliver oxygen and nutrients. Thus, greater placental efficiency among males precipitates faster somatic growth while increasing vulnerability to in utero perturbations (179, 181). This may have deleterious neurodevelopmental consequences, as fetal brain development relies on the availability of oxygen and nutrients such as fatty acids, glucose, and amino acids (131, 182, 183). In contrast, female placentas may have superior ability to buffer and adapt to suboptimal prenatal conditions (180).

 

Sex-specific fetal and placental adaptations to maternal adversity. Placentas of male and female fetuses respond differently to mild forms of maternal adversity. In the placenta of female fetuses, multiple changes in glucocorticoid barrier enzyme activity, gene expression, and protein synthesis occur leading to decreased growth (176, 177). This is advantageous as it preserves fetal oxygen and nutrient delivery. In the placenta of male fetuses, minimal changes in gene and protein expression occur, and the male fetus continues to grow incurring increased vulnerability to adverse outcomes (176). 

Figure 3 links heightened in utero stress from inflammation, stressors, and metabolic disturbances to perturbation within the prenatal hormone milieu. Through pCRH stimulation, the placenta upregulates fetal HPA axis activity in response to in utero stress. Subsequently, the fetal adrenal glands increase DHEA(S) synthesis leading to elevated placental estradiol production. Higher placental estradiol and pCRH production promotes HPA axis maturation denoted by fetal adrenal de novo cortisol synthesis. In response to in utero stress, the placental also increases hCG production which stimulates fetal gonadal testosterone synthesis.

 

Linking in utero stress to increased fetal steroidogenic activity and ASD biomarkers at mid-gestation.

 

In utero stress we see raises estradiol in the mother, but also increases testosterone in the males fetus.

The stress hormone, cortisol is elevated in the fetus.

You might imagine that less testosterone and more estradiol would be neuroprotective.

We know that progesterone is neuroprotective and now we know that its use is safe.

 

Conclusion 

Nature does sometimes stumble short of perfection and this is inevitable.  Going too far preventing miscarriages would not be wise, but improving the outlook of a viable fetus looks like a good idea.

Miscarriage is defined as pregnancy loss before 23 weeks’ gestation.

More than 80% of miscarriages occur before the 12th week, and the rate decreases rapidly thereafter.

Chromosomal anomalies cause at least half of these early miscarriages; for example, male fetuses with Rett Syndrome.  This is nature’s way of dealing with a non-viable fetus.  Only girls with Rett Syndrome can survive, since they have one good copy of the the MECP2 gene, males have none. MECP2 is on the X chromosome (girls have XX and boys have XY).

A little helping hand from Progesterone looks like a wise idea.

But, how slowly things move in medical science. The paper below is from 2013.

Use of progestagens during early pregnancy

“During the past 50 years several trials investigated the use of progestagens for the prevention of miscarriage. Actually the therapeutic value of progestagens remains to be established. This might be due to the poor design of the studies which evaluated hormone effectiveness”

 

The issue with using any hormone to prevent/minimize autism is the potential for harm.  This did not seem to worry people in 60 years of trials in miscarriage.

I think we can conclude that progesterone for the prevention/reduction in severity of autism is very likely entirely safe.  Would it be beneficial?

We know that women with Polycystic ovary syndrome (PCOS), a condition in which the ovaries produce an abnormal amount of androgens (male hormones), have an increased chance of producing children with autism.  They might be a good place to start with a clinical trial.

The fact that female placentas give more protection against adversity during pregnancy is interesting and another contributing factor to the lower prevalence of autism in girls.  It is only certain types of autism where girls have protection. In the case of severe autism, girls are more likely to have detectable genetic anomalies than boys, making whole exome sequencing (WES) well worthwhile. It looks like girls are protected somewhat from multifactorial autism, which I think makes sense; they might just end up with some dyslexia or sub-clinical autism.

Multifactorial autism should be the type that you can minimize, by lightening the contributing adverse burdens.  This itself requires a multifactorial approach.

Anorexia, Orthorexia, PCOS, Fertility and Elevated Autism Risk (and don't forget Paternal Obesity)

 Super skinny is a poor role model and another

driver of autism risk via ensuing endocrine problems

While some types of autism cannot easily be prevented, those that relate to the lifestyle of future parents clearly can be reduced.

Rather than just be shocked about an “autism epidemic”, with ever increasing prevalence, why not start doing something about it?  People are staying at home to reduce the incidence of Covid-19; the risk of autism can also be reduced.

Today’s post is about the young females who, under peer pressure and Instagram pressure, choose to starve themselves in the pursuit of looking “good”.

School lunches are a daily subject of conversation in our house, since I always ask Monty, now aged 16 with autism, what he had for lunch at school.  Monty’s assistant tells me that even though the lunches at school are not bad, he is one of the few to eat them all.  The boys generally just eat the meat and potatoes and do not touch the fruit, vegetables and of course not any salad.  The girls eat next to nothing.  Why do the already skinny girls at school eat nothing?  It's cool to be super skinny and the popular role model is Billie Eilish. So, the girls want to be skinny and feel depressed.

In schools in rich Western countries, the perceived eating problem is usually too much, rather than too little.  When I drop off Monty, aged 16 with autism, at school all I see is skinny kids.  Some do a lot of sport and athletic should not be confused with anorexic.

Anorexia is nearly always an issue in young females, rather than males.  It is also very common in females with Asperger’s type autism, who are naturally prone to obsessions.

For most people the skinny look is just a passing issue, does it do any long-term harm?  Apparently, it does.

This post was prompted by reading about a “celebrity” mother with all 3 kids diagnosed with autism.  She is clearly an Instagram type, even in middle age.

She looks healthy (thin), had her children young, she is not one of those high IQ types of autism parent; the Dad is not a maths professor.  Why are all the kids diagnosed with autism?  Fortunately for her, it is not severe autism; the children can talk, her  six year old son is asking about corona virus and they play together for Instagram. They are fussy eaters and do not like loud noises.  

Being a former model and now a “celebrity”, it should not be a surprise that she reveals having had anorexia for ten years, then was diagnosed with PCOS, had the consequential fertility problems, but wanted a large family.  Now she has 3 children with autism; she seems not to have made the connection between PCOS and autism. (Clearly endocrine dysfunction may not be the only contributing factor)

The Mum is an Ambassador for the UK’s National Autism Society (NAS).  I think the most useful role she could perform would be to go into schools and tell skinny girls to eat more, rather than keep pushing her look good (i.e. skinny) and exercise more image on social media.  Perhaps the NAS needs to learn more about autism.

Orthorexia is another common eating disorder. It is characterized by a fixation to eat only healthy foods, or to avoid entire food groups. It is often accompanied by exercise addiction, where exercise is foremost in life, rather than including exercise in a balanced lifestyle. 

I am quite sure you could make an algorithm to identify people with Orthorexia or Anorexia, with or without exercise addiction, based on their Instagram posts. Perhaps they should get sent a warning of likely endocrine disorders later in life, including fertility problems and a substantially higher risk of having children with autism. Perhaps, “You too could become an Ambassador for the UK’s National Autistic Society”, might shock some skinny girls into eating more. These are likely the very same "cool" girls who make their female classmates with Asperger's type autism feel socially excluded. 

      Instagram use is linked to increased symptoms of orthorexia nervosa

PCOS

Polycystic ovary syndrome (PCOS) is a set of symptoms due to elevated androgens (male hormones) in females.

Not everyone with PCOS has polycystic ovaries (PCO), nor does everyone with ovarian cysts have PCOS.

Women diagnosed with PCOS have increased risk of having a child with autism.

Women diagnosed with PCOS have an increased chance of being autistic themselves.  This not surprising since elevated male hormones in women is associated with autism, as in Turner Syndrome, where one of the X chromosomes is missing, or partially missing.

People with Turner syndrome have a lifelong endocrine disorder, that was not of their making; they are almost always infertile.

People with anorexia have given themselves endocrine problems that may lead to a diagnosis of PCOS.

PCOS is associated both with being overweight and with being malnourished/anorexic.

There are different criteria used to diagnose PCOS, but it affects about 5-10% of females.

Anorexia and Endocrine Disorder

For the easy to read version, here is a good article: -

Anorexia nervosa can cause lifelong endocrine problems

Overweight and obese patients are not the only patient group that needs lifestyle modification

Warren said that the incidence of fractures in this population when they are younger is up to eight times that of the normal population. “There is a high incidence of vegetarianism along with anorexia nervosa that may also contribute to osteoporosis because of fat avoidance and low protein, calcium and vitamin D intake,” Warren said. This problem is best treated nutritionally. With a return to a normal weight significant increases in bone density are seen and fractures will also stop, she said.

In addition, a lack of estrogen may also contribute to this extensive bone loss. Hormone replacement or oral contraceptives can be used as a secondary measure but appear to help only if that patient is eating well and near a normal weight.

Another common problem in women with anorexia nervosa is infertility. Many patients with eating disorders will not ovulate. Warren said that although patients may present with a fertility problem, endocrinologists should be sure that any underlying nutritional problem is resolved before a patient is encouraged to conceive. “You can help patients to conceive using drugs, but it is really not recommended until they have a normal BMI,” she said. “There is a higher incidence of miscarriage in these patients and higher incidence of low-weight babies due to intrauterine growth retardation.”

If the return to a normal weight does not solve the fertility problems, endocrinologists should also consider a premorbid hormonal imbalance. Warren said that some patients who have had anorexia nervosa may also have an anovulatory disorder like polycystic ovary syndrome. “Patients are overweight and then lose too much weight,” she said. “As they gain back weight, they return to their premorbid anovulatory state and although they may be making estrogen, they are not ovulating on a regular basis.”

Patients with anorexia nervosa may also present with symptoms that appear to be endocrine disorders but may in fact be a result of altered nutritional intake.

“Sometimes patients have low thyroxine and triiodothyronine,” Warren said. “They present with pseudo-hypothyroidism. It may be very mild, but endocrinologists have to be aware that this syndrome may present and it is not really hypothyroidism. It is just a reaction to severe nutritional deprivation.”

In addition, because patients with eating disorders may be compulsive water drinkers, they may also develop hyponatremia. “You have to look very carefully at how much [water] they are drinking,” she said.

The endocrine manifestations of anorexia nervosa: mechanisms and management

Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotrophic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia, and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5–15% of those affected by anorexia nervosa are men, only limited data exists regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.

Autism four times likelier when mother's thyroid is weakened

Pregnant women who don't make nearly enough thyroid hormone are nearly 4 times likelier to produce autistic children than healthy women, report scientists from the Houston Methodist Neurological Institute and Erasmus Medical Centre in an upcoming Annals of Neurology.

Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory

Elevated levels of prenatal testosterone may increase the risk for autism spectrum conditions (autism). Given that polycystic ovary syndrome (PCOS) is also associated with elevated prenatal testosterone and its precursor sex steroids, a hypothesis from the prenatal sex steroid theory is that women with PCOS should have elevated autistic traits and a higher rate of autism among their children. Using electronic health records obtained from the Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2014, we conducted three matched case-control studies. Studies 1 and 2 examined the risk of PCOS in women with autism (= 971) and the risk of autism in women with PCOS ( n = 26,263), respectively, compared with matched controls. Study 3 examined the odds ratio (OR) of autism in first-born children of women with PCOS ( n = 8588), matched to 41,127 controls. In Studies 1 and 2 we found increased prevalence of PCOS in women with autism (2.3% vs. 1.1%; unadjusted OR: 2.01, 95% CI: 1.22–3.30) and elevated rates of autism in women with PCOS (0.17% vs. 0.09%, unadjusted OR: 1.94 CI: 1.37–2.76). In Study 3 we found the odds of having a child with autism were significantly increased, even after adjustment for maternal psychiatric diagnoses, obstetric complications, and maternal metabolic conditions (unadjusted OR: 1.60, 95% CI: 1.28–2.00; adjusted OR: 1.35, 95% CI: 1.06–1.73). These studies provide further evidence that women with PCOS and their children have a greater risk of autism.

Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis.

There is evidence showing a positive correlation between prenatal androgens and their effect on the development of central nervous system and the autistic spectrum disorder (ASD) phenotype in offspring of mothers with polycystic ovary syndrome (PCOS). We applied a systematic review to investigate whether women with PCOS have increased odds of having a child with ASD, while, secondarily, if these women themselves are at high risk of having the disease. Major databases from inception until 14th October 2018 were searched. The primary outcome measure was the odds of an ASD diagnosis in children of mothers with diagnosed PCOS, while the secondary outcome was the odds of ASD diagnosis in women with PCOS. Scheduled subgroup analyses were according to the time of birth and maternal age.Ten studies were eligible for inclusion, including a total of 33,887 ASD children and 321,661 non-ASD children. Diagnosed PCOS was associated with a 1.66 times increase in the odds of ASD in the offspring [95% CI: 1.51, 1.83, p = 1.99 × 10^-25, 7 studies, I² = 0%, τ² = 0]. Women with PCOS were 1.78 times more likely to be diagnosed with ASD (95% CI: 1.10, 2.87, p = 0.0179, 5 studies, I² = 85.4%, τ² = 0.2432). Additional analyses did not change the initial result. The overall quality of the evidence was high. The pooled effects size displayed low heterogeneity for the primary outcome. While the heterogeneity in the secondary outcome appears to attenuate when only high quality studies are synthesized, still the result exhibits significant heterogeneity. Τhe available data allowed a subgroup analysis only for classification system for PCOS diagnosis and showed a significant increase of ASD diagnosis in the offspring of women with Read Code and ICD diagnosed PCOS. In conclusion, the available evidence suggests that women with PCOS have increased odds of having a child with ASD, an effect size estimate based on a large number of patients from studies of good quality. Regarding the evidence on the prevalence of ASD in PCOS women, results suggest that women with PCOS are more likely to be diagnosed with ASD.

As I have pointed out in earlier posts there is an association between parents who experience fertility problems and those who have children with autism.  PCOS is only one risk factor, auto-immune conditions affect both fertility and autism risk.  This was noted by one American fertility clinic, which decided to create a prevent autism website.

http://www.preventautism.com/

As specialists in reproductive immunology, we treat numerous patients who have suffered previous miscarriages and other pregnancy complications. Many of these women have had at least one child on the autism spectrum.

The most common question we encounter from our patients is, "Are the two outcomes connected?" Our patients want to know if diagnosis and treatment for the immune-related causes of miscarriage may also lessen the chance of a having a second child diagnosed with Autism Spectrum Disorder (ASD).

The Centers for Disease Control & Prevention (CDC) recently reported that about 1 in 68 children are diagnosed with autism. Accordingly, there are millions of couples asking the question, "Can we reduce our chances of a second child with ASD?"

In an effort to discover the answers my patients and countless other families are seeking, we have created this informational website. Our practice is currently investigating the following:

·         Can autism be prevented by treating immune-related issues during pregnancy?

·         Can we identify those babies that are most susceptible to these inflammatory responses from women with known or as yet unknown underlying autoimmune issues?

What We Know So Far

For some time now, we have noticed a trend among patients: Mothers with autoimmune disorders who experience an inflammatory flare during the second trimester appear to have an increased risk of having a child on the autistic spectrum. The correlation seems stronger in mothers who have had previous miscarriages and / or a previous child with ASD. Recent studies have also noticed the connection, citing data gathered from the CDC.

Because the second trimester is when critical brain development takes place, it seems logical to conclude that any hindrance to fetal growth at this time, including a trigger of the baby's autoimmune issues due to an overactive immunological response from the mother, could potentially be detrimental to the cognitive progression of the child.

Autism rates are on the rise, and it is our belief and experience that this is due to the many "triggers" present in our diets, as well as the medications that our "at-risk population of women" (women with underlying or known autoimmune syndromes) are exposed to.

Conclusion

If girls need a role model, best not to choose a skinny one. What about one that smiles (sorry, Billie Eilish) and eats.

Athletic good looks are not the same as being malnourished.

Undereating can be as harmful as over-eating and can cause permanent damage.

Autism is multifactorial, which means a long list of different things, either by themselves, or in combination can cause it.  Since the severity of symptoms needed to warrant a diagnosis of autism has fallen dramatically over the years, issues like PCOS are likely behind many people’s autism diagnosis. Some cases of PCOS are likely genetic, but some are self-induced and so preventable.

Not all people with an endocrine disorder will get a PCOS diagnosis.

All endocrine disorders in mothers are linked to autism.  For example, Type 1 diabetes (T1D), Type 2 diabetes (T2D) and Gestational Diabetes (GDM) all increase autism odds.

Unadjusted average ASD incidence rates per 1000 children in Southern California were:

·         4.4 for exposure to T1D

·         3.6 for T2D

·         2.9 for GDM by 26 weeks

·         2.1 for GDM after 26 weeks

·         1.8 for no diabetes

Source: https://jamanetwork.com/journals/jama/fullarticle/2685775
Data is from Southern California

If you are worried about an “autism epidemic” do something about it.  Encourage healthy eating and a healthy body image; some may need to revise what they think of as healthy.  Models and pop stars are generally a bad example.

There are numerous other preventable factors that increase autism prevalence/severity, some come from the mother, some from the father and some from the environment. (Recreational drug use, alcohol consumption, lack of exposure to the expected bacteria from pets and other domesticated animals etc). 

This post was really about elevated male hormones in females affecting their offspring, but of interest is that obesity in fathers (and as we already knew, in mothers) appears to have a major impact on autism incidence. 

Obesity among fathers appears to have a greater effect on severe autism incidence than obesity in mothers.  "Normal" BMI is often quoted as being 18-25.

Parental body mass index also seems to affect different severity of autism to different degrees.  I did rather suggest this when I wrote about PCOS above, meaning since autism is multifactorial, if you have no genetic predispositions to autism, being super skinny is adding just one set of risks. You are adding one bale of straw to the camel's back, so to speak.  

Here is the effect of body mass index of both parents on the risk of offspring later being diagnosed with Asperger's type autism. OR = Odds Ratio, so greater than one is increased risk and less than one is reduced risk.

Asperger's

Here (above) the skinny mother increases the odds ratio that her children will have mild autism, but this is not severe non-verbal autism. The same risk increase effect applies to skinny fathers.

The effect is not the same when you look at who later gets diagnosed with Autistic Disorder (Severe Autism)

Autistic Disorder (Severe autism)

In the above chart, being an anorexic mother has almost no effect on the odds that her child will have severe autism.  Having a skinny father is associated with a reduced chance of severe autism.

The real takeaway point from the study is don't forget about Paternal Obesity, it is not just about the mother.

Source: Parental Obesity and Risk of Autism Spectrum Disorder

"Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies."